start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=16 article-no= start-page=7832 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria en-subtitle= kn-subtitle= en-abstract= kn-abstract=Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 µg/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 µg/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10× MIC, with killing rates during the first 3 h ranging from 4.04 ± 0.01 to 4.31 ± 0.03 h−1. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 µg/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 µg/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. en-copyright= kn-copyright= en-aut-name=ThonginThanyamai en-aut-sei=Thongin en-aut-mei=Thanyamai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SawatdeeSomchai en-aut-sei=Sawatdee en-aut-mei=Somchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SongnakaNuttapon en-aut-sei=Songnaka en-aut-mei=Nuttapon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UchiyamaJumpei en-aut-sei=Uchiyama en-aut-mei=Jumpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WiwasukuTheanchai en-aut-sei=Wiwasuku en-aut-mei=Theanchai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SrichanaTeerapol en-aut-sei=Srichana en-aut-mei=Teerapol kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakphengTitpawan en-aut-sei=Nakpheng en-aut-mei=Titpawan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AtipairinApichart en-aut-sei=Atipairin en-aut-mei=Apichart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=2 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=3 en-affil= School of Pharmacy, Walailak University kn-affil= affil-num=4 en-affil=Department of Bacteriology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=School of Science, Walailak University kn-affil= affil-num=6 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=7 en-affil=Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University kn-affil= affil-num=8 en-affil= School of Pharmacy, Walailak University kn-affil= en-keyword=antimicrobial peptide kn-keyword=antimicrobial peptide en-keyword=Brevibacillus sp. SPR20 kn-keyword=Brevibacillus sp. SPR20 en-keyword=silver nanoparticle kn-keyword=silver nanoparticle en-keyword=synergistic effect kn-keyword=synergistic effect END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=1554 end-page=1577 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of geostatistics, machine learning algorithms, and their hybrid approaches for modeling soil organic carbon density in tropical forests en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose Understanding the spatial variability of soil organic carbon density (SOCD) in tropical forests is necessary for efficient climate change mitigation initiatives. However, accurately modeling SOCD in these landscapes is challenging due to low-density sampling efforts and the limited availability of in-situ data caused by constrained accessibility. In this study, we aimed to explore the most suitable modeling technique for SOCD estimation in the context of tropical forest ecosystems.
Methods To support the research, thirty predictor covariates derived from remote sensing data, topographic attributes, climatic factors, and geographic positions were utilized, along with 104 soil samples collected from the top 30 cm of soil in Central Vietnamese tropical forests. We compared the effectiveness of geostatistics (ordinary kriging, universal kriging, and kriging with external drift), machine learning (ML) algorithms (random forest and boosted regression tree), and their hybrid approaches (random forest regression kriging and boosted regression tree regression kriging) for the prediction of SOCD. Prediction accuracy was evaluated using the coefficient of determination (R2), the root mean squared error (RMSE), and the mean absolute error (MAE) obtained from leave-one-out cross-validation.
Results The study results indicated that hybrid approaches performed best in predicting forest SOCD with the greatest values of R2 and the lowest values of MAE and RMSE, and the ML algorithms were more accurate than geostatistics. Additionally, the prediction maps produced by the hybridization showed the most realistic SOCD pattern, whereas the kriged maps were prone to have smoother patterns, and ML-based maps were inclined to possess more detailed patterns. The result also revealed the superiority of the ML plus residual kriging approaches over the ML models in reducing the underestimation of large SOCD values in high-altitude mountain areas and the overestimation of low SOCD values in low-lying terrain areas.
Conclusion Our findings suggest that the hybrid approaches of geostatistics and ML models are most suitable for modeling SOCD in tropical forests. en-copyright= kn-copyright= en-aut-name=HoViet Hoang en-aut-sei=Ho en-aut-mei=Viet Hoang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoritaHidenori en-aut-sei=Morita en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HoThanh Ha en-aut-sei=Ho en-aut-mei=Thanh Ha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BachoferFelix en-aut-sei=Bachofer en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NguyenThi Thuong en-aut-sei=Nguyen en-aut-mei=Thi Thuong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=University of Agriculture and Forestry, Hue University kn-affil= affil-num=4 en-affil=German Aerospace Center (DLR), Earth Observation Center kn-affil= affil-num=5 en-affil=University of Agriculture and Forestry, Hue University kn-affil= en-keyword=Digital soil mapping kn-keyword=Digital soil mapping en-keyword=Hybrid approaches kn-keyword=Hybrid approaches en-keyword=Kriging kn-keyword=Kriging en-keyword=Machine learning kn-keyword=Machine learning en-keyword=Soil organic carbon density kn-keyword=Soil organic carbon density en-keyword=Tropical forests kn-keyword=Tropical forests END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=10 article-no= start-page=1215 end-page=1227 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy. en-copyright= kn-copyright= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo 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=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SakaguchiYoshihiko en-aut-sei=Sakaguchi en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=TakahashiTetta en-aut-sei=Takahashi en-aut-mei=Tetta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=RumaI Made Winarsa en-aut-sei=Ruma en-aut-mei=I Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SumardikaI Wayan en-aut-sei=Sumardika en-aut-mei=I Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=HonjoTomoko en-aut-sei=Honjo en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SagayamaKazumi en-aut-sei=Sagayama en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 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=21 ORCID= en-aut-name=KondoEisaku en-aut-sei=Kondo en-aut-mei=Eisaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= affil-num=1 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Microbiology, Tokushima Bunri University kn-affil= affil-num=5 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=6 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine kn-affil= affil-num=15 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=16 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=17 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=18 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=19 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=20 en-affil=Organization for Research and Innovation Strategy, Okayama University kn-affil= affil-num=21 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine kn-affil= affil-num=22 en-affil=Division of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical University kn-affil= affil-num=23 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= en-keyword=Plasmid kn-keyword=Plasmid en-keyword=Gene engineering kn-keyword=Gene engineering en-keyword=Cancer kn-keyword=Cancer en-keyword=Cell culture kn-keyword=Cell culture END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=19 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250813 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology. en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YokotaOsamu en-aut-sei=Yokota en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=HaraguchiTakashi en-aut-sei=Haraguchi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nakashima-YasudaHanae en-aut-sei=Nakashima-Yasuda en-aut-mei=Hanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko 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=HasegawaMasato en-aut-sei=Hasegawa en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HosonoYasuyuki en-aut-sei=Hosono en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TeradaSeishi en-aut-sei=Terada en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 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=16 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=17 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, National Hospital Organisation Minami-Okayama Medical Centre kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Psychiatry, Zikei Hospital kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science kn-affil= affil-num=14 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Amyotrophic lateral sclerosis kn-keyword=Amyotrophic lateral sclerosis en-keyword=Heat shock protein kn-keyword=Heat shock protein en-keyword=DNAJC7 kn-keyword=DNAJC7 en-keyword=TDP-43 kn-keyword=TDP-43 en-keyword=Live-cell imaging kn-keyword=Live-cell imaging en-keyword=Zebrafish disease model kn-keyword=Zebrafish disease model END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=6 article-no= start-page=e00110-25 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=Mycobacterium tuberculosis bacillus induces pyroptosis in human lung fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=We previously reported that live, but not dead, virulent Mycobacterium tuberculosis (Mtb) H37Rv bacilli induce cell death in human lung fibroblast cell lines, MRC-5, MRC-9, and TIG-1. Here, using two distinct Mtb strains from two different lineages (HN878 lineage 2 and H37Rv lineage 4), we confirmed cell death at day 2 after infection with a device that measures cell growth/cytotoxicity in real time (Maestro-Z [AXION]). Mtb bacilli uptake by the fibroblast was confirmed with a transmission electron microscope on day 2. Expressions of inflammatory cytokines and interleukin (IL)−1β, IL-6, and IL-8 were observed when exposed to live, but not dead bacteria. The cell death of fibroblasts induced by both Mtb strains tested was prevented by caspase-1/4 and NLRP3 inflammasome inhibitors, but not by caspase-3 and caspase-9 inhibitors. Therefore, we classified the fibroblast cell death by Mtb infection as pyroptosis. To investigate the biological and pathological relevance of fibroblast cell death by Mtb infection, we performed dual RNA-Seq analysis on Mtb within fibroblasts and Mtb-infected fibroblasts at day 2. In Mtb bacilli tcrR, secE2, ahpD, and mazF8 genes were highly induced during infection. These genes play roles in survival in a hypoxic environment, production of a calcium-binding protein-inducing cytokine, and regulation of transcription in a toxin-antitoxin system. The gene expressions of IL-1β, IL-6, and IL-8, caspase-4, and NLRP3, but not of caspase-3 and caspase-9, were augmented in Mtb bacilli-infected fibroblasts. Taken together, our study suggests that Mtb bacilli attempt to survive in lung fibroblasts and that pyroptosis of the host fibroblasts activates the immune system against the infection. en-copyright= kn-copyright= en-aut-name=TakiiTakemasa en-aut-sei=Takii en-aut-mei=Takemasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamadaHiroyuki en-aut-sei=Yamada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MotozonoChihiro en-aut-sei=Motozono en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamasakiSho en-aut-sei=Yamasaki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TorrellesJordi B. en-aut-sei=Torrelles en-aut-mei=Jordi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TurnerJoanne en-aut-sei=Turner en-aut-mei=Joanne kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimishimaAoi en-aut-sei=Kimishima en-aut-mei=Aoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsamiYukihiro en-aut-sei=Asami en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OharaNaoya en-aut-sei=Ohara en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HidaShigeaki en-aut-sei=Hida en-aut-mei=Shigeaki 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=OnozakiKikuo en-aut-sei=Onozaki en-aut-mei=Kikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=2 en-affil=Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association kn-affil= affil-num=3 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=4 en-affil=Department of Molecular Immunology, Research Institute for Microbial Diseases, The University of Osaka kn-affil= affil-num=5 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) kn-affil= affil-num=6 en-affil=Texas Biomedical Research Institute and International Center for the Advancement of Research & Education (I•CARE) kn-affil= affil-num=7 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=8 en-affil=Laboratory of Applied Microbial Chemistry, Ōmura Satoshi Memorial Institute, Kitasato University kn-affil= affil-num=9 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= affil-num=12 en-affil=Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University kn-affil= en-keyword=Mycobacterium tuberculosis kn-keyword=Mycobacterium tuberculosis en-keyword=pyroptosis kn-keyword=pyroptosis en-keyword=caspase kn-keyword=caspase en-keyword=RNA-Seq kn-keyword=RNA-Seq en-keyword=cytokine kn-keyword=cytokine en-keyword=fibroblasts kn-keyword=fibroblasts END 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=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=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=15 cd-vols= no-issue=10 article-no= start-page=1444 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Canine c-kit Novel Mutation Isolated from a Gastrointestinal Stromal Tumor (GIST) Retains the Ability to Form Dimers but Lacks Autophosphorylation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that develop in the gastrointestinal tract; KIT mutations are present in both canine and human GISTs. In this study, genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 55 canine GIST cases, and mutation searches were performed for exons 8, 9, and 11. The results revealed novel mutations, A434T and F436S, in exon 8. In contrast to the A434T mutation without functional changes, the F436S mutant retained its dimerization ability, but lost its phosphorylation function and attenuated downstream Akt signaling, which is reflected in wound healing and migration activities. A comparison of the subcellular localization of WT KIT and the F436S mutant revealed no differences. In silico simulations indicated that the F436S mutation alters the structure of the near-membrane region and that its effects may extend to the transmembrane and intracellular domains compared to the WT. F436S is a point mutation that affects the entire molecule because co-mutation with the F436S mutation and the known autophosphorylation mutation reduces the autophosphorylation abilities. en-copyright= kn-copyright= en-aut-name=ShimakawaKei en-aut-sei=Shimakawa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DogeSo en-aut-sei=Doge en-aut-mei=So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MichishitaMasaki en-aut-sei=Michishita en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanabeEri en-aut-sei=Tanabe en-aut-mei=Eri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TajimaTsuyoshi en-aut-sei=Tajima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiMasato en-aut-sei=Kobayashi en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BonkobaraMakoto en-aut-sei=Bonkobara en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=OchiaiKazuhiko en-aut-sei=Ochiai en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaYoshikazu en-aut-sei=Tanaka en-aut-mei=Yoshikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=2 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=3 en-affil=Laboratory of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=4 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=5 en-affil=Laboratory of Veterinary Pharmacology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=6 en-affil=Laboratory of Veterinary Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=7 en-affil=Laboratory of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=8 en-affil=Laboratory of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= affil-num=10 en-affil=Laboratory of Veterinary Hygiene, School of Veterinary Science, Nippon Veterinary and Life Science University kn-affil= en-keyword=autophosphorylation kn-keyword=autophosphorylation en-keyword=canine kn-keyword=canine en-keyword=c-kit kn-keyword=c-kit en-keyword=GIST kn-keyword=GIST en-keyword=KIT kn-keyword=KIT en-keyword=loss-of-function mutation kn-keyword=loss-of-function mutation 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=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=9 cd-vols= no-issue=34 article-no= start-page=36114 end-page=36121 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Engineering Zeolitic-Imidazolate-Framework-Derived Mo-Doped Cobalt Phosphide for Efficient OER Catalysts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Designing a cheap, competent, and durable catalyst for the oxygen evolution reaction (OER) is exceedingly necessary for generating oxygen through a water-splitting reaction. In this project, we have designed a ZIF-67-originated molybdenum-doped cobalt phosphide (CoP) using a simplistic dissolution–regrowth method using Na2MoO4 and a subsequent phosphidation process. This leads to the formation of an exceptional hollow nanocage morphology that is useful for enhanced catalytic activity. Metal–organic frameworks, especially ZIF-67, can be used both as a template and as a metal (cobalt) precursor. Molybdenum-doped CoP was fabricated through a two-step synthesis process, and the fabricated Mo-doped CoP showed excellent catalytic activity during the OER with a lower value of overpotential. Furthermore, the effect of the Mo amount on the catalytic activity has been explored. The best catalyst (CoMoP-2) showed an onset potential of around 1.49 V at 10 mA cm–2 to give rise to a Tafel slope of 62.1 mV dec–1. The improved catalytic activity can be attributed to the increased porosity and surface area of the resultant catalyst. en-copyright= kn-copyright= en-aut-name=RahmanMohammad Atiqur en-aut-sei=Rahman en-aut-mei=Mohammad Atiqur kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=CaiZe en-aut-sei=Cai en-aut-mei=Ze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoushumyZannatul Mumtarin en-aut-sei=Moushumy en-aut-mei=Zannatul Mumtarin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TagawaRyuta en-aut-sei=Tagawa en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HidakaYoshiharu en-aut-sei=Hidaka en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=IslamMd. Saidul en-aut-sei=Islam en-aut-mei=Md. Saidul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SekineYoshihiro en-aut-sei=Sekine en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=IdaShintaro en-aut-sei=Ida en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayamiShinya en-aut-sei=Hayami en-aut-mei=Shinya 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 Science and Technology, Kumamoto University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=3 en-affil=Department of Applied Chemistry and Biochemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=5 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=6 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=8 en-affil=Department of Chemistry, Graduate School of Science and Technology, Kumamoto University kn-affil= affil-num=9 en-affil=Research Core for Interdisciplinary Sciences, Okayama University kn-affil= affil-num=10 en-affil=Institute of Industrial Nanomaterials (IINa), Kumamoto University kn-affil= affil-num=11 en-affil=Institute of Industrial Nanomaterials (IINa), Kumamoto University kn-affil= 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=17 cd-vols= no-issue=7 article-no= start-page=902 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250711 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of an Antimicrobial Coating Film for Denture Lining Materials en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Objectives: Denture hygiene is essential for the prevention of oral candidiasis, a condition frequently associated with Candida albicans colonization on denture surfaces. Cetylpyridinium chloride (CPC)-loaded montmorillonite (CPC-Mont) has demonstrated antimicrobial efficacy in tissue conditioners and demonstrates potential for use in antimicrobial coatings. In this study, we aimed to develop and characterize CPC-Mont-containing coating films for dentures, focusing on their physicochemical behaviors and antifungal efficacies. Methods: CPC was intercalated into sodium-type montmorillonite to prepare CPC-Mont; thereafter, films containing CPC-Mont were fabricated using emulsions of different polymer types (nonionic, cationic, and anionic). CPC loading, release, and recharging behaviors were assessed at various temperatures, and activation energies were calculated using Arrhenius plots. Antimicrobial efficacy against Candida albicans was evaluated for each film using standard microbial assays. Results: X-ray diffraction analysis confirmed the expansion of montmorillonite interlayer spacing by approximately 3 nm upon CPC loading. CPC-Mont showed temperature-dependent release and recharging behavior, with higher temperatures enhancing its performance. The activation energy for CPC release was 38 kJ/mol, while that for recharging was 26 kJ/mol. Nonionic emulsions supported uniform CPC-Mont dispersion and successful film formation, while cationic and anionic emulsions did not. CPC-Mont-containing coatings maintained antimicrobial activity against Candida albicans on dentures. Conclusions: CPC-Mont can be effectively incorporated into nonionic emulsion-based films to create antimicrobial coatings for denture applications. The films exhibited temperature-responsive, reversible CPC release and recharging behaviors, while maintaining antifungal efficacy, findings which suggest the potential utility of CPC-Mont-containing films as a practical strategy to prevent denture-related candidiasis. en-copyright= kn-copyright= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KameyamaTakeru en-aut-sei=Kameyama en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Van MeerbeekBart en-aut-sei=Van Meerbeek en-aut-mei=Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkiharaTakumi en-aut-sei=Okihara en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute kn-affil= affil-num=2 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Dental School, Advanced Research Center for Oral and Craniofacial Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=5 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=6 en-affil=BIOMAT, Department of Oral Health Sciences, KU Leuvem kn-affil= affil-num=7 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=antimicrobial kn-keyword=antimicrobial en-keyword=denture liner kn-keyword=denture liner en-keyword=cetylpyridiniumchloride kn-keyword=cetylpyridiniumchloride en-keyword=drug release kn-keyword=drug release en-keyword=drug recharge kn-keyword=drug recharge 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=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=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=71 cd-vols= no-issue=3 article-no= start-page=321 end-page=343 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=Physiological and Biochemical Traits of Dormancy Release and Growth Resumption in Japanese Cedar in the Warm-Temperate Zone en-subtitle= kn-subtitle= en-abstract= kn-abstract=Global warming will disturb dormancy release and growth resumption of trees. To better understand this process, it is important to investigate physiological and biochemical traits related to these stages. We examined dormancy release and growth resumption in Japanese cedar (Cryptomeria japonica [L.] D. Don), an evergreen needle-leaved tree, in the warm-temperate zone by evaluating budbreak under growth-promoting conditions, and simultaneously examining respiration rates and contents of carbohydrates and phytohormones in shoots from November 2022 to March 2023. A long time to budbreak and the lowest budbreak rates of 75% in November indicated shallow dormancy. Budbreak rates of 98%, short time to budbreak, and first appearance of budbreak in the field in March indicated growth resumption. Continuous changes in budbreak rates and time to budbreak between dormancy and growth resumption indicated dormancy was gradually released. Surges in budbreak rates in December indicated dormancy was almost completely released by early winter. Contents of abscisic acid (ABA) and salicylic acid (SA) decreased from November, remained low in March, and were strongly associated with budbreak rates according to principal component analysis. It was suggested that the depletion of SA led to the depletion of ABA, contributing to dormancy release and growth resumption. Fructose and trans-zeatin accumulated until February, and low levels of starch, indole-3-acetic acid, jasmonic acid, and jasmonic acid-isoleucine during winter was followed by accumulation in March. Although these biochemical traits were less related to budbreak rates compared to ABA and SA, they seemed to assist either dormancy release or growth resumption. en-copyright= kn-copyright= en-aut-name=HiejimaShoma en-aut-sei=Hiejima en-aut-mei=Shoma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeinoHiroto en-aut-sei=Seino en-aut-mei=Hiroto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HachisukaRico en-aut-sei=Hachisuka en-aut-mei=Rico kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeYuka en-aut-sei=Watanabe en-aut-mei=Yuka 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=UgawaShin en-aut-sei=Ugawa en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= affil-num=2 en-affil=Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University kn-affil= affil-num=3 en-affil=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Forestry and Fisheries, Kagoshima 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=The United Graduate School of Agricultural Sciences, Kagoshima University kn-affil= en-keyword=Japanese cedar kn-keyword=Japanese cedar en-keyword=Warm-temperate zone kn-keyword=Warm-temperate zone en-keyword=Dormancy release kn-keyword=Dormancy release en-keyword=Growth resumption kn-keyword=Growth resumption en-keyword=Physio-biochemical traits kn-keyword=Physio-biochemical traits END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=3 article-no= start-page=337 end-page=345 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Study on the Grinding Temperature of Workpiece in Side Plunge Grinding Process en-subtitle= kn-subtitle= en-abstract= kn-abstract=Grinding is used to finish thrust metal attachment parts, such as crankshafts, which have both journal and thrust surfaces. In side plunge grinding, a thrust surface and a cylindrical surface of a shaft workpiece with collars are finished in a single plunge grinding process. However, the surface quality near the ground internal corner, where grinding fluid may not penetrate, can deteriorate, causing high residual stress and cracks owing to grinding heat. While it has been reported that quality issues at the inner corners of the ground surface can be mitigated by reducing the grinding point temperature through efficient cooling fluid supply, the mechanisms of grinding phenomena and heat generation in side plunge grinding are not yet fully understood. In this study, the variations in the grinding temperature at the thrust surface of a workpiece with a collar were experimentally investigated using a wire/workpiece thermocouple to clarify these phenomena. The results revealed a significant increase in the grinding temperature at the corners of the grinding zone. However, it slightly decreases as the thermocouple output approaches the center of the workpiece, indicating a slight effect of the grinding speed. The surface temperature of the workpiece in side plunge grinding is primarily influenced by the wheel depth-of-cut in the thrust direction. Additionally, the effect of workpiece rotational speed and grinding infeed speed on temperature distribution has been demonstrated. en-copyright= kn-copyright= en-aut-name=GaoLingxiao en-aut-sei=Gao en-aut-mei=Lingxiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuidaMotoki en-aut-sei=Kuida en-aut-mei=Motoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KodamaHiroyuki en-aut-sei=Kodama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhashiKazuhito en-aut-sei=Ohashi en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=Faculty 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=grinding kn-keyword=grinding en-keyword=thrust surface kn-keyword=thrust surface en-keyword=grinding temperature kn-keyword=grinding temperature en-keyword=thermocouple kn-keyword=thermocouple END start-ver=1.4 cd-journal=joma no-vol=301 cd-vols= no-issue=7 article-no= start-page=110291 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=A repertoire of visible light–sensitive opsins in the deep-sea hydrothermal vent shrimp Rimicaris hybisae en-subtitle= kn-subtitle= en-abstract= kn-abstract=Unlike terrestrial environments, where humans reside, there is no sunlight in the deep sea. Instead, dim visible light from black-body radiation and bioluminescence illuminates hydrothermal vent areas in the deep sea. A deep-sea hydrothermal vent shrimp, Rimicaris hybisae, is thought to detect this dim light using its enlarged dorsal eye; however, the molecular basis of its photoreception remains unexplored. Here, we characterized the molecular properties of opsins, universal photoreceptive proteins in animals, found in R. hybisae. Transcriptomic analysis identified six opsins: three Gq-coupled opsins, one Opn3, one Opn5, and one peropsin. Functional analysis revealed that five of these opsins exhibited light-dependent G protein activity, whereas peropsin exhibited the ability to convert all-trans-retinal to 11-cis-retinal like photoisomerases. Notably, all the R. hybisae opsins, including Opn5, convergently show visible light sensitivity (around 457–517 nm), whereas most opsins categorized as Opn5 have been demonstrated to be UV sensitive. Mutational analysis revealed that the unique visible light sensitivity of R. hybisae Opn5 is achieved through the stabilization of a protonated Schiff base by a counterion residue at position 83 (Asp83), which differs from the position identified in other opsins. These findings suggest that the vent shrimp R. hybisae has adapted its photoreceptive devices to dim deep-sea hydrothermal light by selectively maintaining a repertoire of visible light–sensitive opsins, including the uniquely tuned Opn5. en-copyright= kn-copyright= en-aut-name=NagataYuya en-aut-sei=Nagata en-aut-mei=Yuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoNorio en-aut-sei=Miyamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoKeita en-aut-sei=Sato en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishimuraYosuke en-aut-sei=Nishimura en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TaniokaYuki en-aut-sei=Tanioka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamanakaYuji en-aut-sei=Yamanaka en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshizawaSusumu en-aut-sei=Yoshizawa en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiKuto en-aut-sei=Takahashi en-aut-mei=Kuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ObayashiKohei en-aut-sei=Obayashi en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukamotoHisao en-aut-sei=Tsukamoto en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakaiKen en-aut-sei=Takai en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OhuchiHideyo en-aut-sei=Ohuchi en-aut-mei=Hideyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaTakahiro en-aut-sei=Yamashita en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SudoYuki en-aut-sei=Sudo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KojimaKeiichi en-aut-sei=Kojima en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Research Center for Bioscience and Nanoscience (CeBN), Research Institute for Marine Resources Utilization, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=5 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Atmosphere and Ocean Research Institute, The University of Tokyo kn-affil= affil-num=8 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=10 en-affil=Department of Biology, Graduate School of Science, Kobe University kn-affil= affil-num=11 en-affil=Institute for Extra-Cutting-Edge Science and Technology Avant-Garde Research (X-Star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Biophysics, Graduate School of Science, Kyoto University kn-affil= affil-num=14 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=rhodopsin kn-keyword=rhodopsin en-keyword=opsin kn-keyword=opsin en-keyword=G protein–coupled receptor kn-keyword=G protein–coupled receptor en-keyword=signal transduction kn-keyword=signal transduction en-keyword=photoreceptor kn-keyword=photoreceptor en-keyword=vision kn-keyword=vision en-keyword=photobiology kn-keyword=photobiology en-keyword=vent shrimp kn-keyword=vent shrimp en-keyword=deep sea kn-keyword=deep sea en-keyword=molecular evolution kn-keyword=molecular evolution END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=RP99858 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein–protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingJian en-aut-sei=Xing en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumazawaMinoru en-aut-sei=Kumazawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaHaruya en-aut-sei=Ogawa en-aut-mei=Haruya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IfukuKentaro en-aut-sei=Ifuku en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Shizuoka 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= kn-title=マイクロ・ナノバブルを用いた集水井横ボーリング等閉塞物除去システムの研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SHINANOKenzo en-aut-sei=SHINANO en-aut-mei=Kenzo kn-aut-name=科野健三 kn-aut-sei=科野 kn-aut-mei=健三 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= kn-title=環境中親電子物質によるDNAメチル化制御を介したケモカイン発現誘導機構 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TSUCHIDATomoki en-aut-sei=TSUCHIDA en-aut-mei=Tomoki kn-aut-name=土田知貴 kn-aut-sei=土田 kn-aut-mei=知貴 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= kn-title=小胞体ストレスセンサー IRE1α に対する S-ニトロシル化阻害薬の同定とその薬効評価 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KUROGIHaruna en-aut-sei=KUROGI en-aut-mei=Haruna kn-aut-name=黒木春那 kn-aut-sei=黒木 kn-aut-mei=春那 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=救急外来での気道管理における代謝性アシドーシスと挿管後低血圧の関連性 kn-title=Association between metabolic acidosis and post-intubation hypotension in airway management performed in the emergency department en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUGAMasafumi en-aut-sei=SUGA en-aut-mei=Masafumi kn-aut-name=須賀将文 kn-aut-sei=須賀 kn-aut-mei=将文 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=ヒト正常軟骨細胞におけるメカニカルストレスに対するタンキラーゼ阻害剤の効果と作用機序の解明 kn-title=Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HOTTAYoshifumi en-aut-sei=HOTTA en-aut-mei=Yoshifumi kn-aut-name=堀田佳史 kn-aut-sei=堀田 kn-aut-mei=佳史 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=肺腺癌におけるSPRED2の発現 kn-title=Expression of SPRED2 in the lung adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OTAYoko en-aut-sei=OTA en-aut-mei=Yoko kn-aut-name=太田陽子 kn-aut-sei=太田 kn-aut-mei=陽子 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=腫瘍融解アデノウイルスによる腹腔内マクロファージの機能的再構築により、胃癌腹膜播種に対する抗腫瘍免疫が回復する kn-title=Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TABUCHIMotoyasu en-aut-sei=TABUCHI en-aut-mei=Motoyasu kn-aut-name=田渕幹康 kn-aut-sei=田渕 kn-aut-mei=幹康 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=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=22 cd-vols= no-issue=6 article-no= start-page=97 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of aged garlic extract on experimental periodontitis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aged garlic extract (AGE) has been reported to exert anti‑inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5‑0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription‑quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation‑induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE‑treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption. en-copyright= kn-copyright= en-aut-name=KuangCanyan en-aut-sei=Kuang en-aut-mei=Canyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiAnna en-aut-sei=Hirai en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Kamei‑ΝagataChiaki en-aut-sei=Kamei‑Νagata en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NangoHiroshi en-aut-sei=Nango en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtaniMasahiro en-aut-sei=Ohtani en-aut-mei=Masahiro 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=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathophysiology‑Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Periodontics and Endodontics, Department of Dentistry, Okayama University Hospital kn-affil= affil-num=4 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. kn-affil= affil-num=5 en-affil=Central Research Institute, Wakunaga Pharmaceutical Co., Ltd. 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=Department of Pathophysiology‑Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=AGE kn-keyword=AGE en-keyword=experimental periodontitis kn-keyword=experimental periodontitis en-keyword=bone resorption kn-keyword=bone resorption en-keyword=inflammation kn-keyword=inflammation en-keyword=osteoclasts kn-keyword=osteoclasts 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=14 cd-vols= no-issue=7 article-no= start-page=2287 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250327 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki 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=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=adverse events kn-keyword=adverse events en-keyword=balloon-assisted ERCP kn-keyword=balloon-assisted ERCP en-keyword=benzodiazepine kn-keyword=benzodiazepine en-keyword=sedation kn-keyword=sedation 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=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=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=6 cd-vols= no-issue= article-no= start-page=1547222 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=Interleukin-6/soluble IL-6 receptor-induced secretion of cathepsin B and L from human gingival fibroblasts is regulated by caveolin-1 and ERK1/2 pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims: Cathepsins are essential lysosomal enzymes that maintain organismal homeostasis by degrading extracellular substrates. The inflammatory cytokine interleukin-6 (IL-6) increases the production of cathepsins through the caveolin-1 (Cav-1) and c-Jun N-terminal kinase (JNK) signaling pathways, which have been implicated in the destruction of periodontal tissue. This study investigated the effect of the IL-6/soluble IL-6 receptor (sIL-6R) complex on the extracellular secretion of cathepsins in human gingival fibroblasts (HGFs) and examined the function of extracellularly secreted cathepsins B and L under acidic culture conditions in vitro.
