start-ver=1.4 cd-journal=joma no-vol=779 cd-vols= no-issue= article-no= start-page=152453 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=1,2-naphthoquinone enhances IFN-γ-induced MHC-I expression in dendritic cells, thereby inducing CD8 T cell activation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells play a crucial role in immune responses by capturing pathogens and presenting antigens to T cells via major histocompatibility complex (MHC) molecules, thus triggering adaptive immune responses. 1,2-naphthoquinone (1,2-NQ), a quinone found in diesel exhaust and cigarette smoke, has various physiological functions. In this study, we investigated the effect of 1,2-NQ on the expression of antigen presentation-related molecules in the dendritic cell line DC2.4. The results revealed that 1,2-NQ enhanced the IFN-γ-induced upregulation of MHC-I expression at the transcriptional level. Moreover, it upregulated the expression of NLRC5, a transcriptional activator of MHC-I. 1,2-NQ is a reactive oxygen species (ROS) producing reagent. The 1,2-NQ-induced upregulation of MHC-I expression and downregulation of MHC-II expression were abolished by the ROS scavenger N-acetylcysteine. Similar effects on MHC expression were also observed with ROS-inducing reagents, such as paraquat and diethyl maleate. In addition, dendritic cells stimulated with 1,2-NQ exhibited enhanced efficacy in CD8 T cell activation, which was accompanied by increased IFN-γ production by T cells. These findings demonstrate that 1,2-NQ enhances the IFN-γ-induced activation of dendritic cells and promotes the activation of CD8 T cells. en-copyright= kn-copyright= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazatoKanon en-aut-sei=Miyazato en-aut-mei=Kanon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobataKai en-aut-sei=Kobata en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=1,2-Napthoquinone kn-keyword=1,2-Napthoquinone en-keyword=Dendritic cell kn-keyword=Dendritic cell en-keyword=IFN-γ kn-keyword=IFN-γ en-keyword=MHC-I kn-keyword=MHC-I en-keyword=CD8 T cell kn-keyword=CD8 T cell END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=8 article-no= start-page=3474 end-page=3475 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gene replacement therapy for centronuclear myopathy: A breakthrough in complex genetic muscle disease en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TakedaTetsuya en-aut-sei=Takeda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=8 article-no= start-page=522 end-page=532 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240625 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6–305 µM, MIC: 0.5–128 µg ml−1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity. en-copyright= kn-copyright= en-aut-name=IshikawaTeruhiko en-aut-sei=Ishikawa en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiYoko en-aut-sei=Eguchi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgarashiMasayuki en-aut-sei=Igarashi en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkajimaToshihide en-aut-sei=Okajima en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitaKohei en-aut-sei=Mita en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamasakiYuri en-aut-sei=Yamasaki en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SumikuraKaho en-aut-sei=Sumikura en-aut-mei=Kaho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkumuraTaisei en-aut-sei=Okumura en-aut-mei=Taisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TabuchiYuna en-aut-sei=Tabuchi en-aut-mei=Yuna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HayashiChigusa en-aut-sei=Hayashi en-aut-mei=Chigusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PasquaMartina en-aut-sei=Pasqua en-aut-mei=Martina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ColucciaMarco en-aut-sei=Coluccia en-aut-mei=Marco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ProssedaGianni en-aut-sei=Prosseda en-aut-mei=Gianni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ColonnaBianca en-aut-sei=Colonna en-aut-mei=Bianca kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KohayakawaChie en-aut-sei=Kohayakawa en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TaniAkiyoshi en-aut-sei=Tani en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HarutaJun-ichi en-aut-sei=Haruta en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UtsumiRyutaro en-aut-sei=Utsumi en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University kn-affil= affil-num=3 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=4 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= affil-num=5 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Education, Okayama University kn-affil= affil-num=10 en-affil=Institute of Microbial Chemistry (BIKAKEN) kn-affil= affil-num=11 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=12 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=13 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=14 en-affil=Istituto Pasteur Italy, Department of Biology and Biotechnology, “C. Darwin”, Sapienza University of Rome kn-affil= affil-num=15 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=16 en-affil=Compound Library Screening Center, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=17 en-affil=Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University kn-affil= affil-num=18 en-affil=SANKEN (The Institute of Scientific and Industrial Research), Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=11 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250707 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual roles of suberin deposition at the endodermal Casparian strip in manganese uptake of rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rice roots are characterized by having two Casparian strips (CSs) at the exodermis and endodermis, where transporters for mineral nutrients are expressed. However, the exact role of the CS in expression of the transporters and subsequent nutrient uptake is poorly understood. Here, we first investigated the role of the CS in manganese (Mn) uptake by using a rice mutant (oscasp1) defective in formation of the endodermal CS. Knockout of OsCASP1 resulted in decreased Mn uptake under limited Mn conditions, but increased Mn uptake at high Mn concentration. Immunostaining revealed that knockout of OsCASP1 did not affect the cell specificity of localization of two transporters (OsNramp5 and OsMTP9) required for Mn uptake, but decreased the protein abundance of these transporters at the endodermis regardless of Mn concentrations tested. Furthermore, we found that overaccumulation of suberin at the endodermis of the mutants suppressed the expression of two transporters; the expression of the two transporters was only observed in the endodermal cells without suberin deposition, but not in the cells with suberin deposition. Taken together, our results indicate that there are two roles for the CS in Mn uptake; maintaining normal expression of the transporters at limited Mn concentration and preventing Mn diffusion to the stele at high Mn concentration. en-copyright= kn-copyright= en-aut-name=FujiiToshiki en-aut-sei=Fujii en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamajiNaoki en-aut-sei=Yamaji en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaJian Feng en-aut-sei=Ma en-aut-mei=Jian Feng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Casparian strip kn-keyword=Casparian strip en-keyword=endodermis kn-keyword=endodermis en-keyword=manganese transporter kn-keyword=manganese transporter en-keyword=rice kn-keyword=rice en-keyword=root kn-keyword=root en-keyword=suberin deposition kn-keyword=suberin deposition END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=3 article-no= start-page=99 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP en-subtitle= kn-subtitle= en-abstract= kn-abstract=Golli–myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli–myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli–myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli–myelin basic protein knockout through the generation of conditional knockout mice (Golli–myelin basic proteinsfl/fl; E3CreN), in which Golli–myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli–myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli–myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli–myelin basic proteinsfl/fl; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli–myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli–myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system. en-copyright= kn-copyright= en-aut-name=MiyazakiHaruko en-aut-sei=Miyazaki en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiokaSaki en-aut-sei=Nishioka en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamanakaTomoyuki en-aut-sei=Yamanaka en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeManabu en-aut-sei=Abe en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImamuraYukio en-aut-sei=Imamura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyasakaTomohiro en-aut-sei=Miyasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakudaNobuto en-aut-sei=Kakuda en-aut-mei=Nobuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimogoriTomomi en-aut-sei=Shimogori en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamakawaKazuhiro en-aut-sei=Yamakawa en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkawaMasahito en-aut-sei=Ikawa en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NukinaNobuyuki en-aut-sei=Nukina en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=3 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=4 en-affil=Department of Animal Model Development, Brain Research Institute, Niigata University kn-affil= affil-num=5 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= affil-num=6 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=7 en-affil=Faculty of Life and Medical Sciences, Doshisha University kn-affil= affil-num=8 en-affil=Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science kn-affil= affil-num=10 en-affil=Laboratory for Neurogenetics, RIKEN Center for Brain Science kn-affil= affil-num=11 en-affil=Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University kn-affil= affil-num=12 en-affil=Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University kn-affil= en-keyword=Golli-MBP kn-keyword=Golli-MBP en-keyword=Cerebellar granule neuron kn-keyword=Cerebellar granule neuron en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Conditional knockout kn-keyword=Conditional knockout END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=e70146 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Gastric Atypical Lipomatous Tumor/Well‐Differentiated Liposarcoma With Endoscopic Morphological Changes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lipomatous tumor/well-differentiated liposarcoma is a locally aggressive mesenchymal neoplasm composed of adipocytes and stromal cells. Gastric cases are exceedingly rare, and their malignant potential remains unclear. We report a case of a woman in her 60s who was found to have multiple submucosal tumor-like lesions of the stomach. Over time, the tumors increased in size, requiring a laparoscopic partial gastrectomy. Histological examination revealed a tumor composed of both fatty tissue and fibrous stroma with nuclear atypia. Immunohistochemistry showed positivity for CDK4 and MDM2, and fluorescence in situ hybridization confirmed MDM2 amplification, leading to a diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma. This case presented an unusual gastric manifestation, with multiple submucosal tumor-like lesions on endoscopy and exhibiting progressive morphological changes over several years. en-copyright= kn-copyright= en-aut-name=OmoteRika en-aut-sei=Omote en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmoteShizuma en-aut-sei=Omote en-aut-mei=Shizuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SonobeHiroshi en-aut-sei=Sonobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamanoRyosuke en-aut-sei=Hamano en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanaiHiroyuki en-aut-sei=Yanai en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InagakiMasaru en-aut-sei=Inagaki en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Fukuyama Minami Hospital kn-affil= affil-num=3 en-affil=Department of Diagnostic Pathology, NHO Fukuyama Medical Center kn-affil= affil-num=4 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Gastroenterology, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=atypical lipomatous tumor kn-keyword=atypical lipomatous tumor en-keyword=CDK4 kn-keyword=CDK4 en-keyword=MDM2 kn-keyword=MDM2 en-keyword=stomach kn-keyword=stomach en-keyword=well-differentiated liposarcoma kn-keyword=well-differentiated liposarcoma END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue= article-no= start-page=104719 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Near-infrared photoimmunotherapy for recurrent cancer at the base of the tongue en-subtitle= kn-subtitle= en-abstract= kn-abstract=Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapeutic approach that targets epidermal growth factor receptor (EGFR). In NIR-PIT, administration of cetuximab sarotalocan sodium is followed by laser irradiation of the affected area, which theoretically should induce tumor cell death. However, residual tumors are occasionally observed. This study investigated factors that influence the therapeutic efficacy of NIR-PIT in cases of recurrence of cancer at the base of the tongue. Six patients undergoing 11 treatment cycles were analyzed, focusing on the puncture interval of cylindrical diffusers and the expression of EGFR in tumors. The results demonstrated that a puncture interval of ≤12 mm significantly enhanced therapeutic efficacy, with one case achieving complete response. EGFR expression was positive in all cases and expression score showed no significant change between before and after treatment. These findings suggest that puncture interval plays a critical role in therapeutic outcomes, whereas EGFR expression may not directly influence treatment efficacy. en-copyright= kn-copyright= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaoiYuto en-aut-sei=Naoi en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoJunya en-aut-sei=Matsumoto en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoShohei en-aut-sei=Fujimoto en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AndoMizuo en-aut-sei=Ando en-aut-mei=Mizuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=ear-infrared photoimmunotherapy (NIR-PIT) kn-keyword=ear-infrared photoimmunotherapy (NIR-PIT) en-keyword=Epidermal growth factor receptor (EGFR) kn-keyword=Epidermal growth factor receptor (EGFR) en-keyword=Cylindrical diffuser kn-keyword=Cylindrical diffuser en-keyword=Puncture interval kn-keyword=Puncture interval en-keyword=Base of tongue cancer kn-keyword=Base of tongue cancer END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250719 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs. en-copyright= kn-copyright= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OkadaNaohiro en-aut-sei=Okada en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InoueHiroaki en-aut-sei=Inoue en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoNaoyuki en-aut-sei=Hashimoto en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Neutron Therapy Research Center, Okayama University Hospital kn-affil= affil-num=14 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=199 cd-vols= no-issue= article-no= start-page=108027 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy—61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group—42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group—37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. en-copyright= kn-copyright= en-aut-name=HorinouchiHidehito en-aut-sei=Horinouchi en-aut-mei=Hidehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MurakamiHaruyasu en-aut-sei=Murakami en-aut-mei=Haruyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaHideyuki en-aut-sei=Harada en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SobueTomotaka en-aut-sei=Sobue en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoTomohiro en-aut-sei=Kato en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AtagiShinji en-aut-sei=Atagi en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KozukiToshiyuki en-aut-sei=Kozuki en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokitoTakaaki en-aut-sei=Tokito en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OizumiSatoshi en-aut-sei=Oizumi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeMasahiro en-aut-sei=Seike en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MioTadashi en-aut-sei=Mio en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoneTakashi en-aut-sei=Sone en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwaoChikako en-aut-sei=Iwao en-aut-mei=Chikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwaneTakeshi en-aut-sei=Iwane en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KotoRyo en-aut-sei=Koto en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TsuboiMasahiro en-aut-sei=Tsuboi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Oncology, Shizuoka Cancer Center kn-affil= affil-num=3 en-affil=Division of Radiation Therapy, Shizuoka Cancer Center kn-affil= affil-num=4 en-affil=Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente kn-affil= affil-num=6 en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center kn-affil= affil-num=7 en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=8 en-affil=Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center kn-affil= affil-num=10 en-affil=Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Kanazawa University Hospital kn-affil= affil-num=14 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=15 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=16 en-affil=Department of Medical, AstraZeneca K.K. kn-affil= affil-num=17 en-affil=Department of Thoracic Surgery, National Cancer Center Hospital East kn-affil= en-keyword=Non-small cell lung cancer kn-keyword=Non-small cell lung cancer en-keyword=Surgery kn-keyword=Surgery en-keyword=Adjuvant therapy kn-keyword=Adjuvant therapy en-keyword=Neoadjuvant therapy kn-keyword=Neoadjuvant therapy en-keyword=Chemoradiotherapy kn-keyword=Chemoradiotherapy en-keyword=Observational study kn-keyword=Observational study en-keyword=Retrospective study kn-keyword=Retrospective study END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=40 article-no= start-page=3355- end-page=3364 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plain language summary: tarlatamab for patients with previously treated small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AhnMyung-Ju en-aut-sei=Ahn en-aut-mei=Myung-Ju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KorantzisIppokratis en-aut-sei=Korantzis en-aut-mei=Ippokratis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MajemMargarita en-aut-sei=Majem en-aut-mei=Margarita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Juan-VidalOscar en-aut-sei=Juan-Vidal en-aut-mei=Oscar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HandzhievSabin en-aut-sei=Handzhiev en-aut-mei=Sabin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiHiroki en-aut-sei=Izumi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DziadziuszkoRafal en-aut-sei=Dziadziuszko en-aut-mei=Rafal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WolfJürgen en-aut-sei=Wolf en-aut-mei=Jürgen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BlackhallFiona en-aut-sei=Blackhall en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ReckMartin en-aut-sei=Reck en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AlvarezJean Bustamante en-aut-sei=Alvarez en-aut-mei=Jean Bustamante kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=HummelHorst-Dieter en-aut-sei=Hummel en-aut-mei=Horst-Dieter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DingemansAnne-Marie C. en-aut-sei=Dingemans en-aut-mei=Anne-Marie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SandsJacob en-aut-sei=Sands en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AkamatsuHiroaki en-aut-sei=Akamatsu en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OwonikokoTaofeek K. en-aut-sei=Owonikoko en-aut-mei=Taofeek K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=RamalingamSuresh S. en-aut-sei=Ramalingam en-aut-mei=Suresh S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=BorghaeiHossein en-aut-sei=Borghaei en-aut-mei=Hossein kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=JohnsonMelissa L. en-aut-sei=Johnson en-aut-mei=Melissa L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HuangShuang en-aut-sei=Huang en-aut-mei=Shuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=MukherjeeSujoy en-aut-sei=Mukherjee en-aut-mei=Sujoy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=MinochaMukul en-aut-sei=Minocha en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=JiangTony en-aut-sei=Jiang en-aut-mei=Tony kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MartinezPablo en-aut-sei=Martinez en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AndersonErik S. en-aut-sei=Anderson en-aut-mei=Erik S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=Paz-AresLuis en-aut-sei=Paz-Ares en-aut-mei=Luis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= affil-num=1 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=2 en-affil=Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= affil-num=3 en-affil=Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology kn-affil= affil-num=4 en-affil=Department of Medical Oncology, Saint Loukas Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Hospital de la Santa Creu i Sant Pau kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Klinische Abteilung für Pneumologie, Universitätsklinikum Krems kn-affil= affil-num=9 en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East kn-affil= affil-num=10 en-affil=Seoul National University Bundang Hospital kn-affil= affil-num=11 en-affil=Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdansk kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne kn-affil= affil-num=13 en-affil=Christie NHS Foundation Trust and University of Manchester kn-affil= affil-num=14 en-affil=Lungen Clinic, Airway Research Center North, German Center for Lung Research kn-affil= affil-num=15 en-affil=West Virginia University Health Sciences Center kn-affil= affil-num=16 en-affil=Translational Oncology–Early Clinical Trial Unit, Comprehensive Cancer Center Mainfranken and Bavarian Cancer Research Center, Universitätsklinikum Würzburg kn-affil= affil-num=17 en-affil=Department of Pulmonary Medicine, Erasmus MC Cancer Institute kn-affil= affil-num=18 en-affil=Dana–Farber Cancer Institute, Harvard Medical School kn-affil= affil-num=19 en-affil=Wakayama Medical University Hospital kn-affil= affil-num=20 en-affil=Division of Hematology–Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center kn-affil= affil-num=21 en-affil=Winship Cancer Institute of Emory University kn-affil= affil-num=22 en-affil=Fox Chase Cancer Center kn-affil= affil-num=23 en-affil=Sarah Cannon Research Institute at Tennessee Oncology kn-affil= affil-num=24 en-affil=Amgen kn-affil= affil-num=25 en-affil=Amgen kn-affil= affil-num=26 en-affil=Amgen kn-affil= affil-num=27 en-affil=Amgen kn-affil= affil-num=28 en-affil=Amgen kn-affil= affil-num=29 en-affil=Amgen kn-affil= affil-num=30 en-affil=Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Complutense University and Ciberonc kn-affil= en-keyword=Clinical trials kn-keyword=Clinical trials en-keyword=DeLLphi-301 kn-keyword=DeLLphi-301 en-keyword=DLL3 kn-keyword=DLL3 en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=SCLC kn-keyword=SCLC en-keyword=Small cell lung cancer kn-keyword=Small cell lung cancer en-keyword=T cell kn-keyword=T cell en-keyword=Tarlatamab kn-keyword=Tarlatamab END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=23 article-no= start-page=2715 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Predicting Surgical Site Infections in Spine Surgery: Association of Postoperative Lymphocyte Reduction en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Postoperative lymphopenia is reported as an excellent indicator to predict surgical-site infection (SSI) after spine surgery. However, there is still controversy concerning which serological markers can predict spinal SSI. This study aims to evaluate excellent and early indicators for detecting SSI, focusing on spine instrumented surgery. Materials and Methods: This study included 268 patients who underwent spinal instrumented surgery from January 2022 to December 2023 (159 female and 109 male, average 62.9 years). The SSI group included 20 patients, and the non-SSI group comprised 248 patients. Surgical time, intraoperative blood loss, and glycemic levels were measured in both groups. The complete blood cell counts, differential counts, albumin, and C-reactive protein (CRP) levels were measured pre-surgery and postoperative on Days 1, 3, and 7. In comparing the groups, the Mann–Whitney U test analysis was used for continuous variables, while the chi-squared test and Fisher’s exact test were used for dichotomous variables. Results: The incidence of SSI after spinal instrumentation was 7.46% and was relatively higher in scoliosis surgery. The SSI group had significantly longer surgical times (248 min vs. 180 min, p = 0.0004) and a higher intraoperative blood loss (772 mL vs. 372 mL, p < 0.0001) than the non-SSI group. In the SSI group, the Day 3 (10.5 ± 6.2% vs. 13.8 ± 6.0%, p = 0.012) and Day 7 (14.4 ± 4.8% vs. 18.8 ± 7.1%, p = 0.012) lymphocyte ratios were lower than the non-SSI group. Albumin levels on Day 1 in the SSI group were lower than in the non-SSI group (2.94 ± 0.30 mg/dL vs. 3.09 ± 0.38 mg/dL, p = 0.045). There is no difference in CRP and lymphocyte count between the two groups. Conclusions: SSI patients had lower lymphocyte percentages than non-SSI patients, which was a risk factor for SSI, with constant high inflammation. The Day 3 lymphocyte percentage may predict SSI after spinal instrumented surgery. en-copyright= kn-copyright= en-aut-name=MiyamotoAkiyoshi en-aut-sei=Miyamoto en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaMasato en-aut-sei=Tanaka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FloresAngel Oscar Paz en-aut-sei=Flores en-aut-mei=Angel Oscar Paz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YuDongwoo en-aut-sei=Yu en-aut-mei=Dongwoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JainMukul en-aut-sei=Jain en-aut-mei=Mukul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HengChristan en-aut-sei=Heng en-aut-mei=Christan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KomatsubaraTadashi en-aut-sei=Komatsubara en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AratakiShinya en-aut-sei=Arataki en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OdaYoshiaki en-aut-sei=Oda en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShinoharaKensuke en-aut-sei=Shinohara en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopedic Surgery, Okayama University Hospital kn-affil= en-keyword=surgical site infection kn-keyword=surgical site infection en-keyword=spine surgery kn-keyword=spine surgery en-keyword=instrumentation kn-keyword=instrumentation en-keyword=diagnosis kn-keyword=diagnosis en-keyword=lymphocyte kn-keyword=lymphocyte END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=2 article-no= start-page=395 end-page=412.e6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tissue-level oscillation is achieved by tissue-intrinsic clocks along with network-dependent signals originating from distal organs and organismal behavior. Yet, it remains unexplored whether maternal circadian rhythms during pregnancy influence fetal rhythms and impact long-term susceptibility to dietary challenges in offspring. Here, we demonstrate that circadian disruption during pregnancy decreased placental and neonatal weight yet retained transcriptional and structural maturation. Intriguingly, diet-induced obesity was exacerbated in parallel with arrhythmic feeding behavior, hypothalamic leptin resistance, and hepatic circadian reprogramming in offspring of chronodisrupted mothers. In utero circadian desynchrony altered the phase-relationship between the mother and fetus and impacted placental efficiency. Temporal feeding restriction in offspring failed to fully prevent obesity, whereas the circadian alignment of caloric restriction with the onset of the active phase virtually ameliorated the phenotype. Thus, maternal circadian rhythms during pregnancy confer adaptive properties to metabolic functions in offspring and provide insights into the developmental origins of health and disease. en-copyright= kn-copyright= en-aut-name=YaoNa en-aut-sei=Yao en-aut-mei=Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinouchiKenichiro en-aut-sei=Kinouchi en-aut-mei=Kenichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatohManami en-aut-sei=Katoh en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AshtianiKousha Changizi en-aut-sei=Ashtiani en-aut-mei=Kousha Changizi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbdelkarimSherif en-aut-sei=Abdelkarim en-aut-mei=Sherif kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimotoHiroyuki en-aut-sei=Morimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TorimitsuTakuto en-aut-sei=Torimitsu en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KozumaTakahide en-aut-sei=Kozuma en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwaharaAkihide en-aut-sei=Iwahara en-aut-mei=Akihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KosugiShotaro en-aut-sei=Kosugi en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KomuroJin en-aut-sei=Komuro en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatoKyosuke en-aut-sei=Kato en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TonomuraShun en-aut-sei=Tonomura en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NakamuraToshifumi en-aut-sei=Nakamura en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItohArata en-aut-sei=Itoh en-aut-mei=Arata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaguchiShintaro en-aut-sei=Yamaguchi en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YoshinoJun en-aut-sei=Yoshino en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=IrieJunichiro en-aut-sei=Irie en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HashimotoHisayuki en-aut-sei=Hashimoto en-aut-mei=Hisayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=SatohAkiko en-aut-sei=Satoh en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MikamiYohei en-aut-sei=Mikami en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UchidaShusaku en-aut-sei=Uchida en-aut-mei=Shusaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=UekiTakatoshi en-aut-sei=Ueki en-aut-mei=Takatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NomuraSeitaro en-aut-sei=Nomura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=BaldiPierre en-aut-sei=Baldi en-aut-mei=Pierre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiKaori en-aut-sei=Hayashi en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=ItohHiroshi en-aut-sei=Itoh en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=2 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Computer Science, University of California kn-affil= affil-num=5 en-affil=Department of Computer Science, University of California kn-affil= affil-num=6 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=7 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=8 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=10 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=11 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=12 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=13 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=14 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=15 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=16 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=17 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=19 en-affil=Department of Cardiology, Keio University School of Medicine kn-affil= affil-num=20 en-affil=Department of Cardiovascular Medicine, Academic Field, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=21 en-affil=Department of Integrative Physiology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=22 en-affil=Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=23 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=24 en-affil=Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=25 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=26 en-affil=Department of Computer Science, University of California kn-affil= affil-num=27 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=28 en-affil=Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine kn-affil= en-keyword=circadian rhythm kn-keyword=circadian rhythm en-keyword=metabolism kn-keyword=metabolism en-keyword=circadian clock kn-keyword=circadian clock en-keyword=pregnancy kn-keyword=pregnancy en-keyword=developmental origins of health and disease kn-keyword=developmental origins of health and disease en-keyword=obesity kn-keyword=obesity en-keyword=leptin kn-keyword=leptin en-keyword=time-restricted feeding kn-keyword=time-restricted feeding en-keyword=caloric restriction kn-keyword=caloric restriction en-keyword=eating behavior kn-keyword=eating behavior END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=7 article-no= start-page=002114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses from the Plant Viruses Subcommittee, 2025 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. en-copyright= kn-copyright= en-aut-name=RubinoLuisa en-aut-sei=Rubino en-aut-mei=Luisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbrahamianPeter en-aut-sei=Abrahamian en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AnWenxia en-aut-sei=An en-aut-mei=Wenxia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArandaMiguel A. en-aut-sei=Aranda en-aut-mei=Miguel A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Ascencio-IbañezJosé T. en-aut-sei=Ascencio-Ibañez en-aut-mei=José T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BejermanNicolas en-aut-sei=Bejerman en-aut-mei=Nicolas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BlouinArnaud G. en-aut-sei=Blouin en-aut-mei=Arnaud G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CandresseThierry en-aut-sei=Candresse en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CantoTomas en-aut-sei=Canto en-aut-mei=Tomas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaoMengji en-aut-sei=Cao en-aut-mei=Mengji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=CarrJohn P. en-aut-sei=Carr en-aut-mei=John P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ChoWon Kyong en-aut-sei=Cho en-aut-mei=Won Kyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ConstableFiona en-aut-sei=Constable en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=DasguptaIndranil en-aut-sei=Dasgupta en-aut-mei=Indranil kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=DebatHumberto en-aut-sei=Debat en-aut-mei=Humberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=DietzgenRalf G. en-aut-sei=Dietzgen en-aut-mei=Ralf G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DigiaroMichele en-aut-sei=Digiaro en-aut-mei=Michele kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DonaireLivia en-aut-sei=Donaire en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ElbeainoToufic en-aut-sei=Elbeaino en-aut-mei=Toufic kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=FargetteDenis en-aut-sei=Fargette en-aut-mei=Denis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=FilardoFiona en-aut-sei=Filardo en-aut-mei=Fiona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FischerMatthias G. en-aut-sei=Fischer en-aut-mei=Matthias G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FontdevilaNuria en-aut-sei=Fontdevila en-aut-mei=Nuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FoxAdrian en-aut-sei=Fox en-aut-mei=Adrian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=Freitas-AstuaJuliana en-aut-sei=Freitas-Astua en-aut-mei=Juliana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FuchsMarc en-aut-sei=Fuchs en-aut-mei=Marc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=GeeringAndrew D.W. en-aut-sei=Geering en-aut-mei=Andrew D.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=GhafariMahan en-aut-sei=Ghafari en-aut-mei=Mahan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HafrénAnders en-aut-sei=Hafrén en-aut-mei=Anders kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=HammondJohn en-aut-sei=Hammond en-aut-mei=John kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=HammondRosemarie en-aut-sei=Hammond en-aut-mei=Rosemarie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=Hasiów-JaroszewskaBeata en-aut-sei=Hasiów-Jaroszewska en-aut-mei=Beata kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=HebrardEugenie en-aut-sei=Hebrard en-aut-mei=Eugenie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HernándezCarmen en-aut-sei=Hernández en-aut-mei=Carmen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=HilyJean-Michel en-aut-sei=Hily en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=HosseiniAhmed en-aut-sei=Hosseini en-aut-mei=Ahmed kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=HullRoger en-aut-sei=Hull en-aut-mei=Roger kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= en-aut-name=Inoue-NagataAlice K. en-aut-sei=Inoue-Nagata en-aut-mei=Alice K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=38 ORCID= en-aut-name=JordanRamon en-aut-sei=Jordan en-aut-mei=Ramon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=39 ORCID= en-aut-name=KondoHideki en-aut-sei=Kondo en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=40 ORCID= en-aut-name=KreuzeJan F. en-aut-sei=Kreuze en-aut-mei=Jan F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=41 ORCID= en-aut-name=KrupovicMart en-aut-sei=Krupovic en-aut-mei=Mart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=42 ORCID= en-aut-name=KubotaKenji en-aut-sei=Kubota en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=43 ORCID= en-aut-name=KuhnJens H. en-aut-sei=Kuhn en-aut-mei=Jens H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=44 ORCID= en-aut-name=LeisnerScott en-aut-sei=Leisner en-aut-mei=Scott kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=45 ORCID= en-aut-name=LettJean-Michel en-aut-sei=Lett en-aut-mei=Jean-Michel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=46 ORCID= en-aut-name=LiChengyu en-aut-sei=Li en-aut-mei=Chengyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=47 ORCID= en-aut-name=LiFan en-aut-sei=Li en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=48 ORCID= en-aut-name=LiJun Min en-aut-sei=Li en-aut-mei=Jun Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=49 ORCID= en-aut-name=López-LambertiniPaola M. en-aut-sei=López-Lambertini en-aut-mei=Paola M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=50 ORCID= en-aut-name=Lopez-MoyaJuan J. en-aut-sei=Lopez-Moya en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=51 ORCID= en-aut-name=MaclotFrancois en-aut-sei=Maclot en-aut-mei=Francois kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=52 ORCID= en-aut-name=MäkinenKristiina en-aut-sei=Mäkinen en-aut-mei=Kristiina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=53 ORCID= en-aut-name=MartinDarren en-aut-sei=Martin en-aut-mei=Darren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=54 ORCID= en-aut-name=MassartSebastien en-aut-sei=Massart en-aut-mei=Sebastien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=55 ORCID= en-aut-name=MillerW. Allen en-aut-sei=Miller en-aut-mei=W. Allen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=56 ORCID= en-aut-name=MohammadiMusa en-aut-sei=Mohammadi en-aut-mei=Musa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=57 ORCID= en-aut-name=MollovDimitre en-aut-sei=Mollov en-aut-mei=Dimitre kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=58 ORCID= en-aut-name=MullerEmmanuelle en-aut-sei=Muller en-aut-mei=Emmanuelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=59 ORCID= en-aut-name=NagataTatsuya en-aut-sei=Nagata en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=60 ORCID= en-aut-name=Navas-CastilloJesús en-aut-sei=Navas-Castillo en-aut-mei=Jesús kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=61 ORCID= en-aut-name=NeriyaYutaro en-aut-sei=Neriya en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=62 ORCID= en-aut-name=Ochoa-CoronaFrancisco M. en-aut-sei=Ochoa-Corona en-aut-mei=Francisco M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=63 ORCID= en-aut-name=OhshimaKazusato en-aut-sei=Ohshima en-aut-mei=Kazusato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=64 ORCID= en-aut-name=PallásVicente en-aut-sei=Pallás en-aut-mei=Vicente kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=65 ORCID= en-aut-name=PappuHanu en-aut-sei=Pappu en-aut-mei=Hanu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=66 ORCID= en-aut-name=PetrzikKarel en-aut-sei=Petrzik en-aut-mei=Karel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=67 ORCID= en-aut-name=PoogginMikhail en-aut-sei=Pooggin en-aut-mei=Mikhail kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=68 ORCID= en-aut-name=PrigigalloMaria Isabella en-aut-sei=Prigigallo en-aut-mei=Maria Isabella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=69 ORCID= en-aut-name=Ramos-GonzálezPedro L. en-aut-sei=Ramos-González en-aut-mei=Pedro L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=70 ORCID= en-aut-name=RibeiroSimone en-aut-sei=Ribeiro en-aut-mei=Simone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=71 ORCID= en-aut-name=Richert-PöggelerKatja R. en-aut-sei=Richert-Pöggeler en-aut-mei=Katja R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=72 ORCID= en-aut-name=RoumagnacPhilippe en-aut-sei=Roumagnac en-aut-mei=Philippe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=73 ORCID= en-aut-name=RoyAvijit en-aut-sei=Roy en-aut-mei=Avijit kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=74 ORCID= en-aut-name=SabanadzovicSead en-aut-sei=Sabanadzovic en-aut-mei=Sead kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=75 ORCID= en-aut-name=ŠafářováDana en-aut-sei=Šafářová en-aut-mei=Dana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=76 ORCID= en-aut-name=SaldarelliPasquale en-aut-sei=Saldarelli en-aut-mei=Pasquale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=77 ORCID= en-aut-name=SanfaçonHélène en-aut-sei=Sanfaçon en-aut-mei=Hélène kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=78 ORCID= en-aut-name=SarmientoCecilia en-aut-sei=Sarmiento en-aut-mei=Cecilia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=79 ORCID= en-aut-name=SasayaTakahide en-aut-sei=Sasaya en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=80 ORCID= en-aut-name=ScheetsKay en-aut-sei=Scheets en-aut-mei=Kay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=81 ORCID= en-aut-name=SchravesandeWillem E.W. en-aut-sei=Schravesande en-aut-mei=Willem E.W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=82 ORCID= en-aut-name=SealSusan en-aut-sei=Seal en-aut-mei=Susan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=83 ORCID= en-aut-name=ShimomotoYoshifumi en-aut-sei=Shimomoto en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=84 ORCID= en-aut-name=SõmeraMerike en-aut-sei=Sõmera en-aut-mei=Merike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=85 ORCID= en-aut-name=StavoloneLivia en-aut-sei=Stavolone en-aut-mei=Livia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=86 ORCID= en-aut-name=StewartLucy R. en-aut-sei=Stewart en-aut-mei=Lucy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=87 ORCID= en-aut-name=TeycheneyPierre-Yves en-aut-sei=Teycheney en-aut-mei=Pierre-Yves kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=88 ORCID= en-aut-name=ThomasJohn E. en-aut-sei=Thomas en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=89 ORCID= en-aut-name=ThompsonJeremy R. en-aut-sei=Thompson en-aut-mei=Jeremy R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=90 ORCID= en-aut-name=TiberiniAntonio en-aut-sei=Tiberini en-aut-mei=Antonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=91 ORCID= en-aut-name=TomitakaYasuhiro en-aut-sei=Tomitaka en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=92 ORCID= en-aut-name=TzanetakisIoannis en-aut-sei=Tzanetakis en-aut-mei=Ioannis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=93 ORCID= en-aut-name=UmberMarie en-aut-sei=Umber en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=94 ORCID= en-aut-name=UrbinoCica en-aut-sei=Urbino en-aut-mei=Cica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=95 ORCID= en-aut-name=van den BurgHarrold A. en-aut-sei=van den Burg en-aut-mei=Harrold A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=96 ORCID= en-aut-name=Van der VlugtRené A.A. en-aut-sei=Van der Vlugt en-aut-mei=René A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=97 ORCID= en-aut-name=VarsaniArvind en-aut-sei=Varsani en-aut-mei=Arvind kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=98 ORCID= en-aut-name=VerhageAdriaan en-aut-sei=Verhage en-aut-mei=Adriaan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=99 ORCID= en-aut-name=VillamorDan en-aut-sei=Villamor en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=100 ORCID= en-aut-name=von BargenSusanne en-aut-sei=von Bargen en-aut-mei=Susanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=101 ORCID= en-aut-name=WalkerPeter J. en-aut-sei=Walker en-aut-mei=Peter J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=102 ORCID= en-aut-name=WetzelThierry en-aut-sei=Wetzel en-aut-mei=Thierry kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=103 ORCID= en-aut-name=WhitfieldAnna E. en-aut-sei=Whitfield en-aut-mei=Anna E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=104 ORCID= en-aut-name=WylieStephen J. en-aut-sei=Wylie en-aut-mei=Stephen J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=105 ORCID= en-aut-name=YangCaixia en-aut-sei=Yang en-aut-mei=Caixia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=106 ORCID= en-aut-name=ZerbiniF. Murilo en-aut-sei=Zerbini en-aut-mei=F. Murilo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=107 ORCID= en-aut-name=ZhangSong en-aut-sei=Zhang en-aut-mei=Song kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=108 ORCID= affil-num=1 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=2 en-affil=USDA-ARS, BARC, National Germplasm Resources Laboratory kn-affil= affil-num=3 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=4 en-affil=Centro de Edafología y Biología Aplicada del Segura-CSIC kn-affil= affil-num=5 en-affil=Department of Molecular and Structural Biochemistry, North Carolina State University kn-affil= affil-num=6 en-affil=Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=7 en-affil=Plant Protection Department kn-affil= affil-num=8 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=9 en-affil=Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) kn-affil= affil-num=10 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= affil-num=11 en-affil=Department of Plant Sciences, University of Cambridge kn-affil= affil-num=12 