start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=8
article-no=
start-page=e89864
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250812
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Higher Liver Fibrosis-4 Index Is Associated With More Severe Hearing Loss in Idiopathic Sudden Sensorineural Hearing Loss
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
Liver fibrosis is an important medical issue increasing over time in developed countries.
Aims/objectives
This study aimed to investigate whether liver fibrosis, as indicated by routine blood test parameters, influences the risk and severity of idiopathic sudden sensorineural hearing loss (ISSNHL).
Material and methods
Sixty-six patients with ISSNHL and 198 patients with benign parotid gland tumors (BPTs) (controls) were enrolled. Indices for liver fibrosis (Liver Fibrosis-4 index (FIB-4 index) and aspartate aminotransferase-to-platelet ratio index (APRI)) were calculated from the blood laboratory data. The pure tone average (PTA) was calculated as the mean of hearing levels at the six frequencies at the onset of ISSNHL. Severe hearing loss was defined as PTA?60 decibels Hearing Level (dB HL).
Results
In risk evaluation, the FIB-4 index did not differ significantly between ISSNHL patients and controls. Regarding the severity of ISSNHL, the FIB-4 index was significantly higher in ISSNHL patients with severe hearing loss than in those with PTA<60 dB HL (P<0.05) on univariate comparison. After adjusting for age, sex, and indices of inflammation, both the FIB-4 index and APRI showed a significant association with severe hearing loss (odds ratio (OR): 5.9, 95% confidence interval (CI): 1.3-25.7, and OR: 2.2, 95% CI: 1.1-4.7).
Conclusions and significance
Higher liver fibrosis indices (FIB-4 index and APRI), derived from routine blood laboratory data, are associated with a more severe phenotype of ISSNHL.
en-copyright=
kn-copyright=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TakaoSoshi
en-aut-sei=Takao
en-aut-mei=Soshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=AndoMizuo
en-aut-sei=Ando
en-aut-mei=Mizuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
affil-num=1
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=aspartate aminotransferase-to-platelet ratio index
kn-keyword=aspartate aminotransferase-to-platelet ratio index
en-keyword=audiometry
kn-keyword=audiometry
en-keyword=fatty liver disease
kn-keyword=fatty liver disease
en-keyword=incidence
kn-keyword=incidence
en-keyword=liver fibrosis-4 index
kn-keyword=liver fibrosis-4 index
en-keyword=severity
kn-keyword=severity
en-keyword=sudden hearing loss
kn-keyword=sudden hearing loss
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=7506
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250303
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=FKBP5 is a 51-Da FK506-binding protein and member of the immunophilin family involved in controlling the signaling of glucocorticoid receptor from the cytosol to nucleus. Fkbp5 has previously been shown to be expressed in murine cochlear tissue, including the organ of Corti (i.e., the sensory epithelium of the cochlea). Fkbp5-/- mice as used in this study show hearing loss in the low-frequency (8-kHz) range and click-evoked auditory brainstem response (ABR) threshold compared to wild-type mice. Both Fkbp5-/- and wild-type mice showed hearing loss at all frequencies and click-ABR thresholds at 24 h and 14 days following acoustic overexposure (AO). Tissues of the organ of Corti were subjected to RNA sequencing and KEGG pathway analysis. In Fkbp5-/- mice before AO, the mitogen-activated protein kinase (MAPK) signaling pathway was dysregulated compared to wild-type mice. In wild-type mice at 12 h following AO, the most significantly modulated KEGG pathway was the TNF signaling pathway and major MAPK molecules p38 and Jun were involved in the TNF signaling pathway. In Fkbp5-/- mice at 12 h following AO, the MAPK signaling pathway was dysregulated compared to wild-type mice following AO. In conclusion, Fkbp5 interacts with MAPK signaling in the organ of Corti in mice cochleae.