Methods: HGFs were isolated from healthy volunteer donors. The expression of Cav-1 was suppressed via transfection with small interfering RNA (siRNA) targeting Cav-1. The expression levels of cathepsins B and L induced by extracellular IL-6/sIL-6R were measured using western blotting and enzyme-linked immunosorbent assay. Extracellular cathepsin activity following IL-6/sIL-6R stimulation was assessed using a methylcoumarylamide substrate in a fluorescence-based assay. IL-6/sIL-6R-induced expression of cathepsins B and L in HGFs was quantified under inhibitory conditions for extracellular signal-regulated kinase (ERK) 1/2 and/or JNK signaling, both of which are transduction pathways activated by IL-6/sIL-6R. This quantification was also performed in HGFs with suppressed Cav-1 expression using western blotting.
Results: Cathepsins B and L were secreted in their precursor forms from HGFs, with significantly elevated protein levels observed at 24, 48, and 72 h post-IL-6/sIL-6R stimulation. Under acidic culture conditions, cathepsin B activity increased at 48 and 72 h. Cav-1 suppression inhibited the secretion of cathepsin B regardless of IL-6/sIL-6R stimulation, whereas the secretion of cathepsin L was reduced only after 48 h of IL-6/sIL-6R stimulation. Inhibition of ERK1/2 and JNK pathways decreased the secretion of cathepsin B after 48 h of IL-6/sIL-6R stimulation, and JNK inhibition reduced the secretion of cathepsin L under similar conditions.
Conclusion: IL-6/sIL-6R stimulation increased the extracellular secretion of cathepsin B and L precursors in HGFs, and these precursors became activated under acidic conditions. Cav-1 and ERK1/2 are involved in regulating the secretion of cathepsin B precursors. en-copyright= kn-copyright= en-aut-name=GotoAyaka en-aut-sei=Goto en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=Yamaguchi-TomikawaTomoko en-aut-sei=Yamaguchi-Tomikawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiHiroya en-aut-sei=Kobayashi en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Shinoda-ItoYuki en-aut-sei=Shinoda-Ito en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HiraiKimito en-aut-sei=Hirai en-aut-mei=Kimito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaAtsushi en-aut-sei=Ikeda en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cathepsin B kn-keyword=cathepsin B en-keyword=cathepsin L kn-keyword=cathepsin L en-keyword=human gingival fibroblast kn-keyword=human gingival fibroblast en-keyword=interleukin-6 kn-keyword=interleukin-6 en-keyword=caveolin kn-keyword=caveolin 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=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=14 cd-vols= no-issue=1 article-no= start-page=2 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241225 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancing Campus Environment: Real-Time Air Quality Monitoring Through IoT and Web Technologies en-subtitle= kn-subtitle= en-abstract= kn-abstract=Nowadays, enhancing campus environments through mitigations of air pollutions is an essential endeavor to support academic achievements, health, and safety of students and staffs in higher educational institutes. In laboratories, pollutants from welding, auto repairs, or chemical experiments can drastically degrade the air quality in the campus, endangering the respiratory and cognitive health of students and staffs. Besides, in universities in Indonesia, automobile emissions of harmful substances such as carbon monoxide (CO), nitrogen dioxide (NO2), and hydrocarbon (HC) have been a serious problem for a long time. Almost everybody is using a motorbike or a car every day in daily life, while the number of students is continuously increasing. However, people in many campuses including managements do not be aware these problems, since air quality is not monitored. In this paper, we present a real-time air quality monitoring system utilizing Internet of Things (IoT) integrated sensors capable of detecting pollutants and measuring environmental conditions to visualize them. By transmitting data to the SEMAR IoT application server platform via an ESP32 microcontroller, this system provides instant alerts through a web application and Telegram notifications when pollutant levels exceed safe thresholds. For evaluations of the proposed system, we adopted three sensors to measure the levels of CO, NO2, and HC and conducted experiments in three sites, namely, Mechatronics Laboratory, Power and Emission Laboratory, and Parking Lot, at the State Polytechnic of Malang, Indonesia. Then, the results reveal Good, Unhealthy, and Dangerous for them, respectively, among the five categories defined by the Indonesian government. The system highlighted its ability to monitor air quality fluctuations, trigger warnings of hazardous conditions, and inform the campus community. The correlation of the sensor levels can identify the relationship of each pollutant, which provides insight into the characteristics of pollutants in a particular scenario. en-copyright= kn-copyright= en-aut-name=RahmadaniAlfiandi Aulia en-aut-sei=Rahmadani en-aut-mei=Alfiandi Aulia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SyaifudinYan Watequlis en-aut-sei=Syaifudin en-aut-mei=Yan Watequlis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SetiawanBudhy en-aut-sei=Setiawan en-aut-mei=Budhy kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PandumanYohanes Yohanie Fridelin en-aut-sei=Panduman en-aut-mei=Yohanes Yohanie Fridelin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunabikiNobuo en-aut-sei=Funabiki en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Electrical Engineering, State Polytechnic of Malang kn-affil= affil-num=2 en-affil=Department of Information Technology, State Polytechnic of Malang kn-affil= affil-num=3 en-affil=Department of Electrical Engineering, State Polytechnic of Malang kn-affil= affil-num=4 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= affil-num=5 en-affil=Department of Information and Communication Systems, Okayama University kn-affil= en-keyword=Internet of Things kn-keyword=Internet of Things en-keyword= campus air quality kn-keyword= campus air quality en-keyword= pollutant detection kn-keyword= pollutant detection en-keyword= SEMAR kn-keyword= SEMAR en-keyword= sensor technology kn-keyword= sensor technology en-keyword= web application kn-keyword= web application END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=3 article-no= start-page=1007 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=LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration. en-copyright= kn-copyright= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NasuYoshihisa en-aut-sei=Nasu en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HottaYoshifumi en-aut-sei=Hotta en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShimizuNoriyuki en-aut-sei=Shimizu en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchikawaChinatsu en-aut-sei=Ichikawa en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LinDeting en-aut-sei=Lin en-aut-mei=Deting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukaNoriaki en-aut-sei=Otsuka en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=5 en-affil=Locomotive Pain Center, Okayama University Hospital 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 Orthopaedic Surgery, Sayo Central Hospital kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=12 en-affil=Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=osteoarthritis kn-keyword=osteoarthritis en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=LRP4 kn-keyword=LRP4 en-keyword=Agrin kn-keyword=Agrin en-keyword=β-catenin kn-keyword=β-catenin en-keyword=SOX9 kn-keyword=SOX9 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=13 cd-vols= no-issue= article-no= start-page=RP99858 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein-protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms. en-copyright= kn-copyright= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingJian en-aut-sei=Xing en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KumazawaMinoru en-aut-sei=Kumazawa en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgawaHaruya en-aut-sei=Ogawa en-aut-mei=Haruya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IfukuKentaro en-aut-sei=Ifuku en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NagaoRyo en-aut-sei=Nagao en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=5 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Agriculture, Kyoto University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Shizuoka University kn-affil= 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=41 cd-vols= no-issue=4 article-no= start-page=2679 end-page=2687 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250118 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Formation of Nanowindow between Graphene Oxide and Carbon Nanohorn Assisted by Metal Ions en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study presents a novel nanostructured material formed by inserting oxidized carbon nanohorns (CNHox) between layered graphene oxide (GO) nanosheets using metal ions (M) from nitrate as intermediates. The resulting GO–CNHox-M structure effectively mitigated interlayer aggregation of the GO nanosheets. This insertion strategy promoted the formation of nanowindows on the surface of the GO sheets and larger mesopores between the GO nanosheets, improving material porosity. Characterization revealed successful CNHox insertion, which increased interlayer spacing and reduced GO stacking. The GO–CNHox-Ca exhibited a significantly higher specific surface area (SSA) and pore volume than pure GO, with values of 374 m2 g–1 and 0.36 mL g–1, respectively. The GO–CNHox-K composite also exhibited a well-developed pore structure with an SSA of 271 m2 g–1 and pore volume of 0.26 mL g–1. These findings demonstrate that Ca2+ or K+ ions effectively link GO and CNHox, validating the success of this insertion approach in reducing GO aggregation. Metal ions played a crucial role in the insertion process by facilitating electrostatic interactions and coordination bonds between GO and CNHox. This study provides new insights into reducing GO agglomeration and expanding the application of GO-based materials. en-copyright= kn-copyright= en-aut-name=LiZhao en-aut-sei=Li en-aut-mei=Zhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ToyotaMoeto en-aut-sei=Toyota en-aut-mei=Moeto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhkuboTakahiro en-aut-sei=Ohkubo en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue= article-no= start-page=106672 end-page= 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=Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. en-copyright= kn-copyright= en-aut-name=OkamotoSaki en-aut-sei=Okamoto en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=SakamotoMika en-aut-sei=Sakamoto en-aut-mei=Mika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=AndoHideya en-aut-sei=Ando en-aut-mei=Hideya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=National Institute of Genetics, ROIS kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Applied Chemistry and Biotechnology, Okayama University of Science kn-affil= affil-num=7 en-affil=Graduate School of Science, Technology, and Innovation, Kobe University kn-affil= affil-num=8 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=Antioxidant kn-keyword=Antioxidant en-keyword=Lysosomes kn-keyword=Lysosomes en-keyword=Autophagy kn-keyword=Autophagy en-keyword=Resveratrol kn-keyword=Resveratrol en-keyword=Skin fibroblasts kn-keyword=Skin fibroblasts en-keyword=Bioactive compounds kn-keyword=Bioactive compounds 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=159 cd-vols= no-issue=19 article-no= start-page=194504 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231121 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficiency and energy balance for substitution of CH4 in clathrate hydrates with CO2 under multiple-phase coexisting conditions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many experimental and theoretical studies on CH4–CO2 hydrates have been performed aiming at the extraction of CH4 as a relatively clean energy resource and concurrent sequestration of CO2. However, vague or insufficient characterization of the environmental conditions prevents us from a comprehensive understanding of even equilibrium properties of CH4–CO2 hydrates for this substitution. We propose possible reaction schemes for the substitution, paying special attention to the coexisting phases, the aqueous and/or the fluid, where CO2 is supplied from and CH4 is transferred to. We address the two schemes for the substitution operating in three-phase and two-phase coexistence. Advantages and efficiencies of extracting CH4 in the individual scheme are estimated from the chemical potentials of all the components in all the phases involved in the substitution on the basis of a statistical mechanical theory developed recently. It is found that although substitution is feasible in the three-phase coexistence, its working window in temperature–pressure space is much narrower compared to the two-phase coexistence condition. Despite that the substitution normally generates only a small amount of heat, a large endothermic substitution is suggested in the medium pressure range, caused by the vaporization of liquid CO2 due to mixing with a small amount of the released CH4. This study provides the first theoretical framework toward the practical use of hydrates replacing CH4 with CO2 and serves as a basis for quantitative planning. en-copyright= kn-copyright= en-aut-name=TanakaHideki en-aut-sei=Tanaka en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoMasakazu en-aut-sei=Matsumoto en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YagasakiTakuma en-aut-sei=Yagasaki en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= affil-num=3 en-affil=Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=391 cd-vols= no-issue= article-no= start-page=158 end-page=176 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates en-subtitle= kn-subtitle= en-abstract= kn-abstract=Magnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones. en-copyright= kn-copyright= en-aut-name=ZhangWei en-aut-sei=Zhang en-aut-mei=Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitagawaHiroshi en-aut-sei=Kitagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HuangFang en-aut-sei=Huang en-aut-mei=Fang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=2 en-affil=The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University kn-affil= affil-num=3 en-affil=CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China kn-affil= en-keyword=Magnesium isotopes kn-keyword=Magnesium isotopes en-keyword=Arc magmas kn-keyword=Arc magmas en-keyword=Mantle wedge serpentinite kn-keyword=Mantle wedge serpentinite en-keyword=Slab serpentinite kn-keyword=Slab serpentinite en-keyword=Carbonate recycle kn-keyword=Carbonate recycle END start-ver=1.4 cd-journal=joma no-vol=228 cd-vols= no-issue= article-no= start-page=30 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exogenous expression of PGC-1α during in vitro maturation impairs the developmental competence of porcine oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives of the current study were to examine the effects of exogenous expression of PGC-1α, which is a transcription factor responsive for controlling mitochondrial DNA (mtDNA) replication, mitochondria quantity control, mitochondrial biogenesis, and reactive oxygen species (ROS) maintenance, in porcine oocytes during in-vitro maturation (IVM) on the developmental competence, as well as mitochondrial quantity and function. Exogenous over-expression of PGC-1α by injection of the mRNA construct into oocytes 20 h after the start of IVM culture significantly increased the copy number of mtDNA in the oocytes, but reduced the incidences of oocytes matured to the metaphase-II stage after the IVM culture for totally 44 h and completely suppressed the early development in vitro to the blastocyst stage following parthenogenetic activation. The exogenous expression of PGC-1α also significantly induced spindle defects and chromosome misalignments. Furthermore, markedly higher ROS levels were observed in the PGC-1α-overexpressed mature oocytes, whereas mRNA level of SOD1, encoded for a ROS scavenging enzyme, was decreased. These results conclude that forced expression of PGC-1α successfully increase mtDNA copy number but led to increased ROS production, evidently by downregulation of SOD1 gene expression, inducement of spindle aberration/chromosomal misalignment, and consequently reduction in the meiotic and developmental competences of porcine oocytes. en-copyright= kn-copyright= 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=1 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=2 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=3 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=4 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= en-keyword=Porcine kn-keyword=Porcine en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Oocytes kn-keyword=Oocytes en-keyword=PGC-1 alpha kn-keyword=PGC-1 alpha en-keyword=In vitro maturation kn-keyword=In vitro maturation 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=4 cd-vols= no-issue= article-no= start-page=19 end-page=52 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=Mineralogy and geochemistry of magnetite-garnet bearing skarn deposits surrounding iron-smelting sites in the Kibi region of Japan kn-title=吉備製鉄遺跡周辺地域の磁鉄鉱ざくろ石スカルン鉄鉱石の鉱物学的・地球化学的特徴 en-subtitle= kn-subtitle= en-abstract= kn-abstract=We conducted mineralogical and geochemical analysis of ore samples taken from locations surrounding the Jinmu, Sanpō, and Kōmoto mines in order to determine the source of iron ore uncovered from archaeological sites. The mineral composition of the magnetite-garnet bearing skarn deposits varies from mine to mine: while clinopyroxene and amphibole are present in the Jinmu and Sanpō samples, only a small amount of clinopyroxene occurs in the Kōmoto samples. The chemical compositions of magnetite and garnet are distinctive for each mine. Among the trace elements contained in the magnetite, Mg and Mn tend to be higher in the Kōmoto samples, Ti in the Jinmu samples, and Ca and Si in the Sanpō samples. The garnet from all the mines is andradite, but while the Kōmoto samples contain almost no Al, it is present in the Jinmu and Sanpō samples. Although samples were taken from a limited number of mine areas (three), our analysis provides an index for comparison with iron ore uncovered from archaeological sites, which will aid in provenance determination. en-copyright= kn-copyright= en-aut-name=TAKECHIYasushi en-aut-sei=TAKECHI en-aut-mei=Yasushi kn-aut-name=武智泰史 kn-aut-sei=武智 kn-aut-mei=泰史 aut-affil-num=1 ORCID= en-aut-name=NAKAMURADaisuke en-aut-sei=NAKAMURA en-aut-mei=Daisuke kn-aut-name=中村大輔 kn-aut-sei=中村 kn-aut-mei=大輔 aut-affil-num=2 ORCID= en-aut-name=SUZUKIShigeyuki en-aut-sei=SUZUKI en-aut-mei=Shigeyuki kn-aut-name=鈴木茂之 kn-aut-sei=鈴木 kn-aut-mei=茂之 aut-affil-num=3 ORCID= en-aut-name=RYANJoseph en-aut-sei=RYAN en-aut-mei=Joseph kn-aut-name=ライアンジョセフ kn-aut-sei=ライアン kn-aut-mei=ジョセフ aut-affil-num=4 ORCID= en-aut-name=UWAGAKITakeshi en-aut-sei=UWAGAKI en-aut-mei=Takeshi kn-aut-name=上栫武 kn-aut-sei=上栫 kn-aut-mei=武 aut-affil-num=5 ORCID= en-aut-name=NAGAHARAMasato en-aut-sei=NAGAHARA en-aut-mei=Masato kn-aut-name=長原正人 kn-aut-sei=長原 kn-aut-mei=正人 aut-affil-num=6 ORCID= en-aut-name=YOSHIEYuta en-aut-sei=YOSHIE en-aut-mei=Yuta kn-aut-name=吉江雄太 kn-aut-sei=吉江 kn-aut-mei=雄太 aut-affil-num=7 ORCID= en-aut-name=IKEHATAKei en-aut-sei=IKEHATA en-aut-mei=Kei kn-aut-name=池端慶 kn-aut-sei=池端 kn-aut-mei=慶 aut-affil-num=8 ORCID= en-aut-name=KIMURAOsamu en-aut-sei=KIMURA en-aut-mei=Osamu kn-aut-name=木村理 kn-aut-sei=木村 kn-aut-mei=理 aut-affil-num=9 ORCID= en-aut-name=HATTORIRyoichi en-aut-sei=HATTORI en-aut-mei=Ryoichi kn-aut-name=服部亮一 kn-aut-sei=服部 kn-aut-mei=亮一 aut-affil-num=10 ORCID= affil-num=1 en-affil=Kurashiki Museum of Natural History kn-affil= affil-num=2 en-affil=Okayama University, Department of Earth Sciences kn-affil= affil-num=3 en-affil=Okayama University, Department of Earth Sciences kn-affil= affil-num=4 en-affil=Okayama University, Research Institute for the Dynamics of Civilizations kn-affil= affil-num=5 en-affil=Okayama Prefectural Board of Education kn-affil= affil-num=6 en-affil=The Historical Study Group of Mining and Metallurgy of Japan kn-affil= affil-num=7 en-affil=Mitsui Mining & Smelting Co., Ltd. kn-affil= affil-num=8 en-affil=University of Tsukuba, Faculty of Life and Environmental Sciences kn-affil= affil-num=9 en-affil=Okayama University, Research Institute for the Dynamics of Civilizations kn-affil= affil-num=10 en-affil=Osaka University, Graduate School of Humanities kn-affil= en-keyword=Iron-smithing sites kn-keyword=Iron-smithing sites en-keyword=skarn deposits kn-keyword=skarn deposits en-keyword=mineral composition of ore kn-keyword=mineral composition of ore en-keyword=geochemical analysis kn-keyword=geochemical analysis END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=49 article-no= start-page=33264 end-page=33275 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mass Production of Graphene Oxide Beyond the Laboratory: Bridging the Gap Between Academic Research and Industry en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mass production of graphene oxide (GO) has garnered significant attention in recent years due to its potential applications in various fields, from materials science to biomedicine. Graphene, known for its unique properties, such as high conductivity and mechanical strength, has been extensively studied. However, traditional production methods such as the exfoliation of graphite with scotch tape are not suitable for large-scale production. This has led to an increased focus on GO as a viable alternative to graphene production. Nonetheless, challenges, including the optimization of oxidation processes, the control of structural uniformity, and the reproducibility of production, have not been solved so far. This review critically examines GO production advancements by analyzing experimental and mechanistic studies to identify significant developments that enable high-yield and reproducible methods suitable for industrial-scale production. Special attention is given to oxidation techniques and postsynthesis purification and storage, with a focus on controlled oxidation to achieve homogeneous and single-layer GO. Through this lens, the review outlines the path forward for the industrialization of GO, aiming to bridge the gap between academic research and industrial production. en-copyright= kn-copyright= en-aut-name=NishinaYuta en-aut-sei=Nishina en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science, Okayama University kn-affil= en-keyword=Graphene oxide kn-keyword=Graphene oxide en-keyword=Graphite kn-keyword=Graphite en-keyword=Chemical oxidation kn-keyword=Chemical oxidation en-keyword=Electrochemical oxidation kn-keyword=Electrochemical oxidation en-keyword=Mass production kn-keyword=Mass production en-keyword=Purification kn-keyword=Purification en-keyword=Optimization kn-keyword=Optimization en-keyword=Industrialization kn-keyword=Industrialization en-keyword=Safety kn-keyword=Safety en-keyword=Stability kn-keyword=Stability END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=23 article-no= start-page=10342 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Assessing CO2 Reduction Effects Through Decarbonization Scenarios in the Residential and Transportation Sectors: Challenges and Solutions for Japan's Hilly and Mountainous Areas en-subtitle= kn-subtitle= en-abstract= kn-abstract=Depopulation, aging, and regional decline are becoming increasingly serious issues in Japan's hilly and mountainous areas. Focusing on mitigating environmental damage and envisioning a sustainable future for these regions, this study examines the potential for reducing CO2 emissions in the residential and transportation sectors by 2050. Bottom-up simulations were used to estimate CO2 emissions. Subsequently, six decarbonization scenarios were formulated, considering various measures from the perspectives of population distribution and technological progress. Based on these scenarios, this study analyzes changes in future population, energy consumption, and CO2 emissions by 2050. The results of this study show the following. (1) Depopulation and aging problems in these regions are expected to become more severe in the future. It is necessary to take action to promote sustainable regional development. (2) Pursuing decarbonization has a positive impact on enhancing regional sustainability; however, maintaining the intensity of measures at the current level could lead to a reduction of only 40% in CO2 emissions per capita by 2050 compared with 2020. (3) Scenarios that strengthen decarbonization measures could achieve a reduction of over 95% by 2050, indicating that carbon neutrality is attainable. However, this will require implementing measures at a higher intensity, especially in the transportation sector. en-copyright= kn-copyright= en-aut-name=HaoXiyue en-aut-sei=Hao en-aut-mei=Xiyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanChuyue en-aut-sei=Yan en-aut-mei=Chuyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NarumiDaisuke en-aut-sei=Narumi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Socio-Environmental Energy Science, Graduate School of Energy Science, Kyoto University kn-affil= affil-num=3 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=decarbonization measures kn-keyword=decarbonization measures en-keyword=CO2 reduction kn-keyword=CO2 reduction en-keyword=residential sector kn-keyword=residential sector en-keyword=transportation sector kn-keyword=transportation sector en-keyword=energy consumption kn-keyword=energy consumption en-keyword=CO2 emissions kn-keyword=CO2 emissions en-keyword=hilly and mountainous areas kn-keyword=hilly and mountainous areas en-keyword=area management kn-keyword=area management 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=61 cd-vols= no-issue=1 article-no= start-page=46 end-page=60 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=Terpolymerization reactions of epoxides, CO2, and the third monomers toward sustainable CO2-based polymers with controllable chemical and physical properties en-subtitle= kn-subtitle= en-abstract= kn-abstract=Carbon dioxide (CO2) serves as a cheap, abundant, and renewable C1 building block for the synthesis of organic compounds and polymers. Selective and efficient CO2 fixation processes are still challenging because of the kinetic and thermodynamic stability of CO2. Among various CO2 fixation processes, the ring-opening copolymerization (ROCOP) of epoxides and CO2 gives aliphatic polycarbonates with high atom economy, although the chemical and physical properties of the resulting polycarbonates are not necessarily satisfactory. Introducing the third monomers into this ROCOP system provides new terpolymers, and the thermal, optical, mechanical or degradation properties can be added or tuned by incorporating new polymer backbones derived from the third monomers at the expense of the CO2 content. Here we review the terpolymerization reactions of epoxides, CO2, and the third monomers such as cyclic anhydrides, lactones, lactides, heteroallenes, and olefins. The development of catalysts and the control of the polymer structures are described together with the chemical and physical properties of the resulting polymers. en-copyright= kn-copyright= en-aut-name=NakaokaKoichi en-aut-sei=Nakaoka en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EmaTadashi