en-affil=Agriculture and Life Sciences Research Institute, Kangwon National University kn-affil= affil-num=13 en-affil=Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University kn-affil= affil-num=14 en-affil=University of Delhi South Campu kn-affil= affil-num=15 en-affil=Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=16 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=17 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=18 en-affil=Centro de Edafología y Biología Aplicada del Segura-CSIC kn-affil= affil-num=19 en-affil=CIHEAM, Istituto Agronomico Mediterraneo of Bari kn-affil= affil-num=20 en-affil=Virus South Data kn-affil= affil-num=21 en-affil=Queensland Department of Primary Industries kn-affil= affil-num=22 en-affil=Max Planck Institute for Marine Microbiology kn-affil= affil-num=23 en-affil=Plant Protection Department kn-affil= affil-num=24 en-affil=Fera Science Ltd (Fera), York Biotech Campus kn-affil= affil-num=25 en-affil=Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation kn-affil= affil-num=26 en-affil=Plant Pathology, Cornell University kn-affil= affil-num=27 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=28 en-affil=Department of Biology, University of Oxford kn-affil= affil-num=29 en-affil=Swedish University of Agriculture kn-affil= affil-num=30 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=31 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory kn-affil= affil-num=32 en-affil=Institute of Plant Protection-NRI kn-affil= affil-num=33 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=34 en-affil=Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC kn-affil= affil-num=35 en-affil=Institut Français de la Vigne et du Vin kn-affil= affil-num=36 en-affil=Vali-e-Asr University of Rafsanjan, Department of Plant Protection kn-affil= affil-num=37 en-affil=Retired from John Innes Centre kn-affil= affil-num=38 en-affil=Embrapa Hortaliças kn-affil= affil-num=39 en-affil=USDA-ARS, USNA, Floral and Nursery Plants Research Unit kn-affil= affil-num=40 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=41 en-affil=International Potato Center (CIP) kn-affil= affil-num=42 en-affil=Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit kn-affil= affil-num=43 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=44 en-affil=Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health kn-affil= affil-num=45 en-affil=Department of Biological Sciences, University of Toledo kn-affil= affil-num=46 en-affil=CIRAD, UMR PVBMT kn-affil= affil-num=47 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=48 en-affil=State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University kn-affil= affil-num=49 en-affil=Institute of Plant Virology, Ningbo University kn-affil= affil-num=50 en-affil=Instituto de Patología Vegetal (IPAVE), INTA, Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET kn-affil= affil-num=51 en-affil=Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) kn-affil= affil-num=52 en-affil=UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE kn-affil= affil-num=53 en-affil=Department of Agricultural Sciences, University of Helsinki kn-affil= affil-num=54 en-affil=Institute of Infectious Disease and Molecular Medicine, University of Cape Town kn-affil= affil-num=55 en-affil=Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege kn-affil= affil-num=56 en-affil=Department of Plant Pathology, Entomology and Microbiology, Iowa State University kn-affil= affil-num=57 en-affil=Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources kn-affil= affil-num=58 en-affil=USDA-APHIS, Plant Protection and Quarantine kn-affil= affil-num=59 en-affil=CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE kn-affil= affil-num=60 en-affil=Instituto de Ciências Biológicas, Universidade de Brasília kn-affil= affil-num=61 en-affil=Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Científicas kn-affil= affil-num=62 en-affil=Utsunomiya University kn-affil= affil-num=63 en-affil=Oklahoma State University, Institute for Biosecurity & Microbial Forensics kn-affil= affil-num=64 en-affil=Saga University kn-affil= affil-num=65 en-affil=Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC kn-affil= affil-num=66 en-affil=Department of Plant Pathology, Washington State University kn-affil= affil-num=67 en-affil=Institute of Plant Molecular Biology kn-affil= affil-num=68 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD kn-affil= affil-num=69 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=70 en-affil=Applied Molecular Biology Laboratory, Instituto Biológico de São Paulo kn-affil= affil-num=71 en-affil=Embrapa Recursos Genéticos e Biotecnologia kn-affil= affil-num=72 en-affil=Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics kn-affil= affil-num=73 en-affil=CIRAD, UMR PHIM kn-affil= affil-num=74 en-affil=USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA kn-affil= affil-num=75 en-affil=Department of Agricultural Science and Plant Protection, Mississippi State University kn-affil= affil-num=76 en-affil=Department of Cell Biology and Genetics, Faculty of Science, Palacký University Olomouc kn-affil= affil-num=77 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=78 en-affil=Summerland Research and Development Centre, Agriculture and Agri-Food Canada kn-affil= affil-num=79 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=80 en-affil=Strategic Planning Headquarters, NARO kn-affil= affil-num=81 en-affil=Department of Plant Pathology, Ecology and Evolution, Oklahoma State University kn-affil= affil-num=82 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=83 en-affil=Natural Resources Institute, University of Greenwich kn-affil= affil-num=84 en-affil=Kochi Agricultural Research Center kn-affil= affil-num=85 en-affil=Department of Chemistry and Biotechnology, Tallinn University of Technology kn-affil= affil-num=86 en-affil=Istituto per la Protezione Sostenibile delle Piante, CNR kn-affil= affil-num=87 en-affil=Currently unaffiliated kn-affil= affil-num=88 en-affil=CIRAD, UMR PVBMT & UMR PVBMT, Université de la Réunion kn-affil= affil-num=89 en-affil=Queensland Alliance for Agriculture and Food Innovation, The University of Queensland kn-affil= affil-num=90 en-affil=Plant Health and Environment Laboratory kn-affil= affil-num=91 en-affil=Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification kn-affil= affil-num=92 en-affil=Institute for Plant Protection, NARO kn-affil= affil-num=93 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=94 en-affil=INRAE, UR ASTRO kn-affil= affil-num=95 en-affil=PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro kn-affil= affil-num=96 en-affil=Molecular Plant Pathology, University of Amsterdam kn-affil= affil-num=97 en-affil=Wageningen University and Research kn-affil= affil-num=98 en-affil=The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University kn-affil= affil-num=99 en-affil=Rijk Zwaan Breeding B.V. kn-affil= affil-num=100 en-affil=Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System kn-affil= affil-num=101 en-affil=Humboldt-Universität zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences kn-affil= affil-num=102 en-affil=The University of Queensland kn-affil= affil-num=103 en-affil=Dienstleistungszentrum Ländlicher Raum Rheinpfalz kn-affil= affil-num=104 en-affil=North Carolina State University kn-affil= affil-num=105 en-affil=Food Futures Institute, Murdoch University kn-affil= affil-num=106 en-affil=Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University kn-affil= affil-num=107 en-affil=Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa kn-affil= affil-num=108 en-affil=National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=12 article-no= start-page=2429 end-page=2437 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Discovery of a Compound That Inhibits IRE1α S-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes S-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, S-nitrosylation of IRE1α compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the S-nitrosylation of IRE1α by targeting nitrosylated cysteine residues. We ultimately identified a compound (1ACTA) that selectively inhibits the S-nitrosylation of IRE1α and prevents the NO-induced reduction of RNase activity. Furthermore, 1ACTA reduces the rate of NO-induced cell death. Our research identified S-nitrosylation as a novel target for drug development for IRE1α and provides a suitable screening strategy. en-copyright= kn-copyright= en-aut-name=KurogiHaruna en-aut-sei=Kurogi en-aut-mei=Haruna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumarAshutosh en-aut-sei=Kumar en-aut-mei=Ashutosh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiTakehiro en-aut-sei=Suzuki en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SawadaDaisuke en-aut-sei=Sawada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhangKam Y.J. en-aut-sei=Zhang en-aut-mei=Kam Y.J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=Department of Fine Organic Synthesis, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=466 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. en-copyright= kn-copyright= en-aut-name=TanabeShihori en-aut-sei=Tanabe en-aut-mei=Shihori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=QuaderSabina en-aut-sei=Quader en-aut-mei=Sabina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OnoRyuichi en-aut-sei=Ono en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaHiroyoshi Y. en-aut-sei=Tanaka en-aut-mei=Hiroyoshi Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoAkihisa en-aut-sei=Yamamoto en-aut-mei=Akihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaMotohiro en-aut-sei=Kojima en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PerkinsEdward J. en-aut-sei=Perkins en-aut-mei=Edward J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=CabralHoracio en-aut-sei=Cabral en-aut-mei=Horacio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Innovation Centre of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion kn-affil= affil-num=3 en-affil=Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Mechanical Systems Engineering, Graduate School of Systems Design Tokyo Metropolitan University kn-affil= affil-num=6 en-affil=Department of Surgical Pathology, Kyoto Prefecture University of Medicine kn-affil= affil-num=7 en-affil=US Army Engineer Research and Development Center kn-affil= affil-num=8 en-affil=Department of Bioengineering, Graduate School of Engineering, The University of Tokyo kn-affil= en-keyword=artificial intelligence kn-keyword=artificial intelligence en-keyword=coronavirus kn-keyword=coronavirus en-keyword=coronaviral infection kn-keyword=coronaviral infection en-keyword=machine learning kn-keyword=machine learning en-keyword=pathway analysis kn-keyword=pathway analysis en-keyword=predictionmodel kn-keyword=predictionmodel en-keyword=molecular network kn-keyword=molecular network en-keyword=molecular pathway image kn-keyword=molecular pathway image en-keyword=network analysis kn-keyword=network analysis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=11 article-no= start-page=4984 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=induced pluripotent stem cells kn-keyword=induced pluripotent stem cells en-keyword=cardiomyopathy kn-keyword=cardiomyopathy en-keyword=disease modeling kn-keyword=disease modeling en-keyword=drug screening kn-keyword=drug screening en-keyword=regenerative therapy kn-keyword=regenerative therapy END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=13 article-no= start-page=7238 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250627 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH. en-copyright= kn-copyright= en-aut-name=LeeYoung-Hyeon en-aut-sei=Lee en-aut-mei=Young-Hyeon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YeoMin-Ho en-aut-sei=Yeo en-aut-mei=Min-Ho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChangKyung-Soo en-aut-sei=Chang en-aut-mei=Kyung-Soo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoonWeon-Jong en-aut-sei=Yoon en-aut-mei=Weon-Jong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimHye-Sook en-aut-sei=Kim en-aut-mei=Hye-Sook kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimJongwan en-aut-sei=Kim en-aut-mei=Jongwan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimHye-Ran en-aut-sei=Kim en-aut-mei=Hye-Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=2 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=3 en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan kn-affil= affil-num=4 en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP) kn-affil= affil-num=5 en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Anatomy, College of Medicine, Dongguk University kn-affil= affil-num=7 en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology kn-affil= en-keyword=metabolic dysfunction-associated steatohepatitis kn-keyword=metabolic dysfunction-associated steatohepatitis en-keyword=Distylium racemosum kn-keyword=Distylium racemosum en-keyword=ethyl acetate fraction kn-keyword=ethyl acetate fraction en-keyword=extract kn-keyword=extract END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=8 article-no= start-page=1621 end-page=1630 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Percutaneous cryoablation versus robot-assisted partial nephrectomy for small renal cell carcinoma: a retrospective cost analysis at Japanese single-institution en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: No direct cost comparison has been conducted between percutaneous cryoablation (PCA) and robot-assisted partial nephrectomy (RAPN) for clinical T1a renal cell carcinoma (RCC) in Japan. This study aimed to compare their costs.
Methods: We retrospectively analyzed data from 212 PCAs (including 155 with transcatheter arterial embolization) and 119 RAPN cases performed between December 2017 and May 2022.
Results: PCA patients were older with higher American Society of Anesthesiologists scores, Charlson Comorbidity Index, and history of previous RCC treatment, cardiovascular disease, and antithrombotic drug use than RAPN patients. PCA was associated with a significantly shorter procedure time and hospitalization duration with fewer major complications than those associated with RAPN. While PCA incurred a slightly lower total cost (1,123,000 vs. 1,155,000 yen), it had a significantly higher procedural cost (739,000 vs. 693,000 yen) and markedly worse total (− 93,000 vs. 249,000 yen) and procedural income-expenditure balance (− 189,000 vs. 231,000 yen) than those of RAPN. After statistical adjustment, PCA demonstrated significantly higher total (difference: 114,000 yen) and procedural costs (difference: 72,000 yen), alongside significantly worse total (difference: − 358,000 yen) and procedural income-expenditure balances (difference: − 439,000 yen). The incremental cost-effectiveness ratio was more favorable for PCA than for RAPN.
Conclusion: For high- risk patients, PCA demonstrated a safer option with shorter hospitalization duration than those of RAPN. Although PCA was more cost-effective, its higher procedural cost and unfavorable income-expenditure balance require careful evaluation, especially for large tumors that require three or more needles. en-copyright= kn-copyright= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GobaraHideo en-aut-sei=Gobara en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UmakoshiNoriyuki en-aut-sei=Umakoshi en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawabataTakahiro en-aut-sei=Kawabata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TomitaKoji en-aut-sei=Tomita en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuiYusuke en-aut-sei=Matsui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Medical Informatics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Renal cancer kn-keyword=Renal cancer en-keyword=Cryoablation kn-keyword=Cryoablation en-keyword=Robot-assisted partial nephrectomy kn-keyword=Robot-assisted partial nephrectomy en-keyword=Cost kn-keyword=Cost en-keyword=Cost effectiveness kn-keyword=Cost effectiveness END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=27163 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23–4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39–5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriKeiichiro en-aut-sei=Mori en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FukuokayaWataru en-aut-sei=Fukuokaya en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomuraKazumasa en-aut-sei=Komura en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujinoTakuya en-aut-sei=Tsujino en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaenosonoRyoichi en-aut-sei=Maenosono en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakaharaKiyoshi en-aut-sei=Takahara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NukayaTakuhisa en-aut-sei=Nukaya en-aut-mei=Takuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InokiLan en-aut-sei=Inoki en-aut-mei=Lan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToyodaShingo en-aut-sei=Toyoda en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HashimotoTakeshi en-aut-sei=Hashimoto en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HirasawaYosuke en-aut-sei=Hirasawa en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SadahiraTakuya en-aut-sei=Sadahira en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TominagaYusuke en-aut-sei=Tominaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YamanoiTomoaki en-aut-sei=Yamanoi en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YoshinagaKasumi en-aut-sei=Yoshinaga en-aut-mei=Kasumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KuroseKyohei en-aut-sei=Kurose en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KimuraTakahiro en-aut-sei=Kimura en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=AzumaHaruhito en-aut-sei=Azuma en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ShirokiRyoichi en-aut-sei=Shiroki en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=FujitaKazutoshi en-aut-sei=Fujita en-aut-mei=Kazutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=OhnoYoshio en-aut-sei=Ohno en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=4 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=5 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=6 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=8 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=9 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=10 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=11 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=13 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=14 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=15 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=27 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=28 en-affil=Department of Urology, The Jikei University School of Medicine kn-affil= affil-num=29 en-affil=Department of Urology, Osaka Medical and Pharmaceutical University kn-affil= affil-num=30 en-affil=Department of Urology, Fujita Health University School of Medicine kn-affil= affil-num=31 en-affil=Department of Urology, Kindai University Faculty of Medicine kn-affil= affil-num=32 en-affil=Department of Urology, Tokyo Medical University kn-affil= affil-num=33 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor en-keyword=ICI kn-keyword=ICI en-keyword=Eosinophil kn-keyword=Eosinophil en-keyword=Immune-related adverse event kn-keyword=Immune-related adverse event en-keyword=Treatment-related adverse event kn-keyword=Treatment-related adverse event END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=13 article-no= start-page=e172988 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250513 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LAG3 regulates antibody responses in a murine model of kidney transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lymphocyte activation gene 3 (LAG3) is a coinhibitory receptor expressed by various immune cells. Although the immunomodulatory potential of LAG3 is being explored in cancer and autoimmunity, there is no information on its role after organ transplantation. Our study investigated the functions of LAG3 in a mouse model of renal allograft rejection. LAG3–/– recipients rapidly rejected MHC-mismatched renal allografts that were spontaneously accepted by WT recipients, with graft histology characteristic of antibody-mediated rejection. Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3–/– recipients. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The studies of conditional LAG3–/– recipients and mixed bone marrow chimeras demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity but not to induce acute allograft rejection. The numbers and proinflammatory functions of graft-infiltrating NK cells were markedly increased in LAG3–/– recipients, suggesting that LAG3 also regulates the effector stage of antibody-mediated rejection. These findings identified LAG3 as a regulator of immune responses to kidney allografts and a potential therapeutic target for antibody-mediated rejection prevention and treatment. en-copyright= kn-copyright= en-aut-name=NicosiaMichael en-aut-sei=Nicosia en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FanRan en-aut-sei=Fan en-aut-mei=Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeJuyeun en-aut-sei=Lee en-aut-mei=Juyeun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AllGabriella en-aut-sei=All en-aut-mei=Gabriella kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GorbachevaVictoria en-aut-sei=Gorbacheva en-aut-mei=Victoria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ValenzuelaJosé I. en-aut-sei=Valenzuela en-aut-mei=José I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoYosuke en-aut-sei=Yamamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BeaversAshley en-aut-sei=Beavers en-aut-mei=Ashley kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DvorinaNina en-aut-sei=Dvorina en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=BaldwinWilliam M. en-aut-sei=Baldwin en-aut-mei=William M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ChuluyanEduardo en-aut-sei=Chuluyan en-aut-mei=Eduardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=GaudetteBrian T. en-aut-sei=Gaudette en-aut-mei=Brian T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FairchildRobert L. en-aut-sei=Fairchild en-aut-mei=Robert L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MinBooki en-aut-sei=Min en-aut-mei=Booki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ValujskikhAnna en-aut-sei=Valujskikh en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=2 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=4 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=5 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=6 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=7 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=8 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=9 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=10 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=11 en-affil=Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina kn-affil= affil-num=12 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=14 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=15 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= affil-num=16 en-affil=Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=15 article-no= start-page=7275 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acquired Radioresistance Through Adaptive Evolution with Gamma Radiation as Selection Pressure: Increased Expression and Induction of Anti-Stress Genes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Elucidating the mechanisms of radioresistance in highly radiotolerant organisms can provide valuable insights into the adaptation and evolution of organisms. However, research has been limited on many naturally occurring radioresistant organisms due to a lack of information regarding their genetic and biochemical characteristics and the difficulty of handling them experimentally. To address this, we conducted an experiment on adaptive evolution using gamma radiation as the selection pressure to generate evolved Escherichia coli with gamma radiation resistance approximately one order of magnitude greater than that of wild-type E. coli. Gene expressions in all wild-type and evolved radioresistant E. coli in the presence or absence of gamma irradiation were analyzed and compared using RNA sequencing. Under steady-state conditions, the genes involved in survival, cell recovery, DNA repair, and response following stress exposure were upregulated in evolved E. coli compared with those in wild-type E. coli. Furthermore, the evolved E. coli induced these genes more efficiently following gamma irradiation and greater DNA repair activity than that in the wild-type E. coli. Our results indicate that an increased steady-state expression of various anti-stress genes, including DNA repair-related genes, and their highly efficient induction under irradiation are responsible for the remarkable radioresistance of evolved E. coli. en-copyright= kn-copyright= en-aut-name=SaitoTakeshi en-aut-sei=Saito en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeratoHiroaki en-aut-sei=Terato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Radiation Life Science, Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=2 en-affil=Department of Radiation Research, Advanced Science Research Center, Okayama University kn-affil= en-keyword=radioresistant bacteria kn-keyword=radioresistant bacteria en-keyword=Escherichia coli kn-keyword=Escherichia coli en-keyword=adaptive evolution kn-keyword=adaptive evolution en-keyword=gene expression changes kn-keyword=gene expression changes en-keyword=anti-stress genes kn-keyword=anti-stress genes en-keyword=DNA repair kn-keyword=DNA repair en-keyword=cell recovery kn-keyword=cell recovery END start-ver=1.4 cd-journal=joma no-vol=37 cd-vols= no-issue=7 article-no= start-page=koaf142 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pancentromere analysis of Allium species reveals diverse centromere positions in onion and gigantic centromeres in garlic en-subtitle= kn-subtitle= en-abstract= kn-abstract=In eukaryotes, centromeres interact with the kinetochore for distribution of genetic information in cell division, yet their sequence and size are diverse among species. However, their position on chromosomes is considered to be conserved within a species. In this study, we analyzed the centromeres of 3 Allium species, namely, Welsh onion (Allium fistulosum), onion (Allium cepa), and garlic (Allium sativum) via pancentromere analysis and repetitive sequence analysis of centromeres and their neighborhoods and revealed their mobility, sequence organization, and size. Among the 3 species, Welsh onion and garlic had stable centromeres, but the onion centromere appeared to be polymorphic and frequently differed in position by up to 28.0 Mb among cultivars and between multiple individuals of the same cultivar. This mobility was stabilized by hybridization with Welsh onions. Furthermore, these 3 species have very different centromere sequence organization, including differences in the existence and maturity of centromeric satellites, and differences in centromere size, with Welsh onion having a centromere of 1.9 Mb, and garlic having a centromere of ∼10.6 Mb, the largest of any organism with monocentric chromosomes analyzed to date. Our pancentromere analysis of these Allium species reveals the variation in sequence organization, size, and position of this important chromosomal region. en-copyright= kn-copyright= en-aut-name=NagakiKiyotaka en-aut-sei=Nagaki en-aut-mei=Kiyotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UshijimaKoichiro en-aut-sei=Ushijima en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkagiTakashi en-aut-sei=Akagi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaKeisuke en-aut-sei=Tanaka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHisato en-aut-sei=Kobayashi en-aut-mei=Hisato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= affil-num=5 en-affil=NODAI Genome Research Center, Tokyo University of Agriculture kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=10 article-no= start-page=2401783 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biocompatibility of Water-Dispersible Pristine Graphene and Graphene Oxide Using a Close-to-Human Animal Model: A Pilot Study on Swine en-subtitle= kn-subtitle= en-abstract= kn-abstract=Graphene-based materials (GBMs) are of considerable interest for biomedical applications, and the pilot study on the toxicological and immunological impact of pristine graphene (GR) and graphene oxide (GO) using swine as a close-to-human provides valuable insights. First, ex vivo experiments are conducted on swine blood cells, then GBMs are injected intraperitoneally (i.p.) into swine. Hematological and biochemical analyses at various intervals indicate that neither GO nor GR cause systemic inflammation, pro-coagulant responses, or renal or hepatic dysfunction. Importantly, no systemic toxicity is observed. Analysis of a panel of 84 immune-related genes shows minimal impact of GO and GR. The animals are sacrificed 21 days post-injection, and transient absorption imaging and Raman mapping show the presence of GO and GR in the mesentery only. Histological evaluation reveals no signs of alterations in other organs. Thus, clusters of both materials are detected in the mesentery, and GO aggregates are surrounded only by macrophages with the formation of granulomas. In contrast, modest local reactions are observed around the GR clusters. Overall, these results reveal that i.p. injection of GBMs resulted in a modest local tissue reaction without systemic toxicity. This study, performed in swine, provides essential guidance for future biomedical applications of graphene. en-copyright= kn-copyright= en-aut-name=NicolussiPaola en-aut-sei=Nicolussi en-aut-mei=Paola kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PiloGiovannantonio en-aut-sei=Pilo en-aut-mei=Giovannantonio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CanceddaMaria Giovanna en-aut-sei=Cancedda en-aut-mei=Maria Giovanna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PengGuotao en-aut-sei=Peng en-aut-mei=Guotao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChauNgoc Do Quyen en-aut-sei=Chau en-aut-mei=Ngoc Do Quyen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=De la CadenaAlejandro en-aut-sei=De la Cadena en-aut-mei=Alejandro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VannaRenzo en-aut-sei=Vanna en-aut-mei=Renzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SamadYarjan Abdul en-aut-sei=Samad en-aut-mei=Yarjan Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AhmedTanweer en-aut-sei=Ahmed en-aut-mei=Tanweer kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MarcellinoJeremia en-aut-sei=Marcellino en-aut-mei=Jeremia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeddeGiuseppe en-aut-sei=Tedde en-aut-mei=Giuseppe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GiroLinda en-aut-sei=Giro en-aut-mei=Linda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YlmazerAcelya en-aut-sei=Ylmazer en-aut-mei=Acelya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=LoiFederica en-aut-sei=Loi en-aut-mei=Federica kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CartaGavina en-aut-sei=Carta en-aut-mei=Gavina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SecchiLoredana en-aut-sei=Secchi en-aut-mei=Loredana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Dei GiudiciSilvia en-aut-sei=Dei Giudici en-aut-mei=Silvia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MacciocuSimona en-aut-sei=Macciocu en-aut-mei=Simona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=PolliDario en-aut-sei=Polli en-aut-mei=Dario kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LigiosCiriaco en-aut-sei=Ligios en-aut-mei=Ciriaco kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=CerulloGiulio en-aut-sei=Cerullo en-aut-mei=Giulio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FerrariAndrea en-aut-sei=Ferrari en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=BiancoAlberto en-aut-sei=Bianco en-aut-mei=Alberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=FadeelBengt en-aut-sei=Fadeel en-aut-mei=Bengt kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FranzoniGiulia en-aut-sei=Franzoni en-aut-mei=Giulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=DeloguLucia Gemma en-aut-sei=Delogu en-aut-mei=Lucia Gemma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= affil-num=1 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=2 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=3 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=4 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=5 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=6 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=7 en-affil=Istituto di Fotonica e Nanotecnologie – CNR kn-affil= affil-num=8 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=9 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=10 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=11 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=12 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= affil-num=13 en-affil=Department of Biomedical Engineering, Ankara University kn-affil= affil-num=14 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=15 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=16 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=17 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=18 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=19 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=20 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=22 en-affil=Dipartimento di Fisica, Politecnico di Milano kn-affil= affil-num=23 en-affil=Cambridge Graphene Centre, University of Cambridge kn-affil= affil-num=24 en-affil=CNRS, Immunology, Immunopathology and Therapeutic Chemistry kn-affil= affil-num=25 en-affil=Institute of Environmental Medicine, Karolinska Institutet kn-affil= affil-num=26 en-affil=Istituto Zooprofilattico Sperimentale della Sardegna kn-affil= affil-num=27 en-affil=ImmuneNano Laboratory, Department of Biomedical Sciences kn-affil= en-keyword=2D materials kn-keyword=2D materials en-keyword=biocompatibility kn-keyword=biocompatibility en-keyword=immune system kn-keyword=immune system en-keyword=porcine model kn-keyword=porcine model en-keyword=toxicity kn-keyword=toxicity END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=4 article-no= start-page=263 end-page=272 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240607 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering en-subtitle= kn-subtitle= en-abstract= kn-abstract=While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings. en-copyright= kn-copyright= en-aut-name=FerrerasAndrea en-aut-sei=Ferreras en-aut-mei=Andrea kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatesanzAna en-aut-sei=Matesanz en-aut-mei=Ana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MendizabalJabier en-aut-sei=Mendizabal en-aut-mei=Jabier kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArtolaKoldo en-aut-sei=Artola en-aut-mei=Koldo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AcedoPablo en-aut-sei=Acedo en-aut-mei=Pablo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=JorcanoJosé L. en-aut-sei=Jorcano en-aut-mei=José L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=RuizAmalia en-aut-sei=Ruiz en-aut-mei=Amalia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ReinaGiacomo en-aut-sei=Reina en-aut-mei=Giacomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MartínCristina en-aut-sei=Martín en-aut-mei=Cristina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=2 en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=3 en-affil=Domotek ingeniería prototipado y formación S.L. kn-affil= affil-num=4 en-affil=Domotek ingeniería prototipado y formación S.L. kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Department of Electronic Technology, Universidad Carlos III de Madrid kn-affil= affil-num=7 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= affil-num=8 en-affil=Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford kn-affil= affil-num=9 en-affil=Empa Swiss Federal Laboratories for Materials Science and Technology kn-affil= affil-num=10 en-affil=Department of Bioengineering, Universidad Carlos III de Madrid kn-affil= en-keyword=photothermal therapy kn-keyword=photothermal therapy en-keyword=graphene derivatives kn-keyword=graphene derivatives en-keyword=4D bioprinting kn-keyword=4D bioprinting en-keyword=alginate kn-keyword=alginate en-keyword=tissue engineering kn-keyword=tissue engineering END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=12 article-no= start-page=4932 end-page=4951 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto en-subtitle= kn-subtitle= en-abstract= kn-abstract=Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack. en-copyright= kn-copyright= en-aut-name=GotoYukihisa en-aut-sei=Goto en-aut-mei=Yukihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KadotaYasuhiro en-aut-sei=Kadota en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MbengueMalick en-aut-sei=Mbengue en-aut-mei=Malick kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LewisJennifer D en-aut-sei=Lewis en-aut-mei=Jennifer D kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MakiNoriko en-aut-sei=Maki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NgouBruno Pok Man en-aut-sei=Ngou en-aut-mei=Bruno Pok Man kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SklenarJan en-aut-sei=Sklenar en-aut-mei=Jan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DerbyshirePaul en-aut-sei=Derbyshire en-aut-mei=Paul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShibataArisa en-aut-sei=Shibata en-aut-mei=Arisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IchihashiYasunori en-aut-sei=Ichihashi en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GuttmanDavid S en-aut-sei=Guttman en-aut-mei=David S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakagamiHirofumi en-aut-sei=Nakagami en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiTakamasa en-aut-sei=Suzuki en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MenkeFrank L H en-aut-sei=Menke en-aut-mei=Frank L H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=RobatzekSilke en-aut-sei=Robatzek en-aut-mei=Silke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=DesveauxDarrell en-aut-sei=Desveaux en-aut-mei=Darrell kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=ZipfelCyril en-aut-sei=Zipfel en-aut-mei=Cyril kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShirasuKen en-aut-sei=Shirasu en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=2 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=3 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=4 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=7 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=8 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=9 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=10 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=11 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= affil-num=12 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=13 en-affil=Plant Proteomics Research Unit, RIKEN CSRS kn-affil= affil-num=14 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=15 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=16 en-affil=The Sainsbury Laboratory, University of East Anglia kn-affil= affil-num=17 en-affil=Department of Cell and System Biology, Centre for the Analysis of Genome Function and Evolution, University of Toronto kn-affil= affil-num=18 en-affil=Institute of Plant and Microbial Biology, Zurich-Basel Plant Science Center, University of Zurich kn-affil= affil-num=19 en-affil=Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science (CSRS) kn-affil= END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=7 article-no= start-page=e88945 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Six-Year Remission With No Relapse After Four-Time Weekly Rituximab Only for Bilateral Ocular Adnexal Follicular Lymphoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Follicular lymphoma mostly takes an indolent course, and thus, observation with watchful waiting is a main therapeutic strategy. Recent long-term studies suggest earlier treatment with rituximab monotherapy may benefit patients by delaying the need for treatment in the later phase of exacerbation. In this study, we reported a patient with bilateral orbital follicular lymphoma who received four-time weekly rituximab monotherapy as an induction therapy only and maintained the remission for 5 years with no treatment. The patient was a 51-year-old woman who developed a right upper orbital mass and was diagnosed with follicular lymphoma grade 1 by the excisional biopsy. Two years later, at the age of 53 years, she developed a left lacrimal gland mass and underwent excision. The pathological diagnosis was follicular lymphoma grade 1. She did not have any other systemic lesions by fluorodeoxyglucose positron emission tomography. At the age of 54 years, she developed a new mass on the nasal side of the right orbit and underwent weekly rituximab monotherapy (375 mg/m2) four times a month, leading to the reduction of the mass in 3 months. Two high uptake sites on the temporal and nasal side of the right superior orbit by fluorodeoxyglucose positron emission tomography disappeared one year later at the age of 55 years. She was followed with no treatment for 6 years until the age of 60 years at the latest visit. In case of a local orbital relapse, local radiotherapy would be the standard, but rituximab monotherapy as an induction therapy only was chosen in the present patient. Rituximab monotherapy in place of local radiotherapy would be a treatment option for orbital follicular lymphoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, and Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Transfusion and Cell Therapy, Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=claustrophobia kn-keyword=claustrophobia en-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type kn-keyword=extranodal marginal zone b-cell lymphoma mucosa-associated lymphoid tissue (malt) type en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=follicular lymphoma kn-keyword=follicular lymphoma en-keyword=magnetic resonance imaging kn-keyword=magnetic resonance imaging en-keyword=mucosaassociated lymphoid tissue (malt) lymphoma kn-keyword=mucosaassociated lymphoid tissue (malt) lymphoma en-keyword=ocular adnexa kn-keyword=ocular adnexa en-keyword=orbital mass kn-keyword=orbital mass en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=rituximab kn-keyword=rituximab END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=6 article-no= start-page=271 end-page=285 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Sediment Microbial Fuel Cells on CH4 and CO2 Emissions from Straw Amended Paddy Soil en-subtitle= kn-subtitle= en-abstract= kn-abstract=Straw returning into paddy soil enhances soil organic matter which usually promotes the emission of greenhouse gases to the atmosphere. The application of sediment microbial fuel cells (SMFCs) to paddy soil activates power-generating microorganisms and enhances organic matter biodegradation. In the present study, rice straw addition in SMFCs was examined to determine its effect on CH4 and CO2 emissions. Columns (height, 25 cm; inner diameter, 9 cm) with four treatments: soil without and with rice straw under SMFC and without SMFC conditions were incubated at 25°C for 70 days. Anodic potential values at 7 cm depth sediment were kept higher by SMFCs than those without SMFCs. Cumulative CH4 emission was significantly reduced by SMFC with straw amendment (p < 0.05) with no significant effect on CO2 emission. 16S rRNA gene analysis results showed that Firmicutes at the phylum, Closteridiales and Acidobacteriales at order level were dominant on the anode of straw-added SMFC, whereas Methanomicrobiales were in the treatment without SMFC, indicating that a certain group of methanogens were suppressed by SMFC. Our results suggest that the anodic redox environment together with the enrichment of straw-degrading bacteria contributed to a competitive advantage of electrogenesis over methanogenesis in straw-added SMFC system. en-copyright= kn-copyright= en-aut-name=BekeleAdhena Tesfau en-aut-sei=Bekele en-aut-mei=Adhena Tesfau kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMorihiro en-aut-sei=Maeda en-aut-mei=Morihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AkaoSatoshi en-aut-sei=Akao en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SomuraHiroaki en-aut-sei=Somura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakanoChiyu en-aut-sei=Nakano en-aut-mei=Chiyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Science and Engineering, Doshisha University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Organization for Research Strategy and Development, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=straw kn-keyword=straw en-keyword=methane mitigation kn-keyword=methane mitigation en-keyword=SMFC kn-keyword=SMFC en-keyword=microorganisms kn-keyword=microorganisms en-keyword=current generation kn-keyword=current generation END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=14 article-no= start-page=6927 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling. en-copyright= kn-copyright= en-aut-name=ItohYoshihiko en-aut-sei=Itoh en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InagakiKenichi en-aut-sei=Inagaki en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TerasakaTomohiro en-aut-sei=Terasaka en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MorimotoEisaku en-aut-sei=Morimoto en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshiiTakahiro en-aut-sei=Ishii en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamaokaKimitomo en-aut-sei=Yamaoka en-aut-mei=Kimitomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujisawaSatoshi en-aut-sei=Fujisawa en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=tyrosine kinase inhibitor kn-keyword=tyrosine kinase inhibitor en-keyword=multiple endocrine neoplasia type 2 kn-keyword=multiple endocrine neoplasia type 2 en-keyword=paraganglioma kn-keyword=paraganglioma en-keyword=RET kn-keyword=RET en-keyword=ERK kn-keyword=ERK en-keyword=AKT kn-keyword=AKT END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=118030 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=(+)-Terrein exerts anti-obesity and anti-diabetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: (+)-Terrein, a low-molecular-weight secondary metabolite from Aspergillus terreus, inhibits adipocyte differentiation in vitro. However, the precise mechanisms underlying the effects of (+)-terrein on adipocytes remain unclear. We hypothesized that (+)-terrein modulates adipogenesis and glucose homeostasis in obesity and diabetes via anti-inflammatory action and regulation of adipocyte differentiation. Hence, in this study, we aimed to investigate the in vivo anti-diabetic and anti-obesity effects of (+)-terrein.