en-copyright=
kn-copyright=
en-aut-name=SatoAsuka
en-aut-sei=Sato
en-aut-mei=Asuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=AndoMizuo
en-aut-sei=Ando
en-aut-mei=Mizuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
affil-num=1
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=The organ of Corti
kn-keyword=The organ of Corti
en-keyword=Acoustic trauma
kn-keyword=Acoustic trauma
en-keyword=RNA sequencing
kn-keyword=RNA sequencing
en-keyword=51-Da FK506-binding protein
kn-keyword=51-Da FK506-binding protein
en-keyword=Mitogen-activated protein kinase signaling
kn-keyword=Mitogen-activated protein kinase signaling
en-keyword=Tumor necrosis factor signaling
kn-keyword=Tumor necrosis factor signaling
END
start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=6
article-no=
start-page=589
end-page=593
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202312
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of ‘better-hearing ear’ was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient’s age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and ?0.33, 95% confidence intervals [11.75-37.45] and [?0.58 to ?0.09], respectively), but the CI surgery side did not (?6.76, [?14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing.
en-copyright=
kn-copyright=
en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KariyaShin
en-aut-sei=Kariya
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=FukushimaKunihiro
en-aut-sei=Fukushima
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KataokaYuko
en-aut-sei=Kataoka
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugayaAkiko
en-aut-sei=Sugaya
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoMizuo
en-aut-sei=Ando
en-aut-mei=Mizuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Otolaryngology-Head and Neck Surgery, Kawasaki Medial University
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Hayashima Clinic of Otolaryngology and Dermatology
kn-affil=
affil-num=5
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cochlear implantation
kn-keyword=cochlear implantation
en-keyword=poorer hearing ear
kn-keyword=poorer hearing ear
en-keyword=better hearing ear
kn-keyword=better hearing ear
en-keyword=hearing aids
kn-keyword=hearing aids
en-keyword=speech recognition
kn-keyword=speech recognition
END
start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=10
article-no=
start-page=e0258977
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-kappa B subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-kappa B would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-kappa B-interacting inflammatory molecules, TNF alpha and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.
en-copyright=
kn-copyright=
en-aut-name=UraguchiKensuke
en-aut-sei=Uraguchi
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TakaharaJunko
en-aut-sei=Takahara
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OmichiRyotaro
en-aut-sei=Omichi
en-aut-mei=Ryotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=FujimotoShohei
en-aut-sei=Fujimoto
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KariyaShin
en-aut-sei=Kariya
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoMizuo
en-aut-sei=Ando
en-aut-mei=Mizuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=4
article-no=
start-page=e0249909
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210413
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lack of collagen alpha 6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen alpha 6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen alpha 6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the alpha 6(IV) chain and/or alpha 5 alpha 6 alpha 5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.
en-copyright=
kn-copyright=
en-aut-name=TangShaoying
en-aut-sei=Tang
en-aut-mei=Shaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=
en-aut-name=MaebaTakahiro
en-aut-sei=Maeba
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=
en-aut-name=MomotaRyusuke
en-aut-sei=Momota
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=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 Otolaryngology-Head and Neck Surgery, 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=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Division of Molecular and Cell Biology, Shigei Medical Research Institute
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=
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=2020
dt-pub=20200515
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Immediate changes in transcription factors and synaptic transmission in the cochlea following acoustic trauma: A gene transcriptome study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss.
en-copyright=
kn-copyright=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KariyaShin
en-aut-sei=Kariya
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=UraguchiKensuke
en-aut-sei=Uraguchi
en-aut-mei=Kensuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakaharaJunko
en-aut-sei=Takahara
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=FujimotoShohei
en-aut-sei=Fujimoto
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugayaAkiko
en-aut-sei=Sugaya
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
affil-num=1
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=DNA microarray
kn-keyword=DNA microarray
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
en-keyword=Mouse cochlea
kn-keyword=Mouse cochlea
en-keyword=Neurotransmission
kn-keyword=Neurotransmission
en-keyword=Noise-induced hearing loss
kn-keyword=Noise-induced hearing loss
en-keyword=RNA-seq
kn-keyword=RNA-seq
en-keyword=Real-time RT-PCR
kn-keyword=Real-time RT-PCR
en-keyword=Transcription factor
kn-keyword=Transcription factor
END
start-ver=1.4
cd-journal=joma
no-vol=41
cd-vols=
no-issue=3
article-no=
start-page=364
end-page=370
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202003
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hypothesis:
Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media.
Background:
NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined.
Methods:
Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF?/?) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry.
Results:
In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF?/? mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF?/? mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice.