en-aut-sei=Ema en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, 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=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=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=microRNA-451aはゲムシタビン耐性の胆道癌の増殖をMIFを介したPI3K/Akt経路の制御によって抑制する kn-title=MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OBATATaisuke en-aut-sei=OBATA en-aut-mei=Taisuke kn-aut-name=小幡泰介 kn-aut-sei=小幡 kn-aut-mei=泰介 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=MicroRNA-34a-5pは、胆嚢癌における極めて重要な治療標的である kn-title=MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ODATakashi en-aut-sei=ODA en-aut-mei=Takashi kn-aut-name=織田崇志 kn-aut-sei=織田 kn-aut-mei=崇志 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=癌関連線維芽細胞を標的とした光免疫療法は腫瘍免疫の再構築に寄与する kn-title=Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AKAIMasaaki en-aut-sei=AKAI en-aut-mei=Masaaki kn-aut-name=赤井正明 kn-aut-sei=赤井 kn-aut-mei=正明 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=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=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=115 cd-vols= no-issue=11 article-no= start-page=3660 end-page=3671 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug- resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identi-fied 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extra-cellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sar-coma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1(+)CD6(3+) extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1(+)CD6(3+) extracellular vesicles were detected in serum from Ewing sarcoma- bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P< 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1(+)CD81(+) extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma. en-copyright= kn-copyright= en-aut-name=UotaniKoji en-aut-sei=Uotani en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=UedaKoji en-aut-sei=Ueda en-aut-mei=Koji 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=IwataShintaro en-aut-sei=Iwata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoritaTakuya en-aut-sei=Morita en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KiyonoMasahiro en-aut-sei=Kiyono en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=TakedaKen en-aut-sei=Takeda en-aut-mei=Ken 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=YoshiokaYusuke en-aut-sei=Yoshioka en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OchiyaTakahiro en-aut-sei=Ochiya en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= affil-num=1 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Cancer Precision Medicine Center, Japanese Foundation for Cancer Research kn-affil= affil-num=4 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Musculoskeletal Oncology, National Cancer Center Hospital 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 Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Intelligent Orthopedic System, 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 Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University kn-affil= affil-num=13 en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=circulating biomarker kn-keyword=circulating biomarker en-keyword=Ewing sarcoma kn-keyword=Ewing sarcoma en-keyword=extracellular vesicles kn-keyword=extracellular vesicles en-keyword=liquid biopsy kn-keyword=liquid biopsy en-keyword=proteome kn-keyword=proteome END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=17 article-no= start-page=2824 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240823 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cyclic Oligosaccharide-Induced Modulation of Immunoglobulin A Reactivity to Gut Bacteria Contributes to Alterations in the Bacterial Community Structure en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immunoglobulin A (IgA) is a major gut antibody that coats commensal gut bacteria and contributes to shaping a stable gut bacterial composition. Although previous studies have shown that cyclic oligosaccharides, including cyclic nigerosyl-1,6-nigerose (CNN) and cyclodextrins (CDs, including alpha CD, beta CD, and gamma CD), alter the gut bacterial composition, it remains unclear whether cyclic oligosaccharides modify the IgA coating of gut bacteria, which relates to cyclic oligosaccharide-induced alteration of the gut bacterial composition. To address this issue, mice were maintained for 12 weeks on diets containing CNN, alpha CD, beta CD, or gamma CD; the animals' feces were evaluated for their bacterial composition and the IgA coating index (ICI), a measure of the degree of IgA coating of bacteria. We observed that the intake of each cyclic oligosaccharide altered the gut bacterial composition, with changes in the ICI found at both the phylum and genus levels. The ICI for Bacillota, Lachnospiraceae NK4A136 group, UC Lachnospiraceae, and Tuzzerella were significantly and positively correlated with the relative abundance (RA) in total bacteria for these bacteria; in contrast, significant correlations were not seen for other phyla and genera. Our observations suggest that cyclic oligosaccharide-induced modulation of the IgA coating of gut bacteria may partly relate to changes in the community structure of the gut bacteria. en-copyright= kn-copyright= en-aut-name=MiyamotoTaisei en-aut-sei=Miyamoto en-aut-mei=Taisei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsurutaTakeshi en-aut-sei=Tsuruta en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeraokaMao en-aut-sei=Teraoka en-aut-mei=Mao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangTianyang en-aut-sei=Wang en-aut-mei=Tianyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishinoNaoki en-aut-sei=Nishino en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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= en-keyword=cyclic oligosaccharides kn-keyword=cyclic oligosaccharides en-keyword=gut bacteria kn-keyword=gut bacteria en-keyword=immunoglobulin A kn-keyword=immunoglobulin A END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=17 article-no= start-page=4368 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function. en-copyright= kn-copyright= en-aut-name=OkazakiYohei en-aut-sei=Okazaki en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamoriKiichi en-aut-sei=Nakamori en-aut-mei=Kiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaoChenmin en-aut-sei=Yao en-aut-mei=Chenmin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AhmedMohammed H. en-aut-sei=Ahmed en-aut-mei=Mohammed H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MercelisBenjamin en-aut-sei=Mercelis en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaokaNoriyuki en-aut-sei=Nagaoka en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaruoYukinori en-aut-sei=Maruo en-aut-mei=Yukinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaYasuhiro en-aut-sei=Yoshida en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AbeYasuhiko en-aut-sei=Abe en-aut-mei=Yasuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=Van MeerbeekMeerbeek, Bart en-aut-sei=Van Meerbeek en-aut-mei=Meerbeek, Bart kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshiharaKumiko en-aut-sei=Yoshihara en-aut-mei=Kumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=2 en-affil=Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=3 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=4 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=5 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=6 en-affil=Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School kn-affil= affil-num=7 en-affil=Department of Prosthodontics, Okayama University kn-affil= affil-num=8 en-affil=Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University kn-affil= affil-num=9 en-affil=Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=10 en-affil=Department of Oral Health Sciences, BIOMAT, KU Leuven kn-affil= affil-num=11 en-affil=Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=dental adhesive kn-keyword=dental adhesive en-keyword=antibacterial agent kn-keyword=antibacterial agent en-keyword=dentin kn-keyword=dentin en-keyword=degree of conversion kn-keyword=degree of conversion en-keyword=micro tensile bond strength kn-keyword=micro tensile bond strength en-keyword=scanning microscopy kn-keyword=scanning microscopy END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=5 article-no= start-page=464 end-page=473 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240827 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/Aim: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. Materials and methods: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. Results: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. Conclusion: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate. en-copyright= kn-copyright= en-aut-name=HIROSETAIRA en-aut-sei=HIROSE en-aut-mei=TAIRA 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=KADOYAKOICHI en-aut-sei=KADOYA en-aut-mei=KOICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=SAKAMOTOYUMI en-aut-sei=SAKAMOTO en-aut-mei=YUMI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OBATAKYOICHI en-aut-sei=OBATA en-aut-mei=KYOICHI kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ONOKISHO en-aut-sei=ONO en-aut-mei=KISHO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= en-aut-name=TAKASHIBASHOGO en-aut-sei=TAKASHIBA en-aut-mei=SHOGO kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 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=12 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Head and neck cancer kn-keyword=Head and neck cancer en-keyword=oral cancer kn-keyword=oral cancer en-keyword=malignant melanoma kn-keyword=malignant melanoma en-keyword=angiogenin kn-keyword=angiogenin en-keyword=terrein kn-keyword=terrein END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=8 article-no= start-page=1835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Surface Pre-Reacted Glass-Ionomer Eluate Suppresses Osteoclastogenesis through Downregulation of the MAPK Signaling Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption. en-copyright= kn-copyright= en-aut-name=ChandraJanaki en-aut-sei=Chandra en-aut-mei=Janaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShindoSatoru en-aut-sei=Shindo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LeonElizabeth en-aut-sei=Leon en-aut-mei=Elizabeth kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CastellonMaria en-aut-sei=Castellon en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=PastoreMaria Rita en-aut-sei=Pastore en-aut-mei=Maria Rita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HeidariAlireza en-aut-sei=Heidari en-aut-mei=Alireza kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=WitekLukasz en-aut-sei=Witek en-aut-mei=Lukasz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=CoelhoPaulo G. en-aut-sei=Coelho en-aut-mei=Paulo G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakatsukaToshiyuki en-aut-sei=Nakatsuka en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaiToshihisa en-aut-sei=Kawai en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=4 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=5 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=6 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=7 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=8 en-affil=Biomaterials Division, NYU Dentistry kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami kn-affil= affil-num=10 en-affil=R&D Department, Shofu Inc. kn-affil= affil-num=11 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= en-keyword=S-PRG kn-keyword=S-PRG en-keyword=osteoclast kn-keyword=osteoclast en-keyword=hydroxyapatite kn-keyword=hydroxyapatite en-keyword=TRAP staining kn-keyword=TRAP staining en-keyword=bioactive filler kn-keyword=bioactive filler END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=16 article-no= start-page=1373 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240817 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. en-copyright= kn-copyright= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OsakaHirona en-aut-sei=Osaka en-aut-mei=Hirona kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=ArakiMiu en-aut-sei=Araki en-aut-mei=Miu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=KaiharaKeiko en-aut-sei=Kaihara en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashimaEizo en-aut-sei=Takashima en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchihashiTakayuki en-aut-sei=Uchihashi en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=3 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Malaria Research, Proteo-Science Center, Ehime University kn-affil= affil-num=9 en-affil=Graduate School of Science, Nagoya University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=SYNPO2L kn-keyword=SYNPO2L en-keyword=actinin kn-keyword=actinin en-keyword=actin kn-keyword=actin en-keyword=sarcomere kn-keyword=sarcomere en-keyword=cardiomyocyte kn-keyword=cardiomyocyte END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1403922 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lentil adaptation to drought stress: response, tolerance, and breeding approaches en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lentil (Lens culinaris Medik.) is a cool season legume crop that plays vital roles in food and nutritional security, mostly in the least developed countries. Lentil is often cultivated in dry and semi-dry regions, where the primary abiotic factor is drought, which negatively impacts lentil growth and development, resulting in a reduction of yield. To withstand drought-induced multiple negative effects, lentil plants evolved a variety of adaptation strategies that can be classified within three broad categories of drought tolerance mechanisms (i.e., escape, avoidance, and tolerance). Lentil adapts to drought by the modulation of various traits in the root system, leaf architecture, canopy structure, branching, anatomical features, and flowering process. Furthermore, the activation of certain defensive biochemical pathways as well as the regulation of gene functions contributes to lentil drought tolerance. Plant breeders typically employ conventional and mutational breeding approaches to develop lentil varieties that can withstand drought effects; however, little progress has been made in developing drought-tolerant lentil varieties using genomics-assisted technologies. This review highlights the current understanding of morpho-physiological, biochemical, and molecular mechanisms of lentil adaptation to drought stress. We also discuss the potential application of omics-assisted breeding approaches to develop lentil varieties with superior drought tolerance traits. en-copyright= kn-copyright= en-aut-name=NoorMd. Mahmud Al en-aut-sei=Noor en-aut-mei=Md. Mahmud Al kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Tahjib-Ul-ArifMd. en-aut-sei=Tahjib-Ul-Arif en-aut-mei=Md. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AlimS. M. Abdul en-aut-sei=Alim en-aut-mei=S. M. Abdul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IslamMd. Mohimenul en-aut-sei=Islam en-aut-mei=Md. Mohimenul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HasanMd. Toufiq en-aut-sei=Hasan en-aut-mei=Md. Toufiq kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=BabarMd. Ali en-aut-sei=Babar en-aut-mei=Md. Ali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HossainMohammad Anwar en-aut-sei=Hossain en-aut-mei=Mohammad Anwar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=JewelZilhas Ahmed en-aut-sei=Jewel en-aut-mei=Zilhas Ahmed 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=MostofaMohammad Golam en-aut-sei=Mostofa en-aut-mei=Mohammad Golam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture 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=Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture kn-affil= affil-num=4 en-affil=Horticulture Division, Bangladesh Institute of Nuclear Agriculture kn-affil= affil-num=5 en-affil=Department of Biotechnology, Bangladesh Agricultural University kn-affil= affil-num=6 en-affil=Agronomy Departments, University of Florida kn-affil= affil-num=7 en-affil=Department of Genetics and Plant Breeding, Bangladesh Agricultural University kn-affil= affil-num=8 en-affil=Faculty of Agriculture, Bangabandhu Sheikh Mujibur Rahman Science and Technology University kn-affil= affil-num=9 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=10 en-affil=Department of Biochemistry and Molecular Biology, Michigan State University kn-affil= en-keyword=abiotic stress kn-keyword=abiotic stress en-keyword=morphology kn-keyword=morphology en-keyword=pulse crop kn-keyword=pulse crop en-keyword=plant growth kn-keyword=plant growth en-keyword=omics kn-keyword=omics en-keyword=water-deficit kn-keyword=water-deficit END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=10 article-no= start-page=1164 end-page=1171 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytosolic acidification and oxidation are the toxic mechanisms of SO2 in Arabidopsis guard cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=SO2/H2SO3 can damage plants. However, its toxic mechanism has still been controversial. Two models have been proposed, cytosolic acidification model and cellular oxidation model. Here, we assessed the toxic mechanism of H2SO3 in three cell types of Arabidopsis thaliana, mesophyll cells, guard cells (GCs), and petal cells. The sensitivity of GCs of Chloride channel a (CLCa)-knockout mutants to H2SO3 was significantly lower than those of wildtype plants. Expression of other CLC genes in mesophyll cells and petal cells were different from GCs. Treatment with antioxidant, disodium 4,5-dihydroxy-1,3-benzenedisulfonate (tiron), increased the median lethal concentration (LC50) of H2SO3 in GCs indicating the involvement of cellular oxidation, while the effect was negligible in mesophyll cells and petal cells. These results indicate that there are two toxic mechanisms of SO2 to Arabidopsis cells: cytosolic acidification and cellular oxidation, and the toxic mechanism may vary among cell types. en-copyright= kn-copyright= en-aut-name=MozhganiMahdi en-aut-sei=Mozhgani en-aut-mei=Mahdi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OoiLia en-aut-sei=Ooi en-aut-mei=Lia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EspagneChristelle en-aut-sei=Espagne en-aut-mei=Christelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FilleurSophie en-aut-sei=Filleur en-aut-mei=Sophie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) kn-affil= affil-num=4 en-affil=Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=cytosolic acidification kn-keyword=cytosolic acidification en-keyword=Arabidopsis kn-keyword=Arabidopsis en-keyword=cellular oxidation kn-keyword=cellular oxidation en-keyword=chloride channel a kn-keyword=chloride channel a en-keyword=sulfur dioxide kn-keyword=sulfur dioxide END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=15 article-no= start-page=2114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Light-Driven H2 Production in Chlamydomonas reinhardtii: Lessons from Engineering of Photosynthesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the green alga Chlamydomonas reinhardtii, hydrogen production is catalyzed via the [FeFe]-hydrogenases HydA1 and HydA2. The electrons required for the catalysis are transferred from ferredoxin (FDX) towards the hydrogenases. In the light, ferredoxin receives its electrons from photosystem I (PSI) so that H-2 production becomes a fully light-driven process. HydA1 and HydA2 are highly O-2 sensitive; consequently, the formation of H-2 occurs mainly under anoxic conditions. Yet, photo-H-2 production is tightly coupled to the efficiency of photosynthetic electron transport and linked to the photosynthetic control via the Cyt b(6)f complex, the control of electron transfer at the level of photosystem II (PSII) and the structural remodeling of photosystem I (PSI). These processes also determine the efficiency of linear (LEF) and cyclic electron flow (CEF). The latter is competitive with H-2 photoproduction. Additionally, the CBB cycle competes with H-2 photoproduction. Consequently, an in-depth understanding of light-driven H-2 production via photosynthetic electron transfer and its competition with CO2 fixation is essential for improving photo-H-2 production. At the same time, the smart design of photo-H-2 production schemes and photo-H-2 bioreactors are challenges for efficient up-scaling of light-driven photo-H-2 production. en-copyright= kn-copyright= en-aut-name=HipplerMichael en-aut-sei=Hippler en-aut-mei=Michael kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KhosravitabarFatemeh en-aut-sei=Khosravitabar en-aut-mei=Fatemeh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Department of Biological and Environmental Sciences, University of Gothenburg kn-affil= en-keyword=H-2 production kn-keyword=H-2 production en-keyword=Chlamydomonas reinhardtii kn-keyword=Chlamydomonas reinhardtii en-keyword=electron transfer kn-keyword=electron transfer en-keyword=CBB cycle kn-keyword=CBB cycle END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=6 article-no= start-page=1119 end-page=1122 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240605 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Epigenetic Regulation of Carbonic Anhydrase 9 Expression by Nitric Oxide in Human Small Airway Epithelial Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=DNA methylation is a crucial epigenetic modification that regulates gene expression and determines cell fate; however, the triggers that alter DNA methylation levels remain unclear. Recently, we showed that S-nitrosylation of DNA methyltransferase (DNMT) induces DNA hypomethylation and alters gene expression. Furthermore, we identified DBIC, a specific inhibitor of S-nitrosylation of DNMT3B, to suppress nitric oxide (NO)-induced gene alterations. However, it remains unclear how NO-induced DNA hypomethylation regulates gene expression and whether this mechanism is maintained in normal cells and triggers disease-related changes. To address these issues, we focused on carbonic anhydrase 9 (CA9), which is upregulated under nitrosative stress in cancer cells. We pharmacologically evaluated its regulatory mechanisms using human small airway epithelial cells (SAECs) and DBIC. We demonstrated that nitrosative stress promotes the recruitment of hypoxia-inducible factor 1 alpha to the CA9 promoter region and epigenetically induces CA9 expression in SAECs. Our results suggest that nitrosative stress is a key epigenetic regulator that may cause diseases by altering normal cell function. en-copyright= kn-copyright= en-aut-name=MoriyaYuto en-aut-sei=Moriya en-aut-mei=Yuto 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=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=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=UeharaTakashi en-aut-sei=Uehara 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 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= en-keyword=nitric oxide kn-keyword=nitric oxide en-keyword=human small airway epithelial cell kn-keyword=human small airway epithelial cell en-keyword=epigenetics kn-keyword=epigenetics en-keyword=DNA methylation kn-keyword=DNA methylation en-keyword=carbonic anhydrase 9 kn-keyword=carbonic anhydrase 9 en-keyword=hypoxia-inducible factor 1 alpha kn-keyword=hypoxia-inducible factor 1 alpha END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=43 article-no= start-page=eadi8446 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231025 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPII en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diatoms rely on fucoxanthin chlorophyll a/c-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)-FCPII supercomplex from Thalassiosira pseudonana at 2.68-angstrom resolution by cryo-electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls a/c is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms. en-copyright= kn-copyright= en-aut-name=FengYue en-aut-sei=Feng en-aut-mei=Yue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiZhenhua en-aut-sei=Li en-aut-mei=Zhenhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiXiaoyi en-aut-sei=Li en-aut-mei=Xiaoyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShenLili en-aut-sei=Shen en-aut-mei=Lili kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuXueyang en-aut-sei=Liu en-aut-mei=Xueyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhouCuicui en-aut-sei=Zhou en-aut-mei=Cuicui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangJinyang en-aut-sei=Zhang en-aut-mei=Jinyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SangMin en-aut-sei=Sang en-aut-mei=Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YangWenqiang en-aut-sei=Yang en-aut-mei=Wenqiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=China National Botanical Garden kn-affil= affil-num=9 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=10 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=13 article-no= start-page=2326 end-page= 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=Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin–AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC. en-copyright= kn-copyright= en-aut-name=YoshidaSaori en-aut-sei=Yoshida en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= en-aut-name=SanouSho en-aut-sei=Sanou en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 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=9 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=10 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=11 ORCID= affil-num=1 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Oral and Maxillofacial Radiology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Preliminary Examination Room, Okayama University Hospital kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=CXCR4 kn-keyword=CXCR4 en-keyword=cisplatin kn-keyword=cisplatin en-keyword=antitumor vascular therapy kn-keyword=antitumor vascular therapy END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=13 article-no= start-page=e34206 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240715 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Vital pulp therapy (VPT) is performed to preserve dental pulp. However, the biocompatibility of the existing materials is of concern. Therefore, novel materials that can induce pulp healing without adverse effects need to be developed. Resolvin D2 (RvD2), one of specialized pro-resolving mediators, can resolve inflammation and promote the healing of periapical lesions. Therefore, RvD2 may be suitable for use in VPT. In the present study, we evaluated the efficacy of RvD2 against VPT using in vivo and in vitro models.
Methods: First molars of eight-week-old male Sprague–Dawley rats were used for pulpotomy. They were then divided into three treatment groups: RvD2, phosphate-buffered saline, and calcium hydroxide groups. Treatment results were assessed using radiological, histological, and immunohistochemical (GPR18, TNF-α, Ki67, VEGF, TGF-β, CD44, CD90, and TRPA1) analyses. Dental pulp-derived cells were treated with RvD2 in vitro and analyzed using cell-proliferation and cell-migration assays, real-time PCR (Gpr18, Tnf-α, Il-1β, Tgf-β, Vegf, Nanog, and Trpa1), ELISA (VEGF and TGF-β), immunocytochemistry (TRPA1), and flow cytometry (dental pulp stem cells: DPSCs).
Results: The formation of calcified tissue in the pulp was observed in the RvD2 and calcium hydroxide groups. RvD2 inhibited inflammation in dental pulp cells. RvD2 promoted cell proliferation and migration and the expression of TGF-β and VEGF in vitro and in vivo. RvD2 increased the number of DPSCs. In addition, RvD2 suppressed TRPA1 expression as a pain receptor.