Methods: Male C57BL/6 J mice were fed normal chow or high-fat (HF) diet and administered (+)-terrein (180 mg/kg) via intraperitoneal injection. Glucose and insulin tolerance tests, serum biochemical assays, and histological analyses were also performed. Rat brown preadipocytes, mouse brown preadipocytes (T37i cells), and inguinal white adipose tissue (ingWAT) preadipocytes were exposed to (+)-terrein during in vitro adipocyte differentiation. Molecular markers associated with thermogenesis and differentiation were quantified using real-time polymerase chain reaction and western blotting.
Results: (+)-Terrein-treated mice exhibited improved insulin sensitivity and reduced serum lipid and glucose levels, irrespective of the diet. Furthermore, (+)-terrein suppressed body weight gain and mitigated fat accumulation by activating brown adipose tissue in HF-fed mice. (+)-Terrein facilitated the in vitro differentiation of rat brown preadipocytes, T37i cells, and ingWAT preadipocytes by upregulating peroxisome proliferator-activated receptor-γ (PPARγ). This effect was synergistic with that of a PPARγ agonist.
Conclusion: This study demonstrated that (+)-terrein effectively induces PPARγ expression and brown adipocyte differentiation, leading to reduced weight gain and improved glucose and lipid profiles in HF-fed mice. Thus, (+)-terrein is a potent novel agent with potential anti-obesity and anti-diabetic properties. en-copyright= kn-copyright= en-aut-name=Aoki-SaitoHaruka en-aut-sei=Aoki-Saito en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MandaiHiroki en-aut-sei=Mandai en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakakuraTakashi en-aut-sei=Nakakura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTsutomu en-aut-sei=Sasaki en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraTadahiro en-aut-sei=Kitamura en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriKazuhiro en-aut-sei=Omori en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisadaTakeshi en-aut-sei=Hisada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkadaShuichi en-aut-sei=Okada en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugaSeiji en-aut-sei=Suga en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasanobu en-aut-sei=Yamada en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaitoTsugumichi en-aut-sei=Saito en-aut-mei=Tsugumichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=3 en-affil=Department of Anatomy, Teikyo University School of Medicine kn-affil= affil-num=4 en-affil=Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Gunma University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Diabetes, Soleiyu Asahi Clinic kn-affil= affil-num=9 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Health & Sports Sciences, Faculty of Education, Tokyo Gakugei University kn-affil= en-keyword=(+)-Terrein kn-keyword=(+)-Terrein en-keyword=Brown adipose tissue kn-keyword=Brown adipose tissue en-keyword=Thermogenesis kn-keyword=Thermogenesis en-keyword=Obesity kn-keyword=Obesity en-keyword=PPARγ kn-keyword=PPARγ END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=e00678 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Alkoxy‐Substituted Anthrabis(Thiadiazole)‐Terthiophene Copolymers for Organic Photovoltaics: A Unique Wavy Backbone Enhances Aggregation, Molecular Order, and Device Efficiency en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two polymer donors, PATz3T-o6BO and PATz3T-o6HD, incorporating alkoxy-substituted anthra[1,2-c:5,6-c′]bis([1,2,5]thiadiazole), were strategically designed and synthesized. The unique wavy backbone of these polymers effectively reduced aggregation, leading to enhanced solubility and significantly improved molecular ordering. Consequently, the PATz3T-o6HD:Y12-based solar cells achieved a power conversion efficiency (PCE) of 7.94%. These findings provide valuable insights into the molecular design of high-performance polymer donors for organic photovoltaics (OPVs). en-copyright= kn-copyright= en-aut-name=YanYi en-aut-sei=Yan en-aut-mei=Yi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriHiroki en-aut-sei=Mori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshinoTomoki en-aut-sei=Yoshino en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InamiRyuki en-aut-sei=Inami en-aut-mei=Ryuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChangJiaxin en-aut-sei=Chang en-aut-mei=Jiaxin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoJunqing en-aut-sei=Gao en-aut-mei=Junqing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiharaYasushi en-aut-sei=Nishihara en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Aggregation kn-keyword=Aggregation en-keyword=Backbone conformation kn-keyword=Backbone conformation en-keyword=Conjugated polymers kn-keyword=Conjugated polymers en-keyword=Organic solar cells kn-keyword=Organic solar cells en-keyword=Semiconducting polymers kn-keyword=Semiconducting polymers END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amino Acid Substitutions in Loop C of Arabidopsis PIP2 Aquaporins Alters the Permeability of CO2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The transport of CO2 across biomembranes in plant cells is essential for efficient photosynthesis. Some aquaporins capable of CO2 transport, referred to as ‘COOporins’, are postulated to play a crucial role in leaf CO2 diffusion. However, the structural basis of CO2 permeation through aquaporins remains largely unknown. Here, we show that amino acids in loop C are critical for the CO2 permeability of Arabidopsis thaliana PIP2 aquaporins. We found that swapping tyrosine and serine in loop C to histidine and phenylalanine, which differ between AtPIP2;1 and AtPIP2;3, altered CO2 permeability when examined in the Xenopus laevis oocyte heterologous expression system. AlphaFold2 modelling indicated that these substitution induced a conformational shift in the sidechain of arginine in the aromatic/arginine (ar/R) selectivity filter and in lysine at the extracellular mouth of the monomeric pore in PIP2 aquaporins. Our findings demonstrate that distal amino acid substitutions can trigger conformational changes of the ar/R filter in the monomeric pore, modulating CO2 permeability. Additionally, phylogenetic analysis suggested that aquaporins capable of dual water/CO2 permeability are ancestral to those that are water-selective and CO2-impermeable, and CO2-selective and water impermeable. en-copyright= kn-copyright= en-aut-name=TaniaShaila Shermin en-aut-sei=Tania en-aut-mei=Shaila Shermin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UtsugiShigeko en-aut-sei=Utsugi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuchiyaYoshiyuki en-aut-sei=Tsuchiya en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasanoShizuka en-aut-sei=Sasano en-aut-mei=Shizuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=Arabidopsis thaliana kn-keyword=Arabidopsis thaliana en-keyword=CO2 transport kn-keyword=CO2 transport en-keyword=monomeric pore kn-keyword=monomeric pore en-keyword=PIP2 aquaporin kn-keyword=PIP2 aquaporin en-keyword=Xenopus laevis kn-keyword=Xenopus laevis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=23 article-no= start-page=17720 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A meta-linked isomer of ITIC: influence of aggregation patterns on open-circuit voltage in organic solar cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Improving the open-circuit voltage (VOC) of organic solar cells (OSCs) remains an important challenge. While it is known that the energy levels at the donor/acceptor (D/A) interface affect the VOC, the impact of aggregation patterns on the energy levels at the D/A interface has not been fully elucidated. Herein, we focus on ITIC, a widely used acceptor in OSCs, and designed a meta-linked isomer of ITIC (referred to as im-ITIC) to alter molecular symmetry and modify substitution arrangements. Concentration-dependent 1H NMR spectra revealed that im-ITIC shows stronger aggregation behavior in solution. Single-crystal X-ray analysis showed that im-ITIC forms both tail-to-tail (J-aggregation) and face-to-face (H-aggregation) stacking modes, whereas ITIC exclusively forms tail-to-tail stacking. OSCs based on PBDB-T:im-ITIC showed a high VOC value of 1.02 V, which is 0.12 V higher than that of those based on PBDB-T:ITIC. Time-resolved infrared measurements revealed the lifetime of free electrons for the pristine and blend films. The energy levels of the charge transfer state (ECT) for PBDB-T:im-ITIC- and PBDB-T:ITIC OSCs were determined to be 1.57 and 1.39 eV, respectively, correlating with the VOC values. Theoretical calculations indicated that pronounced H-aggregation in im-ITIC increases the ECT compared with J-aggregation, contributing to the improved VOC. This study underscores the critical impact of molecular aggregation patterns on energy alignment and VOC enhancement, offering insights into molecular design for achieving high VOC in OSCs. en-copyright= kn-copyright= en-aut-name=WangKai en-aut-sei=Wang en-aut-mei=Kai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JinnaiSeihou en-aut-sei=Jinnai en-aut-mei=Seihou kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UesakaKaito en-aut-sei=Uesaka en-aut-mei=Kaito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamakataAkira en-aut-sei=Yamakata en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IeYutaka en-aut-sei=Ie en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=2 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= affil-num=3 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science & Technology, Okayama University kn-affil= affil-num=5 en-affil=The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka kn-affil= END start-ver=1.4 cd-journal=joma no-vol=262 cd-vols= no-issue=2 article-no= start-page=385 end-page=395 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm−1). We found that the relative value of the hydraulic resistance (rLpm−1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm−1 = ρmCs + 1, where ρm is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp−1. We used their data to estimate Lpm−1 and rLpm−1. The values of rLpm−1 fit the above relation we found for alcohols. When we plotted the ρm values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M−1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm−1) as a function of the external (π0) and internal (πi) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (ρm) were linearly related to the MW of the permeant solutes with a slope of 0.012 M−1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (ρm) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449–461, 2004) is the decisive factor in a solute’s influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. en-copyright= kn-copyright= en-aut-name=TazawaMasashi en-aut-sei=Tazawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WayneRandy en-aut-sei=Wayne en-aut-mei=Randy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatsuharaMaki en-aut-sei=Katsuhara en-aut-mei=Maki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Yoshida Biological Laboratory kn-affil= affil-num=2 en-affil=Laboratory of Natural Philosophy, Plant Biology Section, Cornell University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources (IPSR), Okayama University kn-affil= en-keyword=Chara corallina kn-keyword=Chara corallina en-keyword=Effective osmotic pressure kn-keyword=Effective osmotic pressure en-keyword=Hydraulic resistance kn-keyword=Hydraulic resistance en-keyword=Plasma membrane kn-keyword=Plasma membrane en-keyword=Reflection coefficient kn-keyword=Reflection coefficient END start-ver=1.4 cd-journal=joma no-vol=599 cd-vols= no-issue=13 article-no= start-page=1914 end-page=1924 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250525 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characterization of molecular mechanisms of CaMKKα/1 oligomerization en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain. en-copyright= kn-copyright= en-aut-name=UenoyamaShun en-aut-sei=Uenoyama en-aut-mei=Shun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NittaHayato en-aut-sei=Nitta en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukaSatomi en-aut-sei=Ohtsuka en-aut-mei=Satomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuizuFutoshi en-aut-sei=Suizu en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TokumitsuHiroshi en-aut-sei=Tokumitsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=3 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Kagawa Prefectural University of Health Sciences kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=calmodulin kn-keyword=calmodulin en-keyword=calmodulin-kinase cascade kn-keyword=calmodulin-kinase cascade en-keyword=CaMKKa/ kn-keyword=CaMKKa/ en-keyword=oligomerization kn-keyword=oligomerization en-keyword=protein–protein interaction kn-keyword=protein–protein interaction en-keyword=regulatory domain kn-keyword=regulatory domain END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=5 article-no= start-page=705 end-page=721 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development en-subtitle= kn-subtitle= en-abstract= kn-abstract=The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) “Akashinriki” is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group–associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development. en-copyright= kn-copyright= en-aut-name=NakamuraKoki en-aut-sei=Nakamura en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiYuichi en-aut-sei=Kikuchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiragaMizuho en-aut-sei=Shiraga en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KotakeToshihisa en-aut-sei=Kotake en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKiwamu en-aut-sei=Hyodo en-aut-mei=Kiwamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TaketaShin en-aut-sei=Taketa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaYoko en-aut-sei=Ikeda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Science and Engineering, Saitama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=7 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=barley kn-keyword=barley en-keyword=awn development kn-keyword=awn development en-keyword=EMBRYONIC FLOWER 1 (EMF1) kn-keyword=EMBRYONIC FLOWER 1 (EMF1) en-keyword=homeotic genes kn-keyword=homeotic genes en-keyword=H3K27 trimethylation kn-keyword=H3K27 trimethylation en-keyword=epigenetic regulation kn-keyword=epigenetic regulation END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250710 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tumor Microvessels with Specific Morphology as a Prognostic Factor in Esophageal Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Angiogenesis is essential for tumor progression. Microvessel density (MVD) is a widely used histological method to assess angiogenesis using immunostained sections, but its prognostic significance in esophageal cancer remains controversial. Recently, the evaluation of microvascular architecture has gained importance as a method to assess tumor aggressiveness. The present study aimed to identify the histological characteristics of tumor microvessels that are associated with the aggressiveness of esophageal squamous cell carcinoma.
Patients and Methods A total of 108 esophageal squamous cell carcinoma tissues were immunohistochemically stained with blood vessel markers and angiogenesis-related markers, including CD31, alpha smooth muscle actin, vascular endothelial growth factor A (VEGF-A), CD206, and D2-40. MVD, microvessel pericyte coverage index (MPI), and tumor vascular morphology were evaluated by microscopy.
Results MVD was significantly associated with patient outcomes, whereas neither MPI nor VEGF-A expression throughout the tumor showed a significant correlation. In addition, the presence of blood vessels encircling clusters of tumor cells, termed C-shaped microvessels, and excessively branching microvessels, termed X-shaped microvessels, was significantly associated with poor prognosis. These vessel types were also correlated with clinicopathological parameters, including deeper invasion of the primary tumor, presence of lymph node metastasis, advanced pathological stage, and distant metastasis. Focal VEGF-A immunoexpression in tumor cells was higher in areas containing C-shaped or X-shaped microvessels compared with areas lacking these vessel morphologies.
Conclusions The data suggest that tumor microvessels with specific morphologies (C-shaped and X-shaped microvessels) may serve as a promising prognostic factor in esophageal squamous cell carcinoma. en-copyright= kn-copyright= en-aut-name=TunHnin Thida en-aut-sei=Tun en-aut-mei=Hnin Thida kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraSeitaro en-aut-sei=Nishimura en-aut-mei=Seitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Esophageal neoplasms kn-keyword=Esophageal neoplasms en-keyword=Angiogenesis kn-keyword=Angiogenesis en-keyword=Microvessel density kn-keyword=Microvessel density en-keyword=Pericytes kn-keyword=Pericytes en-keyword=VEGF-A kn-keyword=VEGF-A en-keyword=Immunohistochemistry kn-keyword=Immunohistochemistry en-keyword=Prognosis kn-keyword=Prognosis END start-ver=1.4 cd-journal=joma no-vol=177 cd-vols= no-issue=4 article-no= start-page=e70396 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana en-subtitle= kn-subtitle= en-abstract= kn-abstract=In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22– and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. en-copyright= kn-copyright= en-aut-name=AkterRojina en-aut-sei=Akter en-aut-mei=Rojina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueYasuhiro en-aut-sei=Inoue en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasumotoSaori en-aut-sei=Masumoto en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MimataYoshiharu en-aut-sei=Mimata en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraToshiyuki en-aut-sei=Nakamura en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MunemasaShintaro en-aut-sei=Munemasa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=6 en-affil= kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=calcium signaling kn-keyword=calcium signaling en-keyword=CNGC kn-keyword=CNGC en-keyword=stomata kn-keyword=stomata END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster en-subtitle= kn-subtitle= en-abstract= kn-abstract=Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. en-copyright= kn-copyright= en-aut-name=YoshinariYuto en-aut-sei=Yoshinari en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakashi en-aut-sei=Nishimura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShu en-aut-sei=Kondo en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanimotoHiromu en-aut-sei=Tanimoto en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiTomoe en-aut-sei=Kobayashi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NiwaRyusuke en-aut-sei=Niwa en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=2 en-affil=Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science kn-affil= affil-num=5 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=6 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=7 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=8 en-affil=Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba kn-affil= END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=5 article-no= start-page=489 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutagenesis Targeting the S153 Residue Within the Transmembrane β-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa en-subtitle= kn-subtitle= en-abstract= kn-abstract=We constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane β-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins. en-copyright= kn-copyright= en-aut-name=HayakawaTohru en-aut-sei=Hayakawa en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaokaSyun en-aut-sei=Yamaoka en-aut-mei=Syun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsakuraMami en-aut-sei=Asakura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoMinako en-aut-sei=Hirano en-aut-mei=Minako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeToru en-aut-sei=Ide en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Bacillus thuringiensis kn-keyword=Bacillus thuringiensis en-keyword=mosquito-larvicidal proteins kn-keyword=mosquito-larvicidal proteins en-keyword=synergistic toxicity kn-keyword=synergistic toxicity en-keyword=Culex pipiens mosquito larvae kn-keyword=Culex pipiens mosquito larvae en-keyword=side-directed mutagenesis kn-keyword=side-directed mutagenesis en-keyword=electrophysiologic analysis kn-keyword=electrophysiologic analysis END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=100242 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers en-subtitle= kn-subtitle= en-abstract= kn-abstract=mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications. en-copyright= kn-copyright= en-aut-name=MaemotoHayaki en-aut-sei=Maemoto en-aut-mei=Hayaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzakiRyohei en-aut-sei=Suzaki en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ItakaKeiji en-aut-sei=Itaka en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=mRNA kn-keyword=mRNA en-keyword=Photochemical internalization kn-keyword=Photochemical internalization en-keyword=Photosensitizer kn-keyword=Photosensitizer END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=311 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250703 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Co-occurrence of interstitial lung disease and pulmonary embolism as adverse events of adjuvant osimertinib treatment for EGFR mutant non-small cell lung cancer: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Postoperative osimertinib for EGFR mutant non-small cell lung cancer has become the standard of care. However, its adverse events in clinical practice remain unclear. We report a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment.
Case presentation A 74-year-old woman, diagnosed with left lower lobe lung adenocarcinoma harboring an EGFR mutation, underwent a left lower lobectomy with lymph node dissection. During adjuvant osimertinib therapy, the patient developed respiratory distress with hypoxia, leading to the diagnosis of interstitial lung disease. Despite immediate steroid therapy, respiratory distress persisted, the patient developed leg edema. She was diagnosed with deep vein thrombosis and pulmonary embolism via contrast-enhanced computed tomography scan. Following treatment with steroid and anticoagulation, her clinical symptoms improved rapidly, and she showed no recurrence of interstitial lung disease, pulmonary embolism, or lung cancer over the following nine months.
Conclusions We encountered a case of interstitial lung disease and pulmonary embolism occurring simultaneously as adverse events during adjuvant osimertinib treatment. In patients with osimertinib-induced interstitial lung disease, particularly when respiratory symptoms show poor improvement with steroid treatment, the possibility of pulmonary embolism complications should be suspected. en-copyright= kn-copyright= en-aut-name=ManabeKenta en-aut-sei=Manabe en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShienKazuhiko en-aut-sei=Shien en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaShinichi en-aut-sei=Furukawa en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SenoTomoya en-aut-sei=Seno en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshimuraKousei en-aut-sei=Ishimura en-aut-mei=Kousei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Thoracic Surgery, Okayama University Hospital kn-affil= en-keyword=Osimertinib kn-keyword=Osimertinib en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Interstitial lung disease kn-keyword=Interstitial lung disease en-keyword=Pulmonary embolism kn-keyword=Pulmonary embolism END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=7 article-no= start-page=808 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NAD+ Cleavage Activity, Ameliorates Symptoms of Peripheral Neuropathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD+-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaKazuki en-aut-sei=Ogawa en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuiYu en-aut-sei=Yasui en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OchiToshiki en-aut-sei=Ochi en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoKen-Ichi en-aut-sei=Yamamoto en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WadaYoji en-aut-sei=Wada en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraHiromichi en-aut-sei=Nakamura en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=3 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=9 en-affil=Tama Biochemical Co., Ltd. kn-affil= affil-num=10 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SARM1 kn-keyword=SARM1 en-keyword=carnosol kn-keyword=carnosol en-keyword=NAD+ kn-keyword=NAD+ en-keyword=axon degeneration kn-keyword=axon degeneration en-keyword=peripheral neuropathy kn-keyword=peripheral neuropathy END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=510 end-page=524 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=C1orf50 Drives Malignant Melanoma Progression Through the Regulation of Stemness en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Recent advancements in omics analysis have significantly enhanced our understanding of the molecular pathology of malignant melanoma, leading to the development of novel therapeutic strategies that target specific vulnerabilities within the disease. Despite these improvements, the factors contributing to the poor prognosis of patients with malignant melanoma remain incompletely understood. The aim of this study was to investigate the role of C1orf50 (Chromosome 1 open reading frame 50), a gene previously of unknown function, as a prognostic biomarker in melanoma.
Materials and Methods: We performed comprehensive transcriptome data analysis and subsequent functional validation of the human Skin Cutaneous Melanoma project from The Cancer Genome Atlas (TCGA).
Results: Elevated expression levels of C1orf50 correlated with worse survival outcomes. Mechanistically, we revealed that C1orf50 plays a significant role in the regulation of cell cycle processes and cancer cell stemness, providing a potential avenue for novel therapeutic interventions in melanoma.
Conclusion: This study is the first to identify C1orf50 as a prognostic biomarker in melanoma. The clinical relevance of our results sheds light on the importance of further investigation into the biological mechanisms underpinning C1orf50’s impact on melanoma progression and patient prognosis. en-copyright= kn-copyright= en-aut-name=OTANIYUSUKE en-aut-sei=OTANI en-aut-mei=YUSUKE kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MAEKAWAMASAKI en-aut-sei=MAEKAWA en-aut-mei=MASAKI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TANAKAATSUSHI en-aut-sei=TANAKA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PEÑATIRSO en-aut-sei=PEÑA en-aut-mei=TIRSO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CHINVANESSA D. en-aut-sei=CHIN en-aut-mei=VANESSA D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ROGACHEVSKAYAANNA en-aut-sei=ROGACHEVSKAYA en-aut-mei=ANNA kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TOYOOKASHINICHI en-aut-sei=TOYOOKA en-aut-mei=SHINICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ROEHRLMICHAEL H. en-aut-sei=ROEHRL en-aut-mei=MICHAEL H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FUJIMURAATSUSHI en-aut-sei=FUJIMURA en-aut-mei=ATSUSHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=5 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=melanoma kn-keyword=melanoma en-keyword=cancer stem cells kn-keyword=cancer stem cells en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual functions of SNAP25 in mouse taste buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III cells in mouse taste buds are considered to transmit aversive stimuli, such as sourness, to the gustatory nerve through vesicular synapses. Synaptosome-associated protein 25 (SNAP25) might contribute to synaptic vesicular release in sour sensation, although direct evidence has been lacking. Here, we demonstrated that epithelia-specific Snap25 conditional knockout (cKO) mice exhibited a significant reduction in the number of type III cells. Notably, the proportion of 5-ethynyl 2′-deoxyuridine-positive post-mitotic type III cells in Snap25 cKO mice was significantly lower on tracing day 14, but not at day 7, which suggests that SNAP25 contributes to the maintenance of type III cells. In a short-term lick test, Snap25 cKO (sour taste absent) and Snap25/ transient receptor potential vanilloid 1 double KO (sour taste and somatosensory absent) mice exhibit a significantly higher lick response to sour tastants, confirming the role of SNAP25 for sour sensation. Electrophysiological recordings of the chorda tympani nerve reveal nearly abolished ammonium and sour taste responses in Snap25 cKO mice, which concludes sour-dependent synapse transmission in type III cells. Overall, these data suggest that vesicular synapses in taste buds are indispensable for transmission of information from, and the replenishment of, sour-sensitive type III taste cells. en-copyright= kn-copyright= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangHai en-aut-sei=Huang en-aut-mei=Hai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasumatsuKeiko en-aut-sei=Yasumatsu en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NinomiyaYuzo en-aut-sei=Ninomiya en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Tokyo Dental Junior College kn-affil= affil-num=5 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=sour taste kn-keyword=sour taste en-keyword=synapse kn-keyword=synapse en-keyword=taste buds kn-keyword=taste buds en-keyword=taste nerve kn-keyword=taste nerve en-keyword=Type III cells kn-keyword=Type III cells END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e86695 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250624 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Managing Persistent Pupillary Membranes With Surgery or Medication: A Report of Three Cases en-subtitle= kn-subtitle= en-abstract= kn-abstract=The persistent pupillary membrane, as a congenital anomaly, is a remnant of a network of feeding blood vessels for the lens of the eye, called tunica vasculosa lentis. This study reports three patients with persistent pupillary membrane in both eyes who presented in different situations and were managed differently to achieve better vision. The first child (Case 1) who had been seen initially at the age of two years complained of severe photophobia even though he had good visual acuity, and hence, he and his family chose surgical resection of the pupillary membrane in both eyes at the age of six years just before the admission to an elementary school. He did not develop any surgical complications, such as cataract and glaucoma, and maintained the visual acuity in decimals of 1.2 in both eyes at the age of 17 years.
The second child (Case 2), who was seen first at the age of one month, had persistent pupillary membranes in both eyes, together with Peters' anomaly in the left eye. The iris process adhesion to the corneal inner surface was visualized later by optical coherence tomography. She wore full-correction glasses and obtained the visual acuity of 0.7 in the right eye, so she had no problem studying at an elementary school. She used topical 1% atropine once a week in both eyes to maintain pupillary dilation and also used 0.5% timolol and 1% brinzolamide as pressure-lowering eye drops in the left eye with Peters' anomaly.
The third patient (Case 3) with persistent pupillary membranes in both eyes complained of vision problems for the first time at the age of 49 years when she developed cataract. Surgical resection of the pupillary membrane was done in the initial phase of cataract surgery with intraocular lens implantation in both eyes. At surgical resection of the pupillary membrane, a safe and efficient way was to cut the root of the pupillary membrane on the iris surface with scissors, and then the isolated tissues of the pupillary membrane were pulled out with forceps from the side port at the corneal limbus. Pathological examinations of the excised tissues showed blood vessels with red blood cells in the lumen. In such a rare congenital disease as the persistent pupillary membrane, a case-based approach to choose a better option in different conditions from individual to individual is still required to have a better vision in learning at school and in daily working life. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=anterior segment dysgenesis kn-keyword=anterior segment dysgenesis en-keyword=cataract kn-keyword=cataract en-keyword=forceps kn-keyword=forceps en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=persistent pupillary membrane kn-keyword=persistent pupillary membrane en-keyword=peters anomaly kn-keyword=peters anomaly en-keyword=resection kn-keyword=resection en-keyword=scissors kn-keyword=scissors en-keyword=vitrectomy cutter kn-keyword=vitrectomy cutter END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=e85680 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250610 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Whole-Eye Radiation for the Local Control of Choroidal Lymphoma in Primary Central Nervous System Lymphoma: A 14-Year Case Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Involved-site radiation therapy is effective for curative and palliative treatments of cancers, including lymphoma. This case study describes the use of whole-eye radiation for primary intraocular lymphoma occurring during primary central nervous system lymphoma. The patient, a 68-year-old man, developed personality changes and apathy two weeks after cataract surgery combined with vitrectomy for vitreous opacity in the left eye. Magnetic resonance imaging revealed a mass lesion in the left frontal lobe, and biopsy by craniotomy confirmed diffuse large B-cell lymphoma. He underwent chemotherapy using rituximab combined with high-dose methotrexate and high-dose cytarabine in association with intrathecal methotrexate and cytarabine injections, leading to complete remission. At age 75, he noticed forgetfulness, and fluorodeoxyglucose positron emission tomography and magnetic resonance imaging revealed a relapse of lymphoma in the splenium of the corpus callosum. He underwent chemotherapy using rituximab combined with high-dose methotrexate, followed by monthly rituximab monotherapy for one year and then rituximab monotherapy every two months for one year. He maintained complete remission with no treatment until age 78, when he developed subretinal choroidal lesions in the left eye and underwent whole-eye radiation at 40 Gy. One year later, he developed subretinal choroidal lesions in the right eye and underwent whole-eye radiation at 40 Gy. At age 81, he had lower limb weakness with disorientation. Magnetic resonance imaging showed a relapse of lymphoma in the right frontal to temporal lobe. The brain lesions showed a marked response to four weeks of oral tirabrutinib as a salvage therapy, but the lesions regrew, and the patient died seven months later. Throughout the treatment, he maintained a visual acuity of 0.7 (decimal scale) in both eyes. In conclusion, whole-eye radiation should be considered as a treatment option for the local control of active intraocular lymphoma, especially choroidal lesions, for patients with primary central nervous system lymphoma with no active brain lesions and without systemic treatment. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshioKotaro en-aut-sei=Yoshio en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraHirotake en-aut-sei=Nishimura en-aut-mei=Hirotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=bruton tyrosine kinase (btk) inhibitor kn-keyword=bruton tyrosine kinase (btk) inhibitor en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=fluorodeoxyglucose positron emission tomography kn-keyword=fluorodeoxyglucose positron emission tomography en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=radiation therapy (radiotherapy) kn-keyword=radiation therapy (radiotherapy) en-keyword=tirabrutinib kn-keyword=tirabrutinib en-keyword=whole-eye radiation kn-keyword=whole-eye radiation END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=5 article-no= start-page=e83484 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detailed Ophthalmic and Pathological Features of Choroidal Metastasis From Breast Cancer: A Case Series of Five Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast cancer causes choroidal metastases on rare occasions. This study presented the eye manifestations of choroidal metastases from breast cancer and their response to treatments in detail as well as their pathological correlation in five patients. The patients' age at the diagnosis of breast cancer ranged from 24 to 69 years (median: 37 years). The time from the diagnosis of breast cancer to the detection of metastases was concurrent in one patient, two years later in three patients, and six years later in the other patient. The time from the detection of systemic metastases to the detection of choroidal metastases was the same in one patient, while it ranged from one to seven years later in four patients. Choroidal metastases were in the unilateral eye of four patients, whereas they were in both eyes of one patient. Choroidal metastases manifested as one or a few nodular or flat choroidal lesions with serous retinal detachment. As for the treatment of choroidal metastases, enucleation of the right eye was chosen based on the patient's wish as well as the family's wish in the earliest patient when cancer notification was not the norm in Japan. In the other four patients, whole-eye radiation was performed to reduce the choroidal metastatic lesions. As regards the prognosis, which was available in four patients, three patients died within one year from the diagnosis of choroidal metastases, while one patient died one year and eight months later. Regarding the pathology of breast cancer, which was available in four patients, immunostaining of the preserved enucleated eye in the earliest patient revealed that breast cancer cells in the choroidal metastatic lesion were positive for estrogen receptor and negative for progesterone receptor and human epidermal growth factor receptor 2 (HER2). Invasive ductal carcinoma in two patients was positive for estrogen receptor and negative for HER2, while invasive ductal carcinoma in the other patient was triple-negative for estrogen receptor, progesterone receptor, and HER2 with a high Ki-67 index. In conclusion, the prognosis for life was poor in patients with breast cancer who developed choroidal metastases. Choroidal metastatic lesions showed a response to whole-eye radiation to improve the quality of vision at the end of life. Vision-related symptoms should be monitored in the course of chemotherapy for systemic metastases. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShienTadahiko en-aut-sei=Shien en-aut-mei=Tadahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MuraokaAtsushi en-aut-sei=Muraoka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Division of Healthcare Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Kagawa Rosai Hospital kn-affil= affil-num=5 en-affil=Department of Breast and Endocrine Surgery, Okayama University Hospital kn-affil= en-keyword=breast cancer kn-keyword=breast cancer en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=choroidal metastasis kn-keyword=choroidal metastasis en-keyword=estrogen receptor kn-keyword=estrogen receptor en-keyword=her2 kn-keyword=her2 en-keyword=immunostaining kn-keyword=immunostaining en-keyword=invasive ductal carcinoma kn-keyword=invasive ductal carcinoma en-keyword=ki-67 kn-keyword=ki-67 en-keyword=progesterone receptor kn-keyword=progesterone receptor en-keyword=radiation kn-keyword=radiation END start-ver=1.4 cd-journal=joma no-vol=166 cd-vols= no-issue=8 article-no= start-page=bqaf102 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-running Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)–expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone. en-copyright= kn-copyright= en-aut-name=OtsukaMai en-aut-sei=Otsuka en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiYu en-aut-sei=Takeuchi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriyamaMaho en-aut-sei=Moriyama en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgoshiSakura en-aut-sei=Egoshi en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GotoYuki en-aut-sei=Goto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GuTingting en-aut-sei=Gu en-aut-mei=Tingting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimuraAtsushi P en-aut-sei=Kimura en-aut-mei=Atsushi P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaraguchiShogo en-aut-sei=Haraguchi en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshiiTaishi en-aut-sei=Yoshii en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuyamaMakoto en-aut-sei=Matsuyama en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=BentleyGeorge E en-aut-sei=Bentley en-aut-mei=George E kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Biology, Faculty of Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Biological Sciences, Faculty of Science, Hokkaido University kn-affil= affil-num=8 en-affil=Department of Biochemistry, Showa University School of Medicine kn-affil= affil-num=9 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=11 en-affil=Division of Molecular Genetics, Shigei Medical Research Institute kn-affil= affil-num=12 en-affil=Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley kn-affil= affil-num=13 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Neuromedin U kn-keyword=Neuromedin U en-keyword=rat kn-keyword=rat en-keyword=motivation kn-keyword=motivation en-keyword=activity kn-keyword=activity en-keyword=testosterone kn-keyword=testosterone en-keyword=wheel-running kn-keyword=wheel-running END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=2 article-no= start-page=232 end-page=243 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS) ≥ 2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p = 0.092) or higher LDH (4.0 vs. 2.0 months, p = 0.018), whereas PFS in the two cellular therapy groups was similar among those with PS ≥ 2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=CAR-T cell therapy kn-keyword=CAR-T cell therapy en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel en-keyword=Poor prognostic factors kn-keyword=Poor prognostic factors END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=388.e1 end-page=388.e14 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. Multivariate analysis showed that early (days 0 to 4) and late (days 5 to 10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = .002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = .007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = .015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS. en-copyright= kn-copyright= en-aut-name=KonumaTakaaki en-aut-sei=Konuma en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaMachiko en-aut-sei=Fujioka en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuseKyoko en-aut-sei=Fuse en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasamotoYosuke en-aut-sei=Masamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshikawaJun en-aut-sei=Ishikawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraKoji en-aut-sei=Kawamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhbikiMarie en-aut-sei=Ohbiki en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ItonagaHidehiro en-aut-sei=Itonaga en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Hematology, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Hematology, Endocrinology and Metabolism, Niigata University kn-affil= affil-num=4 en-affil=Department of Hematology/Oncology, Wakayama Medical University kn-affil= affil-num=5 en-affil=Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Osaka International Cancer Institute kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Hematology and oncology, Kurashiki Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=20 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Transfusion and Cell Therapy Unit, Nagasaki University Hospital kn-affil= en-keyword=Granulocyte colony-stimulating factor kn-keyword=Granulocyte colony-stimulating factor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Peripheral blood stem cell transplantation kn-keyword=Peripheral blood stem cell transplantation en-keyword=Cord blood transplantation kn-keyword=Cord blood transplantation en-keyword=Myelodysplastic syndrome kn-keyword=Myelodysplastic syndrome END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=2 article-no= start-page=145 end-page=148 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The trochlea for the intermediate tendon of the digastric muscle: a review en-subtitle= kn-subtitle= en-abstract= kn-abstract=This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea. en-copyright= kn-copyright= en-aut-name=du PlooyXander en-aut-sei=du Plooy en-aut-mei=Xander kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CardonaJuan J. en-aut-sei=Cardona en-aut-mei=Juan J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabiraYoko en-aut-sei=Tabira en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BubbKathleen Carol en-aut-sei=Bubb en-aut-mei=Kathleen Carol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaeburnKazzara en-aut-sei=Raeburn en-aut-mei=Kazzara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Tulane University School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=4 en-affil=Division of Gross and Clinical Anatomy, Department of Anatomy, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Anatomy Division, Department of Radiology, Weill Cornell Medical College kn-affil= affil-num=6 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= affil-num=9 en-affil=Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine kn-affil= en-keyword=Digastric muscles kn-keyword=Digastric muscles en-keyword=Intermediate tendon kn-keyword=Intermediate tendon en-keyword=Trochlea kn-keyword=Trochlea en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Fascia kn-keyword=Fascia END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sulfur dioxide-induced guard cell death and stomatal closure are attenuated in nitrate/proton antiporter AtCLCa mutants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Guard cells surrounding the stomata play a crucial role in regulating the entrance of hazardous gases such as SO2 into leaves. Stomatal