Conclusion:
Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.
en-copyright=
kn-copyright=
en-aut-name=KariyaShin
en-aut-sei=Kariya
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OkanoMitsuhiro
en-aut-sei=Okano
en-aut-mei=Mitsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=ZhaoPengfei
en-aut-sei=Zhao
en-aut-mei=Pengfei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KataokaYuko
en-aut-sei=Kataoka
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HigakiTakaya
en-aut-sei=Higaki
en-aut-mei=Takaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MakiharaSeiichiro
en-aut-sei=Makihara
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NishihiraJun
en-aut-sei=Nishihira
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TachibanaTomoyasu
en-aut-sei=Tachibana
en-aut-mei=Tomoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Otolaryngology?Head and Neck Surgery, Kagawa Rosai Hospital
kn-affil=
affil-num=8
en-affil=Department of Medical Bioinformatics, Hokkaido Information University
kn-affil=
affil-num=9
en-affil=Departments of Otolaryngology, Japanese Red Cross Society Himeji Hospital
kn-affil=
affil-num=10
en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Cytokine
kn-keyword=Cytokine
en-keyword=Infection
kn-keyword=Infection
en-keyword=Inflammation
kn-keyword=Inflammation
en-keyword=Interleukin
kn-keyword=Interleukin
en-keyword=NOD-like receptor
kn-keyword=NOD-like receptor
en-keyword=Toll-like receptor
kn-keyword=Toll-like receptor
END
start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=13
article-no=
start-page=652
end-page=654
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=20110914
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Expression analysis of microRNAs in murine cochlear explants
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=MicroRNAs (miRNAs) play functional roles in sound transduction in cochlea. This study focuses on the validity of cochlear culture as an in vitro experimental tool, in view of miRNA expression. E15 cochleae were dissected and maintained in vitro for 48 h before extraction of miRNAs. MiRNA expression was comprehensively screened in explanted cochleae using a miRNA array that covers 380 miRNAs. A strong correlation was observed between expression levels of miRNAs in in vitro and in in vivo cochleae. Levels of 43 miRNAs were altered in vitro and these changes were reproducible over three trials. These findings indicate that in vitro miRNA profiling is a viable method for analysis of gene expression and action of chemical compounds on cochleae.
en-copyright=
kn-copyright=
en-aut-name=HiraiMisato
en-aut-sei=Hirai
en-aut-mei=Misato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FukushimaKunihiro
en-aut-sei=Fukushima
en-aut-mei=Kunihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=SugayaAkiko
en-aut-sei=Sugaya
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KataokaYuko
en-aut-sei=Kataoka
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishizakiKazunori
en-aut-sei=Nishizaki
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharm, Dept Otolaryngol Head & Neck Surg
en-keyword=embryonic cochlea
kn-keyword=embryonic cochlea
en-keyword=microRNA array
kn-keyword=microRNA array
en-keyword=organ culture of cochlea
kn-keyword=organ culture of cochlea
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=2000
dt-pub=20000331
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ラット海馬の錐体細胞におけるDNAトポイソメラーゼUβ発現の領域による違い
kn-title=Regional differences in the expression of DNA topoisomerase IIbeta in the pyramidal neurons of the rat hippocampus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A detailed analysis of the differential expression of a nuclear enzyme, DNA topoisomerase (topo) IIβ, was performed in the rat hippocampal pyramidal layer. Three-dimensional (3-D) reconstruction from serial sections immunostained with anti-topo IIβ antibody showed that the immunoreactivity was apparently weak in the entire CA3 region. Almost all CA1 pyramidal cells showed similar immunoreactivity to that seen in the dentate granular cells, the subicular neurons, and the cerebral neocortical neurons. In addition, immunoblotting analysis in the adult dorsal hippocampus showed that the expression level of topo IIβ in the CA3 was significantly lower than that in the CA1 region. The dissociation in the expression level between CA1 and CA3 occurred in postnatal days 4 (P4) through P6. The present finding suggests that the enzyme is possibly involved in activities of the hippocampal pyramidal neurons.
en-copyright=
kn-copyright=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=前田幸英
kn-aut-sei=前田
kn-aut-mei=幸英
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学
en-keyword=DNA topoisomerase IIβ
kn-keyword=DNA topoisomerase IIβ
en-keyword=Hippocampal pyramidal cells
kn-keyword=Hippocampal pyramidal cells
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
en-keyword=3-D reconstruction
kn-keyword=3-D reconstruction
en-keyword=Western blotting
kn-keyword=Western blotting
en-keyword=Postnatal development
kn-keyword=Postnatal development
END