Conclusion: RvD2 induced the formation of reparative dentin, anti-inflammatory effects, and decreased pain, along with the proliferation of DPSCs via the expression of VEGF and TGF-β, on the pulp surface in pulpotomy models. en-copyright= kn-copyright= en-aut-name=YonedaMitsuhiro en-aut-sei=Yoneda en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraShin en-aut-sei=Nakamura en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AriasZulema en-aut-sei=Arias en-aut-mei=Zulema kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki 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=YamamotoTadashi en-aut-sei=Yamamoto en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University kn-affil= affil-num=4 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 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=The Center for Graduate Medical Education (Dental Division), Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Dental pulp kn-keyword=Dental pulp en-keyword=Regeneration kn-keyword=Regeneration en-keyword=Pulp-capping agents kn-keyword=Pulp-capping agents en-keyword=Specialized pro-resolving mediators kn-keyword=Specialized pro-resolving mediators en-keyword=Resolvin D2 kn-keyword=Resolvin D2 en-keyword=Calcification kn-keyword=Calcification en-keyword=Cytokine kn-keyword=Cytokine en-keyword=TRPA1 kn-keyword=TRPA1 en-keyword=Animal model kn-keyword=Animal model END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=11 article-no= start-page=2632 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy. en-copyright= kn-copyright= en-aut-name=ZhouShengli en-aut-sei=Zhou en-aut-mei=Shengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsutsumiuchiKaname en-aut-sei=Tsutsumiuchi en-aut-mei=Kaname kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImaiRitsuko en-aut-sei=Imai en-aut-mei=Ritsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MikiYukiko en-aut-sei=Miki en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KondoAnna en-aut-sei=Kondo en-aut-mei=Anna kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NakagawaHiroshi en-aut-sei=Nakagawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=3 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=4 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=5 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=6 en-affil=College of Bioscience and Biotechnology, Chubu University kn-affil= affil-num=7 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=8 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= en-keyword=tumor-homing peptide kn-keyword=tumor-homing peptide en-keyword=magnetic hyperthermia kn-keyword=magnetic hyperthermia en-keyword=magnetic nanoparticles kn-keyword=magnetic nanoparticles en-keyword=ferroptosis kn-keyword=ferroptosis en-keyword=tumor-specific delivery kn-keyword=tumor-specific delivery END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=11 article-no= start-page=5889 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240528 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components—thrombin, heme, and ferrous ion— prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery. en-copyright= kn-copyright= en-aut-name=GaoShangze en-aut-sei=Gao en-aut-mei=Shangze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TomonoYasuko en-aut-sei=Tomono en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuLi en-aut-sei=Fu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoYuan en-aut-sei=Gao en-aut-mei=Yuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiYohei en-aut-sei=Takahashi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YataMariko en-aut-sei=Yata en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= affil-num=1 en-affil=Department of Translational Research & Drug Development, 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 Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=epidural hematoma kn-keyword=epidural hematoma en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=inflammatory response kn-keyword=inflammatory response END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=5 article-no= start-page=e0300644 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240517 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= 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=Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma. en-copyright= kn-copyright= en-aut-name=ThuYin Min en-aut-sei=Thu en-aut-mei=Yin Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=OchiKosuke en-aut-sei=Ochi en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsudakaShimpei en-aut-sei=Tsudaka en-aut-mei=Shimpei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakatsuFumiaki en-aut-sei=Takatsu en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DateKeiichi en-aut-sei=Date en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsudaNaoki en-aut-sei=Matsuda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= en-aut-name=YamamotoHiromasa en-aut-sei=Yamamoto en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 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=15 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=Center for Comprehensive Genomic Medicine, Okayama University Hospital 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine 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 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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 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=15 en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=807 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism. en-copyright= kn-copyright= en-aut-name=MuXindi en-aut-sei=Mu en-aut-mei=Xindi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NguyenHa Thi Thu en-aut-sei=Nguyen en-aut-mei=Ha Thi Thu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ZhaoKun en-aut-sei=Zhao en-aut-mei=Kun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KomoriTaishi en-aut-sei=Komori en-aut-mei=Taishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil= kn-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cell differentiation kn-keyword=cell differentiation en-keyword=epithelia kn-keyword=epithelia en-keyword=growth factor(s) kn-keyword=growth factor(s) en-keyword=bioinformatics kn-keyword=bioinformatics en-keyword=extracellular matrix (ECM) kn-keyword=extracellular matrix (ECM) en-keyword=mucocutaneous disorders kn-keyword=mucocutaneous disorders END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=10 article-no= start-page=e174618 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= 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=Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro -tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph -circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC. en-copyright= kn-copyright= 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=1 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=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= en-aut-name=ShanQuisheng en-aut-sei=Shan en-aut-mei=Quisheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= en-aut-name=MizukawaNobuyoshi en-aut-sei=Mizukawa en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and 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 Universit kn-affil= affil-num=6 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, 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=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=光共生性無腸動物Praesagittifera naikaiensisの行動メカニズムに関する研究 kn-title=Studies on behavioral mechanisms in a photosymbiotic acoel flatworm, Praesagittifera naikaiensis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SAKAGAMITosuke en-aut-sei=SAKAGAMI en-aut-mei=Tosuke kn-aut-name=坂上登亮 kn-aut-sei=坂上 kn-aut-mei=登亮 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=鉄添加した底質微生物燃料電池を用いた農業排水路におけるリン内部負荷の削減 kn-title=Reduction of internal phosphorus loading in agricultural drainages using iron-incorporated sediment microbial fuel cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=GAMAMADA LIYANAGE ERANDI PRIYANGIKA PERERA en-aut-sei=GAMAMADA LIYANAGE ERANDI PRIYANGIKA PERERA 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=二酸化炭素を化学原料に用いる化学物質のワンポット合成 kn-title=One-Pot Synthesis of Chemicals Using CO2 as Chemical Feedstock en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NAKAOKAKoichi en-aut-sei=NAKAOKA en-aut-mei=Koichi kn-aut-name=中岡弘一 kn-aut-sei=中岡 kn-aut-mei=弘一 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama university kn-affil=岡山大学大学院自然科学研究科 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=タンパク質付加体形成を介したメチルビニルケトンの成長因子シグナル伝達調節機構 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MORIMOTOAtsushi en-aut-sei=MORIMOTO en-aut-mei=Atsushi kn-aut-name=森本睦 kn-aut-sei=森本 kn-aut-mei=睦 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=核内SphK2/S1Pシグナルによるアストロサイト制御機構の解析 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOMAIMasato en-aut-sei=KOMAI en-aut-mei=Masato kn-aut-name=駒井真人 kn-aut-sei=駒井 kn-aut-mei=真人 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=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Streptococcus mutans の Cnm は細胞表面構造と膜透過性に重要である kn-title=Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MATSUOKADaiki en-aut-sei=MATSUOKA en-aut-mei=Daiki kn-aut-name=松岡大貴 kn-aut-sei=松岡 kn-aut-mei=大貴 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=軟骨細胞におけるCCN2に由来する環状RNAの発現とその機能 kn-title=Expression and function of CCN2-derived circRNAs in chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KATOSoma en-aut-sei=KATO en-aut-mei=Soma kn-aut-name=加藤壮真 kn-aut-sei=加藤 kn-aut-mei=壮真 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=S-アデノシルメチオニンはポリアミン産生および軟骨分化関連因子の遺伝子発現を介して軟骨分化を正に制御する。 kn-title=Positive regulation of S-adenosylmethionine on chondrocytic differentiation via stimulation of polyamine production and the gene expression of chondrogenic differentiation factors en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Hoang Dinh Loc en-aut-sei=Hoang Dinh Loc 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Rab11はEGFR発現とEpCAM含有エクソソームの分泌を制御することで頭頸部癌を抑制する kn-title=Rab11 Suppresses Head and Neck Carcinoma by Regulating EGFR and EpCAM Exosome Secretion en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YOSHIDAKunihiro en-aut-sei=YOSHIDA en-aut-mei=Kunihiro kn-aut-name=吉田国弘 kn-aut-sei=吉田 kn-aut-mei=国弘 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=EpCAMの可溶性細胞外ドメインであるEpEXは、EGFR高発現頭頸部扁平上皮癌のセツキシマブ治療抵抗性に関与する kn-title=EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UMEMORIKoki en-aut-sei=UMEMORI en-aut-mei=Koki kn-aut-name=梅森洸樹 kn-aut-sei=梅森 kn-aut-mei=洸樹 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ヒト副腎皮質細胞ステロイド合成におけるオレキシンとBMPの相互作用 kn-title=Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SOEJIMAYoshiaki en-aut-sei=SOEJIMA en-aut-mei=Yoshiaki kn-aut-name=副島佳晃 kn-aut-sei=副島 kn-aut-mei=佳晃 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=非アルコール性脂肪性肝炎の併発はマウスモデルにおけるアディポネクチン発現低下に関連し乾癬を悪化させる kn-title=Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKEZAKIDaiki en-aut-sei=TAKEZAKI en-aut-mei=Daiki kn-aut-name=竹﨑大輝 kn-aut-sei=竹﨑 kn-aut-mei=大輝 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=マウスにおける鈍的胸部外傷後の肺挫傷に対する水素吸入療法 kn-title=Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AGETAKohei en-aut-sei=AGETA en-aut-mei=Kohei kn-aut-name=上田浩平 kn-aut-sei=上田 kn-aut-mei=浩平 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=非小細胞肺癌におけるがん関連線維芽細胞由来ペリオスチンの腫瘍促進効果および薬剤耐性誘導効果 kn-title=Periostin secreted by cancer-associated fibroblasts promotes cancer progression and drug resistance in non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAKATSUFumiaki en-aut-sei=TAKATSU en-aut-mei=Fumiaki kn-aut-name=髙津史明 kn-aut-sei=髙津 kn-aut-mei=史明 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=CDK4/6シグナル伝達は、EGFR変異型非小細胞肺がんにおける上皮成長因子受容体チロシンキナーゼ阻害剤の効果を減弱させる kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HARANaofumi en-aut-sei=HARA en-aut-mei=Naofumi kn-aut-name=原尚史 kn-aut-sei=原 kn-aut-mei=尚史 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=p53搭載腫瘍融解アデノウイルスは、KRASおよびBRAF変異結腸直腸癌細胞において、オートファジーとアポトーシスを誘導する kn-title=p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=TAMURAShuta en-aut-sei=TAMURA en-aut-mei=Shuta kn-aut-name=田村周太 kn-aut-sei=田村 kn-aut-mei=周太 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=二重抗血小板療法は好中球細胞外トラップを阻害することで、肝内胆管癌の微小肝転移を抑制する kn-title=Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YOSHIMOTOMasashi en-aut-sei=YOSHIMOTO en-aut-mei=Masashi kn-aut-name=吉本匡志 kn-aut-sei=吉本 kn-aut-mei=匡志 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=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=マウス系統によって異なる耐寒性が系統別ES細胞においても存在する kn-title=Mouse embryonic stem cells embody organismal-level cold resistance en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SUITAKoukyou en-aut-sei=SUITA en-aut-mei=Koukyou kn-aut-name=吹田晃享 kn-aut-sei=吹田 kn-aut-mei=晃享 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=58 cd-vols= no-issue=2 article-no= start-page=88 end-page=97 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Enhancing effect of the coexisting alpha-tocopherol on quercetin absorption and metabolism en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study is to investigate the modulating effect of coexisting food components on the absorption and metabolism of quercetin and blood plasma antioxidant potentials. The combination of quercetin with α-tocopherol (αT), cellulose, or a commercially available vegetable beverage containing αT and dietary fiber was orally administered to mice. Compared to the single administration of quercetin aglycone, the coadministration of αT with quercetin significantly increased the plasma quercetin concentration at 0.5 h, whereas the combination of quercetin and cellulose decreased it. Interestingly, the administration of quercetin mixed with the vegetable beverage showed no significant change in the quercetin concentration in the mice plasma. The treatment of the cells with the blood plasma after the coadministration of αT with quercetin significantly upregulated the gene expression of the antioxidant enzyme (heme oxygenase-1), whereas the quercetin and cellulose combination did not. In the plasma of the quercetin-administered mice, eight types of quercetin metabolites were detected, and their quantities were affected by the combination with αT. The potentials of the heme oxygenase-1 gene expression by these metabolites were very limited, although several metabolites showed radical scavenging activities comparable to aglycone in the in vitro assays. These results suggested that the combination of αT potentiates the quercetin absorption and metabolism and thus the plasma antioxidant potentials, at least in part, by the quantitative changes in the quercetin metabolites. en-copyright= kn-copyright= en-aut-name=MitsuzaneRikito en-aut-sei=Mitsuzane en-aut-mei=Rikito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkuboReiko en-aut-sei=Okubo en-aut-mei=Reiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishikawaMiyu en-aut-sei=Nishikawa en-aut-mei=Miyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IkushiroShinichi en-aut-sei=Ikushiro en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 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=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=Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University kn-affil= affil-num=4 en-affil=Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University kn-affil= affil-num=5 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Graduate School of Environmental and Life Science, Okayama 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= en-keyword=quercetin kn-keyword=quercetin en-keyword=metabolite kn-keyword=metabolite en-keyword=absorption kn-keyword=absorption en-keyword=metabolism kn-keyword=metabolism en-keyword=antioxidant activity kn-keyword=antioxidant activity END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=4 article-no= start-page=746 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pyrene-Modified Cyclic Peptides Detect Cu2+ Ions by Fluorescence in Water en-subtitle= kn-subtitle= en-abstract= kn-abstract=The detection of metal ions is an option for maintaining water quality and diagnosing metal ion-related diseases. In this study, we successfully detected metal ions using fluorescent peptides in water. First, we prepared seven linear (L1-L7) and seven cyclic (C1-C7) peptides containing two pyrenyl (Pyr) units and assessed the response to various metal ions by fluorescence. The results indicated that C1, which contains a hexameric cyclic peptide moiety consisting of Pyr and Gly units, did not show a fluorescent response to metal ions, while the linear L1 corresponding to C1 showed a response to Cu2+, but its selectivity was found to be poor through a competition assay for each metal ion. We then assessed C2-C7 and L2-L7, in which Gly was replaced by His units at various positions in the same manner. The results showed that C2-C7 responded to Cu2+ in a manner dependent on the His position. Additionally, superior selectivity was observed in C7 through a competition assay. These results demonstrate that the structural restriction of peptides and the sequence affect the selective detection of Cu2+ and reveal that peptides with an appropriate structure can accomplish the fluorescent detection of Cu2+ specifically. en-copyright= kn-copyright= en-aut-name=MaekawaYuhi en-aut-sei=Maekawa en-aut-mei=Yuhi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakuraSora en-aut-sei=Sakura en-aut-mei=Sora kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurutaniYuji en-aut-sei=Furutani en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujiharaRento en-aut-sei=Fujihara en-aut-mei=Rento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SugimeHisashi en-aut-sei=Sugime en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Faculty of Science and Engineering, Kindai 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 Applied Chemistry, Faculty of Science and Engineering, Kindai University kn-affil= affil-num=5 en-affil=Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University kn-affil= en-keyword=peptide kn-keyword=peptide en-keyword=pyrene kn-keyword=pyrene en-keyword=metal ion kn-keyword=metal ion en-keyword=fluorescence kn-keyword=fluorescence END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.
Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.
Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.
Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC. en-copyright= kn-copyright= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi 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=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya 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=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 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=17 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=18 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=19 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=20 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 Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical 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=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 Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Epidermal growth factor receptor (EGFR) kn-keyword=Epidermal growth factor receptor (EGFR) en-keyword=non-small cell lung cancer (NSCLC) kn-keyword=non-small cell lung cancer (NSCLC) en-keyword=cell cycle kn-keyword=cell cycle en-keyword=CDK4/6 inhibitor kn-keyword=CDK4/6 inhibitor END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=100297 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiation evaluation assay using a human three-dimensional oral cancer model for clinical radiation therapy. en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the development of various radiation -based cancer therapies, radiobiological evaluation methods instead of traditional clonogenic assays with monolayer single cell culture are required to bridge gaps in clinical data. Heterogeneity within cancer tissues is the reason for bridging the gap between basic and clinical research in cancer radiotherapy. To solve this problem, we investigated an evaluation assay using a three-dimensional (3D) model of cancer tissue. In this study, a 3D model consisting of tumor and stromal layers was used to compare and verify radiobiological effects with conventional two-dimensional (2D) methods. A significant difference in the response to radiation was observed between the 2D and 3D models. The relative number of cancer cells decreased with X-ray dose escalations in the 2D and 3D models. In contrast, the relative number of normal cells was quite different between the 2D and 3D models. Considering the ability of cells to recover from radiation-induced damage, the histological results of the 3D model were reflected in the clinical data. Histopathological analysis using a 3D model is a potential method for evaluating radiobiological effects on the tumor and tumor margins. en-copyright= kn-copyright= en-aut-name=SercombeLucie en-aut-sei=Sercombe en-aut-mei=Lucie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= affil-num=1 en-affil=Biomedical Engineering Department, Grenoble Institute of Technology kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Oral cancer model kn-keyword=Oral cancer model en-keyword=3D-cell culture kn-keyword=3D-cell culture en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=Histopathological assay kn-keyword=Histopathological assay en-keyword=Radiobiological evaluation kn-keyword=Radiobiological evaluation END start-ver=1.4 cd-journal=joma no-vol=154 cd-vols= no-issue=3 article-no= start-page=209 end-page=217 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=Attenuation of protein arginine dimethylation via S-nitrosylation of protein arginine methyltransferase 1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Upregulation of nitric oxide (NO) production contributes to the pathogenesis of numerous diseases via S-nitro- sylation, a post-translational modification of proteins. This process occurs due to the oxidative reaction between NO and a cysteine thiol group; however, the extent of this reaction remains unknown. S-Nitrosylation of PRMT1, a major asymmetric arginine methyltransferase of histones and numerous RNA metabolic proteins, was induced by NO donor treatment. We found that nitrosative stress leads to S-nitrosylation of cysteine 119, located near the active site, and attenuates the enzymatic activity of PRMT1. Interestingly, RNA sequencing analysis revealed similarities in the changes in expression elicited by NO and PRMT1 inhibitors or knockdown. A comprehensive search for PRMT1 substrates using the proximity-dependent biotin identification method highlighted many known and new substrates, including RNA-metabolizing enzymes. To validate this result, we selected the RNA helicase DDX3 and demonstrated that arginine methylation of DDX3 is induced by PRMT1 and attenuated by NO treatment. Our results suggest the existence of a novel regulatory system associated with transcription and RNA metabolism via protein S-nitrosylation. en-copyright= kn-copyright= en-aut-name=TaniguchiRikako en-aut-sei=Taniguchi en-aut-mei=Rikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaYuto en-aut-sei=Moriya en-aut-mei=Yuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 ORCID= en-aut-name=NakaharaKengo en-aut-sei=Nakahara en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=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=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science kn-affil= affil-num=4 en-affil=Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science 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=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Nitric oxide kn-keyword=Nitric oxide en-keyword=S-Nitrosylation kn-keyword=S-Nitrosylation en-keyword=Protein arginine methyltransferase 1 (PRMT1) kn-keyword=Protein arginine methyltransferase 1 (PRMT1) en-keyword=RNA metabolism kn-keyword=RNA metabolism en-keyword=Dead-box helicase 3X-linxed (DDX3) kn-keyword=Dead-box helicase 3X-linxed (DDX3) END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=3 article-no= start-page=100510 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=Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The link between changes in astrocyte function and the pathological progression of Alzheimer's disease (AD) has attracted considerable attention. Interestingly, activated astrocytes in AD show abnormalities in their lipid content and metabolism. In particular, the expression of apolipoprotein E (ApoE), a lipid transporter, is decreased. Because ApoE has anti-inflammatory and amyloid β (Aβ)-metabolizing effects, the nuclear receptors, retinoid X receptor (RXR) and LXR, which are involved in ApoE expression, are considered promising therapeutic targets for AD. However, the therapeutic effects of agents targeting these receptors are limited or vary considerably among groups, indicating the involvement of an unknown pathological factor that modifies astrocyte and ApoE function. Here, we focused on the signaling lipid, sphingosine-1-phosphate (S1P), which is mainly produced by sphingosine kinase 2 (SphK2) in the brain. Using astrocyte models, we found that upregulation of SphK2/S1P signaling suppressed ApoE induction by both RXR and LXR agonists. We also found that SphK2 activation reduced RXR binding to the APOE promoter region in the nucleus, suggesting the nuclear function of SphK2/S1P. Intriguingly, suppression of SphK2 activity by RNA knockdown or specific inhibitors upregulated lipidated ApoE induction. Furthermore, the induced ApoE facilitates Aβ uptake in astrocytes. Together with our previous findings that SphK2 activity is upregulated in AD brain and promotes Aβ production in neurons, these results indicate that SphK2/S1P signaling is a promising multifunctional therapeutic target for AD that can modulate astrocyte function by stabilizing the effects of RXR and LXR agonists, and simultaneously regulate neuronal pathogenesis. en-copyright= kn-copyright= en-aut-name=KomaiMasato en-aut-sei=Komai en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NodaYuka en-aut-sei=Noda en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkedaAtsuya en-aut-sei=Ikeda en-aut-mei=Atsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaneshiroNanaka en-aut-sei=Kaneshiro en-aut-mei=Nanaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KamikuboYuji en-aut-sei=Kamikubo en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakuraiTakashi en-aut-sei=Sakurai en-aut-mei=Takashi 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= en-aut-name=TakasugiNobumasa en-aut-sei=Takasugi en-aut-mei=Nobumasa 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 Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=alzheimer's disease kn-keyword=alzheimer's disease en-keyword=apolipoproteins kn-keyword=apolipoproteins en-keyword=nuclear receptors/RXR kn-keyword=nuclear receptors/RXR en-keyword=transcription kn-keyword=transcription en-keyword=sphingosine phosphate kn-keyword=sphingosine phosphate en-keyword=astrocytes kn-keyword=astrocytes en-keyword=amyloid β kn-keyword=amyloid β en-keyword=sphingosine kinase 2 kn-keyword=sphingosine kinase 2 en-keyword=low-density lipoprotein receptor-related protein 4 kn-keyword=low-density lipoprotein receptor-related protein 4 END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=6 article-no= start-page=3523 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240320 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system. en-copyright= kn-copyright= en-aut-name=SasakiShigenori en-aut-sei=Sasaki en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OgawaHirohito en-aut-sei=Ogawa en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KatohHirokazu en-aut-sei=Katoh en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HondaTomoyuki en-aut-sei=Honda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=antiviral kn-keyword=antiviral en-keyword=antivirals kn-keyword=antivirals en-keyword=Borna disease virus kn-keyword=Borna disease virus en-keyword=CRISPR/Cas13b kn-keyword=CRISPR/Cas13b en-keyword=persistent infection kn-keyword=persistent infection END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=5 article-no= start-page=719 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Impact of Phenological Gaps on Leaf Characteristics and Foliage Dynamics of an Understory Dwarf Bamboo, Sasa kurilensis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phenological gaps exert a significant influence on the growth of dwarf bamboos. However, how dwarf bamboos respond to and exploit these phenological gaps remain enigmatic. The light environment, soil nutrients, leaf morphology, maximum photosynthetic rate, foliage dynamics, and branching characteristics of Sasa kurilensis were examined under the canopies of Fagus crenata and Magnolia obovata. The goal was to elucidate the adaptive responses of S. kurilensis to phenological gaps in the forest understory. The findings suggest that phenological gaps under an M. obovata canopy augment the available biomass of S. kurilensis, enhancing leaf area, leaf thickness, and carbon content per unit area. However, these gaps do not appreciably influence the maximum photosynthetic rate, total leaf number, leaf lifespan, branch number, and average branch length. These findings underscore the significant impact of annually recurring phenological gaps on various aspects of S. kurilensis growth, such as its aboveground biomass, leaf morphology, and leaf biochemical characteristics. It appears that leaf morphology is a pivotal trait in the response of S. kurilensis to phenological gaps. Given the potential ubiquity of the influence of phenological gaps on dwarf bamboos across most deciduous broadleaf forests, this canopy phenomenon should not be overlooked. en-copyright= kn-copyright= en-aut-name=WuChongyang en-aut-sei=Wu en-aut-mei=Chongyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaRyota en-aut-sei=Tanaka en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiyoshiKyohei en-aut-sei=Fujiyoshi en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkajiYasuaki en-aut-sei=Akaji en-aut-mei=Yasuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HirobeMuneto en-aut-sei=Hirobe en-aut-mei=Muneto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MikiNaoko en-aut-sei=Miki en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiJuan en-aut-sei=Li en-aut-mei=Juan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakamotoKeiji en-aut-sei=Sakamoto en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GaoJian en-aut-sei=Gao en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration kn-affil= affil-num=2 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Agriculture, Okayama University kn-affil= affil-num=4 en-affil=Biodiversity Division, National Institute for Environmental Studies kn-affil= affil-num=5 en-affil=Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=6 en-affil=Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration kn-affil= affil-num=8 en-affil=Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=9 en-affil=Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration kn-affil= en-keyword=bamboo kn-keyword=bamboo en-keyword=sasa kn-keyword=sasa en-keyword=beech forest kn-keyword=beech forest en-keyword=phenological gap kn-keyword=phenological gap en-keyword=canopy kn-keyword=canopy en-keyword=understory plant kn-keyword=understory plant en-keyword=plant morphology kn-keyword=plant morphology en-keyword=plastically kn-keyword=plastically en-keyword=leaf phenology kn-keyword=leaf phenology END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=8164 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structural insights into photosystem II supercomplex and trimeric FCP antennae of a centric diatom Cyclotella meneghiniana en-subtitle= kn-subtitle= en-abstract= kn-abstract=Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana. en-copyright= kn-copyright= en-aut-name=ZhaoSonghao en-aut-sei=Zhao en-aut-mei=Songhao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShenLili en-aut-sei=Shen en-aut-mei=Lili kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiXiaoyi en-aut-sei=Li en-aut-mei=Xiaoyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TaoQiushuang en-aut-sei=Tao en-aut-mei=Qiushuang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiZhenhua en-aut-sei=Li en-aut-mei=Zhenhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=XuCaizhe en-aut-sei=Xu en-aut-mei=Caizhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhouCuicui en-aut-sei=Zhou en-aut-mei=Cuicui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YangYanyan en-aut-sei=Yang en-aut-mei=Yanyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SangMin en-aut-sei=Sang en-aut-mei=Min kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HanGuangye en-aut-sei=Han en-aut-mei=Guangye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YuLong-Jiang en-aut-sei=Yu en-aut-mei=Long-Jiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KuangTingyun en-aut-sei=Kuang en-aut-mei=Tingyun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=WangWenda en-aut-sei=Wang en-aut-mei=Wenda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=2 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=3 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=4 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=5 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=6 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=9 en-affil=China National Botanical Garden kn-affil= affil-num=10 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=11 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=12 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= affil-num=13 en-affil=Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=14 en-affil=Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=7 article-no= start-page=104839 end-page= 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=Structural insights into the action mechanisms of artificial electron acceptors in photosystem II en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem II (PSII) utilizes light energy to split water, and the electrons extracted from water are transferred to QB, a plastoquinone molecule bound to the D1 subunit of PSII. Many artificial electron acceptors (AEAs) with molecular structures similar to that of plastoquinone can accept electrons from PSII. However, the molecular mechanism by which AEAs act on PSII is unclear. Here, we solved the crystal structure of PSII treated with three different AEAs, 2,5-dibromo-1,4-benzoquinone, 2,6dichloro-1,4-benzoquinone, and 2-phenyl-1,4-benzoquinone, at 1.95 to 2.10 angstrom resolution. Our results show that all AEAs substitute for QB and are bound to the QB-binding site (QB site) to receive electrons, but their binding strengths are different, resulting in differences in their efficiencies to accept electrons. The acceptor 2-phenyl-1,4-benzoquinone binds most weakly to the QB site and showed the highest oxygen-evolving activity, implying a reverse relationship between the binding strength and oxygen-evolving activity. In addition, a novel quinonebinding site, designated the QD site, was discovered, which is located in the vicinity of QB site and close to QC site, a binding site reported previously. This QD site is expected to play a role as a channel or a storage site for quinones to be transported to the QB site. These results provide the structural basis for elucidating the actions of AEAs and exchange mechanism of QB in PSII and also provide information for the design of more efficient electron acceptors. en-copyright= kn-copyright= en-aut-name=KamadaShinji en-aut-sei=Kamada en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaYoshiki en-aut-sei=Nakajima en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Faculty of Science, Okayama University kn-affil= affil-num=2 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=photosynthesis kn-keyword=photosynthesis en-keyword=electron transfer kn-keyword=electron transfer en-keyword=structural biology kn-keyword=structural biology en-keyword=crystal structure kn-keyword=crystal structure en-keyword=electron acceptor kn-keyword=electron acceptor END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=3 article-no= start-page=1443 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. en-copyright= kn-copyright= en-aut-name=HottaYoshifumi en-aut-sei=Hotta en-aut-mei=Yoshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 ORCID= en-aut-name=NasuYoshihisa en-aut-sei=Nasu en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakaharaRyuichi en-aut-sei=Nakahara en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaniwaShuichi en-aut-sei=Naniwa en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimizuNoriyuki en-aut-sei=Shimizu en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchikawaChinatsu en-aut-sei=Ichikawa en-aut-mei=Chinatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinDeting en-aut-sei=Lin en-aut-mei=Deting kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Locomotive Pain Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Orthopaedic Surgery, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=osteoarthritis kn-keyword=osteoarthritis en-keyword=chondrocyte kn-keyword=chondrocyte en-keyword=mechanical stress kn-keyword=mechanical stress en-keyword=tankyrases kn-keyword=tankyrases en-keyword=XAV939 kn-keyword=XAV939 en-keyword=SOX9 kn-keyword=SOX9 en-keyword=ADAMTS-5 kn-keyword=ADAMTS-5 en-keyword=MMP-13 kn-keyword=MMP-13 en-keyword=IL-1β kn-keyword=IL-1β en-keyword=NF-κB kn-keyword=NF-κB en-keyword=β-catenin kn-keyword=β-catenin END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue= article-no= start-page=1338669 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240129 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tetrathionate hydrolase from the acidophilic microorganisms en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tetrathionate hydrolase (TTH) is a unique enzyme found in acidophilic sulfur-oxidizing microorganisms, such as bacteria and archaea. This enzyme catalyzes the hydrolysis of tetrathionate to thiosulfate, elemental sulfur, and sulfate. It is also involved in dissimilatory sulfur oxidation metabolism, the S-4-intermediate pathway. TTHs have been purified and characterized from acidophilic autotrophic sulfur-oxidizing microorganisms. All purified TTHs show an optimum pH in the acidic range, suggesting that they are localized in the periplasmic space or outer membrane. In particular, the gene encoding TTH from Acidithiobacillus ferrooxidans (Af-tth) was identified and recombinantly expressed in Escherichia coli cells. TTH activity could be recovered from the recombinant inclusion bodies by acid refolding treatment for crystallization. The mechanism of tetrathionate hydrolysis was then elucidated by X-ray crystal structure analysis. Af-tth is highly expressed in tetrathionate-grown cells but not in iron-grown cells. These unique structural properties, reaction mechanisms, gene expression, and regulatory mechanisms are discussed in this review. en-copyright= kn-copyright= en-aut-name=KanaoTadayoshi en-aut-sei=Kanao en-aut-mei=Tadayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Agricultural and Biological Chemistry, Graduate School of Environment, Life, Natural Science, and Technology, Okayama University kn-affil= en-keyword=tetrathionate hydrolase kn-keyword=tetrathionate hydrolase en-keyword=reduced inorganic sulfur compounds kn-keyword=reduced inorganic sulfur compounds en-keyword=dissimilatory sulfur metabolism kn-keyword=dissimilatory sulfur metabolism en-keyword=S4-intermediate pathway kn-keyword=S4-intermediate pathway en-keyword=acidophiles kn-keyword=acidophiles en-keyword=chemoautotroph kn-keyword=chemoautotroph END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=3 article-no= start-page=1585 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240127 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine beta-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells. 