closure could be a plant response to mitigate SO2 damage, although the mechanism for SO2-induced closure remains controversial. Proposed mediators for SO2-induced stomatal closure include phytohormones, reactive oxygen species, gasotransmitters, and cytosolic acidification. In this study, we investigated the mechanism of stomatal closure in Arabidopsis in response to SO2. Despite an increment in auxin and jasmonates after SO2 exposure, the addition of auxin did not cause stomatal closure and jasmonate-insensitive mutants exhibited SO2-induced stomatal closure suggesting auxin and jasmonates are not mediators leading to the closure. In addition, supplementation of scavenging reagents for reactive oxygen species and gasotransmitters did not inhibit SO2-induced closure. Instead, we found that cytosolic acidification is a credible mechanism for SO2-induced stomatal closure in Arabidopsis. CLCa mutants coding H+/nitrate antiporter, involved in cytosolic pH homeostasis, showed less sensitive stomatal phenotype against SO2. These results suggest that cytosolic pH homeostasis plays a tenable role in SO2 response in guard cells. en-copyright= kn-copyright= en-aut-name=OoiLia en-aut-sei=Ooi en-aut-mei=Lia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuuraTakakazu en-aut-sei=Matsuura en-aut-mei=Takakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoriIzumi C. en-aut-sei=Mori en-aut-mei=Izumi C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=3 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=airborne pollutants kn-keyword=airborne pollutants en-keyword=cytosolic acidification kn-keyword=cytosolic acidification en-keyword=stomatal closure kn-keyword=stomatal closure en-keyword=sulfur dioxide kn-keyword=sulfur dioxide END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=5 article-no= start-page=733 end-page=747 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A PRA-Rab trafficking machinery modulates NLR immune receptor plasma membrane microdomain anchoring and blast resistance in rice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nucleotide-binding leucine-rich repeat (NLR) receptors mediate pathogen effector-triggered immunity (ETI) in plants, and a subclass of NLRs are hypothesized to function at the plasma membrane (PM). However, how NLR traffic and PM delivery are regulated during immune responses remains largely unknown. The rice NLR PigmR confers broad-spectrum resistance to the blast fungus Magnaporthe oryzae. Here, we report that a PRA (Prenylated Rab acceptor) protein, PIBP4 (PigmR-INTERACTING and BLAST RESISTANCE PROTEIN 4), interacts with both PigmR and the active form of the Rab GTPase, OsRab5a, thereby loads a portion of PigmR on trafficking vesicles that target to PM microdomains. Microdomain-localized PigmR interacts with and activates the small GTPase OsRac1, which triggers reactive oxygen species signaling and hypersensitive response, leading to immune responses against blast infection. Thus, our study discovers a previously unknown mechanism that deploys a PRA-Rab protein delivering hub to ensure ETI, linking the membrane trafficking machinery with NLR function and immune activation in plants. en-copyright= kn-copyright= en-aut-name=LiangDi en-aut-sei=Liang en-aut-mei=Di kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YangDongyong en-aut-sei=Yang en-aut-mei=Dongyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiTai en-aut-sei=Li en-aut-mei=Tai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhuZhe en-aut-sei=Zhu en-aut-mei=Zhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YanBingxiao en-aut-sei=Yan en-aut-mei=Bingxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HeYang en-aut-sei=He en-aut-mei=Yang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiXiaoyuan en-aut-sei=Li en-aut-mei=Xiaoyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ZhaiKeran en-aut-sei=Zhai en-aut-mei=Keran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LiuJiyun en-aut-sei=Liu en-aut-mei=Jiyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawanoYoji en-aut-sei=Kawano en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DengYiwen en-aut-sei=Deng en-aut-mei=Yiwen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WuXu Na en-aut-sei=Wu en-aut-mei=Xu Na kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=LiuJunzhong en-aut-sei=Liu en-aut-mei=Junzhong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HeZuhua en-aut-sei=He en-aut-mei=Zuhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=4 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=5 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=School of Life Science and Technology, ShanghaiTech University kn-affil= affil-num=8 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=11 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=13 en-affil=Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University kn-affil= affil-num=14 en-affil=CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences kn-affil= en-keyword=Prenylated Rab acceptor kn-keyword=Prenylated Rab acceptor en-keyword=PigmR kn-keyword=PigmR en-keyword=Trafficking vesicles kn-keyword=Trafficking vesicles en-keyword=OsRab5a kn-keyword=OsRab5a en-keyword=Blast resistance kn-keyword=Blast resistance END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The maxillary vein: an anatomical narrative review with clinical implications for oral and maxillofacial surgeons en-subtitle= kn-subtitle= en-abstract= kn-abstract=The maxillary vein, despite its clinical significance, remains underexplored in anatomical literature. It plays a crucial role in venous drainage of the maxillofacial region and is closely associated with surgical procedures such as sagittal split ramus osteotomy, mandibuloplasty, and condylar or parotid surgeries. Due to its variable anatomy and proximity to critical structures, the maxillary vein poses a risk of significant hemorrhage if injured. Its small size and deep location make preoperative identification challenging, especially without contrast-enhanced imaging. Embryologically, the maxillary vein originates from the primitive maxillary vein and develops through complex anastomoses with other craniofacial veins. Anatomical studies have revealed several variations, including the presence of accessory mandibular foramina and unusual venous connections, which may increase surgical risk. Understanding the detailed anatomy and potential variations of the maxillary vein is essential for minimizing complications and improving surgical outcomes. Despite its importance, more anatomical and clinical research is needed to better define its course, variations, and implications in oral and maxillofacial surgery. en-copyright= kn-copyright= en-aut-name=RaeburnKazzara en-aut-sei=Raeburn en-aut-mei=Kazzara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakakuraHiroaki en-aut-sei=Takakura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikutaShogo en-aut-sei=Kikuta en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IbaragiSoichiro en-aut-sei=Ibaragi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SamridRarinthorn en-aut-sei=Samrid en-aut-mei=Rarinthorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LoukasMarios en-aut-sei=Loukas en-aut-mei=Marios kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TubbsR. Shane en-aut-sei=Tubbs en-aut-mei=R. Shane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwanagaJoe en-aut-sei=Iwanaga en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil= kn-affil= affil-num=8 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=9 en-affil=Department of Anatomical Sciences, St. George’s University kn-affil= affil-num=10 en-affil=Dental and Oral Medical Center, Kurume University School of Medicine kn-affil= en-keyword=Embryology kn-keyword=Embryology en-keyword=Anatomy kn-keyword=Anatomy en-keyword=Radiology kn-keyword=Radiology en-keyword=Cadaver kn-keyword=Cadaver en-keyword=Mandible kn-keyword=Mandible END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=18981 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of galectin-9 in the development of gestational diabetes mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. Lgals9 knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with controls (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3 + trNK increased, while early apoptosis percentage in Tim-3 + trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3 + trNK cells. en-copyright= kn-copyright= en-aut-name=AlbuayjanHaya Hamed Hassan en-aut-sei=Albuayjan en-aut-mei=Haya Hamed Hassan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugawaraRyosuke en-aut-sei=Sugawara en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OiYukiko en-aut-sei=Oi en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KannoAyaka en-aut-sei=Kanno en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YangBoXuan en-aut-sei=Yang en-aut-mei=BoXuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TaharaToshihisa en-aut-sei=Tahara en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NojimaIchiro en-aut-sei=Nojima en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EtoEriko en-aut-sei=Eto en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HayataKei en-aut-sei=Hayata en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=孔辺細胞のシグナル伝達におけるGUARD CELL HYDROGEN PEROXIDE-RESISTANT1と内因性アブシジン酸の役割 kn-title=Roles of GUARD CELL HYDROGEN PEROXIDE-RESISTANT1 and endogenous abscisic acid in guard-cell signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SHAIEK Oumayma en-aut-sei=SHAIEK Oumayma en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=持続可能な発展に向けた携帯電話リサイクルの推進：消費者行動分析、デジタルトランスフォーメーション戦略、および革新的インセンティブメカニズムの統合 kn-title=Optimizing cell phone recycling for sustainable development: Integrating consumer behavior analysis, digital transformation strategies, and innovative incentive mechanisms en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DUYuxin en-aut-sei=DU en-aut-mei=Yuxin kn-aut-name=杜余鑫 kn-aut-sei=杜 kn-aut-mei=余鑫 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=稲わら施用水田土壌からのCH4およびCO2 排出抑制に向けた底質微生物燃料電池の開発 kn-title=Development of sediment microbial fuel cells to reduce CH4 and CO2 emissions from straw-amended paddy soil en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ADHENA TESFAU BEKELE en-aut-sei=ADHENA TESFAU BEKELE en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=マウスIII型細胞におけるCcn3の機能の探索 kn-title=Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Kuanyu Wang en-aut-sei=Kuanyu Wang en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=上顎洞に認められた扁平上皮癌および非扁平上皮癌のCT画像の評価 kn-title=Evaluation of CT Findings in Squamous and Non-Squamous Cell Carcinomas of the Maxillary Sinus en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ASAUMIYuka en-aut-sei=ASAUMI en-aut-mei=Yuka kn-aut-name=浅海結華 kn-aut-sei=浅海 kn-aut-mei=結華 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=細胞自己凝集化技術を用いた内皮層反転血管構造を有するユニークなin vitro血管モデルの開発 kn-title=Development of a unique tissue-engineered in vitro vascular model with endothelial layer-inverted vascular tissue structure using a cell self-aggregation technique en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HASHIMOTOShingo en-aut-sei=HASHIMOTO en-aut-mei=Shingo kn-aut-name=橋本真悟 kn-aut-sei=橋本 kn-aut-mei=真悟 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=腫瘍特異的疲弊CD8⁺T細胞に発現するCD106はTCRシグナル伝達を阻害し免疫抑制を引き起こす kn-title=CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAOIYuto en-aut-sei=NAOI en-aut-mei=Yuto kn-aut-name=直井勇人 kn-aut-sei=直井 kn-aut-mei=勇人 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=CTLA-4阻害の抗腫瘍効果はTreg細胞のCTLA-4非依存性免疫抑制機構の活性化によって減弱する kn-title=Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WATANABETomofumi en-aut-sei=WATANABE en-aut-mei=Tomofumi kn-aut-name=渡部智文 kn-aut-sei=渡部 kn-aut-mei=智文 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=血管内皮細胞、線維芽細胞、およびiPS心筋細胞からなるヒト心臓チップマイクロ生理システム kn-title=Human heart‑on‑a‑chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC‑derived cardiomyocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIUYUN en-aut-sei=LIU en-aut-mei=YUN kn-aut-name=劉云 kn-aut-sei=劉 kn-aut-mei=云 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=樹状細胞の成熟は、腫瘍由来エクソソームを介してp53搭載腫瘍融解アデノウイルスによって誘導され、全身の抗腫瘍免疫を誘導する kn-title=Dendritic cell maturation is induced by p53‑armed oncolytic adenovirus via tumor‑derived exosomes enhancing systemic antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OTANITomoko en-aut-sei=OTANI en-aut-mei=Tomoko kn-aut-name=大谷朋子 kn-aut-sei=大谷 kn-aut-mei=朋子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ヒト肥満細胞における重合開始剤によるヒスタミン産生の誘導 kn-title=Photoinitiators Induce Histamine Production in Human Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MIURATaro en-aut-sei=MIURA en-aut-mei=Taro kn-aut-name=三浦太郎 kn-aut-sei=三浦 kn-aut-mei=太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=心停止ドナーからの肺移植においてNr4a1の欠損は内皮細胞障害を抑制し血管外漏出を改善する　 kn-title=Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KAWANAShinichi en-aut-sei=KAWANA en-aut-mei=Shinichi kn-aut-name=川名伸一 kn-aut-sei=川名 kn-aut-mei=伸一 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ヒト臍帯血内皮前駆細胞はラット脳卒中モデルにおける動脈損傷の内膜過形成を緩和する kn-title=Human Cord Blood–Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUNHONGMING en-aut-sei=SUN en-aut-mei=HONGMING kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=アドレナリンβ2受容体はリガンド非依存的にマスト細胞の IgE 誘導性カルシウム流入を促進する kn-title=Ligand-independent function of β2-adrenergic receptor affects IgE-mediated Ca2+ influx in mast cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAGAOKei en-aut-sei=NAGAO en-aut-mei=Kei kn-aut-name=長尾圭 kn-aut-sei=長尾 kn-aut-mei=圭 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=p53を搭載した腫瘍融解ウイルス療法は免疫原性細胞死を促進することにより骨肉腫にアブスコパル効果を誘導する kn-title=p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DEMIYAKoji en-aut-sei=DEMIYA en-aut-mei=Koji kn-aut-name=出宮光二 kn-aut-sei=出宮 kn-aut-mei=光二 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=38 cd-vols= no-issue=8 article-no= start-page=100782 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Involvement of PI3K–Akt Signaling in the Clinical and Pathological Findings of Idiopathic Multicentric Castleman Disease–Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, and Organomegaly and Not Otherwise Specified Subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Idiopathic multicentric Castleman disease is a rare lymphoproliferative disorder that is clinically classified into idiopathic plasmacytic lymphadenopathy (IPL); thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO); and not otherwise specified (NOS). Although each subtype shows varying degrees of hypervascularity, no statistical data on the degree of vascularization have been reported. Additionally, the mechanisms underlying vascularization in each clinical subtype are poorly understood. Here, we aimed to clarify these mechanisms by evaluating the histopathological characteristics of each clinical subtype across 37 patients and performing a whole-transcriptome analysis focusing on angiogenesis-related gene expression. Histologically, TAFRO and NOS exhibited a significantly higher degree of vascularization than IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .002). In addition, the germinal centers (GCs) were significantly more atrophic in TAFRO than in IPL. In TAFRO and NOS, “whirlpool vessels” in GCs were seen in most cases (TAFRO, 9/9, 100%; NOS, 6/8, 75%) but not in IPL (IPL vs TAFRO, P < .001; IPL vs NOS, P = .007). Likewise, immunostaining for Ets-related gene revealed higher levels in endothelial cells of GCs in TAFRO than in IPL (P = .014), and TAFRO and NOS were associated with a significantly higher number of endothelial cells in interfollicular areas compared with that in IPL (TAFRO vs IPL, P < .001; NOS vs IPL, P = .002). Gene expression analysis revealed that the PI3K–Akt signaling pathway was significantly enriched in the TAFRO and NOS (TAFRO/NOS) groups. This pathway, which may be activated by vascular endothelial growth factor A and some integrins, is known to affect angiogenesis by increasing vascular permeability, which may explain the clinical manifestations of anasarca and/or fluid retention in TAFRO/NOS. These results suggest that the PI3K–Akt pathway plays an important role in the pathogenesis of TAFRO/NOS. en-copyright= kn-copyright= en-aut-name=HaratakeTomoka en-aut-sei=Haratake en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GonzalezMichael V. en-aut-sei=Gonzalez en-aut-mei=Michael V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LaiYou Cheng en-aut-sei=Lai en-aut-mei=You Cheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OchiSayaka en-aut-sei=Ochi en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsunodaManaka en-aut-sei=Tsunoda en-aut-mei=Manaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FajgenbaumDavid C. en-aut-sei=Fajgenbaum en-aut-mei=David C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=van RheeFrits en-aut-sei=van Rhee en-aut-mei=Frits kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=4 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=5 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Medical Biotechnology and Laboratory Science, Chang Gung University kn-affil= affil-num=7 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=9 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=10 en-affil=Center for Cytokine Storm Treatment and Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=11 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=12 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=idiopathic multicentric Castleman disease kn-keyword=idiopathic multicentric Castleman disease en-keyword=integrin subunit alpha 5 kn-keyword=integrin subunit alpha 5 en-keyword=PI3K–Akt signaling pathway kn-keyword=PI3K–Akt signaling pathway en-keyword=platelet-derived growth factor receptor beta kn-keyword=platelet-derived growth factor receptor beta en-keyword=vascular endothelial growth factor A kn-keyword=vascular endothelial growth factor A en-keyword=vascularity kn-keyword=vascularity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250519 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution A en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin.
Study Design and Methods: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively.
Results: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar.
Discussion: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional method en-copyright= kn-copyright= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=3 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= en-keyword=anticoagulant kn-keyword=anticoagulant en-keyword=apheresis kn-keyword=apheresis en-keyword=high sodium citrate concentration kn-keyword=high sodium citrate concentration en-keyword=Spectra Optia kn-keyword=Spectra Optia END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=213 end-page=219 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Chromophobe Renal Cell Carcinoma Metastasizing to the Cervical Lymph Nodes after Long-term Follow-up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Renal cell carcinoma (RCC) can metastasize hematogenously and recur after a long dormancy. Chromophobe RCC metastasized to the cervical lymph nodes 10 years after the primary resection in a woman who underwent nephrectomy for RCC (T1aN0M0 stage I). Metastatic RCC diagnosis was confirmed by aspiration. The lymph node mass was resected, and the tumor cells matched chromophobe RCC metastasis. No adjuvant therapy was administered due to the lack of evidence regarding adjuvant therapy for chromophobe RCC. Long-term surveillance is crucial in RCC because of the possibility of late metastasis. We reviewed the clinical aspects and literature on metastatic cervical RCC. en-copyright= kn-copyright= en-aut-name=WatanabeMakoto en-aut-sei=Watanabe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaTomoyuki en-aut-sei=Ogawa en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKanao en-aut-sei=Kobayashi en-aut-mei=Kanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatsuyaNarutaka en-aut-sei=Katsuya en-aut-mei=Narutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshikawaAkira en-aut-sei=Ishikawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HamamotoTakao en-aut-sei=Hamamoto en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TaharaHiroaki en-aut-sei=Tahara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UedaTsutomu en-aut-sei=Ueda en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakenoSachio en-aut-sei=Takeno en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Otolaryngology, Chugoku Rosai Hospital kn-affil= affil-num=3 en-affil=Department of Nephrology and Urological Surgery, Chugoku Rosai Hospital kn-affil= affil-num=4 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=5 en-affil=Department of Molecular Pathology, Graduate School of Medical Sciences, Hiroshima University kn-affil= affil-num=6 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=7 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=8 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital kn-affil= en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma en-keyword=cervical lymph node metastasis kn-keyword=cervical lymph node metastasis en-keyword=late recurrence kn-keyword=late recurrence en-keyword=head and neck kn-keyword=head and neck END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=197 end-page=203 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rheumatoid Arthritis with Rapid Destructive Arthropathy of the Shoulder due to Calcium Pyrophosphate Deposition en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 67-year-old woman with rheumatoid arthritis presented with an untriggered hematoma in the right shoulder joint. Radiographic findings showed humeral head collapse and destruction of the glenoid fossa with ectopic calcification. Calcium pyrophosphate deposition (CPPD) in the synovial fluid was observed using a polarizing microscope. Histopathological findings revealed chronic inflammatory cell infiltration and giant cells surrounded by CPPD. The patient was diagnosed with rapid destructive arthropathy (RDA). Endoscopic shoulder joint debridement was performed. Postoperatively, active flexion improved from 40 to 75 degrees. This case highlights that CPPD can cause RDA in the shoulder, detectable with detailed histopathology. en-copyright= kn-copyright= en-aut-name=KondoNaoki en-aut-sei=Kondo en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KakutaniRika en-aut-sei=Kakutani en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MochizukiTomoharu en-aut-sei=Mochizuki en-aut-mei=Tomoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakuiJunichi en-aut-sei=Wakui en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaoNariaki en-aut-sei=Hao en-aut-mei=Nariaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KinoshitaEiji en-aut-sei=Kinoshita en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawashimaHiroyuki en-aut-sei=Kawashima en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=2 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=3 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=4 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=5 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=6 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= affil-num=7 en-affil=Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences kn-affil= en-keyword=rheumatoid arthritis kn-keyword=rheumatoid arthritis en-keyword=calcium pyrophosphate deposition kn-keyword=calcium pyrophosphate deposition en-keyword=rapid destructive arthropathy kn-keyword=rapid destructive arthropathy en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=167 end-page=176 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Promising Effectiveness of Combined Chemotherapy and Immunotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Real-World Prospective Observational Study (CS-Lung-003) en-subtitle= kn-subtitle= en-abstract= kn-abstract=This prospective observational study investigated the clinical status of patients with advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy+an immune checkpoint inhibitor (chemo + IO) as first-line treatment in a real-world setting. The cases of 98 patients treated with chemo + IO were prospectively collected and analyzed for effectiveness and safety. The response rate to chemo + IO was 46.9%, and the disease control rate was 76.5%. The median progression-free survival and overall survival (OS) in the total population were 5.2 and 22.3 months, respectively. The patients positive for PD-L1 (≥ 1%) showed significantly longer OS than the negative group (<1%) (median 26.7 vs. 18.7 months, p=0.04). Pre-existing interstitial lung disease (ILD) was associated with shorter OS than the absence of ILD (median 9.0 vs. 22.6 months, p<0.01). Immunerelated adverse events (irAEs) were observed in 28 patients (28.6%). The most frequent irAE was ILD (n=11); Grade 1 (n=1 patient), G2 (n=5), G3 (n=4), and only a single patient with a G5 irAE. In this CS-Lung-003 study, first-line chemo + IO in a real-world setting showed good effectiveness, comparable to that observed in international clinical trials. In real-world practice, chemo + IO is a promising and steadfast strategy. en-copyright= kn-copyright= en-aut-name=KanajiNobuhiro en-aut-sei=Kanaji en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiiKazuya en-aut-sei=Nishii en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsubataYukari en-aut-sei=Tsubata en-aut-mei=Yukari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakaoMika en-aut-sei=Nakao en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkunoTakae en-aut-sei=Okuno en-aut-mei=Takae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakataKenji en-aut-sei=Takata en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KodaniMasahiro en-aut-sei=Kodani en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamasakiMasahiro en-aut-sei=Yamasaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujitakaKazunori en-aut-sei=Fujitaka en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KubotaTetsuya en-aut-sei=Kubota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=WatanabeNaoki en-aut-sei=Watanabe en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=CS-Lung-003 Investigator en-aut-sei=CS-Lung-003 Investigator en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=2 en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University kn-affil= affil-num=9 en-affil=Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital kn-affil= affil-num=10 en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=11 en-affil=Department of Respiratory Medicine and Allergology, Kochi University kn-affil= affil-num=12 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=13 en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University kn-affil= affil-num=14 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil= kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=real-world kn-keyword=real-world en-keyword=first-line kn-keyword=first-line en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=combined immunotherapy kn-keyword=combined immunotherapy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=157 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Continuous Stimulation with Glycolaldehyde-derived Advanced Glycation End Product Reduces Aggrecan and COL2A1 Production via RAGE in Human OUMS-27 Chondrosarcoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chondrocytes are responsible for the production of extracellular matrix (ECM) components such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With age, advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, causing and accelerating pathological changes associated with chronic diseases such as OA. Glycolaldehyde-derived AGE (AGE3), which is toxic to a variety of cell types, have a stronger effect on cartilage compared with other AGEs. To understand the long-term effects of AGE3 on cartilage, we stimulated a human chondrosarcoma cell line (OUMS-27), which exhibits a chondrocytic phenotype, with 10 μg/ml AGE3 for 4 weeks. As a result, the expressions of COL2A1 and aggrecan were significantly downregulated in the OUMS-27 cells without inducing cell death, but the expressions of proteases that play an important role in cartilage destruction were not affected. Inhibition of the receptor for advanced glycation end products (RAGE) suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3. en-copyright= kn-copyright= en-aut-name=HatipogluOmer Faruk en-aut-sei=Hatipoglu en-aut-mei=Omer Faruk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishinakaTakashi en-aut-sei=Nishinaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaykasliKursat Oguz en-aut-sei=Yaykasli en-aut-mei=Kursat Oguz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WatanabeMasahiro en-aut-sei=Watanabe en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ToyomuraTakao en-aut-sei=Toyomura en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=3 en-affil=Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen kn-affil= affil-num=4 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=5 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=6 en-affil=Department of Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=7 en-affil=Department of Translational Research & Dug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=10 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= en-keyword=advanced glycation end product kn-keyword=advanced glycation end product en-keyword=aging kn-keyword=aging en-keyword=cartilage kn-keyword=cartilage en-keyword=collagen kn-keyword=collagen en-keyword=aggrecan kn-keyword=aggrecan END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=147 end-page=155 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=interferon kn-keyword=interferon en-keyword=tricarboxylic acid cycle kn-keyword=tricarboxylic acid cycle en-keyword=innate immune memory kn-keyword=innate immune memory en-keyword=trained immunity kn-keyword=trained immunity END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Supplement-induced acute kidney injury reproduced in kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements. Methods: KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts. Results: Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin. Conclusion: These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Acute kidney injury kn-keyword=Acute kidney injury en-keyword=Drug-induced nephrotoxicity kn-keyword=Drug-induced nephrotoxicity en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250429 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparative inhibitory effects of bepotastine and diphenhydramine on rituximab-induced infusion reactions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Infusion-related reaction (IRR) is a common adverse event induced by rituximab. Although first-generation histamine 1 receptor antagonists (H1RAs) are commonly used to prevent IRR, evidence on IRR suppression by the second-generation H1RA bepotastine is scarce. In this study, we assessed the inhibitory effects of bepotastine on rituximab-induced IRR and compared them with those of the first-generation H1RA diphenhydramine.
Methods We retrospectively evaluated IRR incidence in patients with B-cell non-Hodgkin lymphoma who received their first dose of rituximab.
Results The incidence of any grade IRR was 9.8% in the bepotastine group (n = 92), which was significantly lower than the 30.2% rate in the diphenhydramine group (n = 96; p < 0.001). The incidence of grade 2 or higher IRR was similar between the two groups (6.5% vs. 12.5%; p = 0.16). Multivariable logistic regression analysis revealed that the risk of any grade IRR incidence was higher in patients with B symptoms and bulky disease. Premedication with bepotastine was an independent factor in reducing the risk of any grade IRR incidence (odds ratio = 0.19, 95% confidence interval: 0.08–0.47).
Conclusion Bepotastine may be more effective than diphenhydramine in reducing the incidence of rituximab-induced IRR, particularly low-grade reactions. en-copyright= kn-copyright= en-aut-name=HoriTomoki en-aut-sei=Hori en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoKazuhiro en-aut-sei=Yamamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakagawaTomoaki en-aut-sei=Nakagawa en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaRinako en-aut-sei=Nakagawa en-aut-mei=Rinako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkayamaMasami en-aut-sei=Okayama en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SudouTamika en-aut-sei=Sudou en-aut-mei=Tamika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HamasakiMoe en-aut-sei=Hamasaki en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasudaMai en-aut-sei=Yasuda en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiShinya en-aut-sei=Kobayashi en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraFumihiko en-aut-sei=Nakamura en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YagiHideo en-aut-sei=Yagi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KitahiroYumi en-aut-sei=Kitahiro en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IkushimaShigeki en-aut-sei=Ikushima en-aut-mei=Shigeki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YanoIkuko en-aut-sei=Yano en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=2 en-affil=Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=4 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=5 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=6 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=7 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=8 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=10 en-affil=Department of Laboratory Medicine, Nara Prefecture General Medical Center kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Nara Prefecture General Medical Center kn-affil= affil-num=12 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= affil-num=13 en-affil=Department of Pharmacy, Nara Prefecture General Medical Center kn-affil= affil-num=14 en-affil=Department of Pharmacy, Kobe University Hospital kn-affil= en-keyword=Rituximab kn-keyword=Rituximab en-keyword=Infusion reaction kn-keyword=Infusion reaction en-keyword=Bepotastine kn-keyword=Bepotastine en-keyword=Diphenhydramine kn-keyword=Diphenhydramine END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=193 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs. en-copyright= kn-copyright= en-aut-name=KondoHiroya en-aut-sei=Kondo en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaAki en-aut-sei=Yoshida en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KureMiho en-aut-sei=Kure en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DemiyaKoji en-aut-sei=Demiya en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HataToshiaki en-aut-sei=Hata en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HaseiJoe en-aut-sei=Hasei en-aut-mei=Joe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KunisadaToshiyuki en-aut-sei=Kunisada en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Molecular and Cellular Medicine, Tokyo Medical University kn-affil= affil-num=14 en-affil=Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Osteosarcoma kn-keyword=Osteosarcoma en-keyword=Lung metastasis kn-keyword=Lung metastasis en-keyword=Tumor-associated macrophage kn-keyword=Tumor-associated macrophage en-keyword=CCL2 kn-keyword=CCL2 en-keyword=Extracellular vesicle kn-keyword=Extracellular vesicle END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=1559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. en-copyright= kn-copyright= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=dental follicle cells kn-keyword=dental follicle cells en-keyword=periodontal ligament cells kn-keyword=periodontal ligament cells en-keyword=bone invasion kn-keyword=bone invasion en-keyword=receptor activator of NF-kappa B ligand kn-keyword=receptor activator of NF-kappa B ligand en-keyword=parathyroid hormone-related peptide kn-keyword=parathyroid hormone-related peptide END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=7 article-no= start-page=192 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1 alpha, thereby augmenting antitumor effector functions. HIF-1 alpha upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.
Methods The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms.
Results HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells.
Conclusion Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamadaYusuke en-aut-sei=Hamada en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TianMiao en-aut-sei=Tian en-aut-mei=Miao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Colorectal cancer kn-keyword=Colorectal cancer en-keyword=Microsatellite stable kn-keyword=Microsatellite stable en-keyword=Hypoxia-inducible factor kn-keyword=Hypoxia-inducible factor en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=5 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pseudomonas syringae pv. tabaci 6605 Requires Seven Type III Effectors to Infect Nicotiana benthamiana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type III effectors (T3Es), virulence factors injected into plant cells via the type III secretion system (T3SS), play essential roles in the infection of host plants. Pseudomonas syringae pv. tabaci 6605 (Pta 6605) is the causal agent of wildfire disease in tobacco and harbours at least 22 T3Es in its genome. However, the specific T3Es required by Pta 6605 to infect Nicotiana benthamiana remain unidentified. In this study, we investigated the T3Es that contribute to Pta 6605 infection of N. benthamiana. We constructed Pta 6605 poly-T3E-deficient mutants (Pta DxE) and inoculated them into N. benthamiana. Flood assay, which mimics natural opening-based entry, showed that mutant strains lacking 14-22 T3Es, namely, Pta D14E-D22E mutants, exhibited reduced disease symptoms. By contrast, infiltration inoculation, which involves direct injection into leaves, showed that the Pta D14E to Pta D20E mutants developed disease symptoms. Notably, the Pta D20E, containing AvrE1 and HopM1, induced weak but observable symptoms upon infiltration inoculation. Conversely, no symptoms were observed in either the flood assay or infiltration inoculation for Pta D21E and Pta D22E. Taken together, these findings indicate that the many T3Es such as AvrPto4/AvrPtoB, HopW1/HopAE1, and HopM1/AvrE1 in Pta 6605 collectively contribute to invasion through natural openings and symptom development in N. benthamiana. This study provides the basis for understanding virulence in the host by identifying the minimum T3E repertoire required by Pta 6605 to infect N. benthamiana. en-copyright= kn-copyright= en-aut-name=KuroeKana en-aut-sei=Kuroe en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishimuraTakafumi en-aut-sei=Nishimura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KashiharaSachi en-aut-sei=Kashihara en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakataNanami en-aut-sei=Sakata en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoMikihiro en-aut-sei=Yamamoto en-aut-mei=Mikihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NoutoshiYoshiteru en-aut-sei=Noutoshi en-aut-mei=Yoshiteru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ToyodaKazuhiro en-aut-sei=Toyoda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchinoseYuki en-aut-sei=Ichinose en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHidenori en-aut-sei=Matsui en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=poly T3E mutant kn-keyword=poly T3E mutant en-keyword=type III effector kn-keyword=type III effector en-keyword=type III secretion system kn-keyword=type III secretion system END start-ver=1.4 cd-journal=joma no-vol=116 cd-vols= no-issue=5 article-no= start-page=1214 end-page=1226 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb. en-copyright= kn-copyright= en-aut-name=MatsuuraHiroaki en-aut-sei=Matsuura en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MutoYoshinori en-aut-sei=Muto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=7 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=8 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=9 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine,Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= affil-num=13 en-affil=Department of Tumor Microenvironment, Okayama University kn-affil= en-keyword=antigenicity kn-keyword=antigenicity en-keyword=cancer immunotherapy kn-keyword=cancer immunotherapy en-keyword=CTLA-4 kn-keyword=CTLA-4 en-keyword=PD-1 kn-keyword=PD-1 en-keyword=regulatory T cell kn-keyword=regulatory T cell END start-ver=1.4 cd-journal=joma no-vol=214 cd-vols= no-issue= article-no= start-page=32 end-page=41 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Medaka approach to evolutionary social neuroscience en-subtitle= kn-subtitle= en-abstract= kn-abstract=Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies. en-copyright= kn-copyright= en-aut-name=AnsaiSatoshi en-aut-sei=Ansai en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Hiraki-KajiyamaTowako en-aut-sei=Hiraki-Kajiyama en-aut-mei=Towako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaRyutaro en-aut-sei=Ueda en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekiTakahide en-aut-sei=Seki en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YokoiSaori en-aut-sei=Yokoi en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakeuchiHideaki en-aut-sei=Takeuchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Ushimado Marine Institute, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=3 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=4 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Hokkaido University kn-affil= affil-num=6 en-affil=School of Medicine, Kitasato University kn-affil= affil-num=7 en-affil=Graduate School of Life Sciences, Tohoku University kn-affil= en-keyword=Evolutionary neuroscience kn-keyword=Evolutionary neuroscience en-keyword=Comparative neuroscience kn-keyword=Comparative neuroscience en-keyword=Medaka bioresource kn-keyword=Medaka bioresource en-keyword=Visual mate preference kn-keyword=Visual mate preference en-keyword=Sexual selection kn-keyword=Sexual selection en-keyword=Genetic manipulation kn-keyword=Genetic manipulation END start-ver=1.4 cd-journal=joma no-vol=4 cd-vols= no-issue=2 article-no= start-page=e70091 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250427 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.
Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.
Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. en-copyright= kn-copyright= en-aut-name=YokodeAkiyoshi en-aut-sei=Yokode en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraMasaki en-aut-sei=Fujiwara en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraYuko en-aut-sei=Nakamura en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakamotoShinji en-aut-sei=Sakamoto en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakakiManabu en-aut-sei=Takaki en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neuropsychiatry, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=psycho-oncology kn-keyword=psycho-oncology en-keyword=lorlatinib kn-keyword=lorlatinib en-keyword=lung cancer kn-keyword=lung cancer en-keyword=medication-induced psychosis kn-keyword=medication-induced psychosis END start-ver=1.4 cd-journal=joma no-vol=137 cd-vols= no-issue=1 article-no= start-page=4 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in General Medical Science (2023 Yuuki Prize) kn-title=令和５年度岡山医学会賞　総合研究奨励賞（結城賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name=住居優一 kn-aut-sei=住居 kn-aut-mei=優一 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=116 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.
Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.
Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.
Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC. en-copyright= kn-copyright= en-aut-name=UmedaHibiki en-aut-sei=Umeda en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriwakeKazuya en-aut-sei=Moriwake en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKazuhiro en-aut-sei=Yoshida en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakedaSho en-aut-sei=Takeda en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KishimotoHiroyuki en-aut-sei=Kishimoto en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasuiKazuya en-aut-sei=Yasui en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KayanoMasashi en-aut-sei=Kayano en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MoriYoshiko en-aut-sei=Mori en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=UmedaYuzo en-aut-sei=Umeda en-aut-mei=Yuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=GoelAjay en-aut-sei=Goel en-aut-mei=Ajay kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=17 en-affil=Department of Obstetrics and Gynecology, Okayama University Gradu�ate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute, City of Hope Comprehensive Cancer Center kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RNA-editing kn-keyword=RNA-editing en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Chemoresistance kn-keyword=Chemoresistance en-keyword=Biomarker kn-keyword=Biomarker en-keyword=Colorectal cancer kn-keyword=Colorectal cancer END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=8 article-no= start-page=e70793 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250418 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes.
Methods: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (<= 39 years; n = 143) and late-onset (>= 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro.
Results: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations.
Conclusion: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies. en-copyright= kn-copyright= en-aut-name=KamioTomohiro en-aut-sei=Kamio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirosunaKensuke en-aut-sei=Hirosuna en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OzatoToshiki en-aut-sei=Ozato en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoHideki en-aut-sei=Yamamoto en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirasawaAkira en-aut-sei=Hirasawa en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=comprehensive genomic profiling kn-keyword=comprehensive genomic profiling en-keyword=early-onset gastric cancer kn-keyword=early-onset gastric cancer en-keyword=oxaliplatin kn-keyword=oxaliplatin en-keyword=TP53 kn-keyword=TP53 END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=4 article-no= start-page=e70151 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood.
Methods: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF.
Results: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older.