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=IwataNahoko en-aut-sei=Iwata en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 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= en-keyword=bone morphogenetic protein (BMP) kn-keyword=bone morphogenetic protein (BMP) en-keyword=orexin kn-keyword=orexin en-keyword=catecholamine and adrenal kn-keyword=catecholamine and adrenal END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=8 article-no= start-page=707 end-page=713 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=Terpolymerizations of cyclohexene oxide, CO2, and isocyanates or isothiocyanates for the synthesis of poly(carbonate–urethane)s or poly(carbonate–thioimidocarbonate)s en-subtitle= kn-subtitle= en-abstract= kn-abstract=Terpolymerization of cyclohexene oxide (CHO), CO2, and aryl isothiocyanates produced poly(carbonate–thioimidocarbonate)s with gradient character, while that of CHO, CO2, and aryl isocyanates furnished poly(carbonate–urethane)s with random sequences. The former underwent partial degradation upon acid treatment or UV irradiation, while the latter was stable under the same conditions. en-copyright= kn-copyright= en-aut-name=NakaokaKoichi en-aut-sei=Nakaoka en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MuranakaSatoshi en-aut-sei=Muranaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoIo en-aut-sei=Yamamoto en-aut-mei=Io kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=EmaTadashi en-aut-sei=Ema en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=11 article-no= start-page=e0294491 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis. en-copyright= kn-copyright= en-aut-name=TamuraShuta en-aut-sei=Tamura en-aut-mei=Shuta 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=HoriNaoto en-aut-sei=Hori en-aut-mei=Naoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LiYuncheng en-aut-sei=Li en-aut-mei=Yuncheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=UrataYasuo en-aut-sei=Urata en-aut-mei=Yasuo 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=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=Oncolys BioPharma, Inc. 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= END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue= article-no= start-page=102054 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs. en-copyright= kn-copyright= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=UetaEijiro en-aut-sei=Ueta en-aut-mei=Eijiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaTakashi en-aut-sei=Oda en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuchiTatsuya en-aut-sei=Kikuchi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkoSoichiro en-aut-sei=Ako en-aut-mei=Soichiro 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=YamazakiTatsuhiro en-aut-sei=Yamazaki en-aut-mei=Tatsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=KatoHironari en-aut-sei=Kato en-aut-mei=Hironari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=14 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital 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= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=14 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= END start-ver=1.4 cd-journal=joma no-vol=186 cd-vols= no-issue= article-no= start-page=4189 end-page=4203.e22 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230914 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thrombopoietin (THPO or TPO) is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Here, we report the 3.4 Å resolution cryoelectron microscopy structure of the extracellular TPO-TPO receptor (TpoR or MPL) signaling complex, revealing the basis for homodimeric MPL activation and providing a structural rationalization for genetic loss-of-function thrombocytopenia mutations. The structure guided the engineering of TPO variants (TPOmod) with a spectrum of signaling activities, from neutral antagonists to partial- and super-agonists. Partial agonist TPOmod decoupled JAK/STAT from ERK/AKT/CREB activation, driving a bias for megakaryopoiesis and platelet production without causing significant HSC expansion in mice and showing superior maintenance of human HSCs in vitro. These data demonstrate the functional uncoupling of the two primary roles of TPO, highlighting the potential utility of TPOmod in hematology research and clinical HSC transplantation. en-copyright= kn-copyright= en-aut-name=TsutsumiNaotaka en-aut-sei=Tsutsumi en-aut-mei=Naotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MasoumiZahra en-aut-sei=Masoumi en-aut-mei=Zahra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JamesSophie C. en-aut-sei=James en-aut-mei=Sophie C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TuckerJulie A. en-aut-sei=Tucker en-aut-mei=Julie A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WinkelmannHauke en-aut-sei=Winkelmann en-aut-mei=Hauke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GreyWilliam en-aut-sei=Grey en-aut-mei=William kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=PictonLora K. en-aut-sei=Picton en-aut-mei=Lora K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MossLucie en-aut-sei=Moss en-aut-mei=Lucie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WilsonSteven C. en-aut-sei=Wilson en-aut-mei=Steven C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=CaveneyNathanael A. en-aut-sei=Caveney en-aut-mei=Nathanael A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=JudeKevin M. en-aut-sei=Jude en-aut-mei=Kevin M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GatiCornelius en-aut-sei=Gati en-aut-mei=Cornelius kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=PiehlerJacob en-aut-sei=Piehler en-aut-mei=Jacob kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HitchcockIan S. en-aut-sei=Hitchcock en-aut-mei=Ian S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=GarciaK. Christopher en-aut-sei=Garcia en-aut-mei=K. Christopher kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=3 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=4 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=5 en-affil=Department of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabrück University kn-affil= affil-num=6 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=7 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=8 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=9 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=10 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=11 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= affil-num=12 en-affil=Department of Structural Biology, Stanford University School of Medicine kn-affil= affil-num=13 en-affil=Department of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabrück University kn-affil= affil-num=14 en-affil=York Biomedical Research Institute, Department of Biology, University of York kn-affil= affil-num=15 en-affil=Department of Molecular and Cellular Physiology, Stanford University School of Medicine kn-affil= en-keyword=thrombopoietin kn-keyword=thrombopoietin en-keyword=TpoR kn-keyword=TpoR en-keyword=c-MPL kn-keyword=c-MPL en-keyword=structure kn-keyword=structure en-keyword=cryo-EM kn-keyword=cryo-EM en-keyword=signaling kn-keyword=signaling en-keyword=JAK-STAT kn-keyword=JAK-STAT en-keyword=mTOR kn-keyword=mTOR en-keyword=hematopoiesis kn-keyword=hematopoiesis en-keyword=ligand engineering kn-keyword=ligand engineering END start-ver=1.4 cd-journal=joma no-vol=180 cd-vols= no-issue= article-no= start-page=112270 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202309 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice.
Methods: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury.
Results: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested.
Conclusion: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly. en-copyright= kn-copyright= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IketaniMasumi en-aut-sei=Iketani en-aut-mei=Masumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhsawaIkuroh en-aut-sei=Ohsawa en-aut-mei=Ikuroh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= en-keyword=LPS-induced inflammation kn-keyword=LPS-induced inflammation en-keyword=Elderly sepsis kn-keyword=Elderly sepsis en-keyword=Lipopolysaccharide kn-keyword=Lipopolysaccharide en-keyword=Aged mouse kn-keyword=Aged mouse en-keyword=Senescence-related markers kn-keyword=Senescence-related markers en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas inhalation kn-keyword=Hydrogen gas inhalation END start-ver=1.4 cd-journal=joma no-vol=142 cd-vols= no-issue= article-no= start-page=106433 end-page= 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=EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance.
Materials and methods: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS).
Results: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner.
Conclusion: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab. en-copyright= kn-copyright= en-aut-name=UmemoriKoki en-aut-sei=Umemori en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnoKisho en-aut-sei=Ono en-aut-mei=Kisho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EguchiTakanori en-aut-sei=Eguchi en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=NakamuraTomoya en-aut-sei=Nakamura en-aut-mei=Tomoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaTatsuo en-aut-sei=Ogawa en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaKunihiro en-aut-sei=Yoshida en-aut-mei=Kunihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanemotoHideka en-aut-sei=Kanemoto en-aut-mei=Hideka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoKohei en-aut-sei=Sato en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ObataKyoichi en-aut-sei=Obata en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=RyumonShoji en-aut-sei=Ryumon en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YutoriHirokazu en-aut-sei=Yutori en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KataseNaoki en-aut-sei=Katase en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OkuiTatsuo en-aut-sei=Okui en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 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=15 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=16 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University kn-affil= affil-num=14 en-affil=Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine kn-affil= affil-num=15 en-affil=Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=16 en-affil=Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Cetuximab kn-keyword=Cetuximab en-keyword=epithelial cell adhesion molecule (EpCAM) kn-keyword=epithelial cell adhesion molecule (EpCAM) en-keyword=EpEX kn-keyword=EpEX en-keyword=EpICD kn-keyword=EpICD en-keyword=epidermal growth factor receptor (EGFR) kn-keyword=epidermal growth factor receptor (EGFR) en-keyword=Drug resistance kn-keyword=Drug resistance en-keyword=Head and neck squamous cell carcinoma (HNSC) kn-keyword=Head and neck squamous cell carcinoma (HNSC) END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=6 article-no= start-page=337 end-page=346 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of insulin-like growth factor-1 on the mRNA expression of estradiol receptors, steroidogenic enzymes, and steroid production in bovine follicles en-subtitle= kn-subtitle= en-abstract= kn-abstract=Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are synthesized through the actions of steroidogenic enzymes, specifically STAR, CYP11A1, HSD3B, and CYP19A1 in both theca cells (TCs) and granulosa cells (GCs), under the influence of gonadotropins. Particularly, estradiol 17 beta (E2) assumes a central role in follicular development and selection by activating estrogen receptors beta (ESR2) in GCs. We assessed ESR2 mRNA expression in GCs of developing follicles and investigated the impact of IGF-1 on the mRNA expression of ESR2, CYP19A1, FSHR, and LHCGR, STAR, CYP11A1, and HSD17B in cultured GCs and TCs, respectively. Additionally, we assessed the influence of IGF-1 on androstenedione (A4), progesterone (P4), and testosterone (T) production in TCs. Small-sized follicles (< 6 mm) exhibited the highest levels of ESR2 mRNA expression, whereas medium-sized follicles (7-8 mm) displayed higher levels than large-sized follicles (>= 9 mm) (P < 0.05). IGF-1 increased the mRNA expression of ESR2, CYP19A1, and FSHR in GCs of follicles of both sizes, except for FSHR mRNA in medium-sized follicles (P < 0.05). IGF-1 significantly elevated mRNA expression of LHCGR, STAR, CYP11A1, and CYP17B in TCs of small-and medium-sized follicles (P < 0.05). Moreover, IGF-1 augmented the production of A4 and P4 but had no impact on T production in TCs of small-and medium-sized follicles. Taken together, our findings indicate that IGF-1 upregulates steroidogenic enzymes and steroid hormone production, underscoring the crucial role of IGF-1 in follicle development and selection. en-copyright= kn-copyright= en-aut-name=RawanAhmad Farid en-aut-sei=Rawan en-aut-mei=Ahmad Farid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LangarHikmatullah en-aut-sei=Langar en-aut-mei=Hikmatullah kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MunetomoMaho en-aut-sei=Munetomo en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoYuki en-aut-sei=Yamamoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoKohei en-aut-sei=Kawano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraKoji en-aut-sei=Kimura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=Estradiol receptor kn-keyword=Estradiol receptor en-keyword=Follicle kn-keyword=Follicle en-keyword=Insulin-like growth factor-1 (IGF-1) kn-keyword=Insulin-like growth factor-1 (IGF-1) en-keyword=Steroidogenic enzymes kn-keyword=Steroidogenic enzymes END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=24 article-no= start-page=17294 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes. en-copyright= kn-copyright= en-aut-name=HoangLoc Dinh en-aut-sei=Hoang en-aut-mei=Loc Dinh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AoyamaEriko en-aut-sei=Aoyama en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiasaMiki en-aut-sei=Hiasa en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=S-adenosylmethionine kn-keyword=S-adenosylmethionine en-keyword=chondrocyte differentiation kn-keyword=chondrocyte differentiation en-keyword=CCN2 kn-keyword=CCN2 en-keyword=polyamine kn-keyword=polyamine en-keyword=ODC kn-keyword=ODC en-keyword=gene expression kn-keyword=gene expression 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=1つのRNA上の2つの変異を検出する新規プローブの開発 kn-title=Development of novel probe for detecting two mutations on one RNA en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MYAT THU en-aut-sei=MYAT 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 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=オキシトシンはBMP-15シグナルの増強を伴い卵巣顆粒膜細胞によるプロゲステロン産生を促進する kn-title=Oxytocin enhances progesterone production with upregulation of BMP-15 activity by granulosa cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YAMAMOTOKoichiro en-aut-sei=YAMAMOTO en-aut-mei=Koichiro kn-aut-name=山本紘一郎 kn-aut-sei=山本 kn-aut-mei=紘一郎 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Pacsin 2依存的なN-カドヘリンの細胞内取り込みが悪性がんの運動様式を制御する kn-title=Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WINTHAYMAR en-aut-sei=WINT en-aut-mei=HAYMAR 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=LOXL1 および LOXL4 は、ZEB1 の Zn²⁺結合型の新規標的遺伝子であり、トリプルネガティブ乳がん細胞における浸潤事象の加速に重要な役割を果たす kn-title=LOXL1 and LOXL4 are novel target genes of the Zn²⁺-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HIRABAYASHIDaisuke en-aut-sei=HIRABAYASHI en-aut-mei=Daisuke kn-aut-name=平林大輔 kn-aut-sei=平林 kn-aut-mei=大輔 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=がん関連線維芽細胞による腫瘍免疫抑制の抗インターロイキン6受容体抗体による克服 kn-title=Overcoming cancer‑associated fibroblast‑induced immunosuppression by anti‑interleukin‑6 receptor antibody en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NISHIWAKINoriyuki en-aut-sei=NISHIWAKI en-aut-mei=Noriyuki kn-aut-name=西脇紀之 kn-aut-sei=西脇 kn-aut-mei=紀之 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=従来のがん治療は、食道がんモデルにおいてがん関連線維芽細胞の賦活化によってがん細胞の悪性能を増強しうる kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KOMOTOSatoshi en-aut-sei=KOMOTO en-aut-mei=Satoshi kn-aut-name=河本慧 kn-aut-sei=河本 kn-aut-mei=慧 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=高転移性トリプルネガティブ乳癌細胞では鉄代謝が制限され、鉄キレート剤の治療標的となり得る kn-title=Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WANGYUZE en-aut-sei=WANG en-aut-mei=YUZE kn-aut-name=王宇沢 kn-aut-sei=王 kn-aut-mei=宇沢 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=2023 dt-pub=20230925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=臼蓋関節唇の血管内皮増殖因子および神経成長因子の発現は変形性股関節症の疼痛に直接関連する：免疫組織化学染色による検討 kn-title=Expression of Acetabular Labral Vascular Endothelial Growth Factor and Nerve Growth Factor Is Directly Associated with Hip Osteoarthritis Pain: Investigation by Immunohistochemical Staining en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SATOYoshihiro en-aut-sei=SATO en-aut-mei=Yoshihiro kn-aut-name=佐藤嘉洋 kn-aut-sei=佐藤 kn-aut-mei=嘉洋 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=43 cd-vols= no-issue=1 article-no= start-page=BSR20220369 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230124 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Remodeling of algal photosystem I through phosphorylation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photosystem I (PSI) with its associated light-harvesting system is the most important generator of reducing power in photosynthesis. The PSI core complex is highly conserved, whereas peripheral subunits as well as light-harvesting proteins (LHCI) reveal a dynamic plasticity. Moreover, in green alga, PSI-LHCI complexes are found as monomers, dimers, and state transition complexes, where two LHCII trimers are associated. Herein, we show light-dependent phosphorylation of PSI subunits PsaG and PsaH as well as Lhca6. Potential consequences of the dynamic phosphorylation of PsaG and PsaH are structurally analyzed and discussed in regard to the formation of the monomeric, dimeric, and LHCII-associated PSI-LHCI complexes. en-copyright= kn-copyright= en-aut-name=YounasMuhammad en-aut-sei=Younas en-aut-mei=Muhammad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 ORCID= affil-num=1 en-affil=Institute of Plant Biology and Biotechnology, University of Munster kn-affil= affil-num=2 en-affil=Institute of Plant Biology and Biotechnology, University of Munster kn-affil= affil-num=3 en-affil=Institute of Plant Biology and Biotechnology, University of Munster kn-affil= affil-num=4 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=green algae kn-keyword=green algae en-keyword=Light harvesting proteins kn-keyword=Light harvesting proteins en-keyword=phosphorylation/dephosphorylation kn-keyword=phosphorylation/dephosphorylation en-keyword=photosystems kn-keyword=photosystems END start-ver=1.4 cd-journal=joma no-vol=3 cd-vols= no-issue=4 article-no= start-page=101786 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A protocol to induce expandable limb-bud mesenchymal cells from human pluripotent stem cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we present a protocol for the selective differentiation of human pluripotent stem cells mimicking human developmental processes into expandable PRRX1+ limb-bud mesenchymal (ExpLBM) cells. This approach enables expansion through serial passage while maintaining capacity for chondrogenic differentiation. For complete details on the use and execution of this protocol, please refer to Yamada et al. (2021, 2022). en-copyright= kn-copyright= en-aut-name=TakaoTomoka en-aut-sei=Takao en-aut-mei=Tomoka 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=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=5 article-no= start-page=382 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line‑derived xenograft model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue‑derived stromal cells (G‑SCs and P‑SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate‑resistant acid phosphatase staining in a cell line‑derived xenograft model. The results demonstrated that G‑SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC‑3 cell line, whereas P‑SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC‑3 cells. Furthermore, the effects of G‑SCs, P‑SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)‑9, membrane type 1 MMP (MT1‑MMP), Snail, parathyroid hormone‑related peptide (PTHrP) and receptor activator of NF‑κB ligand (RANKL) in HSC‑3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G‑SCs had a more prominent effect on the expression of MMP‑9, MT1‑MMP, Snail, PTHrP, and RANKL, whereas P‑SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP‑9, MT1‑MMP and Snail expression. The potential genes underlying the differential effects of G‑SCs and P‑SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin‑dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G‑SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P‑SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC. en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng 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=OmoriHaruka en-aut-sei=Omori en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SanoSho en-aut-sei=Sano en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=bone invasion kn-keyword=bone invasion en-keyword=gingival ligament tissue‑derived stromal cell kn-keyword=gingival ligament tissue‑derived stromal cell en-keyword=periodontal ligament tissue‑derived stromal cell kn-keyword=periodontal ligament tissue‑derived stromal cell en-keyword=xenograft model kn-keyword=xenograft model en-keyword=microarray kn-keyword=microarray END start-ver=1.4 cd-journal=joma no-vol=47 cd-vols= no-issue=4 article-no= start-page=81 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts on bone resorption and the activation of HSC‑3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan‑cytokeratin) and tartrate‑resistant acid phosphatase staining. In addition, the expression levels of matrix metalloproteinase (MMP)9, membrane‑type 1 MMP (MT1‑MMP), Snail, receptor activator of NF‑κB ligand (RANKL) and parathyroid hormone‑related peptide (PTHrP) in the bone invasion regions of HSC‑3 cells were examined by immunohistochemistry. The results suggested that both SCC‑SCs and VSCC‑SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1‑MMP, Snail, RANKL and PTHrP. However, SCC‑SCs had a more prominent effect compared with VSCC‑SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC‑SCs and SCC‑SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC‑SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC. en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng 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=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FushimiShigeko en-aut-sei=Fushimi en-aut-mei=Shigeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=bone invasion kn-keyword=bone invasion en-keyword=osteoclast kn-keyword=osteoclast en-keyword=receptor activator of NF‑κB ligand kn-keyword=receptor activator of NF‑κB ligand en-keyword=parathyroid hormone‑related peptide kn-keyword=parathyroid hormone‑related peptide en-keyword=microarray kn-keyword=microarray en-keyword=cancer‑associated stromal cells kn-keyword=cancer‑associated stromal cells END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=6 article-no= start-page=78 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor‑associated macrophages into the tumor microenvironment of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumor‑associated macrophages (TAMs) are linked to the progression of numerous types of cancer. However, the effects of the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC), particularly the cancer stroma on TAMs, remains to be elucidated. In the present study, the effects of verrucous SCC‑associated stromal cells (VSCC‑SCs), SCC‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the differentiation, proliferation and migration of macrophages in vitro was assayed using Giemsa staining, and immunofluorescence, MTS and Transwell (migration) assays, respectively. The combined results suggested that both VSCC‑SCs and SCC‑SCs promoted the differentiation of macrophages into M2 type TAMs, as well as the proliferation and migration of macrophages following crosstalk with HSC‑3 cells in vitro. Moreover, the SCC‑SCs exerted a more prominent effect on TAMs than the VSCC‑SCs. Immunohistochemical staining was used to examine the expression of CD34, CD45, CD11b and CD163 to assay the effects of VSCC‑SCs, SCC‑SCs and HDFs on microvessel density (MVD) and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type macrophages. The results suggested that both VSCC‑SCs and SCC‑SCs promoted MVD and the infiltration of CD45(+) monocytes, CD11b(+) TAMs and CD163(+) M2 type TAMs into the TME of OSCC following crosstalk with HSC‑3 cells in vivo. The SCC‑SCs exerted a more prominent promoting effect than the VSCC‑SCs. Finally, the potential genes underlying the differential effects of VSCC‑SCs and SCC‑SCs on the infiltration of TAMs were investigated using microarray analysis. The results revealed that interleukin 1β, bone morphogenetic protein 4, interleukin 6 and C‑X‑C motif chemokine ligand 12 had great potential to mediate the differential effects of VSCC‑SCs and SCC‑SCs on TAM infiltration. On the whole, the findings presented herein, demonstrate that both VSCC‑SCs and SCC‑SCs promote the infiltration of TAMs into the TME of OSCC following crosstalk with HSC‑3 cells; the SCC‑SCs were found to exert a more prominent promoting effect. This may represent a potential regulatory mechanism for the infiltration of TAMs into the TME of OSCC. en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng 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=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=tumor-associated macrophages kn-keyword=tumor-associated macrophages en-keyword=cancer stroma kn-keyword=cancer stroma en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=microvessel density kn-keyword=microvessel density en-keyword=microarray kn-keyword=microarray END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=1 article-no= start-page=3 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Skin sensitization is an allergic reaction caused by certain chemical substances, and is an important factor to be taken into consideration when evaluating the safety of numerous types of products. Although animal testing has long been used to evaluate skin sensitization, the recent trend to regulate such testing has led to the development and use of alternative methods. Skin sensitization reactions are summarized in the form of an adverse outcome pathway consisting of four key events (KE), including covalent binding to skin proteins (KE1), keratinocyte activation (KE2), and dendritic cell activation (KE3). Equivalent alternative methods have been developed for KE1 to KE3, but no valid alternative has yet been developed for the evaluation of KE4 and T‑cell activation. Current alternative methods rely on data from KE1 to KE3 to predict the effect of chemicals on skin sensitization. The addition of KE4 data is expected to improve the accuracy and reproducibility of such predictions. The aim of this study was to establish an assay to evaluate KE4 T‑cell activation to supplement data on skin sensitization related to KE4. To evaluate T‑cell activation, the Jurkat T‑cell line stably expressing luciferase downstream of the pro‑inflammatory cytokine interleukin‑2 promoter was used. After exposure to known skin sensitizing agents and control substances, luciferase activity measurements revealed that this assay was valid for evaluating skin sensitization. However, two skin sensitizers known to have immunosuppressive effects on T‑cells reacted negatively in this assay. The results revealed that this assay simultaneously allows for monitoring of the skin sensitization and immuno‑suppressiveness of chemical substances and supplements KE4 T‑cell activation data, and may thus contribute to reducing the use of animal experiments. en-copyright= kn-copyright= en-aut-name=NagahataTaichi en-aut-sei=Nagahata en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=TakayamaEiji en-aut-sei=Takayama en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HikasaHaruka en-aut-sei=Hikasa en-aut-mei=Haruka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=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 Science, Technology and Innovation, Kobe University kn-affil= affil-num=3 en-affil=Department of Oral Biochemistry, Asahi University School of Dentistry 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=skin sensitization kn-keyword=skin sensitization en-keyword=immunotoxicity kn-keyword=immunotoxicity en-keyword=interleukin-2 promoter kn-keyword=interleukin-2 promoter en-keyword=Jurkat kn-keyword=Jurkat en-keyword=T-cell activation kn-keyword=T-cell activation END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=18 article-no= start-page=13296 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Relationship between the Evaluation of Public Transport Services and Travel-Based CO2 Emissions from Private Transport Modes in Regional and Metropolitan Areas in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Promoting public transport use is expected to contribute to reducing CO2 emissions in the transport sector. Using Okayama City and Central Tokyo as representative case studies of regional and metropolitan areas in Japan, this study examines the impact of the evaluation of the 'hard' and 'soft' attributes of rail and bus services on the overall evaluation. This study then explores the relationship between the overall evaluation and usage frequency of rail and bus services, as well as the relationship between the usage frequency and travel-based CO2 emissions from private transport modes. Furthermore, this study investigates whether the emissions cause differences in the evaluation of the 'hard' and 'soft' attributes of public transport services. The findings suggest prioritising an improvement in 'hard' rather than 'soft' attributes in order to reduce emissions through the use of public transport in regional areas. However, in metropolitan areas, no relationship was found between the evaluation of public transport services and emissions, presumably because of the lower ownership rate of private cars that residents can use freely and the markedly higher level of rail and bus services. This study provides a methodological reference for analysing the potential to reduce travel-based emissions from private transport modes by enhancing public transport service contents. en-copyright= kn-copyright= en-aut-name=PradhanShreyas en-aut-sei=Pradhan en-aut-mei=Shreyas kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UjiharaTakehito en-aut-sei=Ujihara en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HashimotoSeiji en-aut-sei=Hashimoto en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Graduate School of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= en-keyword=CO2 emissions kn-keyword=CO2 emissions en-keyword=public transport kn-keyword=public transport en-keyword=evaluation kn-keyword=evaluation en-keyword='hard' and 'soft' attributes kn-keyword='hard' and 'soft' attributes en-keyword=usage frequency kn-keyword=usage frequency en-keyword=private transport modes kn-keyword=private transport modes END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=1261330 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230907 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.
Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4−), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.
Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4− single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4− SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.
Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions. en-copyright= kn-copyright= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=AkazawaKaoru en-aut-sei=Akazawa en-aut-mei=Kaoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KannoTakayuki en-aut-sei=Kanno en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujimotoYuki en-aut-sei=Fujimoto en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 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=12 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of General Internal Medicine 3, Kawasaki Medical School kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=sodium/iodide symporter kn-keyword=sodium/iodide symporter en-keyword=human induced pluripotent stem cell-derived cardiomyocytes kn-keyword=human induced pluripotent stem cell-derived cardiomyocytes en-keyword=single photon emission computed tomography kn-keyword=single photon emission computed tomography en-keyword=cell-based therapy kn-keyword=cell-based therapy en-keyword=in vivo imaging kn-keyword=in vivo imaging END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=1501 end-page=1515 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230911 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression and function of CCN2-derived circRNAs in chondrocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation. en-copyright= kn-copyright= en-aut-name=KatoSoma en-aut-sei=Kato en-aut-mei=Soma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawataKazumi en-aut-sei=Kawata en-aut-mei=Kazumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishidaTakashi en-aut-sei=Nishida en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MizukawaTomomi en-aut-sei=Mizukawa en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Oral Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Chondrocyte kn-keyword=Chondrocyte en-keyword=CCN2 kn-keyword=CCN2 en-keyword=Circular RNA kn-keyword=Circular RNA en-keyword=ACAN kn-keyword=ACAN en-keyword=Chondrocytic differentiation kn-keyword=Chondrocytic differentiation END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=16 article-no= start-page=12559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis. 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=IwataNahoko en-aut-sei=Iwata en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiokaRan en-aut-sei=Nishioka en-aut-mei=Ran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HondaMako en-aut-sei=Honda en-aut-mei=Mako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=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= 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= en-keyword=bone morphogenetic protein (BMP) kn-keyword=bone morphogenetic protein (BMP) en-keyword=orexin kn-keyword=orexin en-keyword=steroidogenesis and adrenal kn-keyword=steroidogenesis and adrenal END start-ver=1.4 cd-journal=joma no-vol=68 cd-vols= no-issue=4 article-no= start-page=254 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of bovine uterine gland functions in 2D and 3D culture system en-subtitle= kn-subtitle= en-abstract= kn-abstract=In ruminants, uterine glands play key roles in the establishment of pregnancy by secreting various factors into the uterine lumen. Although a three-dimensional (3D) culture system has been used for investigating cellular functions in vitro, the detailed functions of uterine gland have not been fully elucidated. In this study, we examined the benefits of 3D culture system to examine the innate functions of bovine uterine glands. Isolated bovine uterine glands were cultured on Matrigel (2D) or in Matrigel (3D), respectively, and the mRNA levels of secreted proteins (SERPINA14, MEP1B, APOA1, ARSA, CTGF, and SPP1) were measured in isolated and cultured uterine glands. The protein expression of estrogen receptor β (ERβ) and progesterone receptor (PR) and the establishment of apico-basal polarity were examined. In isolated uterine glands, the mRNA levels of secreted proteins changed during the estrous cycle. Although uterine glands cultured in both 2D and 3D expressed ERβ and PR, progesterone did not affect SERPINA14 mRNA expression. The expression of APOA1 mRNA in 2D cultured uterine glands did not respond to estrogen and progesterone. Additionally, the mRNA levels of secreted proteins in the 3D culture system were significantly higher than those in the 2D culture system, which might be attributed to the different cellular morphology between them. The locations of ZO-1 and β-catenin in 2D cultured uterine glands were disordered compared with 3D cultured uterine glands. These results showed that the hormonal responsiveness of secreted factor expression and cellular morphology were different between 2D and 3D cultured bovine uterine glands. en-copyright= kn-copyright= en-aut-name=SUGINOYosuke en-aut-sei=SUGINO en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SATOTaiki en-aut-sei=SATO en-aut-mei=Taiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YAMAMOTOYuki en-aut-sei=YAMAMOTO en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KIMURAKoji en-aut-sei=KIMURA en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Laboratory of Reproductive Physiology, Faculty of Agriculture, Okayama University kn-affil= affil-num=3 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Bovine kn-keyword=Bovine en-keyword=Secreted proteins kn-keyword=Secreted proteins en-keyword=Three-dimensional culture kn-keyword=Three-dimensional culture en-keyword=Uterine glands kn-keyword=Uterine glands END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=15 article-no= start-page=5028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia. en-copyright= kn-copyright= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi 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=KondoMegumi en-aut-sei=Kondo en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 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=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical 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 Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=glycolysis kn-keyword=glycolysis en-keyword=mitochondrial respiration kn-keyword=mitochondrial respiration en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary artery smooth muscle cells kn-keyword=pulmonary artery smooth muscle cells en-keyword=Seahorse technology kn-keyword=Seahorse technology en-keyword=hypoxia kn-keyword=hypoxia en-keyword=ATP production kn-keyword=ATP production END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=7 article-no= start-page=895 end-page=908 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High Expression of MHC Class I Overcomes Cancer Immunotherapy Resistance Due to IFNγ Signaling Pathway Defects en-subtitle= kn-subtitle= en-abstract= kn-abstract=IFNγ signaling pathway defects are well-known mechanisms of resistance to immune checkpoint inhibitors. However, conflicting data have been reported, and the detailed mechanisms remain unclear. In this study, we have demonstrated that resistance to immune checkpoint inhibitors owing to IFNγ signaling pathway defects may be primarily caused by reduced MHC-I expression rather than by the loss of inhibitory effects on cellular proliferation or decreased chemokine production. In particular, we found that chemokines that recruit effector T cells were mainly produced by immune cells rather than cancer cells in the tumor microenvironment of a mouse model, with defects in IFNγ signaling pathways. Furthermore, we found a response to immune checkpoint inhibitors in a patient with JAK-negative head and neck squamous cell carcinoma whose HLA-I expression level was maintained. In addition, CRISPR screening to identify molecules associated with elevated MHC-I expression independent of IFNγ signaling pathways demonstrated that guanine nucleotide-binding protein subunit gamma 4 (GNG4) maintained MHC-I expression via the NF-κB signaling pathway. Our results indicate that patients with IFNγ signaling pathway defects are not always resistant to immune checkpoint inhibitors and highlight the importance of MHC-I expression among the pathways and the possibility of NF-κB–targeted therapies to overcome such resistance. en-copyright= kn-copyright= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=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=TanjiEtsuko en-aut-sei=Tanji en-aut-mei=Etsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute 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=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University kn-affil= affil-num=8 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=24 cd-vols= no-issue=14 article-no= start-page=11768 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230721 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable & alpha;-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery. en-copyright= kn-copyright= en-aut-name=TsuchiyaKeisuke en-aut-sei=Tsuchiya en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HorikoshiKanako en-aut-sei=Horikoshi en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujitaMinami en-aut-sei=Fujita en-aut-mei=Minami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HiranoMotoharu en-aut-sei=Hirano en-aut-mei=Motoharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyamotoMaho en-aut-sei=Miyamoto en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YokooHidetomo en-aut-sei=Yokoo en-aut-mei=Hidetomo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=DemizuYosuke en-aut-sei=Demizu en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=2 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=3 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=4 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=5 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=6 en-affil=Division of Organic Chemistry, National Institute of Health Sciences kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=cell-penetrating peptide kn-keyword=cell-penetrating peptide en-keyword=stapled peptide kn-keyword=stapled peptide en-keyword=hydrophobic peptide kn-keyword=hydrophobic peptide en-keyword=helical structure kn-keyword=helical structure en-keyword=plasmid DNA delivery kn-keyword=plasmid DNA delivery END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=1 article-no= start-page=621 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis en-subtitle= kn-subtitle= en-abstract= kn-abstract=DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-l-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 <= 100nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B. en-copyright= kn-copyright= en-aut-name=OkudaKosaku en-aut-sei=Okuda en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakaharaKengo en-aut-sei=Nakahara en-aut-mei=Kengo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=4 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=5 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=6 ORCID= en-aut-name=FujikawaKana en-aut-sei=Fujikawa en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AdachiKazuya en-aut-sei=Adachi en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimadaYuki en-aut-sei=Shimada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujioSatoshi en-aut-sei=Fujio en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YamamotoReina en-aut-sei=Yamamoto en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 ORCID= en-aut-name=OnumaKunishige en-aut-sei=Onuma en-aut-mei=Kunishige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OsakiMitsuhiko en-aut-sei=Osaki en-aut-mei=Mitsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OkadaFutoshi en-aut-sei=Okada en-aut-mei=Futoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=UkegawaTaichi en-aut-sei=Ukegawa en-aut-mei=Taichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakeuchiYasuo en-aut-sei=Takeuchi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YasuiNorihisa en-aut-sei=Yasui en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamashitaAtsuko en-aut-sei=Yamashita en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MarusawaHiroyuki en-aut-sei=Marusawa en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=MatsushitaYosuke en-aut-sei=Matsushita en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KatagiriToyomasa en-aut-sei=Katagiri en-aut-mei=Toyomasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=ShibataTakahiro en-aut-sei=Shibata en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 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=24 ORCID= en-aut-name=NiuSheng-Yong en-aut-sei=Niu en-aut-mei=Sheng-Yong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=LangNhi B. en-aut-sei=Lang en-aut-mei=Nhi B. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraTomohiro en-aut-sei=Nakamura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 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=28 ORCID= en-aut-name=LiptonStuart A. en-aut-sei=Lipton en-aut-mei=Stuart A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 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=30 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=Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science 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=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=7 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=14 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=15 en-affil=Division of Experimental Pathology, Faculty of Medicine, Tottori University kn-affil= affil-num=16 en-affil=Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=17 en-affil=Department of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=18 en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=19 en-affil=Laboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=21 en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=22 en-affil=Division of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University kn-affil= affil-num=23 en-affil=Graduate School of Bioagricultural Sciences, Nagoya University kn-affil= affil-num=24 en-affil=Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo kn-affil= affil-num=25 en-affil=Broad Institute of MIT and Harvard kn-affil= affil-num=26 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=27 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=28 en-affil=Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN kn-affil= affil-num=29 en-affil=Neurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute kn-affil= affil-num=30 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=12 cd-vols= no-issue=7 article-no= start-page=1438 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combined Effect of Salicylic Acid and Proline Mitigates Drought Stress in Rice (Oryza sativa L.) through the Modulation of Physiological Attributes and Antioxidant Enzymes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Salicylic acid (SA) and proline exhibit protective effects against a wide range of stresses. However, the combined impact of SA and proline on rice under drought stress is still unknown. Therefore, we investigated the protective roles of SA and/or proline in conferring drought tolerance in rice. There were eight treatments comprising the control (T1; 95-100% FC), 1.5 mM SA (T2), 2 mM proline (T3), 0.75 mM SA + 1 mM proline (T4), 45-50% FC (T5, drought stress), T5 + 1.5 mM SA (T6), T5 + 2 mM proline (T7), and T5 + 0.75 mM SA + 1 mM proline (T8), and two rice varieties: BRRI dhan66 and BRRI dhan75. Drought stress significantly decreased the plant growth, biomass, yield attributes, photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), photosynthetic pigments (chlorophyll and carotenoids content), relative water content (RWC), membrane stability index (MSI), soluble sugar and starch content, and uptake of N, P and K+ in roots and shoots. Drought-induced oxidative stress in the form of increased hydrogen peroxide (H2O2) production and lipid peroxidation (MDA) was observed. The combined application of SA (0.75 mM) + proline (1 mM) was found to be more effective than the single application of either for drought stress mitigation in rice. A combined dose of SA + proline alleviated oxidative stress through boosting antioxidant enzymatic activity in contrast to their separate application. The application of SA + proline also enhanced proline, soluble sugar and starch content, which resulted in the amelioration of osmotic stress. Consequently, the combined application of SA and proline significantly increased the gas exchange characteristics, photosynthetic pigments, RWC, MSI, nutrient uptake, plant growth, biomass and yield of rice. Therefore, the combined application of SA and proline alleviated the detrimental impacts of drought stress more pronouncedly than their separate application did by increasing osmoprotectants, improving nutrient transport, up-regulating antioxidant enzyme activity and inhibiting oxidative stress. en-copyright= kn-copyright= en-aut-name=UrmiTahmina Akter en-aut-sei=Urmi en-aut-mei=Tahmina Akter kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IslamMd. Moshiul en-aut-sei=Islam en-aut-mei=Md. Moshiul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZumurKamrun Naher en-aut-sei=Zumur en-aut-mei=Kamrun Naher kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbedinMd. Anwarul en-aut-sei=Abedin en-aut-mei=Md. Anwarul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaqueM. Moynul en-aut-sei=Haque en-aut-mei=M. Moynul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SiddiquiManzer H. en-aut-sei=Siddiqui en-aut-mei=Manzer H. 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=HoqueMd. Anamul en-aut-sei=Hoque en-aut-mei=Md. Anamul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural 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=Department of Agronomy, Faculty of Agriculture, Bangabandhu Sheikh Mujibur Rahman Agricultural University kn-affil= affil-num=4 en-affil=Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= affil-num=5 en-affil=Department of Agronomy, Faculty of Agriculture, Bangabandhu Sheikh Mujibur Rahman Agricultural University kn-affil= affil-num=6 en-affil=Department of Botany and Microbiology, College of Science, King Saud 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=Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural University kn-affil= en-keyword=rice kn-keyword=rice en-keyword=drought stress kn-keyword=drought stress en-keyword=osmolytes kn-keyword=osmolytes en-keyword=reactive oxygen species kn-keyword=reactive oxygen species en-keyword=lipid peroxidation kn-keyword=lipid peroxidation en-keyword=antioxidant kn-keyword=antioxidant END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=14 article-no= start-page=2738 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230723 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Low-Oxygen Responses of Cut Carnation Flowers Associated with Modified Atmosphere Packaging en-subtitle= kn-subtitle= en-abstract= kn-abstract=Gaseous factors affect post-harvest physiological processes in horticultural crops, including ornamental flowers. However, the molecular responses of cut flowers to the low-oxygen conditions associated with modified atmosphere packaging (MAP) have not yet been elucidated. Here, we show that storage of cut carnation flowers in a sealed polypropylene bag decreased the oxygen concentration in the bag to 3-5% and slowed flower opening. The vase life of carnation flowers after storage for seven days under MAP conditions was comparable to that without storage and was improved by the application of a commercial-quality preservative. The adenylate energy charge (AEC) was maintained at high levels in petals from florets stored under MAP conditions. This was accompanied by the upregulation of four hypoxia-related genes, among which the HYPOXIA-RESPONSIVE ETHYLENE RESPONSE FACTOR and PHYTOGLOBIN genes (DcERF19 and DcPGB1) were newly identified. These results suggest that hypoxia-responsive genes contribute to the maintenance of the energy status in carnation flowers stored under MAP conditions, making this gas-controlling technique potentially effective for maintaining cut flower quality without cooling. en-copyright= kn-copyright= en-aut-name=NakayamaMisaki en-aut-sei=Nakayama en-aut-mei=Misaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HaradaNao en-aut-sei=Harada en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MuraiAi en-aut-sei=Murai en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UeyamaSayaka en-aut-sei=Ueyama en-aut-mei=Sayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaradaTaro en-aut-sei=Harada en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=School of Education, Okayama University kn-affil= affil-num=2 en-affil=School of Education, Okayama University kn-affil= affil-num=3 en-affil=School of Education, Okayama University kn-affil= affil-num=4 en-affil=School of Education, Okayama University kn-affil= affil-num=5 en-affil=Faculty of Education, Okayama University kn-affil= en-keyword=carnation kn-keyword=carnation en-keyword=modified atmosphere packaging kn-keyword=modified atmosphere packaging en-keyword=adenylate energy charge kn-keyword=adenylate energy charge en-keyword=hypoxia-responsive genes kn-keyword=hypoxia-responsive genes en-keyword=AP2/ERF superfamily kn-keyword=AP2/ERF superfamily END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=4720 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=ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adenosine deaminase acting on RNA 1 (ADAR1), a recently described epigenetic modifier, is believed to play a critical oncogenic role in human cancers. However, its functional role and clinical significance in cervical cancer (CC) remain unclear. ADAR1 knockdown was performed to investigate its oncogenic functions in SiHa (HPV16), HeLa (HPV18), and Yumoto (non-HPV) CC cell lines. Cytoplasmic and nuclear ADAR1 expression were examined to clarify their correlation with clinicopathological parameters and prognosis in patients with CC. This resulted in increased apoptosis and necroptosis in HPV16 -type SiHa, HPV18-type HeLa, and non-HPV-type Yumoto CC cell lines. Progression-free survival (PFS) rates of patients exhibiting high cytoplasmic and nuclear ADAR1 expression were poorer than those in the other groups (P = 0.016). Multivariate analysis indicated that the combination of higher cytoplasmic and nuclear ADAR1 expression was an independent predictor of prognosis in patients with CC (P = 0.017). ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC. The combination of cytoplasmic and nuclear ADAR1 comprises a better prognostic factor for CC. 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=OkamotoKazuhiro en-aut-sei=Okamoto en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaHirofumi en-aut-sei=Matsuoka en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= affil-num=1 en-affil=Department of Obstetrics and Gynecology, 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 Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=567 cd-vols= no-issue= article-no= start-page=216260 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230728 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy. en-copyright= kn-copyright= en-aut-name=YoshimotoMasashi en-aut-sei=Yoshimoto en-aut-mei=Masashi 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=KajiokaHiroki en-aut-sei=Kajioka en-aut-mei=Hiroki 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=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=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=YagiTomohiko en-aut-sei=Yagi en-aut-mei=Tomohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=10 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=11 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 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=13 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=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=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=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Aspirin kn-keyword=Aspirin en-keyword=Ticagrelor kn-keyword=Ticagrelor en-keyword=P-selectin kn-keyword=P-selectin en-keyword=Platelet kn-keyword=Platelet en-keyword=Time-lapse imaging kn-keyword=Time-lapse imaging END start-ver=1.4 cd-journal=joma no-vol=189 cd-vols= no-issue=1 article-no= start-page=329 end-page=343 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photosystem I light-harvesting proteins regulate photosynthetic electron transfer and hydrogen production en-subtitle= kn-subtitle= en-abstract= kn-abstract=Linear electron flow (LEF) and cyclic electron flow (CEF) compete for light-driven electrons transferred from the acceptor side of photosystem I (PSI). Under anoxic conditions, such highly reducing electrons also could be used for hydrogen (H2) production via electron transfer between ferredoxin and hydrogenase in the green alga Chlamydomonas reinhardtii. Partitioning between LEF and CEF is regulated through PROTON-GRADIENT REGULATION5 (PGR5). There is evidence that partitioning of electrons also could be mediated via PSI remodeling processes. This plasticity is linked to the dynamics of PSI-associated light-harvesting proteins (LHCAs) LHCA2 and LHCA9. These two unique light-harvesting proteins are distinct from all other LHCAs because they are loosely bound at the PSAL pole. Here, we investigated photosynthetic electron transfer and H2 production in single, double, and triple mutants deficient in PGR5, LHCA2, and LHCA9. Our data indicate that lhca2 and lhca9 mutants are efficient in photosynthetic electron transfer, that LHCA2 impacts the pgr5 phenotype, and that pgr5/lhca2 is a potent H2 photo-producer. In addition, pgr5/lhca2 and pgr5/lhca9 mutants displayed substantially different H2 photo-production kinetics. This indicates that the absence of LHCA2 or LHCA9 impacts H2 photo-production independently, despite both being attached at the PSAL pole, pointing to distinct regulatory capacities. en-copyright= kn-copyright= en-aut-name=HoThi Thu Hoai en-aut-sei=Ho en-aut-mei=Thi Thu Hoai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SchwierChris en-aut-sei=Schwier en-aut-mei=Chris kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ElmanTamar en-aut-sei=Elman en-aut-mei=Tamar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FleuterVera en-aut-sei=Fleuter en-aut-mei=Vera kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZinziusKaren en-aut-sei=Zinzius en-aut-mei=Karen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=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=BuchertFelix en-aut-sei=Buchert en-aut-mei=Felix kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=9 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=School of Plant Sciences and Food Security, The George S. Wise Faculty of Life Sciences, Tel Aviv University kn-affil= affil-num=4 en-affil=Institute of Plant Biology and Biotechnology, University of Münster 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 Plant Biology and Biotechnology, University of Münster 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 Plant Biology and Biotechnology, University of Münster kn-affil= affil-num=9 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=174 cd-vols= no-issue=2 article-no= start-page=343 end-page=349 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion.