Conclusions: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above. en-copyright= kn-copyright= en-aut-name=HondaManami en-aut-sei=Honda en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraokaSakiko en-aut-sei=Hiraoka en-aut-mei=Sakiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Practical Gastrointestinal Endoscopy,Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=colonoscopy kn-keyword=colonoscopy en-keyword=esophagogastroduodenoscopy kn-keyword=esophagogastroduodenoscopy en-keyword=gastrointestinal neoplasms kn-keyword=gastrointestinal neoplasms en-keyword=gastrointestinal stromal tumor kn-keyword=gastrointestinal stromal tumor en-keyword=neurofibromatosis kn-keyword=neurofibromatosis END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=139 end-page=144 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring en-subtitle= kn-subtitle= en-abstract= kn-abstract=In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. en-copyright= kn-copyright= en-aut-name=TakedaYasushige en-aut-sei=Takeda en-aut-mei=Yasushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaNaoaki en-aut-sei=Maeda en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizusawaYohei en-aut-sei=Mizusawa en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoHijiri en-aut-sei=Matsumoto en-aut-mei=Hijiri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoYuhei en-aut-sei=Kondo en-aut-mei=Yuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KunitomoTomoyoshi en-aut-sei=Kunitomo en-aut-mei=Tomoyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanoueYukinori en-aut-sei=Tanoue en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Hospital kn-affil= en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=intraoperative nerve monitoring kn-keyword=intraoperative nerve monitoring en-keyword=aberrant right subclavian artery kn-keyword=aberrant right subclavian artery en-keyword=non-recurrent inferior laryngeal nerve kn-keyword=non-recurrent inferior laryngeal nerve en-keyword=thoracoscopic esophagectomy kn-keyword=thoracoscopic esophagectomy END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=129 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Retinitis Pigmentosa Diagnosed with Severe Anterior Capsule Contraction after Cataract Surgery en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 66-year-old woman presented with significant anterior capsule contraction and intraocular lens dislocation in both eyes 4 months after cataract surgery. Postoperative examinations such as fluorescein angiography, Goldmann perimetry, and electroretinography revealed retinitis pigmentosa (RP). Patients with significant anterior capsule contraction after cataract surgery should be closely examined because RP may be a contributing factor. en-copyright= kn-copyright= en-aut-name=TsujiAkihiro en-aut-sei=Tsuji en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosokawaMio en-aut-sei=Hosokawa en-aut-mei=Mio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKosuke en-aut-sei=Takahashi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Fukuyama City Hospital, Fukuyama City kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=retinitis pigmentosa kn-keyword=retinitis pigmentosa en-keyword=intraocular lens kn-keyword=intraocular lens en-keyword=anterior capsule contraction kn-keyword=anterior capsule contraction END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=117 end-page=121 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=From a Congenital Defect to Cancer: A Case of Squamous Cell Carcinoma in a Neglected Myelomeningocele en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neural tube defects are common congenital anomalies, typically presenting early due to visible swelling and/or neurological deficits. Rarely, cystic swellings are neglected until adulthood, with only 14 cases of malignancy developing in an untreated meningomyelocele reported to date. We describe the case details of a 26-year-old Indian woman with this rare complication. Magnetic resonance imaging revealed a low-lying spinal cord with spinal dysraphism, cord herniation, and a cystic lesion. The biopsy confirmed a well-differentiated squamous cell carcinoma. Malignant transformation in an untreated myelomeningocele is rare, with chronic irritation and infection as proposed causes. Early biopsy and treatment are crucial for its management. en-copyright= kn-copyright= en-aut-name=GautamAbhishek en-aut-sei=Gautam en-aut-mei=Abhishek kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KenawadekarRahul en-aut-sei=Kenawadekar en-aut-mei=Rahul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HattiholiVirupaxi en-aut-sei=Hattiholi en-aut-mei=Virupaxi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MastePraful Suresh en-aut-sei=Maste en-aut-mei=Praful Suresh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=2 en-affil=Department of General Surgery, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=3 en-affil=Department of Radiology, Jawaharlal Nehru Medical College, KAHER kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Jawaharlal Nehru Medical College, KAHER kn-affil= en-keyword=squamous cell carcinoma kn-keyword=squamous cell carcinoma en-keyword=meningomyelocele kn-keyword=meningomyelocele en-keyword=occult spinal dysraphism kn-keyword=occult spinal dysraphism END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=81 end-page=92 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Outcomes of Neoadjuvant Paclitaxel/Cisplatin/Gemcitabine Compared with Gemcitabine/Cisplatin for Muscle-Invasive Bladder Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=We retrospectively evaluated the oncologic outcomes of paclitaxel, cisplatin, and gemcitabine (PCG) with those of gemcitabine and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients. The primary outcome was efficacy: pathological complete response (pCR), ypT0N0; and pathological objective response (pOR), ypT0N0, ≤ ypT1N0, or ypT0N1. Secondary outcomes included overall survival (OS), recurrence-free survival (RFS), predictive factors for pOR, OS, and RFS, and hematologic adverse events (AEs). Among 113 patients treated (PCG, n=28; GC, n=85), similar pOR and pCR rates were achieved by the groups (pOR: PCG, 57.1% vs. GC, 49. 4%; p=0.52; pCR: PCG, 39.3% vs. GC, 29.4%; p=0.36). No significant differences were observed in OS (p=1.0) or RFS (p=0.20). Multivariate logistic regression analysis showed that hydronephrosis (odds ratio [OR] 0.32, 95%CI: 0.11-0.92) and clinical node-positive status (cN+) (OR 0.22, 95%CI: 0.050-0.99) were significantly associated with a decreased probability of pOR. On multivariate Cox regression analyses, pOR achievement was associated with improved OS (hazard ratio [HR] 0.23, 95%CI: 0.10-0.56) and RFS (HR 0.30, 95%CI: 0.13-0.67). There were no significant between-group differences in the incidence of grade ≥ 3 hematologic AEs or dose-reduction required, but the PCG group had a higher incidence of grade 4 neutropenia. en-copyright= kn-copyright= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugawaTakuji en-aut-sei=Tsugawa en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiKazuma en-aut-sei=Tsuboi en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EbaraShin en-aut-sei=Ebara en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Urology, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=11 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=urothelial carcinoma kn-keyword=urothelial carcinoma en-keyword=paclitaxel kn-keyword=paclitaxel en-keyword=cisplatin kn-keyword=cisplatin en-keyword=gemcitabine kn-keyword=gemcitabine en-keyword=neoadjuvant kn-keyword=neoadjuvant END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=2 article-no= start-page=65 end-page=73 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between the Pretreatment Body Mass Index and Anamorelin’s Efficacy in Patients with Cancer Cachexia: A Retrospective Cohort Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anamorelin (ANAM) is used to treat cancer-associated cachexia, a syndrome involving muscle loss and anorexia. The timing of the initiation of ANAM treatment is crucial to its efficacy. Although the body mass index (BMI) is a diagnostic criterion for cancer cachexia, no studies have explored its association with ANAM efficacy. We conducted a single-center, retrospective cohort study to investigate the association between the pre-treatment BMI and ANAM efficacy in patients with cancer-associated cachexia (n=47). The ANAM treatment was considered effective if the patient’s appetite improved within 30 days of treatment initiation. We calculated a BMI cutoff value (19.5 kg/m2) and used it to divide the patients into high- and low-BMI groups. Their background, clinical laboratory values, cancer types, and treatment lines were investigated. Twenty (42.6%) had a high BMI (≥ 19.5 kg/m2) and 27 (57.4%) had a low BMI (< 19.5 kg/m2). High BMI was significantly associated with ANAM effectiveness (odds ratio 7.86, 95% confidence interval 1.99-31.00, p=0.003). Together these results indicate that it is beneficial to initiate ANAM treatment before a patient’s BMI drops below 19.5 kg/m2. Our findings will help advance cancer cachexia treatment and serve as a reference for clinicians to predict ANAM’s efficacy. en-copyright= kn-copyright= en-aut-name=MakiMasatoshi en-aut-sei=Maki en-aut-mei=Masatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakadaRyo en-aut-sei=Takada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshigoTomoyuki en-aut-sei=Ishigo en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiwaraMiki en-aut-sei=Fujiwara en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiYoko en-aut-sei=Takahashi en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OtsukaShinya en-aut-sei=Otsuka en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TamuraKoji en-aut-sei=Tamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HamaokaTerutaka en-aut-sei=Hamaoka en-aut-mei=Terutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=2 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=3 en-affil=Department of Pharmacy, Sapporo Medical University Hospital kn-affil= affil-num=4 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=6 en-affil=Department of Surgery, NHO Fukuyama Medical Center kn-affil= affil-num=7 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= affil-num=8 en-affil=Department of Hospital Pharmacy, NHO Fukuyama Medical Center kn-affil= en-keyword=anamorelin kn-keyword=anamorelin en-keyword=cancer-associated cachexia kn-keyword=cancer-associated cachexia en-keyword=body mass index kn-keyword=body mass index en-keyword=albumin kn-keyword=albumin en-keyword=efficacy rate kn-keyword=efficacy rate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enterobacterial common antigen repeat-unit flippase WzxE is required for Escherichia coli growth under acidic conditions, low temperature, and high osmotic stress conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many Escherichia coli isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for E. coli resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase wzxE, which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of E. coli BW25113 to acidic conditions. The wzxE-knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of wzxE and wecF (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of wzxE and wcaJ (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The wzxE-knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that lipid-linked ECA repeat units confer E. coli susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that wzxE suppresses this negative effect. en-copyright= kn-copyright= en-aut-name=YamaguchiSaki en-aut-sei=Yamaguchi en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshikawaKazuya en-aut-sei=Ishikawa en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurutaKazuyuki en-aut-sei=Furuta en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaitoChikara en-aut-sei=Kaito en-aut-mei=Chikara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=wzxE flippase kn-keyword=wzxE flippase en-keyword=enterobacterial common antigen kn-keyword=enterobacterial common antigen en-keyword=low pH kn-keyword=low pH en-keyword=low temperature kn-keyword=low temperature en-keyword=hyperosmotic stress kn-keyword=hyperosmotic stress END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=100016 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma. en-copyright= kn-copyright= en-aut-name=AsakaYutaro en-aut-sei=Asaka en-aut-mei=Yutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasumotoToshio en-aut-sei=Masumoto en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ChinVanessa D. en-aut-sei=Chin en-aut-mei=Vanessa D. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PenaTirso en-aut-sei=Pena en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HuangRongsheng en-aut-sei=Huang en-aut-mei=Rongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University kn-affil= affil-num=3 en-affil=Department of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=UMass Chan Medical School, UMass Memorial Medical Center kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University kn-affil= affil-num=11 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Adrenoceptors kn-keyword=Adrenoceptors en-keyword=Glioma stem-like cells kn-keyword=Glioma stem-like cells en-keyword=Differentiated glioma cells kn-keyword=Differentiated glioma cells en-keyword=Noradrenaline kn-keyword=Noradrenaline en-keyword=Cellular plasticity kn-keyword=Cellular plasticity END start-ver=1.4 cd-journal=joma no-vol=213 cd-vols= no-issue= article-no= start-page=128 end-page=137 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The potential mechanism maintaining transactive response DNA binding protein 43 kDa in the mouse stroke model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The disruption of transactive response DNA binding protein 43 kDa (TDP-43) shuttling leads to the depletion of nuclear localization and the cytoplasmic accumulation of TDP-43. We aimed to evaluate the mechanism underlying the behavior of TDP-43 in ischemic stroke. Adult male C57BL/6 J mice were subjected to 30 or 60 min of transient middle cerebral artery occlusion (tMCAO), and examined at 1, 6, and 24 h post reperfusion. Immunostaining was used to evaluate the expression of TDP-43, G3BP1, HDAC6, and RAD23B. The total and cytoplasmic number of TDP-43–positive cells increased compared with sham operation group and peaked at 6 h post reperfusion after tMCAO. The elevated expression of G3BP1 protein peaked at 6 h after reperfusion and decreased at 24 h after reperfusion in ischemic mice brains. We also observed an increase of expression level of HDAC6 and the number of RAD23B-positive cells increased after tMCAO. RAD23B was colocalized with TDP-43 24 h after tMCAO. We proposed that the formation of stress granules might be involved in the mislocalization of TDP-43, based on an evaluation of G3BP1 and HDAC6. Subsequently, RAD23B, may also contribute to the downstream degradation of mislocalized TDP-43 in mice tMCAO model. en-copyright= kn-copyright= en-aut-name=BianYuting en-aut-sei=Bian en-aut-mei=Yuting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Ota-ElliottRicardo Satoshi en-aut-sei=Ota-Elliott en-aut-mei=Ricardo Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HuXinran en-aut-sei=Hu en-aut-mei=Xinran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunHongming en-aut-sei=Sun en-aut-mei=Hongming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BianZhihong en-aut-sei=Bian en-aut-mei=Zhihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhaiYun en-aut-sei=Zhai en-aut-mei=Yun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YuHaibo en-aut-sei=Yu en-aut-mei=Haibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HuXiao en-aut-sei=Hu en-aut-mei=Xiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnHangping en-aut-sei=An en-aut-mei=Hangping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=LiuHongzhi en-aut-sei=Liu en-aut-mei=Hongzhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=ALS kn-keyword=ALS en-keyword=RNA-binding protein kn-keyword=RNA-binding protein en-keyword=Mislocalization kn-keyword=Mislocalization en-keyword=G3BP1 kn-keyword=G3BP1 en-keyword=HDAC6 kn-keyword=HDAC6 en-keyword=RAD23B kn-keyword=RAD23B en-keyword=tMCAO kn-keyword=tMCAO END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 × 103/µL, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=hypopyon kn-keyword=hypopyon en-keyword=myelodysplastic syndromes kn-keyword=myelodysplastic syndromes en-keyword=neutrophilic dermatosis kn-keyword=neutrophilic dermatosis en-keyword=peripheral keratitis kn-keyword=peripheral keratitis en-keyword=pyoderma gangrenosum kn-keyword=pyoderma gangrenosum en-keyword=scleritis kn-keyword=scleritis en-keyword=sweet syndrome kn-keyword=sweet syndrome END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=1 article-no= start-page=100 end-page=107 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigating the Effects of Reconstruction Conditions on Image Quality and Radiomic Analysis in Photon-counting Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction:Photon-counting computed tomography (CT) is equipped with an adaptive iterative reconstruction method called quantum iterative reconstruction (QIR), which allows the intensity to be changed during image reconstruction. It is known that the reconstruction conditions of CT images affect the analysis results when performing radiomic analysis. The aim of this study is to investigate the effect of QIR intensity on image quality and radiomic analysis of renal cell carcinoma (RCC).
Materials and Methods:The QIR intensities were selected as off, 2 and 4. The image quality evaluation items considered were task-based transfer function (TTF), noise power spectrum (NPS), and low-contrast object specific contrast-to-noise ratio (CNRLO). The influence on radiomic analysis was assessed using the discrimination accuracy of clear cell RCC.
Results:For image quality evaluation, TTF and NPS values were lower and CNRLO values were higher with increasing QIR intensity; for radiomic analysis, sensitivity, specificity, and accuracy were higher with increasing QIR intensity. Principal component analysis and receiver operating characteristics analysis also showed higher values with increasing QIR intensity.
Conclusion:It was confirmed that the intensity of the QIR intensity affects both the image quality and the radiomic analysis. en-copyright= kn-copyright= en-aut-name=OhataMiyu en-aut-sei=Ohata en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiRyohei en-aut-sei=Fukui en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiDaichi en-aut-sei=Kobayashi en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamauchiTakatsugu en-aut-sei=Yamauchi en-aut-mei=Takatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HondaMitsugi en-aut-sei=Honda en-aut-mei=Mitsugi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiAiko en-aut-sei=Hayashi en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HasegawaKoshi en-aut-sei=Hasegawa en-aut-mei=Koshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KidaKatsuhiro en-aut-sei=Kida en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=GotoSachiko en-aut-sei=Goto en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HirakiTakao en-aut-sei=Hiraki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Radiological Technology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Radiology, Hiroshima University Hospital kn-affil= affil-num=9 en-affil=Department of Radiological Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical, Okayama University kn-affil= en-keyword=Image quality kn-keyword=Image quality en-keyword=photon-counting computed tomography kn-keyword=photon-counting computed tomography en-keyword=quantum iterative reconstruction kn-keyword=quantum iterative reconstruction en-keyword=radiomics kn-keyword=radiomics en-keyword=renal cell carcinoma kn-keyword=renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=10462 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250326 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion. en-copyright= kn-copyright= en-aut-name=ZhengYilin en-aut-sei=Zheng en-aut-mei=Yilin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WengYao en-aut-sei=Weng en-aut-mei=Yao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangXiu en-aut-sei=Zhang en-aut-mei=Xiu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiotsuNoriko en-aut-sei=Shiotsu en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Comprehensive Dental Clinic, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama University kn-affil= en-keyword=Porphyromonas gingivalis kn-keyword=Porphyromonas gingivalis en-keyword=Gingipain kn-keyword=Gingipain en-keyword=Macrophage kn-keyword=Macrophage en-keyword=Alternative splicing kn-keyword=Alternative splicing en-keyword=PD-L1 kn-keyword=PD-L1 en-keyword=Immune evasion kn-keyword=Immune evasion END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=3 article-no= start-page=033907 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of density measurement at high pressure and high temperature using the x-ray absorption method combined with laser-heated diamond anvil cell en-subtitle= kn-subtitle= en-abstract= kn-abstract=The densities of liquid materials at high pressures and high temperatures are important information to understand the elastic behavior of liquids at extreme conditions, which is closely related to the formation and evolution processes of the Earth and planetary interiors. The x-ray absorption method is an effective method to measure the density of non-crystalline materials at high pressures. However, the temperature condition of the x-ray absorption method using a diamond anvil cell (DAC) has been limited to 720 K to date. To significantly expand the measurable temperature condition of this method, in this study, we developed a density measurement technique using the x-ray absorption method in combination with a laser-heated DAC. The density of solid Ni was measured up to 26 GPa and 1800 K using the x-ray absorption method and evaluated by comparison with the density obtained from the x-ray diffraction. The density of solid Ni with a thickness >17 μm was determined with an accuracy of 0.01%–2.2% (0.001–0.20 g/cm3) and a precision of 0.8%–1.8% (0.07–0.16 g/cm3) in the x-ray absorption method. The density of liquid Ni was also determined to be 8.70 ± 0.15–8.98 ± 0.38 g/cm3 at 16–23 GPa and 2230–2480 K. Consequently, the temperature limit of the x-ray absorption method can be expanded from 720 to 2480 K by combining it with a laser-heated DAC in this study. en-copyright= kn-copyright= en-aut-name=TerasakiHidenori en-aut-sei=Terasaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KaminaHiroyuki en-aut-sei=Kamina en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiSaori I. en-aut-sei=Kawaguchi en-aut-mei=Saori I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadashi en-aut-sei=Kondo en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoriokaKo en-aut-sei=Morioka en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsuruokaRyo en-aut-sei=Tsuruoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiMoe en-aut-sei=Sakurai en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YonedaAkira en-aut-sei=Yoneda en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KamadaSeiji en-aut-sei=Kamada en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiraoNaohisa en-aut-sei=Hirao en-aut-mei=Naohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=3 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= affil-num=4 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=5 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=7 en-affil=Department of Earth Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Earth and Space Science, Osaka University kn-affil= affil-num=9 en-affil=AD Science Incorporation kn-affil= affil-num=10 en-affil=Japan Synchrotron Radiation Research Institute, SPring-8 kn-affil= END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2485 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250311 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. en-copyright= kn-copyright= en-aut-name=NishiiNaoko en-aut-sei=Nishii en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaiTomoko en-aut-sei=Kawai en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasuokaHiroki en-aut-sei=Yasuoka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TatsumiNanami en-aut-sei=Tatsumi en-aut-mei=Nanami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HaradaYuika en-aut-sei=Harada en-aut-mei=Yuika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiShunai en-aut-sei=Li en-aut-mei=Shunai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukanoMoemi en-aut-sei=Tsukano en-aut-mei=Moemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMasami en-aut-sei=Watanabe en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=7 en-affil=Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=VGLUT3 kn-keyword=VGLUT3 en-keyword=glutamate kn-keyword=glutamate en-keyword=podocyte kn-keyword=podocyte en-keyword=glutamatergic transmission kn-keyword=glutamatergic transmission END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=6 article-no= start-page=2713 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250318 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. en-copyright= kn-copyright= en-aut-name=SoejimaYoshiaki en-aut-sei=Soejima en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtsukaYuki en-aut-sei=Otsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawaguchiMarina en-aut-sei=Kawaguchi en-aut-mei=Marina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamamotoKoichiro en-aut-sei=Yamamoto en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakanoYasuhiro en-aut-sei=Nakano en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaMiho en-aut-sei=Yasuda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TokumasuKazuki en-aut-sei=Tokumasu en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UedaKeigo en-aut-sei=Ueda en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IwataNahoko en-aut-sei=Iwata en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fibroblast growth factor receptor 1 (FGFR1) kn-keyword=fibroblast growth factor receptor 1 (FGFR1) en-keyword=gynecomastia kn-keyword=gynecomastia en-keyword=Kallmann syndrome (KS) kn-keyword=Kallmann syndrome (KS) en-keyword=osteoporosis and steroidogenesis kn-keyword=osteoporosis and steroidogenesis END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=3 article-no= start-page=e81476 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Natural Course From Primary Intraocular Lymphoma to Brain Lymphoma in Four Years According to Patient's Choice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Primary intraocular lymphoma or vitreoretinal lymphoma is a rare entity of diffuse large B-cell lymphoma that presents vitreous opacity and retinal and choroidal infiltration. Primary central nervous system lymphoma would occur previously, later, or concurrently with respect to primary intraocular lymphoma. This study reported a 72-year-old patient with a pathological diagnosis of primary intraocular lymphoma who developed central nervous system lymphoma four years later in the course of no treatment. She presented with a four-year history of blurred vision in both eyes after cataract surgeries. Three weeks previously, she underwent a vitrectomy in the left eye at a clinic, and measurements of the vitreous fluid showed a high level of interleukin-10 at 5739 pg/mL, in contrast with interleukin-6 at 142 pg/mL. Cytology of the vitreous fluid was class III on the Papanicolaou classification. Head magnetic resonance imaging detected nothing abnormal. She underwent vitrectomy in the right eye as a diagnostic procedure to show large cells in the vitreous which were positive for CD20 and Ki-67 and negative for CD3, leading to a pathological diagnosis of large B-cell lymphoma. Prophylactic chemotherapy with high-dose methotrexate was recommended as a therapeutic option, but she chose observation since she did not have any eye or systemic symptoms. In the follow-up every three months by an oncologist and an ophthalmologist, she did not have any symptoms, and serum levels of soluble interleukin-2 receptor were in the normal range at each visit. She was well for four years until the age of 76 years when she fell and hit her head, and an emergency head computed tomography scan showed a mass in the left occipital lobe. Magnetic resonance imaging demonstrated a well-defined circular mass in the left occipital lobe with a hyperintense signal in the T2-weighted fluid-attenuated inversion recovery (FLAIR) image and diffusion-weighted image. Fluorodeoxyglucose positron emission tomography showed no abnormal uptake systemically, except for the left occipital lesion. She underwent a brain biopsy by craniotomy to pathologically prove diffuse large B-cell lymphoma. She was recommended to receive first-line chemotherapy as the standard treatment but chose observation with no treatment and died of brain lymphoma nine months later. This case happened to illustrate a natural course of primary intraocular lymphoma which proceeded to central nervous system lymphoma four years later. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoShotaro en-aut-sei=Kondo en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Kurashiki Municipal Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=brain biopsy kn-keyword=brain biopsy en-keyword=cell block pathology kn-keyword=cell block pathology en-keyword=diffuse large b-cell lymphoma kn-keyword=diffuse large b-cell lymphoma en-keyword=natural course kn-keyword=natural course en-keyword=primary central nervous system lymphoma kn-keyword=primary central nervous system lymphoma en-keyword=primary intraocular (vitreoretinal) lymphoma kn-keyword=primary intraocular (vitreoretinal) lymphoma en-keyword=vitrectomy kn-keyword=vitrectomy en-keyword=vitreous opacity kn-keyword=vitreous opacity END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue= article-no= start-page=1551700 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The ketogenic diet increases ketone bodies (beta-hydroxybutyrate and acetoacetate) in the brain, and ameliorates epileptic seizures in vivo. However, ketone bodies exert weak or no effects on electrical activity in rodent hippocampal slices. Especially, it remains unclear what kinds of conditions are required to strengthen the actions of ketone bodies in hippocampal slices. In the present study, we examined the effects of acetoacetate on hippocampal pyramidal cells in normal slices and epileptiform slices of mice. By using patch-clamp recordings from CA1 pyramidal cells, we first confirmed that acetoacetate did not change the membrane potentials and intrinsic properties of pyramidal cells in normal slices. However, we found that acetoacetate weakened spontaneous epileptiform bursts in pyramidal cells of epileptiform slices, which were acutely induced by applying convulsants to normal slices. Interestingly, acetoacetate did not change the frequency of the epileptiform bursts, but attenuated individual epileptiform bursts. We finally examined the effects of acetoacetate on excitatory synaptic barrages during epileptiform activity, and found that acetoacetate weakened epileptiform bursts by reducing synchronous synaptic inputs. These results show that acetoacetate attenuated neuronal bursts in epileptiform slices, but did not affect neuronal activity in normal slices, which leads to seizure-selective actions of ketone bodies. en-copyright= kn-copyright= en-aut-name=WenHao en-aut-sei=Wen en-aut-mei=Hao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaNagisa en-aut-sei=Sada en-aut-mei=Nagisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueTsuyoshi en-aut-sei=Inoue en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=epilepsy kn-keyword=epilepsy en-keyword=ketone body kn-keyword=ketone body en-keyword=ketogenic diet kn-keyword=ketogenic diet en-keyword=hippocampus kn-keyword=hippocampus en-keyword=slice physiology kn-keyword=slice physiology en-keyword=patch-clamp recording kn-keyword=patch-clamp recording END start-ver=1.4 cd-journal=joma no-vol=85 cd-vols= no-issue=6 article-no= start-page=1082 end-page=1096 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Brain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases. en-copyright= kn-copyright= en-aut-name=NinomiyaToshifumi en-aut-sei=Ninomiya en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KemmotsuNaoya en-aut-sei=Kemmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MagariMasaki en-aut-sei=Magari en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoAi en-aut-sei=Miyamoto en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraTomohiro en-aut-sei=Fujiwara en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=OkamotoIsamu en-aut-sei=Okamoto en-aut-mei=Isamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Applied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Medical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama University kn-affil= affil-num=17 en-affil=Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=1757 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Keratinocyte-driven dermal collagen formation in the axolotl skin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Type I collagen is a major component of the dermis and is formed by dermal fibroblasts. The development of dermal collagen structures has not been fully elucidated despite the major presence and importance of the dermis. This lack of understanding is due in part to the opacity of mammalian skin and it has been an obstacle to cosmetic and medical developments. We reveal the process of dermal collagen formation using the highly transparent skin of the axolotl and fluorescent collagen probes. We clarify that epidermal cells, not dermal fibroblasts, contribute to dermal collagen formation. Mesenchymal cells (fibroblasts) play a role in modifying the collagen fibers already built by keratinocytes. We confirm that collagen production by keratinocytes is a widely conserved mechanism in other model organisms. Our findings warrant a change in the current consensus about dermal collagen formation and could lead to innovations in cosmetology and skin medication. en-copyright= kn-copyright= en-aut-name=OhashiAyaka en-aut-sei=Ohashi en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KurodaJunpei en-aut-sei=Kuroda en-aut-mei=Junpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoYohei en-aut-sei=Kondo en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KameiYasuhiro en-aut-sei=Kamei en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NonakaShigenori en-aut-sei=Nonaka en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurukawaSaya en-aut-sei=Furukawa en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamotoSakiya en-aut-sei=Yamamoto en-aut-mei=Sakiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAkira en-aut-sei=Satoh en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Frontier Biosciences, Osaka University kn-affil= affil-num=4 en-affil=Center for One Medicine Innovative Translational Research (COMIT), Nagoya University kn-affil= affil-num=5 en-affil=Laboratory for Biothermology, National Institute for Basic Biology kn-affil= affil-num=6 en-affil=The Graduate University for Advanced Studies (SOKENDAI) kn-affil= affil-num=7 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Environment, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=752 cd-vols= no-issue= article-no= start-page=151481 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Discovery of myeloid zinc finger (MZF) 1 nuclear bodies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein–protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5). en-copyright= kn-copyright= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CalderwoodStuart K. en-aut-sei=Calderwood en-aut-mei=Stuart K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School kn-affil= en-keyword=Myeloid zinc finger 1 kn-keyword=Myeloid zinc finger 1 en-keyword=MZF1 kn-keyword=MZF1 en-keyword=Nuclear body kn-keyword=Nuclear body en-keyword=PML kn-keyword=PML en-keyword=Sumoylation kn-keyword=Sumoylation en-keyword=SCAN domain protein kn-keyword=SCAN domain protein END start-ver=1.4 cd-journal=joma no-vol=2 cd-vols= no-issue=9 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S-nitrosylation of laforin inhibits its phosphatase activity and is implicated in Lafora disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, the relation between S-nitrosylation by nitric oxide (NO), which is over�produced under pathological conditions and neurodegenerative diseases, includingAlzheimer’s and Parkinson’s diseases, has become a focus of attention. Although mostcases of Parkinson’s disease are known to be caused by mutations in the Parkin gene, arecent finding has indicated that S-nitrosylation of Parkin affects its enzymatic activityand leads to the Parkinsonian phenotype. Therefore, it is important to understand thefunction of S-nitrosylated proteins in the pathogenesis of neurodegenerative diseases.Lafora disease (LD, OMIM 254780) is a neurodegenerative disease characterized by theaccumulation of insoluble glucans called Lafora bodies (LBs). LD is caused by mutationsin genes that encode the glucan phosphatase, Laforin, or the E3 ubiquitin ligase, Malin.In this study, we hypothesized that LD may be caused by S-nitrosylation of Laforin,which is similar to the finding that Parkinson’s disease is caused by S-nitrosylation ofParkin. To test this hypothesis, we first determined whether Laforin was S-nitrosylatedusing a biotin switch assay, and compared the three main functions of unmodified andS-nitrosylated Laforin, namely glucan- and Malin-binding activity and phosphataseactivity. Furthermore, we examined whether the numbers of LBs were changed byNO in the cells expressing wild-type Laforin. Here, we report for the first time thatS-nitrosylation of Laforin inhibited its phosphatase activity and that LB formation wasincreased by an NO donor. Our results suggest a possible hypothesis for LD pathogenesis; that is, the decrease in phosphatase activity of Laforin by S-nitrosylation leads toincreased LB formation. Therefore, LD may be caused not only by mutations in theLaforin or Malin genes, but also by the S-nitrosylation of Laforin. en-copyright= kn-copyright= en-aut-name=ToyotaRikako en-aut-sei=Toyota en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HonjoYasuko en-aut-sei=Honjo en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImajoRisa en-aut-sei=Imajo en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima University kn-affil= en-keyword=S-Nitrosylation Of Laforin kn-keyword=S-Nitrosylation Of Laforin en-keyword=Post-Translational Modification kn-keyword=Post-Translational Modification en-keyword=Nitrosylation kn-keyword=Nitrosylation en-keyword=Phosphatase kn-keyword=Phosphatase en-keyword=Glucan-Binding kn-keyword=Glucan-Binding END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=252 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of oral mucositis in patients undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide: marked difference between busulfan and melphalan regimens en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose This study was performed to examine the effects of conditioning regimens on oral mucositis in haploidentical (haplo) donor hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide (PTCy).
Methods Thirty consecutive patients (male, 23; female, 7; 18–68 years, median, 59 years) undergoing haplo-HSCT with PTCy using one of three conditioning regimens—reduced intensity conditioning (RIC)-melphalan (Mel); RIC-Busulfan (Bu); and myeloablative conditioning (MAC)-Bu—were enrolled in this study. Data on the WHO grade of oral mucositis (day − 7 to + 20) were collected retrospectively. The incidences of ulcerative and severe mucositis (Grade 2–4 and Grade 3–4, respectively) were compared between the three groups.
Results Ulcerative mucositis occurred in 0% (0/10) of patients in the RIC-Mel group, 57.1% (4/7) in the RIC-Bu group, and 100% (13/13) in the MAC-Bu group. The differences between the RIC-Mel and RIC-Bu groups and between the RIC-Bu and MAC-Bu groups were significant (all P < 0.05). Severe mucositis occurred in 57.1% (4/7) of patients in the RIC-Bu group and 100% (13/13) of patients in the MAC-Bu group, and the difference was significant (P < 0.05). The rates of ulcerative mucositis (≥ grade 2) and of severe mucositis (≥ grade 3) were significantly higher in the MAC-Bu group than the RIC-Bu group on days 10, 13, 15, and 16 and on days 10, 14, 15, and 16, respectively (all P < 0.05).
Conclusion The risk of oral mucositis in patients undergoing haplo-HSCT with PTCy is highest with the MAC-Bu conditioning regimen, followed by RIC-Bu, and lowest with RIC-Mel. en-copyright= kn-copyright= en-aut-name=OguraSaki en-aut-sei=Ogura en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiuraRumi en-aut-sei=Miura en-aut-mei=Rumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubokiTakuo en-aut-sei=Kuboki en-aut-mei=Takuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Dental Hygienist, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Dental Hygienist, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Division of Dental Hygienist, Okayama University Hospital kn-affil= en-keyword=Oral mucositis kn-keyword=Oral mucositis en-keyword=Hematopoietic cell transplantation kn-keyword=Hematopoietic cell transplantation en-keyword=Posttransplant cyclophosphamide kn-keyword=Posttransplant cyclophosphamide en-keyword=Busulfan kn-keyword=Busulfan en-keyword=Melphalan kn-keyword=Melphalan END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue=1 article-no= start-page=35 end-page=40 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of CT Findings in Squamous and Non-Squamous Cell Carcinomas of the Maxillary Sinus en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of the present study was to compare CT images between squamous cell carcinoma (SCC) and non-SCC found in the maxillary sinus, and to identify features that could be used to differentiate between SCC and non-SCC. Patients who visited the Faculty of Dentistry, Okayama University Hospital, between April 2007 and March 2023, underwent head and neck CT, and had tumors extending into the maxillary sinus that were diagnosed histopathologically as malignancy, were enrolled. The main seat of the mass, bony changes in the maxillary sinus wall, and extension into the surrounding area were assessed. These imaging features were evaluated according to SCC or non-SCC, and the characteristics of the two classes were assessed. Comparisons between the two groups were made using the Fisher exact probability test. There were 11 cases each of SCC and non-SCC. In 11 SCC and 7 non-SCC cases, the main seat of the mass occupied the entire maxillary sinus. The frequency of mass occupying the whole sinus was significantly higher in SCC than in non-SCC (p<0.05). Bone-thickening type disease was found only in squamous cell carcinoma 4/11 (36.4%), with there being a significant difference between SCC and non-SCC (p<0.05). Occupancy of the entire maxillary sinus by the mass and bone thickening on CT images were useful for differentiating between SCC and non-SCC arising in the maxillary sinus. en-copyright= kn-copyright= en-aut-name=AsaumiYuka en-aut-sei=Asaumi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujikuraMamiko en-aut-sei=Fujikura en-aut-mei=Mamiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HisatomiMiki en-aut-sei=Hisatomi en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=E. Al-HammadWlla en-aut-sei=E. Al-Hammad en-aut-mei=Wlla kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeshitaYohei en-aut-sei=Takeshita en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaShunsuke en-aut-sei=Okada en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KawazuToshiyuki en-aut-sei=Kawazu en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YanagiYoshinobu en-aut-sei=Yanagi en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsaumiJunichi en-aut-sei=Asaumi en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Dental Informatics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Maxillary sinus kn-keyword=Maxillary sinus en-keyword=Squamous cell carcinoma kn-keyword=Squamous cell carcinoma en-keyword=Non-squamous cell carcinoma kn-keyword=Non-squamous cell carcinoma en-keyword=CT kn-keyword=CT END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue= article-no= start-page=106690 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=EGF-induced P-gp expression in tumor vasculature contributes to therapeutic resistance to doxorubicin-PEG-liposomes in mice bearing doxorubicin-resistant B16-BL6 tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously indicated that doxorubicin (DOX)-loaded polyethylene glycol (PEG)-modified liposomes (DOX-PEG-liposomes) were therapeutically effective in mice bearing DOX-resistant colon-26 (C26/DOX) tumors, and the efficacy was comparable in mice bearing DOX-sensitive C26 tumors. However, in the current study, DOX-PEG-liposomes exerted no therapeutic activity in DOX-resistant B16-BL6 melanoma (B16/DOX)-bearing mice, although they significantly suppressed DOX-sensitive B16 tumor growth in mice. Although we previously reported that the anti-tumor effects in C26/DOX-bearing mice were derived from the cytotoxic effects of DOX on vascular endothelial cells (VECs) in tumors, the B16/DOX tumor vasculature was not substantially damaged after administration of DOX-PEG-liposomes. In B16/DOX tumors, P-gp expression was significantly induced in the VECs, but not in the C26/DOX tumors, indicating that the high expression of P-gp in the tumor vasculature would be responsible for the lack of therapeutic effect of DOX-PEG-liposomes in B16/DOX-bearing mice. Epidermal growth factor (EGF), a possible induction factor for P-gp expression, was highly expressed in B16/DOX cells and tumor tissues, and significantly induced P-gp expression in human umbilical vein endothelial cells (HUVEC). The EGF receptor (EGFR) was also highly expressed in B16/DOX tumor VECs, suggesting that the activation of EGF/EGFR signaling may induce P-gp expression in VECs in B16/DOX tumors. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaTomoki en-aut-sei=Ueda en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IenakaYusuke en-aut-sei=Ienaka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TojoHaruka en-aut-sei=Tojo en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HyodoKenji en-aut-sei=Hyodo en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaraKen-ichi en-aut-sei=Ogawara en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigakiKazutaka en-aut-sei=Higaki en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Eisai Co., Ltd. kn-affil= affil-num=6 en-affil=Laboratory of Pharmaceutics, Kobe Pharmaceutical University kn-affil= affil-num=7 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug resistance kn-keyword=Drug resistance en-keyword=P-glycoprotein kn-keyword=P-glycoprotein en-keyword=Liposome kn-keyword=Liposome en-keyword=Tumor vascular endothelial cells kn-keyword=Tumor vascular endothelial cells en-keyword=Melanoma kn-keyword=Melanoma END start-ver=1.4 cd-journal=joma no-vol=209 cd-vols= no-issue= article-no= start-page=114663 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Repeated sequential administration of pegylated emulsion of SU5416 and liposomal paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=To improve vascular normalization strategy for intractable triple-negative breast cancer 4T1, we examined the anti-tumor effects of repeated sequential administration of polyethylene glycol (PEG)-modified emulsion of SU5416 (PE-SU5416), a vascular endothelial growth factor (VEGF) receptor-2 kinase inhibitor, and PEG-modified liposomal paclitaxel (PL-PTX) in mice bearing 4T1 cells. Three sequential administrations (Seq×3) of PE-SU5416 and PL-PTX exhibited significantly higher anti-tumor activity than a single sequential administration (Seq×1). The tumor vasculatures were structurally normalized until after two PE-SU5416 (PE-SU5416×2) or sequential (Seq×2) administrations, while the improvement in vascular function, such as oxygen supply, blood flow, and PEG-liposomal distribution, was evident until after three administrations of PE-SU5416 (PE-SU5416×3) and Seq×3. Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416×3 and Seq×3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416×2, PE-SU5416×3, Seq×2, and Seq×3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation. en-copyright= kn-copyright= en-aut-name=MaruyamaMasato en-aut-sei=Maruyama en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToriiReiya en-aut-sei=Torii en-aut-mei=Reiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuiHazuki en-aut-sei=Matsui en-aut-mei=Hazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HayashiHiroki en-aut-sei=Hayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaraKen-ichi en-aut-sei=Ogawara en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiKazutaka en-aut-sei=Higaki en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Pharmaceutics, Kobe Pharmaceutical University kn-affil= affil-num=6 en-affil=Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drug delivery kn-keyword=Drug delivery en-keyword=Vascular normalization kn-keyword=Vascular normalization en-keyword=Breast cancer kn-keyword=Breast cancer en-keyword=Liposome kn-keyword=Liposome en-keyword=Cancer-associated fibroblast kn-keyword=Cancer-associated fibroblast END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Teprenone kn-keyword=Teprenone en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Interleukin-33 kn-keyword=Interleukin-33 END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=61 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: We investigated morphological differences in osteocyte processes between aged mice and our original podoplanin-conditional knockout (cKO) mice in which the floxed exon 3 of podoplanin was deleted by Dmp-1-driven Cre (Dmp1-Cre;PdpnΔ/Δ). Methods: SEM observation on osteocyte cell process, histochemistry for bone remodeling with mechanostress, and RT-PCR for RANKL and M-CSF in podoplanin cKO mouse bone with mechanostress was investigated. Results: SEM observations showed fewer and thinner osteocyte processes in femurs from 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than from 23-week-old wild-type mice, while the numbers of osteocyte processes in femurs and calvarias were similar in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice and 48-week-old wild-type mice. Furthermore, cell process numbers in femurs and calvarias were significantly smaller in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than in 48-week-old wild-type mice. In the test for differences in alveolar bone resorption under mechanical stress between Dmp1-Cre;PdpnΔ/Δ and wild-type mice, the area of TRAP-positive resorption pits was larger in wild-type mice than in Dmp1-Cre;PdpnΔ/Δ mice. In a quantitative tissue PCR analysis, the mRNA expression levels of RANKL and M-CSF in alveolar bone under mechanical stress were significantly lower in Dmp1-Cre;PdpnΔ/Δ mice than in wild-type mice. These results suggest that a reduction in cell process formation in osteocytes with podoplanin cKO affected the absorption of alveolar bone under mechanical stress in Dmp1-Cre;PdpnΔ/Δ mice. Conclusions: In podoplanin-deficient bone, the deformation of osteocyte processes by mechanical stimuli is not recognized as a stress due to the lower number of cell processes with podoplanin deficiency; therefore, the production of osteoclast migration/differentiation factors by activated osteocytes is not fully induced and macrophage migration to alveolar bone with mechanical stress appeared to be suppressed. These results indicate that podoplanin-dependent osteocyte process formation indirectly plays a key role in sensing mechanical stress in bone. en-copyright= kn-copyright= en-aut-name=KanaiTakenori en-aut-sei=Kanai en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsawaKyoko en-aut-sei=Osawa en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoYoshiaki en-aut-sei=Sato en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=2 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=3 en-affil=Department of Oral Growth & Development, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University kn-affil= affil-num=5 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=podoplanin kn-keyword=podoplanin en-keyword=cKO kn-keyword=cKO en-keyword=osteocyte kn-keyword=osteocyte en-keyword=bone kn-keyword=bone en-keyword=remodeling kn-keyword=remodeling END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=2 article-no= start-page=267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: A relationship between malocclusion and the promotion of diabetes has been suggested. In hyperglycemia, the expression of sodium-glucose cotransporter 2 (SGLT2) and the facilitative glucose transporter 2 (GLUT2) is upregulated in proximal tubular cells, leading to an increase in renal glucose reabsorption. The present study aimed to investigate whether malocclusion contributes to diabetic exacerbation. Methods: Streptozotocin (STZ)-induced diabetic mice with malocclusion due to cutting molars were investigated based on increased blood glucose levels. PCR and immunohistochemical analyses were performed on diabetic mice kidneys to investigate the expression of SGLT2 and GLUT2. Results: Animal experiments were performed using 32 mice for 21 days. The time to reach a diabetic condition in STZ-administered mice was shorter with malocclusion than without malocclusion. The increase and mean blood glucose levels in STZ-administered mice were steeper and higher with malocclusion than without malocclusion. Urea albumin, BUN, and CRE levels were higher in diabetic mice with malocclusion than in diabetic mice without. Immunoreaction with anti-SGLT2 and anti-GLUT2 in the renal tissue of STZ-administered mice was stronger with malocclusion than without malocclusion. The amounts of SGLT2 and GLUT2 mRNA in the renal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. The amounts of TNF-a and IL-6 mRNA in the large intestinal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. Conclusions: Our results indicate that malocclusion accelerates the tubular expression of SGLT2 and GLUT2 under hyperglycemia. Malocclusion may be a diabetes-exacerbating factor with increased poor glycemic control due to shortened occlusion time resulting from swallowing food without chewing. en-copyright= kn-copyright= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TamaokiSachio en-aut-sei=Tamaoki en-aut-mei=Sachio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=malocclusion kn-keyword=malocclusion en-keyword= hyperglycemia kn-keyword= hyperglycemia en-keyword= SGLT2 kn-keyword= SGLT2 en-keyword= GLUT2 kn-keyword= GLUT2 END start-ver=1.4 cd-journal=joma no-vol=197 cd-vols= no-issue= article-no= start-page=115301 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Traditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 μM) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 μM vs. 27.5 μM for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation. en-copyright= kn-copyright= en-aut-name=KatoKosuke en-aut-sei=Kato en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkamatsuMiki en-aut-sei=Akamatsu en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KakimaruSaya en-aut-sei=Kakimaru en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoreishiMayuko en-aut-sei=Koreishi en-aut-mei=Mayuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakagiMasahiro en-aut-sei=Takagi en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyashitaMasahiro en-aut-sei=Miyashita en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataYoshiyuki en-aut-sei=Murata en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraYoshimasa en-aut-sei=Nakamura en-aut-mei=Yoshimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujinoYoshio en-aut-sei=Tsujino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=6 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= en-keyword=AhR kn-keyword=AhR en-keyword=Xenobiotic responsive element kn-keyword=Xenobiotic responsive element en-keyword=StemRegenin 1 kn-keyword=StemRegenin 1 en-keyword=ARNT kn-keyword=ARNT en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=Artemin kn-keyword=Artemin END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=97 end-page=106 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “atypical lymphoplasmacytic and immunoblastic lymphadenopathy” from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial. en-copyright= kn-copyright= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiToshiaki en-aut-sei=Takahashi en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaokaKensuke en-aut-sei=Takaoka en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MacapagalSharina en-aut-sei=Macapagal en-aut-mei=Sharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WannaphutChalothorn en-aut-sei=Wannaphut en-aut-mei=Chalothorn kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TodaHiroko en-aut-sei=Toda en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimuraYoshito en-aut-sei=Nishimura en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=2 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=3 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=4 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=5 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=6 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Pathology, Chugoku Central Hospital kn-affil= affil-num=8 en-affil=Department of Medicine, John A. Burns School of Medicine, University of Hawai’i kn-affil= affil-num=9 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= en-keyword=systematic review kn-keyword=systematic review en-keyword=atypical lymphoplasmacytic and immunoblastic proliferation kn-keyword=atypical lymphoplasmacytic and immunoblastic proliferation en-keyword=IgG4-related disease kn-keyword=IgG4-related disease en-keyword=angioimmunoblastic T-cell lymphoma kn-keyword=angioimmunoblastic T-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Spatiotemporal expression pattern of dyslexia susceptibility 1 candidate 1 (DYX1C1) during rat cerebral cortex development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Developmental dyslexia (DD) is a common learning disorder with significant consequences for affected individuals. Although several candidate genes, including dyslexia susceptibility 1 candidate 1 (DYX1C1), have been implicated in dyslexia, their role in brain development remains unclear. We aimed to elucidate the spatiotemporal expression patterns of DYX1C1 during cerebral cortex development in rats.
Methods We investigated DYX1C1 expression during cerebral cortex development using rat embryos at various gestational stages (E13.5, 15.5, 17.5 and 20.5) by immunohistochemistry (n = 7 embryos/stage), quantitative real-time PCR (n = 6), and in situ hybridization (n = 11–15).
Results The DYX1C1-positive cells were predominantly located in the outermost layers of the cortical plate, particularly at E15.5. DYX1C1 mRNA expression peaked at E15.5 and subsequently declined. DYX1C1-positive cells did not co-localize with reelin-positive Cajal-Retzius cells, but co-localized with neuronal markers expressed during development, and had shorter primary cilia than DYX1C1-negative cells.
Conclusions Our findings highlight the dynamic expression of DYX1C1 in the developing cerebral cortex of rats, implicating its involvement in neurodevelopmental processes. Further investigation of the functional interactions of DYX1C1, particularly its relationship with reelin and its role in cerebrocortical and hippocampal development, may provide insights into the pathophysiology of dyslexia and neurodevelopmental disorders. en-copyright= kn-copyright= en-aut-name=ZenshoKazumasa en-aut-sei=Zensho en-aut-mei=Kazumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsseAika en-aut-sei=Isse en-aut-mei=Aika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisawaIchika en-aut-sei=Misawa en-aut-mei=Ichika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaMakio en-aut-sei=Oka en-aut-mei=Makio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Psychosocial Medicine, National Center for Child Health and Development kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=236 cd-vols= no-issue= article-no= start-page=74 end-page=81 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristics of porcine oocyte-cumulus complexes derived from various sizes of antral follicles and classified by brilliant cresyl blue staining, and developmental competence of the oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study sought to determine the characteristics of porcine oocyte-cumulus complexes (OCCs) derived from very small and small antral follicles (with less than 1 mm and 1–3 mm in diameter, respectively; VSF and SF) in comparison with controls from medium ones (with 3–6 mm in diameter; MF). Additionally, the present study examined the utility of brilliant cresyl blue (BCB) staining for assessing these OCCs. The incidence of BCB- oocytes in VSF- and SF-derived OCCs was higher than that in MF-derived OCCs. Although the meiotic and developmental competences of BCB+ oocytes from MF were superior to those from VSF and SF, blastocysts were successfully obtained from BCB+ oocytes even derived from VSF. The mean numbers of both total and viable cumulus cells surrounding an oocyte were significantly affected not only by the origin of the OCCs, but also by the BCB status of the oocytes (largest in MF-derived OCCs containing BCB+ oocytes). Although the outer and inner diameters of zona pellucida were affected by the origin of OCCs and the BCB status of oocytes (largest in MF-derived oocytes), the ooplasmic diameter of BCB+ oocytes did not differ among those derived from VSF, SF, and MF. Regardless of the BCB status, the transcriptional levels of G6PD and TKT in cumulus cells decreased during follicular development from VSF to MF, whereas the RPIA mRNA level in cumulus cells of MF-derived BCB+ OCCs was lower than in the others. These results underscore the utility of BCB staining for selecting MF-, SF-, and even VSF-derived OCCs containing oocytes with relatively higher meiotic and developmental competences, as well as the importance of having a sufficient number of healthy cumulus cells expressing genes related to the pentose phosphate pathway at lower levels. en-copyright= kn-copyright= en-aut-name=VanPhong Ngoc en-aut-sei=Van en-aut-mei=Phong Ngoc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FonsekaWanniarachchige Tharindu Lakshitha en-aut-sei=Fonseka en-aut-mei=Wanniarachchige Tharindu Lakshitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=2 article-no= start-page=376 end-page=382 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A case of pancreatic ductal adenocarcinoma growing within the pancreatic duct mimicking an intraductal tubulopapillary neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection. en-copyright= kn-copyright= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishidaKenji en-aut-sei=Nishida en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Pathology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=Pancreatic intraductal neoplasms kn-keyword=Pancreatic intraductal neoplasms en-keyword=Pancreatic carcinoma kn-keyword=Pancreatic carcinoma en-keyword=Intraductal tubulopapillary neoplasm kn-keyword=Intraductal tubulopapillary neoplasm en-keyword=Genetic testing kn-keyword=Genetic testing END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=51 end-page=58 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photoinitiators Induce Histamine Production in Human Mast Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. en-copyright= kn-copyright= en-aut-name=MiuraTaro en-aut-sei=Miura en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawasakiYoichi en-aut-sei=Kawasaki en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamanoHirofumi en-aut-sei=Hamano en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University kn-affil= affil-num=3 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=photoinitiator kn-keyword=photoinitiator en-keyword=ink kn-keyword=ink en-keyword=injection kn-keyword=injection en-keyword=histamine kn-keyword=histamine en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=3 article-no= start-page=96 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. en-copyright= kn-copyright= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NogiShohei en-aut-sei=Nogi en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaniguchiAtsuki en-aut-sei=Taniguchi en-aut-mei=Atsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuemoriKanto en-aut-sei=Suemori en-aut-mei=Kanto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NagaiYasuo en-aut-sei=Nagai en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujitaShuto en-aut-sei=Fujita en-aut-mei=Shuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TakagiKosei en-aut-sei=Takagi en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Neutrophil kn-keyword=Neutrophil en-keyword=Anti-fibrotic agent kn-keyword=Anti-fibrotic agent en-keyword=Pirfenidone kn-keyword=Pirfenidone END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=1 article-no= start-page=1 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Endothelial Cell Polarity in Health and Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front–rear, apical–basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. en-copyright= kn-copyright= en-aut-name=ThihaMoe en-aut-sei=Thiha en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HikitaTakao en-aut-sei=Hikita en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakayamaMasanori en-aut-sei=Nakayama en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=blood vessel kn-keyword=blood vessel en-keyword=endothelial cell kn-keyword=endothelial cell en-keyword=cell polarity kn-keyword=cell polarity en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=cancer kn-keyword=cancer END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=35 article-no= start-page=e2320189121 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell–specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets. en-copyright= kn-copyright= en-aut-name=MukoharaFumiaki en-aut-sei=Mukohara en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwataKazuma en-aut-sei=Iwata en-aut-mei=Kazuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzawaKen en-aut-sei=Suzawa en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoToshihide en-aut-sei=Ueno en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SaekiYuka en-aut-sei=Saeki en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaKazuo en-aut-sei=Yamashita en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KawaharaYu en-aut-sei=Kawahara en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=WatanabeHiroko en-aut-sei=Watanabe en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SuzukiYutaka en-aut-sei=Suzuki en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=HondaHiroaki en-aut-sei=Honda en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= affil-num=1 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=11 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=13 en-affil=KOTAI Biotechnologies, Inc. kn-affil= affil-num=14 en-affil=Department of Dermatology, Chiba University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=16 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Department of Dermatology, University of Yamanashi kn-affil= affil-num=20 en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa kn-affil= affil-num=21 en-affil=Department of Pathology, Tokyo Women's Medical University kn-affil= affil-num=22 en-affil=Division of Cellular Signaling, National Cancer Center Research Institute kn-affil= affil-num=23 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama University kn-affil= affil-num=24 en-affil=Division of Cell Therapy, Chiba Cancer Research Institute kn-affil= affil-num=25 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cancer immunology kn-keyword=cancer immunology en-keyword=somatic mutation kn-keyword=somatic mutation en-keyword=T cell kn-keyword=T cell en-keyword=tumor-infiltrating lymphocytes kn-keyword=tumor-infiltrating lymphocytes END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=38 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exacerbation of diabetes due to F. Nucleatum LPS-induced SGLT2 overexpression in the renal proximal tubular epithelial cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Diabetes treatments by the control of sodium-glucose cotransporter 2 (SGLT2) is commonly conducted while there are still uncertainties about the mechanisms for the SGLT2 overexpression in kidneys with diabetes. Previously, we have reported that glomeruli and proximal tubules with diabetic nephropathy express toll-like receptor TLR2/4, and that the TLR ligand lipopolysaccharide (LPS) of periodontal pathogens have caused nephropathy in diabetic model mice. Recently, many researchers suggested that the periodontal pathogenic bacteria Fusobacterium (F.) nucleatum has the TLR4-associated strong activator of the colorectal inflammation and cancer. The present study aimed to investigate the possibility of F. nucleatum as an exacerbation factor of diabetes through the renal SGLT2 induction.
Methods The induction of the SGLT2 by F. nucleatum LPS (Fn-LPS) were investigated in the streptozotocin-induced diabetic mouse renal tissue and cultured renal proximal epithelial cells. The changes of blood glucose levels and survival curves in diabetic mice with Fn-LPS were analyzed. The Fn-LPS-induced SGLT2 production in the diabetic mouse renal tissue and in the cultured proximal epithelial cells was examined by ELISA, quantitative RT-PCR, and immunohistochemical analysis.
Results The SGLT2 expression in the cultured mouse tubular epithelial cells was significantly increased by TNF- or co-culture with Fn-LPS-supplemented J774.1 cells. The period to reach diabetic condition was significantly shorter in Fn-LPS-administered diabetic mice than in diabetic mice. All Fn-LPS-administered-diabetic mice reached humane endpoints during the healthy period of all of the mice administered Fn-LPS only. The promotion of the SGLT2 expression at the inner lumen of proximal tubules were stronger in the Fn-LPS-administered-diabetic mice than in diabetic mice. The renal tissue SGLT2 mRNA amounts and the number of renal proximal tubules with overexpressed SGLT2 in the lumen were more in the Fn-LPS-administered-diabetic mice than in diabetic mice.
Conclusions This study suggests that F. nucleatum causes the promotion of diabetes through the overexpression of SGLT2 in proximal tubules under the diabetic condition. Periodontitis with F. nucleatum may be a diabetic exacerbating factor. en-copyright= kn-copyright= en-aut-name=SekiAiko en-aut-sei=Seki en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajiwaraKoichiro en-aut-sei=Kajiwara en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeramachiJumpei en-aut-sei=Teramachi en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EgusaMasahiko en-aut-sei=Egusa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyawakiTakuya en-aut-sei=Miyawaki en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SawaYoshihiko en-aut-sei=Sawa en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Oral Growth & Development, Fukuoka Dental College kn-affil= affil-num=3 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Dental Anesthesiology & Special Care Dentistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Oral Function & Anatomy, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=F. Nucleatum kn-keyword=F. Nucleatum en-keyword=Diabetic exacerbation kn-keyword=Diabetic exacerbation en-keyword=Diabetic nephropathy kn-keyword=Diabetic nephropathy en-keyword=SGLT2 kn-keyword=SGLT2 END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=3267 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250125 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC. en-copyright= kn-copyright= en-aut-name=MitsuiEma en-aut-sei=Mitsui en-aut-mei=Ema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkuraTomohiro en-aut-sei=Okura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UneYuta en-aut-sei=Une en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiwakiNoriyuki en-aut-sei=Nishiwaki en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtsukaJunko en-aut-sei=Ohtsuka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhkiRieko en-aut-sei=Ohki en-aut-mei=Rieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=12 en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Peritoneal metastasis kn-keyword=Peritoneal metastasis en-keyword=Gastric cancer kn-keyword=Gastric cancer en-keyword=Interleukin-6 kn-keyword=Interleukin-6 en-keyword=Cancer-associated fibroblasts kn-keyword=Cancer-associated fibroblasts en-keyword=Interleukin-6 receptor antibody kn-keyword=Interleukin-6 receptor antibody END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=4055-24 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=2025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dyspnea with Hemidiaphragm Elevation in a Patient with Giant Cell Arteritis: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract=We herein report the first case of dyspnea with hemidiaphragm elevation in a 68-year-old woman with active giant cell arteritis (GCA), including successful treatment. Contrast-enhanced computed tomography showed a reduced density of the left ophthalmic artery and the left superficial temporal artery with increased soft tissue compared to the other side, indicating that the GCA had flared up and suggesting that the hemidiaphragm elevation might be caused by vasculitis-associated ischemia of the right phrenic nerve. Hemidiaphragm paralysis due to vasculitis-associated ischemia in patients with GCA needs to be distinguished from local infection, tumors, and hepatomegaly, which are the major causes of hemidiaphragm elevation. en-copyright= kn-copyright= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KubotaNatsuki en-aut-sei=Kubota en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TerajimaYuya en-aut-sei=Terajima en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoKazuya en-aut-sei=Matsumoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShidaharaKenta en-aut-sei=Shidahara en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiroseKei en-aut-sei=Hirose en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakadoiTakato en-aut-sei=Nakadoi en-aut-mei=Takato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=giant cell arteritis kn-keyword=giant cell arteritis en-keyword=dyspnea kn-keyword=dyspnea en-keyword=hemidiaphragm elevation kn-keyword=hemidiaphragm elevation en-keyword=phrenic nerve paralysis kn-keyword=phrenic nerve paralysis en-keyword=FDG-PET kn-keyword=FDG-PET en-keyword=case report kn-keyword=case report END start-ver=1.4 cd-journal=joma no-vol=361 cd-vols= no-issue= article-no= start-page=114657 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crosstalk between prolactin, insulin-like growth factors, and thyroid hormones in feather growth regulation in neonatal chick wings en-subtitle= kn-subtitle= en-abstract= kn-abstract=The elongation of primary feathers in neonatal chicks is delayed by the late-feathering K gene located on the Z chromosome. We recently found that the K gene slows feather growth by reducing the number of functional prolactin (PRL) receptor (PRLR) dimers. In this study, we investigated the molecular mechanisms by which PRL promotes feather elongation. RT-qPCR and immunohistochemistry analyses revealed that PRLRs are predominantly localized in the pulp rather than in the epidermal layer of the feather follicle. Treatment of primary cultured feather pulp cells with PRL increased the expression of mRNAs for insulin-like growth factors (IGFs; IGF-1 and IGF-2) and type 2 deiodinase (DIO2). Furthermore, treatments with IGF-1 and triiodothyronine (T3) reciprocally enhanced the expression of mRNAs for DIO2 and IGFs. Additionally, BrdU staining in neonatal chicks showed that T3 promoted cell proliferation in both the epidermal layer and pulp cells, while this effect was suppressed by an IGF-1 receptor (IGF1R) inhibitor. These findings suggest a novel model in which PRL upregulates IGFs and DIO2 in feather pulp cells, creating a positive feedback loop between IGFs and T3, ultimately leading to the promotion of cell proliferation in both the epidermal layer and the pulp cells by IGFs. This is the first report proposing crosstalk between PRL, thyroid hormone (TH), and IGFs in feather follicles. en-copyright= kn-copyright= en-aut-name=NozawaYuri en-aut-sei=Nozawa en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamuraAyako en-aut-sei=Okamura en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaMasamichi en-aut-sei=Shinohara en-aut-mei=Masamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Prolactin kn-keyword=Prolactin en-keyword=Thyroid hormone kn-keyword=Thyroid hormone en-keyword=IGF kn-keyword=IGF en-keyword=Iodothyronine deiodinase kn-keyword=Iodothyronine deiodinase en-keyword=Feather growth kn-keyword=Feather growth END start-ver=1.4 cd-journal=joma no-vol=941 cd-vols= no-issue= article-no= start-page=149244 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250315 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of pennaceous barbule cell factor (PBCF), a novel gene with spatiotemporal expression in barbule cells during feather development en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bird contour feathers exhibit a complex hierarchical structure composed of a rachis, barbs, and barbules, with barbules playing a crucial role in maintaining feather structure and function. Understanding the molecular mechanisms underlying barbule formation is essential for advancing our knowledge of avian biology and evolution. In this study, we identified a novel gene, pennaceous barbule cell factor (PBCF), using microarray analysis, RT-PCR, and in situ hybridization. PBCF is expressed in barbule cells adjacent to the ramus during pennaceous barbule formation, where these cells fuse with the ramus to establish the feather’s branching structure. PBCF expression occurs transiently after melanin pigmentation of the barbule plates but before the expression of barbule-specific keratin 1 (BlSK1). Orthologues of PBCF, predicted to be secreted proteins, are conserved across avian species, with potential homologues detected in reptiles, suggesting an evolutionary lineage-specific adaptation. Additionally, PBCF is expressed in non-vacuolated notochord cells and the extra-embryonic ectoderm of the yolk sac, hinting at its broader developmental significance. The PBCF gene produces two mRNA isoforms via alternative splicing, encoding a secreted protein and a glycophosphatidylinositol (GPI)-anchored membrane-bound protein, indicating functional versatility. These findings suggest that PBCF may be involved as an avian-specific extracellular matrix component in cell adhesion and/or communication, potentially contributing to both feather development and embryogenesis. Further investigation of PBCF’s role in feather evolution and its potential functions in other vertebrates could provide new insights into the interplay between development and evolution. en-copyright= kn-copyright= en-aut-name=NakaokaMinori en-aut-sei=Nakaoka en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuchiHibiki en-aut-sei=Fukuchi en-aut-mei=Hibiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgoshiMaho en-aut-sei=Ogoshi en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AizawaSayaka en-aut-sei=Aizawa en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeuchiSakae en-aut-sei=Takeuchi en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Feather kn-keyword=Feather en-keyword=Barbule kn-keyword=Barbule en-keyword=Branching kn-keyword=Branching en-keyword=Chicken kn-keyword=Chicken en-keyword=Yolk sac membrane kn-keyword=Yolk sac membrane en-keyword=Notochord kn-keyword=Notochord END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=1 article-no= start-page=7 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Precision Medicine for Patients with Renal Cell Carcinoma Based on Drug-metabolizing Enzyme Expression Levels kn-title=薬物代謝酵素の発現情報を活用した腎がん治療の個別適正化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs. However, there is no consensus on which TKI+ICI therapy is best or how to select the appropriate therapy for individual patients with RCC. The kidney expresses various metabolic enzymes, including CYP and uridine diphosphate glucose (UDP)-glucuronosyltransferase (UGT). Although information on CYP and UGT expression in the kidney is limited compared to our understanding of liver expression, the main CYP and UGT subtypes expressed at high levels in the kidney are estimated to be CYP2B6, CYP3A5, CYP4A11, CYP4F2, UGT1A6, UGT1A9, and UGT2B7. In RCC, the expression profiles and levels of these enzymes are somewhat altered compared with normal kidney. The main known subtypes of CYP and UGT in RCC are CYP1B1, CYP3A5, CYP4A11, UGT1A6, UGT1A9, UGT1A10, and UGT2B7. High CYP expression has been reported in several cancers, possibly conferring resistance to anti-cancer drugs including TKIs, due to extensive drug metabolism. Additionally, CYP and UGT expression levels may possibly affect cancer prognosis by metabolizing endogenous substrates, regardless of their role in anti-cancer drug metabolism. In this review, I discuss CYP and UGT expression level profiles in RCC based on previously published papers, including ours, and examine possible relationships between these enzyme expression profiles and treatment outcomes for patients with RCC. en-copyright= kn-copyright= en-aut-name=MatsumotoJun en-aut-sei=Matsumoto en-aut-mei=Jun kn-aut-name=松本准 kn-aut-sei=松本 kn-aut-mei=准 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域（薬学系）疾患薬理制御科学分野 en-keyword=renal cell carcinoma (RCC) kn-keyword=renal cell carcinoma (RCC) en-keyword=kidney kn-keyword=kidney en-keyword=CYP kn-keyword=CYP en-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase kn-keyword=uridine diphosphate glucose (UDP)-glucuronosyltransferase en-keyword=metabolism kn-keyword=metabolism END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=CadetJean Lud en-aut-sei=Cadet en-aut-mei=Jean Lud kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA kn-affil= en-keyword=Methamphetamine kn-keyword=Methamphetamine en-keyword=Neurotoxicity kn-keyword=Neurotoxicity en-keyword=Nedd4 kn-keyword=Nedd4 en-keyword=Ndfip1 kn-keyword=Ndfip1 en-keyword=Differential display kn-keyword=Differential display END start-ver=1.4 cd-journal=joma no-vol=741 cd-vols= no-issue= article-no= start-page=151006 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=S-adenosylmethionine and S-adenosyl-L-homocysteine metabolism is involved in the sperm motility and in vitro fertility rate in mouse en-subtitle= kn-subtitle= en-abstract= kn-abstract=Increased fragmentation of sperm DNA has been implicated in male infertility. Folate deficiency results in impaired methionine synthesis, depletion of S-adenosylmethionine (SAM) levels, an increase in S-adenosyl-l-homocysteine (SAH) levels, and increased DNA fragmentation. Disruption of the dynamic balance between SAM and SAH may also contribute, although the details of this process are not yet fully understood. We investigated the localization of SAM, SAH, and S-adenosylhomocysteine hydrolase (SAHH), and whether SAM/SAH metabolism contributes to sperm motility and fertilization rate. SAM, SAH, and SAHH levels were assessed in the acrosome, midpiece, and tail of spermatozoa. Chemical inhibition of SAM/SAH metabolism and extracellular SAH significantly decreased the straight-line velocity (VSL), curvilinear velocity (VCL), and amplitude lateral head displacement (ALH) of sperm cells, which were thus unable to swim forward and perform oscillatory movements in place. This significantly reduced the fertilization rate. Therefore, the disruption of the SAM/SAH balance may contribute to male infertility. en-copyright= kn-copyright= en-aut-name=KawaiTomoko en-aut-sei=Kawai en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=SAM/SAH metabolism kn-keyword=SAM/SAH metabolism en-keyword=Sperm motility kn-keyword=Sperm motility en-keyword=Fertilization rate kn-keyword=Fertilization rate END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=2577 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0–1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p = 0.009; median OS: 15.4 vs. 38.0 months, p = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC. en-copyright= kn-copyright= en-aut-name=KuribayashiTadahiro en-aut-sei=Kuribayashi en-aut-mei=Tadahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KinoshitaRie en-aut-sei=Kinoshita en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=RaiKammei en-aut-sei=Rai en-aut-mei=Kammei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=S100A8/A9 kn-keyword=S100A8/A9 en-keyword=Lung cancer kn-keyword=Lung cancer en-keyword=Immune checkpoint inhibitors kn-keyword=Immune checkpoint inhibitors END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=60 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10B (n, alpha) 7Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10B-Carb or 10B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. en-copyright= kn-copyright= en-aut-name=FithroniAbdul Basith en-aut-sei=Fithroni en-aut-mei=Abdul Basith kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueHaruki en-aut-sei=Inoue en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HakimTaufik Fatwa Nur en-aut-sei=Hakim en-aut-mei=Taufik Fatwa Nur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TadaTakashi en-aut-sei=Tada en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SuzukiMinoru en-aut-sei=Suzuki en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshimotoManabu en-aut-sei=Ishimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaNaoyuki en-aut-sei=Yamada en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SauriasariRani en-aut-sei=Sauriasari en-aut-mei=Rani kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SauerweinWolfgang A. G. en-aut-sei=Sauerwein en-aut-mei=Wolfgang A. G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=7 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=8 en-affil=J-BEAM, Inc. kn-affil= affil-num=9 en-affil=Nihon Fukushi Fuiin Holding, Co., Ltd. kn-affil= affil-num=10 en-affil=Faculty of Pharmacy, Universitas Indonesia kn-affil= affil-num=11 en-affil=Deutsche Gesellschaft für Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik für Strahlentherapie kn-affil= affil-num=12 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=13 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=14 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=dual therapeutic effects kn-keyword=dual therapeutic effects en-keyword=Lactosome ® kn-keyword=Lactosome ® en-keyword=hydrophobic boron compound kn-keyword=hydrophobic boron compound en-keyword=neutron irradiation kn-keyword=neutron irradiation en-keyword=theranostics kn-keyword=theranostics END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=52 article-no= start-page=35202 end-page=35213 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bright Quantum-Grade Fluorescent Nanodiamonds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Optically accessible spin-active nanomaterials are promising as quantum nanosensors for probing biological samples. However, achieving bioimaging-level brightness and high-quality spin properties for these materials is challenging and hinders their application in quantum biosensing. Here, we demonstrate bright fluorescent nanodiamonds (NDs) containing 0.6–1.3-ppm negatively charged nitrogen-vacancy (NV) centers by spin-environment engineering via enriching spin-less 12C-carbon isotopes and reducing substitutional nitrogen spin impurities. The NDs, readily introduced into cultured cells, exhibited improved optically detected magnetic resonance (ODMR) spectra; peak splitting (E) was reduced by 2–3 MHz, and microwave excitation power required was 20 times lower to achieve a 3% ODMR contrast, comparable to that of conventional type-Ib NDs. They show average spin-relaxation times of T1 = 0.68 ms and T2 = 3.2 μs (1.6 ms and 5.4 μs maximum) that were 5- and 11-fold longer than those of type-Ib, respectively. Additionally, the extended T2 relaxation times of these NDs enable shot-noise-limited temperature measurements with a sensitivity of approximately 0.28K/√Hz. The combination of bulk-like NV spin properties and enhanced fluorescence significantly improves the sensitivity of ND-based quantum sensors for biological applications. en-copyright= kn-copyright= en-aut-name=OshimiKeisuke en-aut-sei=Oshimi en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IshiwataHitoshi en-aut-sei=Ishiwata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakashimaHiromu en-aut-sei=Nakashima en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MandićSara en-aut-sei=Mandić en-aut-mei=Sara kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHina en-aut-sei=Kobayashi en-aut-mei=Hina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TeramotoMinori en-aut-sei=Teramoto en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsujiHirokazu en-aut-sei=Tsuji en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishibayashiYoshiki en-aut-sei=Nishibayashi en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShikanoYutaka en-aut-sei=Shikano en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AnToshu en-aut-sei=An en-aut-mei=Toshu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMasazumi en-aut-sei=Fujiwara en-aut-mei=Masazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=The National Institutes for Quantum Science and Technology (QST), Institute for Quantum Life Science (iQLS) kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=7 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=8 en-affil=Advanced Materials Laboratory, Sumitomo Electric Industries, Ltd. kn-affil= affil-num=9 en-affil=Institute of Systems and Information Engineering, University of Tsukuba kn-affil= affil-num=10 en-affil=School of Materials Science, Japan Advanced Institute of Science and Technology kn-affil= affil-num=11 en-affil=Department of Chemistry, Graduate School of Life, Environmental, Natural Science and Technology, Okayama University kn-affil= en-keyword=nanodiamonds kn-keyword=nanodiamonds en-keyword=nitrogen-vacancy centers kn-keyword=nitrogen-vacancy centers en-keyword=spins kn-keyword=spins en-keyword=spin-relaxation times kn-keyword=spin-relaxation times en-keyword=quantum biosensor kn-keyword=quantum biosensor en-keyword=cellular probes kn-keyword=cellular probes END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1439705 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HOMA-beta independently predicts survival in patients with advanced cancer on treatment with immune checkpoint inhibitors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown.