Methods: Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion.
Results: Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation.
Conclusion: Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion. en-copyright= kn-copyright= en-aut-name=AgetaKohei en-aut-sei=Ageta en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoHirotsugu en-aut-sei=Yamamoto en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=5 article-no= start-page=104571 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Actin-rich lamellipodia-like protrusions contribute to the integrity of epithelial cell-cell junctions en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metastasis-suppressor 1 (MTSS1) is a membrane-interacting scaffolding protein that regulates the integrity of epithelial cell-cell junctions and functions as a tumor suppressor in a wide range of carcinomas. MTSS1 binds phosphoinositide-rich membranes through its I-BAR domain and is capable of sensing and generating negative membrane curvature in vitro. However, the mechanisms by which MTSS1 localizes to inter-cellular junctions in epithelial cells and contributes to their integrity and maintenance have remained elusive. By carrying out EM and live-cell imaging on cultured Madin-Darby canine kidney cell monolayers, we provide evidence that adherens junctions of epithelial cells harbor lamellipodia-like, dynamic actin-driven membrane folds, which exhibit high negative membrane curvature at their distal edges. BioID proteomics and imaging experiments demonstrated that MTSS1 associates with an Arp2/3 complex activator, the WAVE-2 complex, in dynamic actin-rich protrusions at cell-cell junctions. Inhibi-tion of Arp2/3 or WAVE-2 suppressed actin filament assembly at adherens junctions, decreased the dynamics of junctional membrane protrusions, and led to defects in epithelial integ-rity. Together, these results support a model in which membrane-associated MTSS1, together with the WAVE-2 and Arp2/3 complexes, promotes the formation of dynamic lamellipodia-like actin protrusions that contribute to the integrity of cell-cell junctions in epithelial monolayers. en-copyright= kn-copyright= en-aut-name=SenjuYosuke en-aut-sei=Senju en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MushtaqToiba en-aut-sei=Mushtaq en-aut-mei=Toiba kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=VihinenHelena en-aut-sei=Vihinen en-aut-mei=Helena kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ManninenAki en-aut-sei=Manninen en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaarikangasJuha en-aut-sei=Saarikangas en-aut-mei=Juha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=VenKatharina en-aut-sei=Ven en-aut-mei=Katharina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EngelUlrike en-aut-sei=Engel en-aut-mei=Ulrike kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=VarjosaloMarkku en-aut-sei=Varjosalo en-aut-mei=Markku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JokitaloEija en-aut-sei=Jokitalo en-aut-mei=Eija kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LappalainenPekka en-aut-sei=Lappalainen en-aut-mei=Pekka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Research Institute for Interdisciplinary Science (RIIS), Okayama University kn-affil= affil-num=2 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=3 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=4 en-affil=Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu kn-affil= affil-num=5 en-affil=Helsinki Institute of Life Science (HiLIFE), University of Helsinki kn-affil= affil-num=6 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=7 en-affil=Nikon Imaging Center and Centre for Organismal Studies, Heidelberg University kn-affil= affil-num=8 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=9 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= affil-num=10 en-affil=Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=11 article-no= start-page=2971 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models en-subtitle= kn-subtitle= en-abstract= kn-abstract=Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors. en-copyright= kn-copyright= en-aut-name=KomotoSatoshi en-aut-sei=Komoto en-aut-mei=Satoshi 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=KatoTakuya en-aut-sei=Kato en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiTeruki en-aut-sei=Kobayashi en-aut-mei=Teruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=NarusakaToru en-aut-sei=Narusaka en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SatoHiroaki en-aut-sei=Sato en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatsuraYuki en-aut-sei=Katsura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 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=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=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=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=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= en-keyword=cancer-associated fibroblast kn-keyword=cancer-associated fibroblast en-keyword=chemotherapy kn-keyword=chemotherapy en-keyword=radiotherapy kn-keyword=radiotherapy en-keyword=esophageal cancer kn-keyword=esophageal cancer en-keyword=tumor microenvironment kn-keyword=tumor microenvironment END start-ver=1.4 cd-journal=joma no-vol=299 cd-vols= no-issue=4 article-no= start-page=104587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting molecules on dendritic cells leading to IFN-gamma production by T cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation. 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=OnishiHiroka en-aut-sei=Onishi en-aut-mei=Hiroka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkadaYuki en-aut-sei=Ikada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasakiKento en-aut-sei=Masaki en-aut-mei=Kento kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TanakaSatoshi en-aut-sei=Tanaka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University kn-affil= affil-num=6 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=1 article-no= start-page=596 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism en-subtitle= kn-subtitle= en-abstract= kn-abstract=Two splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC. en-copyright= kn-copyright= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UekiChihiro en-aut-sei=Ueki en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShimazakiMasahiro en-aut-sei=Shimazaki en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsujimotoGoki en-aut-sei=Tsujimoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KohnoSusumu en-aut-sei=Kohno en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MuranakaHayato en-aut-sei=Muranaka en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshikawaKiyotsugu en-aut-sei=Yoshikawa en-aut-mei=Kiyotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakahashiChiaki en-aut-sei=Takahashi en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama University kn-affil= affil-num=5 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= affil-num=6 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University kn-affil= affil-num=7 en-affil=Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts kn-affil= affil-num=8 en-affil=Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=がん発生に関与するシグナル伝達経路及びがん幹細胞標的におけるシグナル伝達阻害剤の効果に関する研究 kn-title=Study on the signaling pathway in tumor initiation and the efficacy of signaling inhibitors for cancer stem cell targeting therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=XuYanning en-aut-sei=Xu en-aut-mei=Yanning kn-aut-name=徐燕宁 kn-aut-sei=徐 kn-aut-mei=燕宁 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=肥満・高脂血症は相乗的に乾癬様皮疹を悪化させる kn-title=Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IKEDAKenta en-aut-sei=IKEDA en-aut-mei=Kenta kn-aut-name=池田賢太 kn-aut-sei=池田 kn-aut-mei=賢太 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=CCN3の関節軟骨における発現は、年齢、荷重の有無に関わらず変形性股関節症と相関する kn-title=Elevated expression of CCN3 in articular cartilage induces osteoarthritis in hip joints irrespective of age and weight bearing en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=HIROSEKazuki en-aut-sei=HIROSE en-aut-mei=Kazuki kn-aut-name=廣瀬一樹 kn-aut-sei=廣瀬 kn-aut-mei=一樹 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=低転移性サブクローン由来のエキソソームwnt7aは、murine 4t1乳がんの高度転移性サブクローンの肺転移を促進する kn-title=Exosomal Wnt7a from a low metastatic subclone promotes lung metastasis of a highly metastatic subclone in the murine 4t1 breast cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LICHUNNING en-aut-sei=LI en-aut-mei=CHUNNING kn-aut-name=李春寧 kn-aut-sei=李 kn-aut-mei=春寧 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=がん関連線維芽細胞でのｐ53の制御は胃癌腹膜播種を抑制する kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of gastric cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OGAWAToshihiro en-aut-sei=OGAWA en-aut-mei=Toshihiro kn-aut-name=小川俊博 kn-aut-sei=小川 kn-aut-mei=俊博 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=膵臓癌における腫瘍融解ウイルス誘導性のp53発現増強は免疫原性細胞死や抗PD-1抗体の治療効果を促進する kn-title=Oncolytic virus–mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ARAKIHiroyuki en-aut-sei=ARAKI en-aut-mei=Hiroyuki kn-aut-name=荒木宏之 kn-aut-sei=荒木 kn-aut-mei=宏之 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=SuraminはKK-AyマウスにおいてNLRP3インフラマソームの活性化を阻害することにより糖尿病性腎臓病の進展を抑制する kn-title=Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ODAKaori en-aut-sei=ODA en-aut-mei=Kaori kn-aut-name=小田香織 kn-aut-sei=小田 kn-aut-mei=香織 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=2023 dt-pub=20230324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=S100A8/A9阻害による、マウス異所性気管移植モデルでの気道閉塞の改善 kn-title=Inhibiting S100A8/A9 attenuates airway obstruction in a mouse model of heterotopic tracheal transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=SHIMIZUDai en-aut-sei=SHIMIZU en-aut-mei=Dai kn-aut-name=清水大 kn-aut-sei=清水 kn-aut-mei=大 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=175 cd-vols= no-issue= article-no= start-page=105921 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain en-subtitle= kn-subtitle= en-abstract= kn-abstract=Thioredoxin, encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of thioredoxin in the central nervous system (CNS) is largely unknown. A phenotype-driven study of N-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed the importance of Txn1 mutations in CNS degeneration. Genetic mapping identified Txn1-F54L in the epileptic rats. The insulin-reducing activity of Txn1-F54L was approximately one-third of that of the wild-type (WT). Bilateral symmetrical vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in the Txn1-F54L rats. The lesions displayed neuronal and oligodendrocytic cell death. Neurons in Txn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration peaked at five weeks of age, and spontaneous repair began at seven weeks. The TUNEL assay showed that fibroblasts derived from homozygotes were susceptible to cell death under oxidative stress. In five-week-old WT rats, energy metabolism in the thalamus was significantly higher than that in the cerebral cortex. In conclusion, in juvenile rats, Txn1 seems to play an essential role in reducing oxidative stress in the midbrains with high energy metabolism. en-copyright= kn-copyright= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImaiHirohiko en-aut-sei=Imai en-aut-mei=Hirohiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshidaSaeko en-aut-sei=Ishida en-aut-mei=Saeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ToyokuniShinya en-aut-sei=Toyokuni en-aut-mei=Shinya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MashimoTomoji en-aut-sei=Mashimo en-aut-mei=Tomoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Section of Developmental Physiology and Pathology, Faculty of Education, Okayama University kn-affil= affil-num=2 en-affil=Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Systems Science, Kyoto University Graduate School of Informatics kn-affil= affil-num=4 en-affil=Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo kn-affil= en-keyword=Txn1 kn-keyword=Txn1 en-keyword=Thioredoxin kn-keyword=Thioredoxin en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Vacuolar degeneration kn-keyword=Vacuolar degeneration en-keyword=Epilepsy kn-keyword=Epilepsy en-keyword=Oxidative stress kn-keyword=Oxidative stress END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=8 article-no= start-page=7394 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230417 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for several ligands, is highly expressed in many kinds of mesenchymal stem cells (MSCs), but its function is poorly understood. In this study, we explored the roles of full-length NRP1 and glycosaminoglycan (GAG)-modifiable NRP1 in adipogenesis in C3H10T1/2 cells. The expression of full-length NRP1 and GAG-modifiable NRP1 increased during adipogenic differentiation in C3H10T1/2 cells. NRP1 knockdown repressed adipogenesis while decreasing the levels of Akt and ERK1/2 phosphorylation. Moreover, the scaffold protein JIP4 was involved in adipogenesis in C3H10T1/2 cells by interacting with NRP1. Furthermore, overexpression of non-GAG-modifiable NRP1 mutant (S612A) greatly promoted adipogenic differentiation, accompanied by upregulation of the phosphorylated Akt and ERK1/2. Taken together, these results indicate that NRP1 is a key regulator that promotes adipogenesis in C3H10T1/2 cells by interacting with JIP4 and activating the Akt and ERK1/2 pathway. Non-GAG-modifiable NRP1 mutant (S612A) accelerates the process of adipogenic differentiation, suggesting that GAG glycosylation is a negative post-translational modification of NRP1 in adipogenic differentiation. en-copyright= kn-copyright= en-aut-name=YuYaqiong en-aut-sei=Yu en-aut-mei=Yaqiong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Uchida-FukuharaYoko en-aut-sei=Uchida-Fukuhara en-aut-mei=Yoko 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=HeYuhan en-aut-sei=He en-aut-mei=Yuhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=YoshidaKaya en-aut-sei=Yoshida en-aut-mei=Kaya 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= en-aut-name=QiuLihong en-aut-sei=Qiu en-aut-mei=Lihong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases 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 Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases 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=Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School kn-affil= affil-num=8 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases kn-affil= en-keyword=neuropilin 1 kn-keyword=neuropilin 1 en-keyword=adipogenic differentiation kn-keyword=adipogenic differentiation en-keyword=mesenchymal stem cells kn-keyword=mesenchymal stem cells END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=314 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230303 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis. en-copyright= kn-copyright= en-aut-name=SakoHidefumi en-aut-sei=Sako en-aut-mei=Hidefumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=NakayamaMasaaki en-aut-sei=Nakayama en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=IdeguchiHidetaka en-aut-sei=Ideguchi en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Yoshimura-NakagawaSaki en-aut-sei=Yoshimura-Nakagawa en-aut-mei=Saki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaidaKyosuke en-aut-sei=Sakaida en-aut-mei=Kyosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Nagata-KameiChiaki en-aut-sei=Nagata-Kamei en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroya en-aut-sei=Kobayashi en-aut-mei=Hiroya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiiSatoki en-aut-sei=Ishii en-aut-mei=Satoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 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=12 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=13 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=14 ORCID= en-aut-name=TakashibaShogo en-aut-sei=Takashiba en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science kn-affil= affil-num=5 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=11 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University kn-affil= affil-num=15 en-affil=Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=synthetic (+)-terrein kn-keyword=synthetic (+)-terrein en-keyword=periodontitis kn-keyword=periodontitis en-keyword= TNF-α kn-keyword= TNF-α END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=1142886 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230223 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LOXL1 and LOXL4 are novel target genes of the Zn2+-bound form of ZEB1 and play a crucial role in the acceleration of invasive events in triple-negative breast cancer cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: EMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated.
Methods: We established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (Delta Zn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively.
Results: MDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (Delta Zn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression.
Conclusions: These findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells. en-copyright= kn-copyright= en-aut-name=HirabayashiDaisuke en-aut-sei=Hirabayashi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=MaruyamaAkihiro en-aut-sei=Maruyama en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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=5 ORCID= en-aut-name=ChenYouyi en-aut-sei=Chen en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KomalasariNi Luh Gede Yoni en-aut-sei=Komalasari en-aut-mei=Ni Luh Gede Yoni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=GoharaYuma en-aut-sei=Gohara en-aut-mei=Yuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ZhouJin en-aut-sei=Zhou en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=RumaI. Made Winarsa en-aut-sei=Ruma en-aut-mei=I. Made Winarsa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SumardikaI. Wayan en-aut-sei=Sumardika en-aut-mei=I. Wayan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YamauchiAkira en-aut-sei=Yamauchi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuribayashiFutoshi en-aut-sei=Kuribayashi en-aut-mei=Futoshi 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=InoueYusuke en-aut-sei=Inoue en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 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=18 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=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University 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=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology kn-affil= affil-num=12 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=13 en-affil=Faculty of Medicine, Udayana University kn-affil= affil-num=14 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=15 en-affil=Department of Biochemistry, Kawasaki Medical School kn-affil= affil-num=16 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=17 en-affil=Faculty of Science and Technology, Division of Molecular Science, Gunma University kn-affil= affil-num=18 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=epithelial-to-mesenchymal transition kn-keyword=epithelial-to-mesenchymal transition en-keyword=triple-negative breast cancer kn-keyword=triple-negative breast cancer en-keyword=zinc kn-keyword=zinc en-keyword=ZEB1 kn-keyword=ZEB1 en-keyword=metastasis kn-keyword=metastasis END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue= article-no= start-page=52 end-page=61 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of hydroxyapatite-coated nonwovens for efficient isolation of somatic stem cells from adipose tissues en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adipose-derived stem cells (ASCs) are an attractive cell source for cell therapy. Despite the increasing number of clinical applications, the methodology for ASC isolation is not optimized for every individual. In this study, we developed an effective material to stabilize explant cultures from small-fragment adipose tissues.
Methods: Polypropylene/polyethylene nonwoven sheets were coated with hydroxyapatite (HA) particles. Adipose fragments were then placed on these sheets, and their ability to trap tissue was monitored during explant culture. The yield and properties of the cells were compared to those of cells isolated by conventional collagenase digestion.
Results: Hydroxyapatite-coated nonwovens immediately trapped adipose fragments when placed on the sheets. The adhesion was stable even in culture media, leading to cell migration and proliferation from the tissue along with the nonwoven fibers. A higher fiber density further enhanced cell growth. Although cells on nonwoven explants could not be fully collected with cell dissociation enzymes, the cell yield was significantly higher than that of conventional monolayer culture without impacting stem cell properties.
Conclusions: Hydroxyapatite-coated nonwovens are useful for the effective primary explant culture of connective tissues without enzymatic cell dissociation. en-copyright= kn-copyright= en-aut-name=ChijimatsuRyota en-aut-sei=Chijimatsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakedaTaiga en-aut-sei=Takeda en-aut-mei=Taiga kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsujiShinsaku en-aut-sei=Tsuji en-aut-mei=Shinsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiKohei en-aut-sei=Sasaki en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKoichi en-aut-sei=Kato en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KojimaRie en-aut-sei=Kojima en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MichihataNoriko en-aut-sei=Michihata en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsubakiToshiya en-aut-sei=Tsubaki en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatuiAya en-aut-sei=Matui en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMiharu en-aut-sei=Watanabe en-aut-mei=Miharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TanakaSakae en-aut-sei=Tanaka en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SaitoTaku en-aut-sei=Saito en-aut-mei=Taku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Okayama University Hospital, Center for Comprehensive Genomic Medicine kn-affil= affil-num=2 en-affil=The University of Tokyo, Bone and Cartilage Regenerative Medicine, Graduate School of Medicine kn-affil= affil-num=3 en-affil=CPC Corporation kn-affil= affil-num=4 en-affil=Japan Vilene Company, Ltd., Central Research Laboratory kn-affil= affil-num=5 en-affil=Japan Vilene Company, Ltd., Central Research Laboratory kn-affil= affil-num=6 en-affil=Japan Vilene Company, Ltd., Central Research Laboratory kn-affil= affil-num=7 en-affil=Japan Vilene Company, Ltd., Central Research Laboratory kn-affil= affil-num=8 en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine kn-affil= affil-num=9 en-affil=CPC Corporation kn-affil= affil-num=10 en-affil=CPC Corporation kn-affil= affil-num=11 en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine kn-affil= affil-num=12 en-affil=The University of Tokyo, Sensory and Motor System Medicine, Graduate School of Medicine kn-affil= en-keyword=Adipose stem cells kn-keyword=Adipose stem cells en-keyword=Explant culture kn-keyword=Explant culture en-keyword=Nonwovens kn-keyword=Nonwovens en-keyword=Hydroxyapatite kn-keyword=Hydroxyapatite END start-ver=1.4 cd-journal=joma no-vol=464 cd-vols= no-issue= article-no= start-page=109815 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quantifying the GCM-related uncertainty for climate change impact assessment of rainfed rice production in Cambodia by a combined hydrologic - rice growth model en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of climate change on agriculture are a major concern for global food security. In this study, the impacts of climate change on rainfed rice production in the granary of Cambodia were examined on a basin scale by developing and applying a combined model consisting of a crop model and a basin-scale distributed hydrological model. The response of rice production to soil-water availability was simulated for past (1981–2000) and future (2041–2060, 2081–2100) periods. From 34 general circulation models (GCMs) that participated in the Coupled Model Intercomparison Project Phase 5 (CMIP5), 5 GCMs were selected by evaluating monthly rainfall in the past. Although annual rainfall was projected to increase by all five selected GCMs, notable decreases in rainfed rice production were projected with 3 GCMs, while small changes were projected with the other 2 GCMs. The main factor restricting future rice production was soil water availability, brought by the projected change in the seasonal distribution of rainfall and the projected more severe dry spells in the early monsoon season. The results suggest the importance of the selection and bias correction of GCMs to force rice crop models and of the simulation of soil water flow on a basin scale for the assessment of rain-fed rice production. In particular, improvements in projections of rainfall amounts over shorter periods rather than annual or seasonal periods, which fit within the time scales of rice plant growth, were suggested to be important. en-copyright= kn-copyright= en-aut-name=TsujimotoK. en-aut-sei=Tsujimoto en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuriyaN. en-aut-sei=Kuriya en-aut-mei=N. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtaT. en-aut-sei=Ohta en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HommaK. en-aut-sei=Homma en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ImM.So en-aut-sei=Im en-aut-mei=M.So kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Faculty of Environmental Science and Technology, Okayama University kn-affil= affil-num=3 en-affil=Assistance Unit for Research and Engineering Development (U-PRIMO) kn-affil= affil-num=4 en-affil=Graduate School of Agricultural Science, Tohoku University kn-affil= affil-num=5 en-affil=Ministry of Water Resources and Meteorology (MOWRAM) of Cambodia kn-affil= en-keyword=Climate change impact assessment kn-keyword=Climate change impact assessment en-keyword=Soil moisture kn-keyword=Soil moisture en-keyword=Crop model kn-keyword=Crop model en-keyword=Rice production kn-keyword=Rice production en-keyword=Rainfed paddy kn-keyword=Rainfed paddy en-keyword=GCM kn-keyword=GCM END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=3 article-no= start-page=2926 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression of Acetabular Labral Vascular Endothelial Growth Factor and Nerve Growth Factor Is Directly Associated with Hip Osteoarthritis Pain: Investigation by Immunohistochemical Staining en-subtitle= kn-subtitle= en-abstract= kn-abstract=The acetabular labrum enhances hip joint stability and plays a key role in osteoarthritis (OA) progression. Labral nerve endings contribute to hip OA pain. Moreover, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are associated with pain. Consequently, we analysed VEGF and NGF expression levels in the labrum and their roles in OA. Labra obtained from OA patients were stained immunohistochemically, and labral cells were cultured and subjected to a reverse transcription (RT)-polymerase chain reaction (PCR) to analyse VEGF and NGF mRNA expression. VEGF and NGF expression were compared in each region of the labrum. Correlations between VEGF and NGF expression and age, body mass index, Kellgren-Lawrence grade, Harris Hip Score, the visual analogue scale (VAS), and Krenn score were analysed, and the RT-PCR confirmed the findings. VEGF and NGF expression were high on the labral articular side, negatively correlated with the Krenn score, and positively correlated with the VAS in early OA. VEGF and NGF mRNA expression increased significantly in patients with severe pain and decreased significantly in severely degenerated labra. In early OA, VEGF and NGF expression in the acetabular labrum was associated with the occurrence of hip pain; therefore, these factors could be effective targets for pain management. en-copyright= kn-copyright= en-aut-name=SatoYoshihiro en-aut-sei=Sato en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawamuraYoshi en-aut-sei=Kawamura en-aut-mei=Yoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Intelligent Orthopaedic System, Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Materials for Musculoskeletal Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=hip osteoarthritis (OA) kn-keyword=hip osteoarthritis (OA) en-keyword=acetabular labrum kn-keyword=acetabular labrum en-keyword=vascular endothelial growth factor (VEGF) kn-keyword=vascular endothelial growth factor (VEGF) en-keyword=nerve growth factor (NGF) kn-keyword=nerve growth factor (NGF) en-keyword=immunochemical staining kn-keyword=immunochemical staining END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue= article-no= start-page=1 end-page=68 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230331 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Annual report / Institute of Plant Science and Resources, Okayama University kn-title=岡山大学資源植物科学研究所報告 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Institute of Plant Science and Resources, Okayama University en-aut-sei=Institute of Plant Science and Resources, Okayama University en-aut-mei= kn-aut-name=岡山大学資源植物科学研究所 kn-aut-sei=岡山大学資源植物科学研究所 kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=2 article-no= start-page=468 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230112 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators en-subtitle= kn-subtitle= en-abstract= kn-abstract=Simple Summary Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate the possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo lung metastatic model. We found that highly metastatic TNBC cells have limited iron metabolism and can be more effectively targeted by iron chelators. Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators. en-copyright= kn-copyright= en-aut-name=WangYuze en-aut-sei=Wang en-aut-mei=Yuze 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=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=LiChunning en-aut-sei=Li en-aut-mei=Chunning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 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=8 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=triple-negative breast cancer kn-keyword=triple-negative breast cancer en-keyword=iron metabolism kn-keyword=iron metabolism en-keyword=iron chelator kn-keyword=iron chelator en-keyword=phosphoinositide-3-kinase-protein kinase kn-keyword=phosphoinositide-3-kinase-protein kinase en-keyword=heterogeneity kn-keyword=heterogeneity en-keyword=metastasis kn-keyword=metastasis END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=822 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230103 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cycloartenyl Ferulate Is the Predominant Compound in Brown Rice Conferring Cytoprotective Potential against Oxidative Stress-Induced Cytotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 +/- 8.07 nmol/g) >> alpha-tocopherol (alpha T) (19.73 +/- 2.28 nmol/g) > gamma-tocotrienol (gamma T3) (18.24 +/- 1.41 nmol/g) > alpha-tocotrienol (alpha T3) (16.02 +/- 1.29 nmol/g) > gamma-tocopherol (gamma T) (3.81 +/- 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of alpha T, alpha T3, and gamma T3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 mu M, which is lower than the minimal concentrations of alpha T and gamma T required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity. en-copyright= kn-copyright= en-aut-name=WuHongyan en-aut-sei=Wu en-aut-mei=Hongyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 ORCID= en-aut-name=GuoYingnan en-aut-sei=Guo en-aut-mei=Yingnan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoRiho en-aut-sei=Matsumoto en-aut-mei=Riho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 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=7 ORCID= affil-num=1 en-affil=School of Food Science and Technology, Dalian Polytechnic University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=School of Food Science and Technology, Dalian Polytechnic 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=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=7 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=cycloartenyl ferulate kn-keyword=cycloartenyl ferulate en-keyword=antioxidative effect kn-keyword=antioxidative effect en-keyword=cytoprotective potential kn-keyword=cytoprotective potential en-keyword=heme oxygenase-1 kn-keyword=heme oxygenase-1 en-keyword=nuclear factor erythroid 2-related factor 2 kn-keyword=nuclear factor erythroid 2-related factor 2 END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=23 article-no= start-page=15311 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221204 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1 beta than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1 beta in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnf alpha, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA. en-copyright= kn-copyright= en-aut-name=HiroseKazuki en-aut-sei=Hirose en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KuwaharaMiho en-aut-sei=Kuwahara en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaigaKenta en-aut-sei=Saiga en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakigawaMasaharu en-aut-sei=Takigawa en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=KubotaSatoshi en-aut-sei=Kubota en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HattoriTakako en-aut-sei=Hattori en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School/Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=hip osteoarthritis kn-keyword=hip osteoarthritis en-keyword=cartilage kn-keyword=cartilage en-keyword=cellular communication network factor 3 (CCN3) kn-keyword=cellular communication network factor 3 (CCN3) en-keyword=senescence-associatedsecretory phenotype (SASP) kn-keyword=senescence-associatedsecretory phenotype (SASP) en-keyword=p16 kn-keyword=p16 en-keyword=ADAMTA4/5 kn-keyword=ADAMTA4/5 en-keyword=IL-6 kn-keyword=IL-6 en-keyword=TNFa kn-keyword=TNFa en-keyword=aging kn-keyword=aging en-keyword=Mankinscore kn-keyword=Mankinscore en-keyword=weight-bearing kn-keyword=weight-bearing en-keyword=non-weight-bearing kn-keyword=non-weight-bearing END start-ver=1.4 cd-journal=joma no-vol=471 cd-vols= no-issue= article-no= start-page=214742 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202211 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Geometric, electronic and spin structures of the CaMn4O5 catalyst for water oxidation in oxygen-evolving photosystem II. Interplay between experiments and theoretical computations en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this review is to elucidate geometric structures of the catalytic CaMn4Ox (x = 5, 6) cluster in the Kok cycle for water oxidation in the oxygen evolving complex (OEC) of photosystem II (PSII) based on the high-resolution (HR) X-ray diffraction (XRD) and serial femtosecond crystallography (SFX) experiments using the X-ray free-electron laser (XFEL). Quantum mechanics (QM) and QM/molecular mechanics (MM) computations are performed to elucidate the electronic and spin structures of the CaMn4Ox (x = 5, 6) cluster in five states S-i (i = 0 similar to 4) on the basis of the X-ray spectroscopy, electron paramagnetic resonance (EPR) and related experiments. Interplay between the experiments and theoretical computations has been effective to elucidate the coordination structures of the CaMn4Ox (x = 5, 6) cluster ligated by amino acid residues of the protein matrix of PSII, valence states of the four Mn ions and total spin states by their exchange-couplings, and proton-shifted isomers of the CaMn4Ox (x = 5, 6) cluster. The HR XRD and SFX XFEL experiments have also elucidated the biomolecular systems structure of OEC of PSII and the hydrogen bonding networks consisting of water molecules, chloride anions, etc., for water inlet and proton release pathways in PSII. Large-scale QM/MM computations have been performed for elucidation of the hydrogen bonding distances and angles by adding invisible hydrogen atoms to the HR XRD structure. Full geometry optimizations by the QM and QM/MM methods have been effective for elucidation of the molecular systems structure around the CaMn4Ox (x = 5, 6) cluster in OEC. DLPNO-CCSD(T-0) method has been applied to elucidate relative energies of possible intermediates in each state of the Kok cycle for water oxidation. Implications of these results are discussed in relation to the blueprint for developments of artificial catalysts for water oxidation. en-copyright= kn-copyright= en-aut-name=YamaguchiKizashi en-aut-sei=Yamaguchi en-aut-mei=Kizashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShojiMitsuo en-aut-sei=Shoji en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsobeHiroshi en-aut-sei=Isobe en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawakamiTakashi en-aut-sei=Kawakami en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MiyagawaKoichi en-aut-sei=Miyagawa en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugaMichihiro en-aut-sei=Suga en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkitaFusamichi en-aut-sei=Akita en-aut-mei=Fusamichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShenJian-Ren en-aut-sei=Shen en-aut-mei=Jian-Ren kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Center for Quantum Information and Quantum Biology, Osaka University kn-affil= affil-num=2 en-affil=Center of Computational Sciences, Tsukuba University kn-affil= affil-num=3 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=4 en-affil=RIKEN Center for Computational Science kn-affil= affil-num=5 en-affil=Center of Computational Sciences, Tsukuba University kn-affil= affil-num=6 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=8 en-affil=Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University kn-affil= en-keyword=Water oxidation kn-keyword=Water oxidation en-keyword=Oxygen evolution kn-keyword=Oxygen evolution en-keyword=Photosystem II kn-keyword=Photosystem II en-keyword=HR XRD kn-keyword=HR XRD en-keyword=SFX XFEL kn-keyword=SFX XFEL en-keyword=QM/MM calculation kn-keyword=QM/MM calculation en-keyword=DLPNO CCSD(T-0) computations, Oxyl radical character kn-keyword=DLPNO CCSD(T-0) computations, Oxyl radical character END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=11 article-no= start-page=2729 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221028 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Tumor angiogenesis is one of the hallmarks of solid tumor development. The progressive tumor cells produce the angiogenic factors and promote tumor angiogenesis. However, how the tumor stromal cells influence tumor vascularization is still unclear. In the present study, we evaluated the effects of oral squamous cell carcinoma (OSCC) stromal cells on tumor vascularization. The tumor stromal cells were isolated from two OSCC patients with different subtypes: low invasive verrucous squamous carcinoma (VSCC) and highly invasive squamous cell carcinoma (SCC) and co-xenografted with the human OSCC cell line (HSC-2) on nude mice. In comparison, the CD34+ vessels in HSC-2+VSCC were larger than in HSC-2+SCC. Interestingly, the vessels in the HSC-2+VSCC expressed vascular endothelial cadherin (VE-cadherin), indicating well-formed vascularization. Our microarray data revealed that the expression of extracellular superoxide dismutase, SOD3 mRNA is higher in VSCC stromal cells than in SCC stromal cells. Moreover, we observed that SOD3 colocalized with VE-cadherin on endothelial cells of low invasive stroma xenograft. These data suggested that SOD3 expression in stromal cells may potentially regulate tumor vascularization in OSCC. Thus, our study suggests the potential interest in SOD3-related vascular integrity for a better OSCC therapeutic strategy. en-copyright= kn-copyright= en-aut-name=OoMay Wathone en-aut-sei=Oo en-aut-mei=May Wathone kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 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=2 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=3 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=4 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=5 ORCID= en-aut-name=SanouSho en-aut-sei=Sanou en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=InadaYasunori en-aut-sei=Inada en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiMasae en-aut-sei=Fujii en-aut-mei=Masae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=SukegawaShintaro en-aut-sei=Sukegawa en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 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=14 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=15 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, kn-affil= affil-num=11 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=tumor microenvironment kn-keyword=tumor microenvironment en-keyword=tumor stroma kn-keyword=tumor stroma en-keyword=tumor vascularization kn-keyword=tumor vascularization en-keyword=extracellular superoxide dismutase (SOD3) kn-keyword=extracellular superoxide dismutase (SOD3) en-keyword=vascular endothelial cadherin (Ve-cadherin) kn-keyword=vascular endothelial cadherin (Ve-cadherin) END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue=2 article-no= start-page=205 end-page=220 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221029 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Aims/Introduction Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-A(y)/TaJcl (KK-Ay) mice against DKD progression. Materials and Methods Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Results Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. Conclusions These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD. en-copyright= kn-copyright= en-aut-name=OdaKaori en-aut-sei=Oda en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoSatoshi en-aut-sei=Miyamoto en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KoderaRyo en-aut-sei=Kodera en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Osafune Clinic kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism kn-affil= affil-num=5 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= en-keyword=Diabetic kidney disease kn-keyword=Diabetic kidney disease en-keyword=Inflammasomes kn-keyword=Inflammasomes en-keyword=Suramin kn-keyword=Suramin 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=植物生育促進メチロトロフ細菌Methylobacterium aquaticum 22A株におけるシデロフォアの多様な役割 kn-title=Diverse roles of a siderophore in a plant-growth promoting methylotroph, Methylobacterium aquaticum strain 22A en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=PATRICK OTIENO JUMA en-aut-sei=PATRICK OTIENO JUMA 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=堆肥施用土壌からの一酸化二窒素および二酸化炭素排出速度の評価 kn-title=Evaluation of nitrous oxide and carbon dioxide emissions from manure compost-amended soil en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=THANUJA DEEPANI PANANGALA LIYANAGE en-aut-sei=THANUJA DEEPANI PANANGALA LIYANAGE 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=口腔扁平上皮癌間質による腫瘍進展促進への直接的関与 kn-title=Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ShanQiusheng en-aut-sei=Shan en-aut-mei=Qiusheng 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=腫瘍間質由来CCL2は骨髄由来免疫抑制細胞の腫瘍微小環境への動員に関与する kn-title=Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=May Wathone Oo en-aut-sei=May Wathone Oo 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=レゾルビンD2は歯髄幹細胞の増殖を促進して断髄面における硬組織形成を誘導する en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YONEDAMitsuhiro en-aut-sei=YONEDA en-aut-mei=Mitsuhiro kn-aut-name=米田光宏 kn-aut-sei=米田 kn-aut-mei=光宏 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ヒト血管内皮細胞における重力感受性遺伝子のメタ分析支援検出 kn-title=Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LIANGYIN en-aut-sei=LIANG en-aut-mei=YIN kn-aut-name=梁茵 kn-aut-sei=梁 kn-aut-mei=茵 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=2022 dt-pub=20220922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ケタミンはフェンタニルの反復投与によるμ−オピオイド受容体の脱感作を改善するが、モルヒネの反復投与による脱感作は改善しない kn-title=Ketamine Improves Desensitization of µ-Opioid Receptors Induced by Repeated Treatment with Fentanyl but not with Morphine en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MIZOBUCHIYusuke en-aut-sei=MIZOBUCHI en-aut-mei=Yusuke kn-aut-name=溝渕有助 kn-aut-sei=溝渕 kn-aut-mei=有助 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=10 cd-vols= no-issue= article-no= start-page=977049 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Does ESG investment reduce carbon emissions in China? en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study explores the relationship between ESG investments and carbon emissions in China. Our results show that 1% increase in environmental investments would cause 0.246% decrease in CO2 emissions and 0.558% decrease in carbon emission intensity. The impact of ESG investment is heterogeneous across the developed and underdeveloped regions. Environmental investments in the advanced eastern region have significantly improved carbon productivity. In contrast, environmental investments in the central and western regions significantly reduced carbon emissions, but they have little impact on carbon productivity. en-copyright= kn-copyright= en-aut-name=CongYingnan en-aut-sei=Cong en-aut-mei=Yingnan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ZhuChen en-aut-sei=Zhu en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HouYufei en-aut-sei=Hou en-aut-mei=Yufei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TianShuairu en-aut-sei=Tian en-aut-mei=Shuairu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=CaiXiaojing en-aut-sei=Cai en-aut-mei=Xiaojing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Business School, China University of Political Science and Law kn-affil= affil-num=2 en-affil=Business School, China University of Political Science and Law kn-affil= affil-num=3 en-affil=Business School, China University of Political Science and Law kn-affil= affil-num=4 en-affil=Research Center of Finance, Shanghai Business School kn-affil= affil-num=5 en-affil=Graduate School of Humanities and Social Sciences, Okayama University kn-affil= en-keyword=ESG investment kn-keyword=ESG investment en-keyword=carbon emission kn-keyword=carbon emission en-keyword=carbon productivity kn-keyword=carbon productivity en-keyword=regional effect kn-keyword=regional effect en-keyword=green transition kn-keyword=green transition END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue= article-no= start-page=3 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221215 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade. en-copyright= kn-copyright= en-aut-name=ArakiHiroyuki en-aut-sei=Araki en-aut-mei=Hiroyuki 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=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=KajiwaraYoshinori en-aut-sei=Kajiwara en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaMotohiko en-aut-sei=Yamada en-aut-mei=Motohiko 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=KikuchiSatoru en-aut-sei=Kikuchi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= en-aut-name=YoshidaRyuichi en-aut-sei=Yoshida en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=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, 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=Oncolys BioPharma, Inc. 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= END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=930683 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histamine induced high mobility group box-1 release from vascular endothelial cells through H-1 receptor en-subtitle= kn-subtitle= en-abstract= kn-abstract=BackgroundSystemic allergic reaction is characterized by vasodilation and vascular leakage, which causes a rapid, precipitous and sustained decrease in arterial blood pressure with a concomitant decrease of cardiac output. Histamine is a major mediator released by mast cells in allergic inflammation and response. It causes a cascade of inflammation and strongly increases vascular permeability within minutes through its four G-protein-coupled receptors (GPCRs) on endothelial cells. High mobility group box-1 (HMGB1), a nonhistone chromatin-binding nuclear protein, can be actively secreted into the extracellular space by endothelial cells. HMGB1 has been reported to exert pro-inflammatory effects on endothelial cells and to increase vascular endothelial permeability. However, the relationship between histamine and HMGB1-mediated signaling in vascular endothelial cells and the role of HMGB1 in anaphylactic-induced hypotension have never been studied. Methods and resultsEA.hy 926 cells were treated with different concentrations of histamine for the indicated periods. The results showed that histamine induced HMGB1 translocation and release from the endothelial cells in a concentration- and time-dependent manner. These effects of histamine were concentration-dependently inhibited by d-chlorpheniramine, a specific H-1 receptor antagonist, but not by H-2 or H-3/4 receptor antagonists. Moreover, an H-1-specific agonist, 2-pyridylethylamine, mimicked the effects of histamine, whereas an H-2-receptor agonist, 4-methylhistamine, did not. Adrenaline and noradrenaline, which are commonly used in the clinical treatment of anaphylactic shock, also inhibited the histamine-induced HMGB1 translocation in endothelial cells. We therefore established a rat model of allergic shock by i.v. injection of compound 48/80, a potent histamine-releasing agent. The plasma HMGB1 levels in compound 48/80-injected rats were higher than those in controls. Moreover, the treatment with anti-HMGB1 antibody successfully facilitated the recovery from compound 48/80-induced hypotension. ConclusionHistamine induces HMGB1 release from vascular endothelial cells solely through H-1 receptor stimulation. Anti-HMGB1 therapy may provide a novel treatment for life-threatening systemic anaphylaxis. en-copyright= kn-copyright= en-aut-name=GaoShangze en-aut-sei=Gao en-aut-mei=Shangze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KuWenhan en-aut-sei=Ku en-aut-mei=Wenhan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 ORCID= en-aut-name=QiaoHandong en-aut-sei=Qiao en-aut-mei=Handong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TeshigawaraKiyoshi en-aut-sei=Teshigawara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 ORCID= affil-num=1 en-affil=Department of Pharmacology, 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 Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Histamine kn-keyword=Histamine en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=vascular endothelial cell kn-keyword=vascular endothelial cell en-keyword=H-1 receptor kn-keyword=H-1 receptor en-keyword=hypotension kn-keyword=hypotension END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=20 article-no= start-page=3307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect en-subtitle= kn-subtitle= en-abstract= kn-abstract=BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. 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=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjiHirotaka en-aut-sei=Uji en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 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=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Material Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Fukushima SiC Applied Engineering Inc. kn-affil= affil-num=5 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=biologically self-degradable amphipathic polymer (Lactosome) kn-keyword=biologically self-degradable amphipathic polymer (Lactosome) en-keyword=hydrophobic boron cluster kn-keyword=hydrophobic boron cluster en-keyword=carborane isomers or o-carborane alkylated derivatives kn-keyword=carborane isomers or o-carborane alkylated derivatives en-keyword=molecular glue effect kn-keyword=molecular glue effect END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=19 article-no= start-page=11035 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. en-copyright= kn-copyright= en-aut-name=ShigehiroTsukasa en-aut-sei=Shigehiro en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UenoMaho en-aut-sei=Ueno en-aut-mei=Maho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KijihiraMayumi en-aut-sei=Kijihira en-aut-mei=Mayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiRyotaro en-aut-sei=Takahashi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UmemuraChiho en-aut-sei=Umemura en-aut-mei=Chiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TahaEman A. en-aut-sei=Taha en-aut-mei=Eman A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KurosakaChisaki en-aut-sei=Kurosaka en-aut-mei=Chisaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsayamaMegumi en-aut-sei=Asayama en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiHiroshi en-aut-sei=Murakami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 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=10 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=11 ORCID= en-aut-name=FutamiJunichiro en-aut-sei=Futami en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MasudaJunko en-aut-sei=Masuda en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science 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=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, 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=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=6 en-affil=Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University kn-affil= affil-num=8 en-affil=Department of Applied Chemistry and Biotechnology, Faculty of Engineering, 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 Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=11 en-affil=Graduate School of Environmental and Life Science, Okayama University 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= en-keyword=breast cancer cells kn-keyword=breast cancer cells en-keyword=dendritic cells kn-keyword=dendritic cells en-keyword=mesenteric lymph node kn-keyword=mesenteric lymph node en-keyword=myeloid-derived suppressor cells kn-keyword=myeloid-derived suppressor cells END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=19 article-no= start-page=2970 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220923 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Treatment of Marmoset Intracerebral Hemorrhage with Humanized Anti-HMGB1 mAb en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intracerebral hemorrhage (ICH) is recognized as a severe clinical problem lacking effective treatment. High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity once released into the extracellular space from the nuclei. We previously demonstrated that intravenous injection of rat anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain injury in a rat ICH model. Therefore, we developed a humanized anti-HMGB1 mAb (OKY001) for clinical use. The present study examined whether and how the humanized anti-HMGB1 mAb ameliorates ICH injury in common marmosets. The results show that administration of humanized anti-HMGB1 mAb inhibited HMGB1 release from the brain into plasma, in association with a decrease of 4-hydroxynonenal (4-HNE) accumulation and a decrease in cerebral iron deposition. In addition, humanized anti-HMGB1 mAb treatment resulted in a reduction in brain injury volume at 12 d after ICH induction. Our in vitro experiment showed that recombinant HMGB1 inhibited hemoglobin uptake by macrophages through CD163 in the presence of haptoglobin, suggesting that the release of excess HMGB1 from the brain may induce a delay in hemoglobin scavenging, thereby allowing the toxic effects of hemoglobin, heme, and Fe2+ to persist. Finally, humanized anti-HMGB1 mAb reduced body weight loss and improved behavioral performance after ICH. Taken together, these results suggest that intravenous injection of humanized anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH. en-copyright= kn-copyright= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OusakaDaiki en-aut-sei=Ousaka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=QiaoHandong en-aut-sei=Qiao en-aut-mei=Handong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=ZhaoKun en-aut-sei=Zhao en-aut-mei=Kun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=GaoShangze en-aut-sei=Gao en-aut-mei=Shangze kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeshigawaraKiyoshi en-aut-sei=Teshigawara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakadaKenzo en-aut-sei=Takada en-aut-mei=Kenzo 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= affil-num=1 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Research Fellow of Japan Society for the Promotion of Science kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=School of Pharmaceutical Sciences, Tsinghua University kn-affil= affil-num=7 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Sapporo Laboratory, EVEC, Inc. kn-affil= affil-num=10 en-affil=Department of Translational Research and Drug Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=intracerebral hemorrhage kn-keyword=intracerebral hemorrhage en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=antibody therapy kn-keyword=antibody therapy en-keyword=non-human primate kn-keyword=non-human primate END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue= article-no= start-page=994014 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220913 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability en-subtitle= kn-subtitle= en-abstract= kn-abstract=Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is a major pathogen of dental caries. The protein Cnm of S. mutans is involved in collagen binding, but its other biological functions are unknown. In this study, a Cnm-deficient isogenic mutant and a complementation strain were generated from a Cnm-positive S. mutans strain to help determine the properties of Cnm. Initially, comparison of the cell surface structure was performed by electron microscopy, which demonstrated that Cnm appears to be localized on the cell surface and associated with a protruding cell surface structure. Deep RNA sequencing of the strains revealed that the defect in Cnm caused upregulated expression of many genes related to ABC transporters and cell-surface proteins, while a few genes were downregulated. The amount of biofilm formed by the Cnm-defective strain increased compared with the parental and complemented strains, but the biofilm structure was thinner because of elevated expression of genes encoding glucan synthesis enzymes, leading to increased production of extracellular polysaccharides. Particular antibiotics, including bacitracin and chloramphenicol, had a lower minimum inhibitory concentration for the Cnm-defective strain than particular antibiotics, including bacitracin and chloramphenicol, compared with the parental and complemented strains. Our results suggest that S. mutans Cnm is located on the cell surface, gives rise to the observed protruding cell surface, and is associated with several biological properties related to membrane permeability. en-copyright= kn-copyright= en-aut-name=NakaShuhei en-aut-sei=Naka en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaDaiki en-aut-sei=Matsuoka en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GotoKana en-aut-sei=Goto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MisakiTaro en-aut-sei=Misaki en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NagasawaYasuyuki en-aut-sei=Nagasawa en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ItoSeigo en-aut-sei=Ito en-aut-mei=Seigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NomuraRyota en-aut-sei=Nomura en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoKazuhiko en-aut-sei=Nakano en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Matsumoto-NakanoMichiyo en-aut-sei=Matsumoto-Nakano en-aut-mei=Michiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Nephrology, Seirei Hamamatsu General Hospital kn-affil= affil-num=5 en-affil=Department of General Internal Medicine, Hyogo College of Medicine kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Japan Self-Defense Iruma Hospital kn-affil= affil-num=7 en-affil=Department of Pediatric Dentistry, Division of Oral infection and Disease Control, Osaka University Graduate School of Dentistry kn-affil= affil-num=8 en-affil=Department of Pediatric Dentistry, Division of Oral infection and Disease Control, Osaka University Graduate School of Dentistry kn-affil= affil-num=9 en-affil=Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Streptococcus mutans kn-keyword=Streptococcus mutans en-keyword=collagen-binding protein kn-keyword=collagen-binding protein en-keyword=membrane permeability kn-keyword=membrane permeability en-keyword=cell structure kn-keyword=cell structure en-keyword=RNA-seq kn-keyword=RNA-seq END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=890048 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220812 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 mu g/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior. en-copyright= kn-copyright= en-aut-name=UshioSoichiro en-aut-sei=Ushio en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WadaYudai en-aut-sei=Wada en-aut-mei=Yudai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraMizuki en-aut-sei=Nakamura en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsumotoDaiki en-aut-sei=Matsumoto en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoshikaKota en-aut-sei=Hoshika en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShiromizuShoya en-aut-sei=Shiromizu en-aut-mei=Shoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataNaohiro en-aut-sei=Iwata en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EsumiSatoru en-aut-sei=Esumi en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KajizonoMakoto en-aut-sei=Kajizono en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 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=11 ORCID= affil-num=1 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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= affil-num=6 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Pharmacy, Okayama University Hospital kn-affil= en-keyword=anxiolytic kn-keyword=anxiolytic en-keyword=inflammation kn-keyword=inflammation en-keyword=immunomodulation kn-keyword=immunomodulation en-keyword=macrophages kn-keyword=macrophages en-keyword=Kampo medicine kn-keyword=Kampo medicine END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue= article-no= start-page=983599 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220825 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC. en-copyright= kn-copyright= en-aut-name=TsujimotoGoki en-aut-sei=Tsujimoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ItoRin en-aut-sei=Ito en-aut-mei=Rin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshikawaKei en-aut-sei=Yoshikawa en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UekiChihiro en-aut-sei=Ueki en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkadaNobuhiro en-aut-sei=Okada en-aut-mei=Nobuhiro 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=hepatocellular carcinoma (HCC) kn-keyword=hepatocellular carcinoma (HCC) en-keyword=cancer metabolism kn-keyword=cancer metabolism en-keyword=gluconeogenesis kn-keyword=gluconeogenesis en-keyword=cell death kn-keyword=cell death en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=NFYA kn-keyword=NFYA en-keyword=PCK1 kn-keyword=PCK1 END