Methods: This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis.
Results: Patients with overall survival (OS) >= 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta >= 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta >= 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value >= 64.24 independently predicted longer OS in ICI-treated patients.
Conclusions: Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy. en-copyright= kn-copyright= en-aut-name=WatanabeMayu en-aut-sei=Watanabe en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakamotoAtsushi en-aut-sei=Takamoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KagawaSyunsuke en-aut-sei=Kagawa en-aut-mei=Syunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Fukuyama City Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=5 en-affil=Department of Urology, Fukuyama City Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=anti-PD1 immune checkpoint inhibitors kn-keyword=anti-PD1 immune checkpoint inhibitors en-keyword= insulin secretory capacity kn-keyword= insulin secretory capacity en-keyword= cancer prognosis kn-keyword= cancer prognosis en-keyword= insulin secretion kn-keyword= insulin secretion en-keyword= glucose metabolism markers kn-keyword= glucose metabolism markers END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=24 article-no= start-page=2045 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=iPSC-Derived Biological Pacemaker-From Bench to Bedside en-subtitle= kn-subtitle= en-abstract= kn-abstract=Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias. en-copyright= kn-copyright= en-aut-name=VoQuan Duy en-aut-sei=Vo en-aut-mei=Quan Duy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IidaToshihiro en-aut-sei=Iida en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AmiokaNaofumi en-aut-sei=Amioka en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=sinoatrial node kn-keyword=sinoatrial node en-keyword=HCN channels kn-keyword=HCN channels en-keyword=induced pluripotent stem cell kn-keyword=induced pluripotent stem cell END start-ver=1.4 cd-journal=joma no-vol=169 cd-vols= no-issue=1 article-no= start-page=e16291 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241222 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds en-subtitle= kn-subtitle= en-abstract= kn-abstract=Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (Ccn3) was highly expressed in Type III taste cells but not in Type II taste cells. Ccn3 is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of Ccn3 in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that Ccn3 was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that Ccn3 knockout (Ccn3-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of Ccn3 in taste cells, bioinformatics analyses were conducted and predicted possible roles of Ccn3 in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although Ccn3 is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of Ccn3 in taste buds and shed light on future research directions. en-copyright= kn-copyright= en-aut-name=WangKuanyu en-aut-sei=Wang en-aut-mei=Kuanyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitohYoshihiro en-aut-sei=Mitoh en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HorieKengo en-aut-sei=Horie en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaRyusuke en-aut-sei=Yoshida en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Physiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=bioinformatics kn-keyword=bioinformatics en-keyword=Ccn3 kn-keyword=Ccn3 en-keyword=Type III taste cell kn-keyword=Type III taste cell END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=2 article-no= start-page=249 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.
Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1−/−) mice.
Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1−/− donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1−/− donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1−/− recipient.
Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD. en-copyright= kn-copyright= en-aut-name=KawanaShinichi en-aut-sei=Kawana en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkazakiMikio en-aut-sei=Okazaki en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaueTomohisa en-aut-sei=Sakaue en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoKohei en-aut-sei=Hashimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakataKentaro en-aut-sei=Nakata en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ChoshiHaruki en-aut-sei=Choshi en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanakaShin en-aut-sei=Tanaka en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiKentaroh en-aut-sei=Miyoshi en-aut-mei=Kentaroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhtaniShinji en-aut-sei=Ohtani en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SugimotoSeiichiro en-aut-sei=Sugimoto en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine kn-affil= affil-num=6 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University kn-affil= affil-num=10 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=lung transplantation kn-keyword=lung transplantation en-keyword=ischemia-reperfusion injury kn-keyword=ischemia-reperfusion injury en-keyword=donation after circulatory death kn-keyword=donation after circulatory death en-keyword=nuclear receptor subfamily 4 group A member 1 kn-keyword=nuclear receptor subfamily 4 group A member 1 en-keyword=endothelial cell kn-keyword=endothelial cell END start-ver=1.4 cd-journal=joma no-vol=226 cd-vols= no-issue= article-no= start-page=158 end-page=166 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240915 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The impact of cumulus cell viability and pre-culture with the healthy cell mass on brilliant cresyl blue (BCB) staining assessment and meiotic competence of suboptimal porcine oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives of the present study were to investigate the characteristics including glucose-6-phosphate dehydrogenase activity, as determined by Brilliant Cresyl Blue (BCB) staining, of suboptimal porcine oocytes and to enhance the meiotic competence of those through pre-culture with cumulus cell masses (CCMs). Percentage of oocyte-cumulus complexes (OCCs) derived from small follicles (SF; <3 mm in diameter) containing the oocytes that were assessed as BCB-negative (BCB-) was significantly higher than those derived from medium follicles (MF; 3–6 mm in diameter). Degrees of dead cumulus cells were significantly higher in OCCs containing BCB- oocytes, regardless of the origin of OCCs (MF vs. SF), than those containing BCB-positive (BCB+) ones. Exposing OCCs containing BCB+ oocytes to the apoptosis inducer, carbonyl cyanide m-chlorophenylhydrazone, for 20 h significantly induced the transition to BCB- and meiotic progression of exposed OCCs were significantly reduced in both SF and MF derived ones. Transit of BCB- oocytes to BCB+ was induced when OCCs were pre-cultured with CCMs of MF derived OCCs containing BCB+ oocytes for 20 h before IVM. This pre-culture also significantly increased the meiotic competence of BCB- oocytes, particularly in SF derived ones. However, reactive oxygen species levels were significantly higher in BCB+ oocytes as compared with BCB- ones, regardless of pre-culture with CCMs, whereas no significant differences were found in the ATP contents among the treatment groups. In conclusion, the BCB result of oocytes could be regulated by the healthy status and content of surrounding cumulus cells and the meiotic competence of suboptimal BCB- porcine oocytes is improved by pre-culture with healthy CCMs. en-copyright= kn-copyright= en-aut-name=FonsekaWanniarachchige Tharindu Lakshitha en-aut-sei=Fonseka en-aut-mei=Wanniarachchige Tharindu Lakshitha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VanPhong Ngoc en-aut-sei=Van en-aut-mei=Phong Ngoc kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Oocytes kn-keyword=Oocytes en-keyword=Meiotic competence kn-keyword=Meiotic competence en-keyword=Brilliant cresyl blue kn-keyword=Brilliant cresyl blue en-keyword=Cumulus cells kn-keyword=Cumulus cells END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=1 article-no= start-page=102494 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease. en-copyright= kn-copyright= en-aut-name=OguniKohei en-aut-sei=Oguni en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukushimaShinnosuke en-aut-sei=Fukushima en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KatoAtsushi en-aut-sei=Kato en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuyamaAtsuhito en-aut-sei=Suyama en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnoSawako en-aut-sei=Ono en-aut-mei=Sawako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IioKoji en-aut-sei=Iio en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Microbiology Division, Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cryptococcosis kn-keyword=Cryptococcosis en-keyword=Fluconazole kn-keyword=Fluconazole en-keyword=Glucocorticoids kn-keyword=Glucocorticoids en-keyword=Prostatitis kn-keyword=Prostatitis en-keyword=Tocilizumab kn-keyword=Tocilizumab END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=e70097 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eyelid Spindle Cell Lipoma: Case Report and Review of Three Patients in Literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 39-year-old woman presented a saucer-shaped mass in the left upper eyelid and underwent the extirpation at local anesthesia. Pathologically, collagen fibers, capillaries, small vessels, and CD34-positive spindle cells were dispersed among mature adipose tissues, indicative of spindle cell lipoma. Long-lasting cyst-like eyelid masses would be usually dermoid cysts, and spindle cell lipoma would be listed as a rare pathological diagnosis in differential diagnoses of cyst-like lesions in the upper and lower eyelid. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaKiyoshi en-aut-sei=Yamada en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MonobeYasumasa en-aut-sei=Monobe en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Plastic and Reconstructive Surgery, Kousei Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, General Medical Center, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=CD34 kn-keyword=CD34 en-keyword=eyelid kn-keyword=eyelid en-keyword=orbital bony edge kn-keyword=orbital bony edge en-keyword=pathology kn-keyword=pathology en-keyword=spindle cell lipoma kn-keyword=spindle cell lipoma END start-ver=1.4 cd-journal=joma no-vol=45 cd-vols= no-issue=1 article-no= start-page=11 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Apoptotic cell death is an important survival system for multicellular organisms because it removes damaged cells. Mutation is also a survival method for dealing with damaged cells in multicellular and also unicellular organisms, when DNA lesions are not removed. However, to the best of our knowledge, no reports have comprehensively explored the direct relationship between apoptosis and somatic cell mutations induced by various mutagenic factors.
Results Mutation was examined by the wing-spot test, which is used to detect somatic cell mutations, including chromosomal recombination. Apoptosis was observed in the wing discs by acridine orange staining in situ. After treatment with chemical mutagens, ultraviolet light (UV), and X-ray, both the apoptotic frequency and mutagenic activity increased in a dose-dependent manner at non-toxic doses. When we used DNA repair-deficient Drosophila strains, the correlation coefficient of the relationship between apoptosis and mutagenicity, differed from that of the wild-type. To explore how apoptosis affects the behavior of mutated cells, we determined the spot size, i.e., the number of mutated cells in a spot. In parallel with an increase in apoptosis, the spot size increased with MNU or X-ray treatment dose-dependently; however, this increase was not seen with UV irradiation. In addition, BrdU incorporation, an indicator of cell proliferation, in the wing discs was suppressed at 6 h, with peak at 12 h post-treatment with X-ray, and that it started to increase again at 24 h; however, this was not seen with UV irradiation.
Conclusion Damage-induced apoptosis and mutation might be coordinated with each other, and the frequency of apoptosis and mutagenicity are balanced depending on the type of DNA damage. From the data of the spot size and BrdU incorporation, it is possible that mutated cells replace apoptotic cells due to their high frequency of cell division, resulting in enlargement of the spot size after MNU or X-ray treatment. We consider that the induction of mutation, apoptosis, and/or cell growth varies in multi-cellular organisms depending on the type of the mutagens, and that their balance and coordination have an important function to counter DNA damage for the survival of the organism. en-copyright= kn-copyright= en-aut-name=Toyoshima-SasataniMegumi en-aut-sei=Toyoshima-Sasatani en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ImuraFumika en-aut-sei=Imura en-aut-mei=Fumika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HamatakeYuko en-aut-sei=Hamatake en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukunagaAkihiro en-aut-sei=Fukunaga en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NegishiTomoe en-aut-sei=Negishi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=School of Nursing, Osaka City University kn-affil= affil-num=5 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Drosophila kn-keyword=Drosophila en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Mutation kn-keyword=Mutation en-keyword=Larval wing disc kn-keyword=Larval wing disc en-keyword=X-ray kn-keyword=X-ray en-keyword=Ultraviolet kn-keyword=Ultraviolet en-keyword=Alkylating agents kn-keyword=Alkylating agents en-keyword=Tobacco smoke kn-keyword=Tobacco smoke en-keyword=Acridine orange kn-keyword=Acridine orange en-keyword=BrdU kn-keyword=BrdU END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=04 article-no= start-page=E351 end-page=E357 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230213 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Degree of pharyngeal deformation caused by pharyngeal endoscopic submucosal dissection is associated with the incidence of aspiration pneumonia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and study aims Endoscopic submucosal dissection (ESD) is one of the most minimally invasive treatments for superficial squamous cell cancer of the pharynx. However, aspiration pneumonia (AsP) associated with postoperative deformity of the pharynx may occur. The purpose of this study was to investigate the frequency of AsP and the degree of pharyngeal deformity after pharyngeal ESD.
Patients and methods This was a retrospective observational study of patients who underwent pharyngeal ESD at Okayama University Hospital between 2006 and 2017. The degree of pharyngeal deformation was assessed using the pharyngeal deformation grade (PDG). The primary endpoint was the frequency of AsP as a long-term adverse event.
Results Among the 52 patients enrolled, nine developed aspiration pneumonia, with a 3-year cumulative incidence of 9.0 % (95 % confidence interval [CI], 3.3 %–22.0 %). There were 16, 18, 16, and two patients that had PDG 0, 1, 2, and 3, respectively. Patients with a history of radiotherapy, as a treatment of head and neck cancer (44.4 % vs. 11.6 %; P = 0.02) and the high PDG group (PDG 2 and 3) (77.8 % vs. 25.6 %; P = 0.005) had a significantly higher incidence of AsP. The 3-year cumulative incidence rate of AsP after ESD in the high PDG group was significantly higher than that in the low PDG group (PDG 0 and 1) (23.9 % [95 %CI, 9.2.–49.5%] vs. 0 %; P = 0.03).
Conclusions The incidence of aspiration pneumonia in the long-term course after pharyngeal ESD was revealed. The incidence of aspiration pneumonia may be associated with pharyngeal deformity, but further studies are needed. en-copyright= kn-copyright= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ObayashiYuka en-aut-sei=Obayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabaYuki en-aut-sei=Baba en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakaeHiroyuki en-aut-sei=Sakae en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanzakiHiromitu en-aut-sei=Kanzaki en-aut-mei=Hiromitu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MakinoTakuma en-aut-sei=Makino en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NodaYohei en-aut-sei=Noda en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MarunakaHidenori en-aut-sei=Marunaka en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=213 end-page=218 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=2024 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=β-catenin Binds to Gsk-3β in Liquid-Liquid Phase Separation Compartment in HEK293 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Liquid-liquid phase separation (LLPS) has emerged as a significant mechanism for cellular organization, impacting various biological processes, including Wnt/β-catenin signaling. This study investigates the role of LLPS in the regulation of β-catenin in HEK293 cells, particularly in response to Wnt3a signaling. Our findings demonstrate that β-catenin is regulated by LLPS, forming spherical droplets indicative of this phenomenon. Fluorescence recovery after photobleaching (FRAP) assays revealed that these droplets exhibit reversible dynamics, further confirming their phase-separated nature. Importantly, treatment with Wnt3a led to an increase in β-catenin levels, while simultaneously reducing the recovery of fluorescence intensity in FRAP experiments, suggesting that enhanced Wnt signaling may stimulate the release of β-catenin from LLPS. Immunoprecipitation studies indicated that β-catenin binds to glycogen synthase kinase 3β (Gsk-3β) within the LLPS state, highlighting a potential regulatory mechanism whereby LLPS facilitates the phosphorylation and subsequent degradation of β-catenin. The addition of 1,6-hexanediol disrupted the β-catenin/Gsk-3β interaction, reinforcing the idea that LLPS plays a critical role in modulating these biochemical interactions. The findings presented in this study suggest that LLPS is not only crucial for the spatial organization of β-catenin but also serves as a regulatory mechanism for its signaling functions in the Wnt pathway. Given the association of aberrant Wnt signaling with various diseases, including cancer and neurodegenerative disorders, understanding the role of LLPS in this context may provide new insights into therapeutic strategies targeting these pathological conditions. en-copyright= kn-copyright= en-aut-name=KatoMari en-aut-sei=Kato en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanaiAiri en-aut-sei=Tanai en-aut-mei=Airi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuharaYoko en-aut-sei=Fukuhara en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhengXinyu en-aut-sei=Zheng en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SitosariHeriati en-aut-sei=Sitosari en-aut-mei=Heriati kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkegameMika en-aut-sei=Ikegame en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamuraHirohiko en-aut-sei=Okamura en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=β-catenin kn-keyword=β-catenin en-keyword=Gsk-3β kn-keyword=Gsk-3β en-keyword=LLPS kn-keyword=LLPS en-keyword=Wnt kn-keyword=Wnt END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=3 article-no= start-page=97 end-page=99 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2023 Incentive Award of the Okayama Medical Association in Cardiovascular and Pulmonary Research (2023 Sunada Prize) kn-title=令和５年度岡山医学会賞　胸部・循環研究奨励賞（砂田賞） en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name=谷口暁彦 kn-aut-sei=谷口 kn-aut-mei=暁彦 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学 END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue= article-no= start-page=110572 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Laparoscopic resection for oesophageal duplication cyst: A case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection.
Presentation of case: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy.
Discussion: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer.
Conclusions: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ. en-copyright= kn-copyright= en-aut-name=HamazakiTomohiro en-aut-sei=Hamazaki en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KawasakiKento en-aut-sei=Kawasaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanabeShunsuke en-aut-sei=Tanabe en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oesophageal duplication cyst kn-keyword=Oesophageal duplication cyst en-keyword=Laparoscopic surgery kn-keyword=Laparoscopic surgery en-keyword=Lower oesophagectomy kn-keyword=Lower oesophagectomy END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=28 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgataTakeshi en-aut-sei=Ogata en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakiTakahiro en-aut-sei=Waki en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AdachiTakuya en-aut-sei=Adachi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=3 en-affil=Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Ocular surface kn-keyword=Ocular surface en-keyword=Conjunctiva kn-keyword=Conjunctiva en-keyword=Malignant melanoma kn-keyword=Malignant melanoma en-keyword=Proton beam therapy kn-keyword=Proton beam therapy en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=PD-1 inhibitor kn-keyword=PD-1 inhibitor en-keyword=Immune checkpoint inhibitor kn-keyword=Immune checkpoint inhibitor END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=4089 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] >= 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy. en-copyright= kn-copyright= en-aut-name=TaokaMasataka en-aut-sei=Taoka en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YokoyamaToshihide en-aut-sei=Yokoyama en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueKoji en-aut-sei=Inoue en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTomoki en-aut-sei=Tamura en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoAkiko en-aut-sei=Sato en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraKayo en-aut-sei=Nakamura en-aut-mei=Kayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawaiHaruyuki en-aut-sei=Kawai en-aut-mei=Haruyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=InoueMasaaki en-aut-sei=Inoue en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiNobuaki en-aut-sei=Ochi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujimotoNobukazu en-aut-sei=Fujimoto en-aut-mei=Nobukazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IchikawaHirohisa en-aut-sei=Ichikawa en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OzeIsao en-aut-sei=Oze en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center kn-affil= affil-num=6 en-affil=Department of Internal Medicine, National Hospital Organization Okayama Medical Center kn-affil= affil-num=7 en-affil=Department of Respiratory Medicine, Fukuyama City Hospital kn-affil= affil-num=8 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=9 en-affil=Department of Respiratory Medicine, Japanese Red Cross Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=11 en-affil=Department of Chest Surgery, Shimonoseki City Hospital kn-affil= affil-num=12 en-affil=Department of General Internal Medicine 4 , Kawasaki Medical School kn-affil= affil-num=13 en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital kn-affil= affil-num=14 en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital kn-affil= affil-num=15 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=16 en-affil=Division of Cancer Information and Control, Aichi Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=non-small cell lung cancer kn-keyword=non-small cell lung cancer en-keyword=body weight loss kn-keyword=body weight loss en-keyword=immune checkpoint inhibitors kn-keyword=immune checkpoint inhibitors en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue= article-no= start-page=3215 end-page=3220 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina en-subtitle= kn-subtitle= en-abstract= kn-abstract=A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR and ECD data with those of the known psammaplysin derivative, psammaplysin F (2). Ceratinadin G (1) is a rare nitrile containing a cyano group as aminoacetonitrile, and is the first psammaplysin derivative possessing a cyano group. In vitro assays indicated that compound 1 displayed moderate cytotoxicity against L1210 murine leukemia cells and KB epidermoid carcinoma cells. en-copyright= kn-copyright= en-aut-name=KurimotoShin-Ichiro en-aut-sei=Kurimoto en-aut-mei=Shin-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueKouta en-aut-sei=Inoue en-aut-mei=Kouta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhnoTaito en-aut-sei=Ohno en-aut-mei=Taito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTakaaki en-aut-sei=Kubota en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Showa Pharmaceutical University kn-affil= affil-num=3 en-affil=Showa Pharmaceutical University kn-affil= affil-num=4 en-affil=Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=ceratinadin kn-keyword=ceratinadin en-keyword=cytotoxicity kn-keyword=cytotoxicity en-keyword=marine sponge kn-keyword=marine sponge en-keyword=psammaplysin kn-keyword=psammaplysin en-keyword=Pseudoceratina sp kn-keyword=Pseudoceratina sp END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=469 end-page=474 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion. en-copyright= kn-copyright= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NagaseTakayuki en-aut-sei=Nagase en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasadaSusumu en-aut-sei=Sasada en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyakeHayato en-aut-sei=Miyake en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaharaChiaki en-aut-sei=Sugahara en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHidetaka en-aut-sei=Yamamoto en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaYoshinao en-aut-sei=Oda en-aut-mei=Yoshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaShota en-aut-sei=Tanaka en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=tenosynovial giant cell tumor kn-keyword=tenosynovial giant cell tumor en-keyword=bone tumor kn-keyword=bone tumor en-keyword=spine kn-keyword=spine END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=29419 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ADAR1 could be a potential diagnostic target for intrauterine infection patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intrauterine infection (IUI) is mainly an ascending infection in which vaginal and cervical pathogens ascend to the uterus and can affect the fetus. Until now, there is still no effective diagnostic biomarker for IUI, such as chorioamnionitis (CAM) and funisitis (FUN). Deoxyribonucleic acid (DNA)/Ribonucleic acid (RNA) editing molecules such as apolipoprotein-B mRNA-editing complex (APOBEC) 3 families and Adenosine deaminase family acting on RNA (ADAR)1 were examined in chorioamniotic membranes and umbilical cord of 83 patient samples. Furthermore, Ureaplasma parvum induced ADAR1 was investigated in human HTR-8/SVneo EVT cell line. ADAR1 had a significantly higher area under the curve (AUC) (0.721 and 0.745) than other APOBEC3s or cytokines in CAM and FUN patients. In vitro, ureaplasma parvum was demonstrated to activate ADAR1 (p = 0.025) and reduce RIG-I, IRF3, IFN-α, and IFN-β expression in EVT cell line (p = 0.005, p = 0.010, p < 0.001, and p = 0.018, respectively). High expression of ADAR1 was strongly associated with CAM and FUN patients (multivariate analyses; p = 0.035 and p = 0.002). ADAR1 could be a potential diagnostic target for IUI, such as CAM and FUN patients. en-copyright= kn-copyright= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VuThuy Ha en-aut-sei=Vu en-aut-mei=Thuy Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MakiJota en-aut-sei=Maki en-aut-mei=Jota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=ADAR1 kn-keyword=ADAR1 en-keyword=Chorioamnionitis kn-keyword=Chorioamnionitis en-keyword=Funisitis kn-keyword=Funisitis en-keyword=Intrauterine infection kn-keyword=Intrauterine infection en-keyword=Diagnostic biomarker kn-keyword=Diagnostic biomarker END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=465 end-page=468 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Secondary Polymyalgia Rheumatica Following SARS-CoV-2 Infection en-subtitle= kn-subtitle= en-abstract= kn-abstract=An 81-year-old Japanese man with a medical history of diabetes mellitus and hypertension was diagnosed with the novel coronavirus disease 2019 (COVID-19). The patient developed pain in the bilateral shoulders and hips 3 days after the disease onset and presented to our outpatient clinic after 1 month. Referring to diagnostic criteria, we diagnosed him with polymyalgia rheumatica (PMR). We initiated prednisolone at 15 mg per day and his symptoms improved immediately. The clinical course of the patient indicated that the SARS-CoV-2 infection triggered the onset of autoimmune disease, PMR in this case. en-copyright= kn-copyright= en-aut-name=OchoKazuki en-aut-sei=Ocho en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IshikawaHisashi en-aut-sei=Ishikawa en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Ishikawa Hospital kn-affil= affil-num=2 en-affil=Department of Infectious Diseases, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Ishikawa Hospital kn-affil= affil-num=4 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=COVID-19 kn-keyword=COVID-19 en-keyword=SARS-CoV-2 kn-keyword=SARS-CoV-2 en-keyword=polymyalgia rheumatica kn-keyword=polymyalgia rheumatica en-keyword=autoimmune diseases kn-keyword=autoimmune diseases en-keyword=human leukocyte antigen kn-keyword=human leukocyte antigen END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=439 end-page=447 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Risk Factors for Gangrenous Cholecystitis and the Outcomes of Early Cholecystectomy: A Retrospective Study of a Single-Center City General Hospital en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gangrenous cholecystitis (GC) is classified as moderate acute cholecystitis according to the Tokyo Guidelines from 2018 (TG18). We evaluated the risk factors for GC and the outcomes of early cholecystectomy. A total of 136 patients who underwent emergency cholecystectomy for acute cholecystitis were retrospectively analyzed; 58 of these patients (42.6%) were diagnosed with GC (GC group) based on our retrospective pathologic diagnosis. We comparatively evaluated the patient backgrounds and surgical outcomes between the GC group and non-GC group. The GC group was significantly older and included more hypertensive patients than the non-GC group. The GC group was prescribed more antibiotics as initial treatment than the non-GC group, and they had more days between onset and surgery. The preoperative white blood cell count and C-reactive protein values were significantly higher in the GC group than in the non-GC group, and these values were predictive factors for GC. Cholecystectomy required a longer operation time and caused greater blood loss in the GC group. The GC group also had longer hospitalization times than the non-GC group; however, no significant differences were observed in terms of postoperative complications. In conclusion, gangrenous changes should be assessed when diagnosing cholecystitis, and appropriate treatment, such as surgery or drainage, should be undertaken. en-copyright= kn-copyright= en-aut-name=YamashitaMampei en-aut-sei=Yamashita en-aut-mei=Mampei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumidaYorihisa en-aut-sei=Sumida en-aut-mei=Yorihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamazakiShoto en-aut-sei=Yamazaki en-aut-mei=Shoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraYuki en-aut-sei=Hara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukudaAkiko en-aut-sei=Fukuda en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisanagaMakoto en-aut-sei=Hisanaga en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WakataKoki en-aut-sei=Wakata en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiMasato en-aut-sei=Araki en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EguchiSusumu en-aut-sei=Eguchi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=2 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=4 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=5 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=6 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=9 en-affil=Department of Surgery, Sasebo City General Hospital kn-affil= affil-num=10 en-affil=Department of Surgery, Nagasaki University Graduate School of Biomedical Science kn-affil= en-keyword=gangrenous kn-keyword=gangrenous en-keyword=cholecystitis kn-keyword=cholecystitis en-keyword=acute cholecystitis kn-keyword=acute cholecystitis en-keyword=laparoscopic cholecystectomy kn-keyword=laparoscopic cholecystectomy END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=6 article-no= start-page=429 end-page=437 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Partial versus Radical Nephrectomy for Small Renal Cancer: Comparative Propensity Score-Matching Analysis of Cardiovascular Event Risk en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although partial nephrectomy (PN) is preferred over radical nephrectomy (RN) for preserving renal function in patients with cT1 renal cancer, its impact on cardiovascular events (CVe) remains controversial. This study aimed to compare PN and RN in regard to the occurrence of CVe, including cerebrovascular events and exacerbation of hypertension (HT). We retrospectively analyzed 418 consecutive patients who underwent PN or RN for cT1 renal cancer. Propensity score-matching analysis was used to adjust for imbalances between patients who underwent PN and RN, leaving 102 patients in each group. The 5-year probability of cumulative CVe incidence was 6% in the PN group and 12% in the RN group (p=0.03), with a median follow-up of 73.5 months. The statistical significance was retained after propensity score matching for patients without preoperative proteinuria (p=0.03). For all CVe including cerebrovascular events and exacerbation of HT analyzed, PN provided a lower probability of occurrence than RN in patients with small renal cancers. en-copyright= kn-copyright= en-aut-name=KubotaRisa en-aut-sei=Kubota en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatayamaSatoshi en-aut-sei=Katayama en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwataTakehiro en-aut-sei=Iwata en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishimuraShingo en-aut-sei=Nishimura en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EdamuraKohei en-aut-sei=Edamura en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiMotoo en-aut-sei=Araki en-aut-mei=Motoo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=chronic kidney disease kn-keyword=chronic kidney disease en-keyword=hypertension kn-keyword=hypertension en-keyword=nephrectomy kn-keyword=nephrectomy en-keyword=proteinuria kn-keyword=proteinuria END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=2 article-no= start-page=292 end-page=305 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241128 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The role of C1orf50 in breast cancer progression and prognosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50’s involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer. en-copyright= kn-copyright= en-aut-name=OtaniYusuke en-aut-sei=Otani en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAtsushi en-aut-sei=Tanaka en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaekawaMasaki en-aut-sei=Maekawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PeñaTirso en-aut-sei=Peña en-aut-mei=Tirso kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=RogachevskayaAnna en-aut-sei=Rogachevskaya en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoTeruhiko en-aut-sei=Ando en-aut-mei=Teruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ItanoTakuto en-aut-sei=Itano en-aut-mei=Takuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatayamaHaruyoshi en-aut-sei=Katayama en-aut-mei=Haruyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakataEiji en-aut-sei=Nakata en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=DoiharaHiroyoshi en-aut-sei=Doihara en-aut-mei=Hiroyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=RoehrlMichael H. en-aut-sei=Roehrl en-aut-mei=Michael H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=2 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=3 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=4 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=5 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=6 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of General Surgery, Kawasaki Medical School General Medical Center kn-affil= affil-num=13 en-affil=Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School kn-affil= affil-num=14 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=C1orf50 kn-keyword=C1orf50 en-keyword=Luminal A breast cancer kn-keyword=Luminal A breast cancer en-keyword=Cell cycle kn-keyword=Cell cycle en-keyword=Immune evasion kn-keyword=Immune evasion en-keyword=YAP/TAZ kn-keyword=YAP/TAZ END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=60 end-page=63 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful immunotherapy with ipilimumab and nivolumab in a patient with pulmonary sclerosing pneumocytoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary sclerosing pneumocytoma (PSP) is a rare form of lung cancer that occasionally presents with lymph node and extrapulmonary metastases, and multiple lesions. The treatment of metastatic PSP remains undefined. This study reports the case of a 48-year-old female patient diagnosed with PSP following surgical intervention for a solitary nodule in the left lower lobe. Four years later, recurrence occurred in the left hilar and mediastinal lymph nodes, necessitating an additional resection. Concurrently, sacral metastases developed and required palliative radiotherapy. Genetic analysis identified an AKT1 E17K mutation, characteristic of PSP, and absence of programmed cell death ligand 1 (PD-L1) expression in the tumor. Two years post-recurrence, the tumor recurred in the left mammary gland and mediastinal lymph nodes. Combination immunotherapy with ipilimumab and nivolumab yielded a significantly positive response in this metastatic PSP case. This is the first reported case of successful treatment of multiple distant metastatic PSP with ipilimumab and nivolumab, following the failure of various local treatments. Further case series are warranted to validate the efficacy of immunotherapy in metastatic PSP. en-copyright= kn-copyright= en-aut-name=Inukai-MotokuraYumi en-aut-sei=Inukai-Motokura en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BabaTakahiro en-aut-sei=Baba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoriHiroki en-aut-sei=Omori en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeguchiTetsuya en-aut-sei=Takeguchi en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UnoMari en-aut-sei=Uno en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Pulmonary sclerosing pneumocytoma kn-keyword=Pulmonary sclerosing pneumocytoma en-keyword=Ipilimumab kn-keyword=Ipilimumab en-keyword=Nivolumab kn-keyword=Nivolumab en-keyword=Programmed cell death ligand 1 kn-keyword=Programmed cell death ligand 1 en-keyword=Case report kn-keyword=Case report END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=20 article-no= start-page=e70288 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=New Anti-Angiogenic Therapy for Glioblastoma With the Anti-Depressant Sertraline en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Anti-angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti-angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti-angiogenic inhibitors and identify novel anti-angiogenic drugs with clinical applications.
Results: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model.
Conclusion: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability. en-copyright= kn-copyright= en-aut-name=TsuboiNobushige en-aut-sei=Tsuboi en-aut-mei=Nobushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UnedaAtsuhito en-aut-sei=Uneda en-aut-mei=Atsuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaJoji en-aut-sei=Ishida en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SurugaYasuki en-aut-sei=Suruga en-aut-mei=Yasuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsumotoYuji en-aut-sei=Matsumoto en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiKentaro en-aut-sei=Fujii en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KurozumiKazuhiko en-aut-sei=Kurozumi en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurosurgery, Hamamatsu University School of Medicine kn-affil= affil-num=11 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=anti-angiogenic therapy kn-keyword=anti-angiogenic therapy en-keyword=antidepressant sertraline kn-keyword=antidepressant sertraline en-keyword=drug repositioning kn-keyword=drug repositioning en-keyword=glioblastoma kn-keyword=glioblastoma en-keyword=tumor derived endothelial cells kn-keyword=tumor derived endothelial cells END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=線維化を伴う膵がん微小環境の立体培養法による新規in vitroモデルの構築と解析 kn-title=Establishment and Analysis of Novel In Vitro 3D Cell Culture Models of the Fibrotic Tumor Microenvironment in Pancreatic Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TANAKAHiroyoshi en-aut-sei=TANAKA en-aut-mei=Hiroyoshi kn-aut-name=田中啓祥 kn-aut-sei=田中 kn-aut-mei=啓祥 aut-affil-num=1 ORCID= affil-num=1 en-affil=Okayama University kn-affil=岡山大学大学院 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=がん細胞へのsiRNA送達のためのペプチドナノミセルの開発 kn-title=Development of Peptide Nanomicelle for siRNA Delivery into Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAUFIK FATWA NUR HAKIM en-aut-sei=TAUFIK FATWA NUR HAKIM en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学大学院ヘルスシステム統合科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=腫瘍ホーミングペプチド修飾磁性ナノ粒子の磁気温熱療法および腫瘍検出への応用 kn-title=Application of novel tumor-homing peptide-modified magnetic nanoparticles for magnetic hyperthermia and tumor cell detection en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ZHOUSHENGLI en-aut-sei=ZHOU en-aut-mei=SHENGLI kn-aut-name=周聖力 kn-aut-sei=周 kn-aut-mei=聖力 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil=岡山大学大学院ヘルスシステム統合科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=卵丘細胞の生存率と前培養が低品質ブタ卵母細胞におけるグルコース-6-リン酸デヒドロゲナーゼ (G6PDH) 活性、減数分裂の進行および発生能力に及ぼす影響 kn-title=The impact of cumulus cell viability and pre-culture on glucose-6-phosphate dehydrogenase (G6PDH) activity, meiotic progression, and developmental competence in suboptimal porcine oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WANNIARACHCHIGE THARINDU LAKSHITHA FONSEKA en-aut-sei=WANNIARACHCHIGE THARINDU LAKSHITHA FONSEKA en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=植物細胞における亜硫酸の毒性機構に関する研究－亜硫酸毒性への細胞質酸性化と細胞酸化の関与の評価 kn-title=A study on toxic mechanisms of SO2 in plant cells - Evaluation of the involvement of cytosolic acidification and cellular oxidation in SO2 toxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MAHDI MOZHGANI en-aut-sei=MAHDI MOZHGANI en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=高悪性度口腔扁平上皮癌において、CX3CL1はリンパ管新生を増強しリンパ節転移に寄与する kn-title=Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Htoo Shwe Eain en-aut-sei=Htoo Shwe Eain en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=一細胞解析を応用した軟骨細胞分化を制御する転写因子の遡及的な再発見法　 kn-title=Retrospective re-discovery of the transcription factor that controls chondrocyte differentiation by single cell RNA-sequencing en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DO Thuy Hang en-aut-sei=DO Thuy Hang en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=悪性末梢神経鞘腫瘍のがん幹細胞性維持に対するカテコラミン合成酵素の役割 kn-title=Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KATAYAMAHaruyoshi en-aut-sei=KATAYAMA en-aut-mei=Haruyoshi kn-aut-name=片山晴喜 kn-aut-sei=片山 kn-aut-mei=晴喜 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=PAI-1は非小細胞肺がんにおけるMET標的治療の獲得耐性に関与する kn-title=PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YIN MIN THU en-aut-sei=YIN MIN THU en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=角化の調節因子の探索： 口腔粘膜におけるBMP-2の役割 kn-title=Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MUXINDI en-aut-sei=MU en-aut-mei=XINDI kn-aut-name=穆欣迪 kn-aut-sei=穆 kn-aut-mei=欣迪 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Lysyl oxidase-like 4は、細胞表面にAnnexin A2/S100A11複合体形成を促進することで、トリプルネガティブ乳がん細胞の浸潤能を促進する kn-title=Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKAHASHITetta en-aut-sei=TAKAHASHI en-aut-mei=Tetta kn-aut-name=髙橋徹多 kn-aut-sei=髙橋 kn-aut-mei=徹多 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=非小細胞肺癌における腫瘍免疫状態の指標としての好中球リンパ球比の有用性 kn-title=Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IWATAKazuma en-aut-sei=IWATA en-aut-mei=Kazuma kn-aut-name=岩田一馬 kn-aut-sei=岩田 kn-aut-mei=一馬 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=SPRED2は、肝細胞癌細胞および正常肝細胞におけるオートファジーの新しい調節因子です kn-title=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WANGTIANYI en-aut-sei=WANG en-aut-mei=TIANYI kn-aut-name=王天禕 kn-aut-sei=王 kn-aut-mei=天禕 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=LOXL4によるトリプルネガティブ乳がん細胞浸潤亢進のシグナル伝達機構の解明 kn-title=Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=JIANGFAN en-aut-sei=JIANG en-aut-mei=FAN kn-aut-name=江帆 kn-aut-sei=江 kn-aut-mei=帆 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=T細胞腫瘍におけるα-ピネンの抗腫瘍活性 kn-title=Antitumor activity of α-pinene in T-cell tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ABEMasaya en-aut-sei=ABE en-aut-mei=Masaya kn-aut-name=阿部将也 kn-aut-sei=阿部 kn-aut-mei=将也 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=老化線維芽細胞はIL-8のクロストークを介し、びまん性胃癌細胞の腹膜転移を促進する kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIYUNCHENG en-aut-sei=LI en-aut-mei=YUNCHENG kn-aut-name=李云成 kn-aut-sei=李 kn-aut-mei=云成 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=4D-CT Angiographyによる腎細胞癌の栄養動脈の描出率 kn-title=Depiction rate of feeding arteries of renal cell carcinoma on four‑dimensional computed tomography angiography en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MUNETOMOKazuaki en-aut-sei=MUNETOMO en-aut-mei=Kazuaki kn-aut-name=宗友一晃 kn-aut-sei=宗友 kn-aut-mei=一晃 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=血中循環遊離DNAのメチル化パターンは、原発巣遺伝子変異プロファイルによらず、大腸癌の治療効果モニタリングを可能とする非侵襲的なバイオマーカーである kn-title=Circulating cell‑free DNA methylation patterns as non‑invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YASUIKazuya en-aut-sei=YASUI en-aut-mei=Kazuya kn-aut-name=安井和也 kn-aut-sei=安井 kn-aut-mei=和也 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=22 article-no= start-page=11942 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, the societal burden of OA is increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in the pathogenesis of OA. Recent studies suggest that crosstalk between cartilage and synovium contributes to OA development, but the mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation and confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We demonstrated that EVs were taken up by human synoviocytes and chondrocytes in vitro, while in vivo experiments revealed that fluorescent-labelled EVs injected into mouse joints were incorporated into chondrocytes and synoviocytes. EV uptake was significantly inhibited by dynamin-mediated endocytosis inhibitors, indicating that endocytosis plays a major role in this process. Additionally, co-culture experiments with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 and the chondrocytic cell line OUMS-27 confirmed the transfer of RFP-positive EVs across a 600-nm but not a 30-nm filter. These findings suggest that EVs from chondrocytes are released into joint fluid and taken up by cells within the cartilage, potentially facilitating communication between cartilage and synovium. The results underscore the importance of EVs in OA pathophysiology. en-copyright= kn-copyright= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SatoIkumi en-aut-sei=Sato en-aut-mei=Ikumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakashitaRen en-aut-sei=Takashita en-aut-mei=Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KodamaShintaro en-aut-sei=Kodama en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkemuraKentaro en-aut-sei=Ikemura en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OpokuGabriel en-aut-sei=Opoku en-aut-mei=Gabriel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WatanabeShogo en-aut-sei=Watanabe en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoMitsuru en-aut-sei=Ando en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AkiyoshiKazunari en-aut-sei=Akiyoshi en-aut-mei=Kazunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Neuroscience, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Laboratory of Biomaterials, Institute for Life and Medical Sciences, Kyoto University kn-affil= affil-num=11 en-affil=Department of Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=12 en-affil=Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= en-keyword=extracellular vesicles (EVs) kn-keyword=extracellular vesicles (EVs) en-keyword=chondrocytes kn-keyword=chondrocytes en-keyword=synoviocytes kn-keyword=synoviocytes en-keyword=osteoarthritis (OA) kn-keyword=osteoarthritis (OA) END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=22 article-no= start-page=12063 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient Production of Chondrocyte Particles from Human iPSC-Derived Chondroprogenitors Using a Plate-Based Cell Self-Aggregation Technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=The limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT (R)), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects. en-copyright= kn-copyright= en-aut-name=HanakiShojiro en-aut-sei=Hanaki en-aut-mei=Shojiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwaiRyosuke en-aut-sei=Iwai en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Institute of Frontier Science and Technology, Okayama University of Science kn-affil= affil-num=5 en-affil=Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=tissue engineering kn-keyword=tissue engineering en-keyword=chondrocyte particles kn-keyword=chondrocyte particles en-keyword=cartilaginous particles kn-keyword=cartilaginous particles en-keyword=ExpLBM kn-keyword=ExpLBM en-keyword=hiPSC kn-keyword=hiPSC en-keyword=chondrocyte kn-keyword=chondrocyte END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=35 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of the Follow-Up Human 3D Oral Cancer Model in Cancer Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=As function preservation cancer therapy, targeted radiation therapies have been developed for the quality of life of cancer patients. However, preclinical animal studies evaluating the safety and efficacy of targeted radiation therapy is challenging from the viewpoints of animal welfare and animal protection, as well as the management of animal in radiation-controlled areas under the regulations. We fabricated the human 3D oral cancer model that considers the time axis of the follow up in cancer treatment. Therefore, in this study, the 3D model with human oral cancer cells and normal oral fibroblasts was treated based on clinical protocol. After cancer treatment, the histological findings of the 3D oral cancer model indicated the clinical correlation between tumor response and surrounding normal tissue. This 3D model has potential as a tool for preclinical studies alternative to animal studies. en-copyright= kn-copyright= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=2 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= en-keyword=3D cancer model kn-keyword=3D cancer model en-keyword=preclinical study kn-keyword=preclinical study en-keyword=cancer treatment kn-keyword=cancer treatment en-keyword=quality of life kn-keyword=quality of life en-keyword=multidisciplinary treatment kn-keyword=multidisciplinary treatment END start-ver=1.4 cd-journal=joma no-vol=193 cd-vols= no-issue=3 article-no= start-page=2122 end-page=2140 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230720 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calredoxin regulates the chloroplast NADPH-dependent thioredoxin reductase in Chlamydomonas reinhardtii en-subtitle= kn-subtitle= en-abstract= kn-abstract=Calredoxin (CRX) is a calcium (Ca2+)-dependent thioredoxin (TRX) in the chloroplast of Chlamydomonas (Chlamydomonas reinhardtii) with a largely unclear physiological role. We elucidated the CRX functionality by performing in-depth quantitative proteomics of wild-type cells compared with a crx insertional mutant (IMcrx), two CRISPR/Cas9 KO mutants, and CRX rescues. These analyses revealed that the chloroplast NADPH-dependent TRX reductase (NTRC) is co-regulated with CRX. Electron transfer measurements revealed that CRX inhibits NADPH-dependent reduction of oxidized chloroplast 2-Cys peroxiredoxin (PRX1) via NTRC and that the function of the NADPH-NTRC complex is under strict control of CRX. Via non-reducing SDS-PAGE assays and mass spectrometry, our data also demonstrated that PRX1 is more oxidized under high light (HL) conditions in the absence of CRX. The redox tuning of PRX1 and control of the NADPH-NTRC complex via CRX interconnect redox control with active photosynthetic electron transport and metabolism, as well as Ca2+ signaling. In this way, an economic use of NADPH for PRX1 reduction is ensured. The finding that the absence of CRX under HL conditions severely inhibited light-driven CO2 fixation underpins the importance of CRX for redox tuning, as well as for efficient photosynthesis. en-copyright= kn-copyright= en-aut-name=ZinziusKaren en-aut-sei=Zinzius en-aut-mei=Karen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MarchettiGiulia Maria en-aut-sei=Marchetti en-aut-mei=Giulia Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FischerRonja en-aut-sei=Fischer en-aut-mei=Ronja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MilradYuval en-aut-sei=Milrad en-aut-mei=Yuval kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OltmannsAnne en-aut-sei=Oltmanns en-aut-mei=Anne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KelterbornSimon en-aut-sei=Kelterborn en-aut-mei=Simon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YacobyIftach en-aut-sei=Yacoby en-aut-mei=Iftach kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HegemannPeter en-aut-sei=Hegemann en-aut-mei=Peter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ScholzMartin en-aut-sei=Scholz en-aut-mei=Martin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HipplerMichael en-aut-sei=Hippler en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=2 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=3 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=4 en-affil=School of Plant Sciences and Food Security, The George S. Wise Faculty of Life Sciences, Tel Aviv University kn-affil= affil-num=5 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=6 en-affil=Institute of Biology, Experimental Biophysics, Humboldt University of Berlin kn-affil= affil-num=7 en-affil=School of Plant Sciences and Food Security, The George S. Wise Faculty of Life Sciences, Tel Aviv University kn-affil= affil-num=8 en-affil=Institute of Biology, Experimental Biophysics, Humboldt University of Berlin kn-affil= affil-num=9 en-affil=Institute of Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=10 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=22 article-no= start-page=e038137 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Cardiosphere‐derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time‐to‐event outcomes at 8 years.
Methods and Results: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time‐dependent CDC treatment effects on death and late complications during 8 years of follow‐up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC‐treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21–1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01–0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05–3.12]; P=0.043). Compared with control participants, CDC‐treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21–0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27–0.94]; P=0.036) at 8 years.
Conclusions: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years.
Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750. en-copyright= kn-copyright= en-aut-name=HiraiKenta en-aut-sei=Hirai en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawadaRyusuke en-aut-sei=Sawada en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashiTomohiro en-aut-sei=Hayashi en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArakiToru en-aut-sei=Araki en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakagawaNaomi en-aut-sei=Nakagawa en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoMaiko en-aut-sei=Kondo en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaKenji en-aut-sei=Yasuda en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirataTakuya en-aut-sei=Hirata en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoTomoyuki en-aut-sei=Sato en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakatsukaYuki en-aut-sei=Nakatsuka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaMichihiro en-aut-sei=Yoshida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=BabaKenji en-aut-sei=Baba en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhHidemasa en-aut-sei=Oh en-aut-mei=Hidemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=the TICAP/PERSEUS Study Group en-aut-sei=the TICAP/PERSEUS Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics Kurashiki Central Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=5 en-affil=Department of Pediatric Cardiology Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatrics Shimane University Faculty of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics Jichi Medical University kn-affil= affil-num=10 en-affil=Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Regenerative Medicine, Center for Innovative Clinical Medicine Okayama University Hospital kn-affil= affil-num=15 en-affil= kn-affil= en-keyword=cardiosphere kn-keyword=cardiosphere en-keyword=heart failure kn-keyword=heart failure en-keyword=restricted mean survival time kn-keyword=restricted mean survival time en-keyword=single ventricle kn-keyword=single ventricle en-keyword=survival kn-keyword=survival END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=198 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross-sectional study from lupus registry of nationwide institutions (LUNA) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis.
Methods This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage.
Results Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 <= PSL < 7.5 mg, 5.2 for 7.5 <= PSL < 10 mg, 9.0 for 10 <= PSL < 20 mg, and 43.1 for PSL >= 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis.
Conclusion This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use. en-copyright= kn-copyright= en-aut-name=OnishiTakahisa en-aut-sei=Onishi en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashiKeigo en-aut-sei=Hayashi en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshimiRyusuke en-aut-sei=Yoshimi en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimojimaYasuhiro en-aut-sei=Shimojima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhnoShigeru en-aut-sei=Ohno en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KajiyamaHiroshi en-aut-sei=Kajiyama en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchinoseKunihiro en-aut-sei=Ichinose en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoShuzo en-aut-sei=Sato en-aut-mei=Shuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraMichio en-aut-sei=Fujiwara en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KidaTakashi en-aut-sei=Kida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsuoYusuke en-aut-sei=Matsuo en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NishimuraKeisuke en-aut-sei=Nishimura en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YamaneTakashi en-aut-sei=Yamane en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Rheumatology, Kakogawa Central City Hospital kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine kn-affil= affil-num=7 en-affil=Center for Rheumatic Diseases, Yokohama City University Medical Center kn-affil= affil-num=8 en-affil=Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University kn-affil= affil-num=9 en-affil=Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=10 en-affil=Department of Rheumatology, Fukushima Medical University School of Medicine kn-affil= affil-num=11 en-affil=Department of Rheumatology, Yokohama Rosai Hospital kn-affil= affil-num=12 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=13 en-affil=Infammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=14 en-affil=Department of Rheumatology, Tokyo Kyosai Hospital kn-affil= affil-num=15 en-affil=Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Rheumatology, Kakogawa Central City Hospital kn-affil= en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Pneumocystis jirovecii pneumonia kn-keyword=Pneumocystis jirovecii pneumonia en-keyword=Glucocorticoid kn-keyword=Glucocorticoid en-keyword=Immunosuppressant kn-keyword=Immunosuppressant en-keyword=Practice pattern kn-keyword=Practice pattern END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=21 article-no= start-page=11592 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact. en-copyright= kn-copyright= en-aut-name=TsuchidaTomoki en-aut-sei=Tsuchida en-aut-mei=Tomoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KamiuezonoShizuki en-aut-sei=Kamiuezono en-aut-mei=Shizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoAkihiro en-aut-sei=Ito en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KumagaiYoshito en-aut-sei=Kumagai en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=School of Life Sciences, Tokyo University of Pharmacy and Life Sciences kn-affil= affil-num=6 en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=DNA methyltransferase kn-keyword=DNA methyltransferase en-keyword=chemical modification kn-keyword=chemical modification en-keyword=chemokine kn-keyword=chemokine en-keyword=cell proliferation kn-keyword=cell proliferation en-keyword=toxicology kn-keyword=toxicology en-keyword=exposome kn-keyword=exposome en-keyword=environmental electrophiles kn-keyword=environmental electrophiles END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=1 article-no= start-page=195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Association between discontinuity of care and patient trust in the usual rheumatologist among patients with systemic lupus erythematosus: a cross-sectional study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Patient trust plays a central role in the patient-physician relationship. This study aimed to determine whether the number of outpatient visits with a covering rheumatologist is associated with patient trust in their usual rheumatologist.
Methods Japanese adults with systemic lupus erythematosus (SLE) who met the 1997 revised classification criteria of the American College of Rheumatology and had outpatient visits with a covering rheumatologist in the past year were included.
We used the 11-item Japanese version of the modified Trust in Physician Scale (range 0–100) to assess patient trust. A general linear model with cluster-robust variance estimation was used to evaluate the association between the number of outpatient visits with covering rheumatologists and the patient’s trust in their usual rheumatologist.
Results Of the 515 enrolled participants, 421 patients with SLE were included in our analyses. Patients were divided into groups according to the number of outpatient visits with a covering rheumatologist in the past year as follows: no visits (59.9%; reference group), one to three visits (24.2%; low-frequency group), and four or more visits (15.9%; high-frequency group). The median Trust in Physician Scale score was 81.8 (interquartile range: 72.7–93.2). Both the low-frequency group (mean difference: -3.03; 95% confidence interval [CI] -5.93 to -0.80) and high-frequency group (mean difference: -4.17; 95% CI -7.77 to -0.58) exhibited lower trust in their usual rheumatologist.
Conclusion This study revealed that the number of outpatient visits with a covering rheumatologist was associated with lower trust in a patient’s usual rheumatologist. en-copyright= kn-copyright= en-aut-name=KatayamaYu en-aut-sei=Katayama en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyawakiYoshia en-aut-sei=Miyawaki en-aut-mei=Yoshia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShidaharaKenta en-aut-sei=Shidahara en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NawachiShoichi en-aut-sei=Nawachi en-aut-mei=Shoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsanoYosuke en-aut-sei=Asano en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatsuyamaEri en-aut-sei=Katsuyama en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KatsuyamaTakayuki en-aut-sei=Katsuyama en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Takano-NarazakiMariko en-aut-sei=Takano-Narazaki en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OguroNao en-aut-sei=Oguro en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IshikawaYuichi en-aut-sei=Ishikawa en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SakuraiNatsuki en-aut-sei=Sakurai en-aut-mei=Natsuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HidekawaChiharu en-aut-sei=Hidekawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YoshimiRyusuke en-aut-sei=Yoshimi en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhnoShigeru en-aut-sei=Ohno en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=IchikawaTakanori en-aut-sei=Ichikawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KishidaDai en-aut-sei=Kishida en-aut-mei=Dai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=ShimojimaYasuhiro en-aut-sei=Shimojima en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SadaKen-Ei en-aut-sei=Sada en-aut-mei=Ken-Ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ThomDavid H. en-aut-sei=Thom en-aut-mei=David H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KuritaNoriaki en-aut-sei=Kurita en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=11 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=12 en-affil=The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health kn-affil= affil-num=13 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Centre for Rheumatic Disease, Yokohama City University Medical Centre kn-affil= affil-num=17 en-affil=Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University kn-affil= affil-num=18 en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine kn-affil= affil-num=19 en-affil=Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine kn-affil= affil-num=20 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Medicine, Stanford University School of Medicine kn-affil= affil-num=23 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Patient-physician relationship kn-keyword=Patient-physician relationship en-keyword=Outpatient visits kn-keyword=Outpatient visits en-keyword=Patient trust kn-keyword=Patient trust en-keyword=Discontinuity of care kn-keyword=Discontinuity of care END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=12 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241105 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect. en-copyright= kn-copyright= en-aut-name=OhtaniTomoko en-aut-sei=Ohtani en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumonKento en-aut-sei=Kumon en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HashimotoMasashi en-aut-sei=Hashimoto en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YagiChiaki en-aut-sei=Yagi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugimotoRyoma en-aut-sei=Sugimoto en-aut-mei=Ryoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TazawaHiroshi en-aut-sei=Tazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Oncolys BioPharma, Inc kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Oncolytic adenovirus kn-keyword=Oncolytic adenovirus en-keyword=p53 kn-keyword=p53 en-keyword=Dendritic cells kn-keyword=Dendritic cells en-keyword=Anti-tumor immunity kn-keyword=Anti-tumor immunity en-keyword=Exosome kn-keyword=Exosome END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue= article-no= start-page=foae032 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241018 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improving the Z3EV promoter system to create the strongest yeast promoter en-subtitle= kn-subtitle= en-abstract= kn-abstract=Promoters for artificial control of gene expression are central tools in genetic engineering. In the budding yeast Saccharomyces cerevisiae, a variety of constitutive and controllable promoters with different strengths have been constructed using endogenous gene promoters, synthetic transcription factors and their binding sequences, and artificial sequences. However, there have been no attempts to construct the highest strength promoter in yeast cells. In this study, by incrementally increasing the binding sequences of the synthetic transcription factor Z3EV, we were able to construct a promoter (P36) with ~1.4 times the strength of the TDH3 promoter. This is stronger than any previously reported promoter. Although the P36 promoter exhibits some leakage in the absence of induction, the expression induction by estradiol is maintained. When combined with a multicopy plasmid, it can express up to ~50% of total protein as a heterologous protein. This promoter system can be used to gain knowledge about the cell physiology resulting from the ultimate overexpression of excess proteins and is expected to be a useful tool for heterologous protein expression in yeast. en-copyright= kn-copyright= en-aut-name=HiguchiRina en-aut-sei=Higuchi en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujitaYuri en-aut-sei=Fujita en-aut-mei=Yuri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NambaShotaro en-aut-sei=Namba en-aut-mei=Shotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=yeast kn-keyword=yeast en-keyword=overexpression kn-keyword=overexpression en-keyword=promoter kn-keyword=promoter END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=11 article-no= start-page=e73775 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241115 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Axillary Reactive Lymphoid Hyperplasia, Likely Due to Unicentric Castleman Disease, and the Concurrent Presence of Orbital Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma: A Six-Year Follow-Up Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Castleman disease is a lymphadenopathy of unknown cause at a single site, which is designated as unicentric Castleman disease, or at multiple sites designated as multicentric Castleman disease. We present a patient who showed axillary reactive lymphoid hyperplasia, likely due to unicentric Castleman disease, and orbital extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma in a six-year follow-up. A 76-year-old man had a painless left axillary mass for an unknown period and also left complete blepharoptosis with no other systemic symptoms. Suspected of lymphoma, iliac bone marrow biopsy showed no anomalous cells, and positron emission tomography demonstrated abnormal uptake at the left axilla and in the left superior anterior orbit. Incisional biopsy of the left axillary mass demonstrated hyperplastic lymphoid follicles with an atrophic germinal center and prominent small vessels in the follicular center, indicative of unicentric Castleman disease. One year later, annual follow-up positron emission tomography disclosed a high uptake site, next to the previously-identified cyst, in the pancreatic body. Trans-gastric fine needle pancreatic biopsy proved adenocarcinoma and he underwent subtotal stomach-preserving pancreaticoduodenectomy with jejunal anastomosis. He was well for six months after the surgery and thus, underwent resection of the left orbital lesion at 78 years old. The pathology of the orbital lesion showed ambiguous nodular structure with massive infiltration with CD20-positive medium-sized lymphoid cells which were κ monotype in immunoglobulin light chain restriction, indicative of MALT lymphoma. In the four-year period of the COVID-19 pandemic, he was healthy and followed with no treatment until the age of 82 years when he underwent radiation (46 Gy) to the left axillary lesion which did not regress. He then underwent eyelid levator muscle plication for left blepharoptosis since the left orbital lesion remained unpalpable. The six-year follow-up showed that concurrent and independent orbital MALT lymphoma and axillary reactive lymphoid hyperplasia, likely due to unicentric Castleman disease, were both stable. The present case illustrates how important it is to make pathological diagnoses in different anatomical lesions after the initial diagnosis of Castleman disease. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiTomokazu en-aut-sei=Fuji en-aut-mei=Tomokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= en-keyword=blepharoptosis kn-keyword=blepharoptosis en-keyword=castleman disease kn-keyword=castleman disease en-keyword=extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue (malt) lymphoma kn-keyword=extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue (malt) lymphoma en-keyword=pancreatic cancer kn-keyword=pancreatic cancer en-keyword=radiation kn-keyword=radiation en-keyword=reactive lymphoid hyperplasia kn-keyword=reactive lymphoid hyperplasia END start-ver=1.4 cd-journal=joma no-vol=300 cd-vols= no-issue=3 article-no= start-page=105679 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202403 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K- Akt signaling by MVK reversed epidermal growth factor- induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species. en-copyright= kn-copyright= en-aut-name=MorimotoAtsushi en-aut-sei=Morimoto en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PanYuexuan en-aut-sei=Pan en-aut-mei=Yuexuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DohmaeNaoshi en-aut-sei=Dohmae en-aut-mei=Naoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbikoYumi en-aut-sei=Abiko en-aut-mei=Yumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaKoji en-aut-sei=Uchida en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KumagaiYoshito en-aut-sei=Kumagai en-aut-mei=Yoshito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=6 en-affil=Graduate School of Biomedical Science, Nagasaki University kn-affil= affil-num=7 en-affil=Laboratory of Food Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= affil-num=8 en-affil=Graduate School of Pharmaceutical Sciences, Kyushu University kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=phosphatidylinositol 3-kinase (PI 3-kinase) kn-keyword=phosphatidylinositol 3-kinase (PI 3-kinase) en-keyword=cell signaling kn-keyword=cell signaling en-keyword=chemical modification kn-keyword=chemical modification en-keyword=autophagy kn-keyword=autophagy en-keyword=glucose uptake kn-keyword=glucose uptake END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=24968 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis. en-copyright= kn-copyright= en-aut-name=VuThuy Ha en-aut-sei=Vu en-aut-mei=Thuy Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKeiichiro en-aut-sei=Nakamura en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashinoChiaki en-aut-sei=Kashino en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KuboKotaro en-aut-sei=Kubo en-aut-mei=Kotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamadaYasuhiko en-aut-sei=Kamada en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MasuyamaHisashi en-aut-sei=Masuyama en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Apolipoprotein-B mRNA-editing complex 3B kn-keyword=Apolipoprotein-B mRNA-editing complex 3B en-keyword=Endometriosis kn-keyword=Endometriosis en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Potential therapeutic target kn-keyword=Potential therapeutic target END start-ver=1.4 cd-journal=joma no-vol=99 cd-vols= no-issue=2 article-no= start-page=563 end-page=574 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241027 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methylmercury (MeHg) is an environmental neurotoxin that induces damage to the central nervous system and is the causative agent in Minamata disease. The mechanisms underlying MeHg neurotoxicity remain largely unknown, and there is a need for effective therapeutic agents, such as those that target MeHg-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which is activated as a defense mechanism. We investigated whether intraperitoneal administration of the chemical chaperone, 4-phenylbutyric acid (4-PBA), at 120 mg/kg/day can alleviate neurotoxicity in the brains of mice administered 50 ppm MeHg in drinking water for 5 weeks. 4-PBA significantly reduced MeHg-induced ER stress, neuronal apoptosis, and neurological symptoms. Furthermore, 4-PBA was effective even when administered 2 weeks after the initiation of exposure to 30 ppm MeHg in drinking water. Our results strongly indicate that ER stress and the UPR are key processes involved in MeHg toxicity, and that 4-PBA is a novel therapeutic candidate for MeHg-induced neurotoxicity. en-copyright= kn-copyright= en-aut-name=MikiRyohei en-aut-sei=Miki en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NomuraRyosuke en-aut-sei=Nomura en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IijimaYuta en-aut-sei=Iijima en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaSho en-aut-sei=Kubota en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwawakiTakao en-aut-sei=Iwawaki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujimuraMasatake en-aut-sei=Fujimura en-aut-mei=Masatake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UeharaTakashi en-aut-sei=Uehara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University kn-affil= affil-num=7 en-affil=Department of International Affairs and Research, National Institute for Minamata Disease kn-affil= affil-num=8 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Methylmercury kn-keyword=Methylmercury en-keyword=Neuronal cell death kn-keyword=Neuronal cell death en-keyword=Endoplasmic reticulum stress kn-keyword=Endoplasmic reticulum stress en-keyword=Unfolded protein response kn-keyword=Unfolded protein response END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=4 article-no= start-page=557 end-page=564 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objective Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer.
Methods This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups.
Results Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group.
Conclusions The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis. en-copyright= kn-copyright= en-aut-name=ObayashiYuka en-aut-sei=Obayashi en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirataShoichiro en-aut-sei=Hirata en-aut-mei=Shoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KonoYoshiyasu en-aut-sei=Kono en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeMakoto en-aut-sei=Abe en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaMasahiro en-aut-sei=Nakagawa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshidaMichihiro en-aut-sei=Ishida en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChodaYasuhiro en-aut-sei=Choda en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=5 en-affil=Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=6 en-affil=Department of Endoscopy, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=7 en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=8 en-affil=Department of Surgery, Hiroshima City Hiroshima Citizens Hospital kn-affil= affil-num=9 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Practical Gastrointestinal Endoscopy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=423 end-page=428 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Occult Nesidioblastosis Detected by 111In-Pentetreotide Single-Photon Emission Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia, is usually observed in children and infants, although more recently adult-onset nesidioblastosis has also been described. We present a case of nesidioblastosis in a 78-year-old man that was detected by 111In-pentetreotide single photon emission computed tomography (SPECT/CT). The patient was transferred to our hospital’s emergency department in a hypoglycemic coma. Dynamic enhanced CT could detect no lesion in the pancreas, but an 111In-pentetreotide SPECT/CT scan performed after a similar episode four weeks later showed increased focal uptake at the head of the pancreas. The results of a selective arterial calcium injection test were negative. After careful consideration and discussion among colleagues, surgical intervention was selected, and a pancreaticoduodenectomy was performed. On histology, there were elevated numbers of Langerhans islets in the pancreatic head, and the islets themselves appeared enlarged. Hypertrophic β-cells comprised the majority, but α-cells, δ-cells and pancreatic polypeptide were also detected in the islets. Based on the histopathological results and repeated hyperinsulinemic hypoglycemic crises, the patient was finally diagnosed with adult-onset nesidioblastosis. He had no hypoglycemic symptoms during outpatient follow-up examination. Since 111In-pentetreotide SPECT/CT may be able to detect nesidioblastosis, clinicians should consider this relatively new-modality examination when encountering such cases. en-copyright= kn-copyright= en-aut-name=SakamotoShinya en-aut-sei=Sakamoto en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TabuchiMotoyasu en-aut-sei=Tabuchi en-aut-mei=Motoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshimatsuRika en-aut-sei=Yoshimatsu en-aut-mei=Rika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HishidaAi en-aut-sei=Hishida en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumotoManabu en-aut-sei=Matsumoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwataJun en-aut-sei=Iwata en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkabayashiTakehiro en-aut-sei=Okabayashi en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= affil-num=2 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= affil-num=3 en-affil=Department of Radiology, Kochi Health Sciences Center kn-affil= affil-num=4 en-affil=Department of Endocrinology and Metabolism, Kochi Health Sciences Center kn-affil= affil-num=5 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=6 en-affil=Department of Diagnostic Pathology, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center kn-affil= en-keyword=111In-pentetreotide kn-keyword=111In-pentetreotide en-keyword=nesidioblastosis kn-keyword=nesidioblastosis en-keyword=single-photon emission computed tomography kn-keyword=single-photon emission computed tomography en-keyword=hyperinsulinemic hypoglycemia kn-keyword=hyperinsulinemic hypoglycemia END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=407 end-page=412 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The First Report of Bickerstaff Brainstem Encephalitis Induced by Atezolizumab for Metastatic Breast Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy. en-copyright= kn-copyright= en-aut-name=ShimoyamaKyoko en-aut-sei=Shimoyama en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaAtsushi en-aut-sei=Nakajima en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MinariYoshimitsu en-aut-sei=Minari en-aut-mei=Yoshimitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Breast Surgery, Takatsuki General Hospital kn-affil= affil-num=2 en-affil=Department of Rehabilitation, Aijinkai Rehabilitation Hospital kn-affil= affil-num=3 en-affil=Department of Breast Surgery, Takatsuki General Hospital kn-affil= en-keyword=Bickerstaff brainstem encephalitis kn-keyword=Bickerstaff brainstem encephalitis en-keyword=immune checkpoint inhibitor kn-keyword=immune checkpoint inhibitor en-keyword=atezolizumab kn-keyword=atezolizumab en-keyword=neurological immune-related adverse event kn-keyword=neurological immune-related adverse event en-keyword=breast cancer kn-keyword=breast cancer END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=5 article-no= start-page=387 end-page=399 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation. en-copyright= kn-copyright= en-aut-name=NaoeShota en-aut-sei=Naoe en-aut-mei=Shota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaAyumi en-aut-sei=Tanaka en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanzakiNorie en-aut-sei=Kanzaki en-aut-mei=Norie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakenakaReiju en-aut-sei=Takenaka en-aut-mei=Reiju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakodaAkihiro en-aut-sei=Sakoda en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamaokaKiyonori en-aut-sei=Yamaoka en-aut-mei=Kiyonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KataokaTakahiro en-aut-sei=Kataoka en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=3 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=4 en-affil=Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency kn-affil= affil-num=6 en-affil=Advanced Science Research Center, Okayama University kn-affil= affil-num=7 en-affil=Faculty of Health Sciences, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Health Sciences, Okayama University kn-affil= en-keyword=radon inhalation kn-keyword=radon inhalation en-keyword=proteomics kn-keyword=proteomics en-keyword=multivariate analysis kn-keyword=multivariate analysis en-keyword=brain kn-keyword=brain en-keyword=oxidative stress kn-keyword=oxidative stress END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=294 end-page=301 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of lymphadenectomy during primary surgery for kidney cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose of review
Lymph node dissection (LND) during radical nephrectomy (RN) for renal cell carcinoma (RCC) is not considered as a standard. The emergence of robot-assisted surgery and effective immune checkpoint inhibitors (ICI) in recent years may change this and lymph node (LN) staging has become easier and has a clinical impact. In this review, we aimed to reconsider the role of LND today.

Recent findings
Although the extent of LND has still not been well established, removal of more LN seems to provide better oncologic outcomes for a select group of patients with high-risk factors such as clinical T3-4. Adjuvant therapy using pembrolizumab has been shown to improve disease free survival if complete resection of metastatic lesions as well as the primary site is obtained in combination. Robot assisted RN for localized RCC has been widespread and the studies regarding LND for RCC has been recently appeared.

Summary
The staging and surgical benefits and its extent of LND during RN for RCC remains unclear, but it is becoming increasingly important. Technologies that allow an easier LND and adjuvant ICI that improve survival in LN-positive patients are engaging the role of LND, a procedure that was needed, but almost never done, is now indicated sometimes. Now, the goal is to identify the clinical and molecular imaging tools that can help identify with sufficient accuracy who needs a LND and which LNs to remove in a targeted personalized approach. en-copyright= kn-copyright= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Cancer Prognostic and Health Outcomes Unit, Division of Urology, University of Montreal Health Center kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=lymph node dissection kn-keyword=lymph node dissection en-keyword=lymph node metastasis kn-keyword=lymph node metastasis en-keyword=lymphadenectomy kn-keyword=lymphadenectomy en-keyword=lymphadenopathy kn-keyword=lymphadenopathy en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=229 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement.
Case representation A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital.
Conclusions Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical. en-copyright= kn-copyright= en-aut-name=MinagiHitoshi en-aut-sei=Minagi en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanayaNobuhiko en-aut-sei=Kanaya en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoYoshitaka en-aut-sei=Kondo en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KakiuchiYoshihiko en-aut-sei=Kakiuchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaShinji en-aut-sei=Kuroda en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShojiRyohei en-aut-sei=Shoji en-aut-mei=Ryohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KashimaHajime en-aut-sei=Kashima en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumiYuki en-aut-sei=Matsumi en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KagawaShunsuke en-aut-sei=Kagawa en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= en-keyword=Myeloid sarcoma kn-keyword=Myeloid sarcoma en-keyword=Chloroma kn-keyword=Chloroma en-keyword=Granulocytic sarcoma kn-keyword=Granulocytic sarcoma en-keyword=Bowel obstruction kn-keyword=Bowel obstruction en-keyword=Abdominal pain kn-keyword=Abdominal pain END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=9 article-no= start-page=1781 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel C-Terminal Truncated Bacteriocin Found by Comparison between Leuconostoc mesenteroides 406 and 213M0 Isolated from Mongolian Traditional Fermented Milk, Airag en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacteriocins produced by lactic acid bacteria are known to be useful tools for food biopreservation and fermentation control. Leuconostoc mesenteroides subsp. mesenteroides 406 and 213M0 isolated from different samples of Mongolian traditional fermented milk, airag, had been reported to produce listericidal bacteriocin-like inhibitory substances with similar but slightly different properties. In this study, the antibacterial properties and the related gene sequences of both strains were compared, and then their bacteriocins were purified and identified. Strain 406 was superior to strain 213M0 in cell growth and antibacterial activity against many strains. However, the activity of 213M0 was stronger than that of 406 against a few strains. DNA sequencing revealed two and three plasmids in 406 and 213M0, respectively, and each one of them harbored an almost identical mesentericin Y105-B105 gene cluster. Removal of these plasmids resulted in a complete loss of activity, indicating that the antibacterial activity of both strains was generated by bacteriocins encoded on the plasmids. Mesentericins Y105 and B105 were purified from both cultures, and another novel bacteriocin, named mesentericin M, was identified from the 213M0 culture only. Its structural gene was coded on a 213M0 plasmid and, surprisingly, its C-terminal three amino acid residues were post-translationally cleaved. To our knowledge, this is the first report of a C-terminal truncated bacteriocin. In conclusion, the novel bacteriocin should be mainly responsible for the difference in antibacterial properties between the two strains. en-copyright= kn-copyright= en-aut-name=HasiqimugeChihiro en-aut-sei=Hasiqimuge en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HanoChihiro en-aut-sei=Hano en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakawaKensuke en-aut-sei=Arakawa en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaSaki en-aut-sei=Yoshida en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoJunliang en-aut-sei=Zhao en-aut-mei=Junliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TohHidehiro en-aut-sei=Toh en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoritaHidetoshi en-aut-sei=Morita en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTaku en-aut-sei=Miyamoto en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Advanced Genomics Center, National Institute of Genetics kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=8 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Leuconostoc mesenteroides kn-keyword=Leuconostoc mesenteroides en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=bacteriocin kn-keyword=bacteriocin en-keyword=Listeria monocytogenes kn-keyword=Listeria monocytogenes en-keyword=fermented milk kn-keyword=fermented milk en-keyword=biopreservation kn-keyword=biopreservation en-keyword=fermentation control kn-keyword=fermentation control en-keyword=post-translational modification kn-keyword=post-translational modification en-keyword=C-terminal cleavage kn-keyword=C-terminal cleavage END