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-1ƒÀ), tumor necrosis factor-alpha (TNF-ƒ¿), 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=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=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= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective
High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-ƒ¿ stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs).

Methods
Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-ƒ¿ (TNF-ƒ¿) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively.

Results
Vascular permeability was increased by TNF-ƒ¿ stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs.

Conclusion
Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS. en-copyright= kn-copyright= en-aut-name=NambaTakahiro en-aut-sei=Namba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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=6 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, 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 Pediatrics, Aichi Medical University kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Influenza kn-keyword=Influenza en-keyword=Acute respiratory distress syndrome kn-keyword=Acute respiratory distress syndrome en-keyword=High mobility group box 1 kn-keyword=High mobility group box 1 en-keyword=Human pulmonary microvascular endothelial cell kn-keyword=Human pulmonary microvascular endothelial cell en-keyword=Cytokine kn-keyword=Cytokine en-keyword=Tumor necrosis factor-ƒ¿ kn-keyword=Tumor necrosis factor-ƒ¿ END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue= article-no= start-page=1511 end-page=1523 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation. Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg x 2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia, and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injections was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity. en-copyright= kn-copyright= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KurodaKeita en-aut-sei=Kuroda en-aut-mei=Keita kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamimaiSunao en-aut-sei=Kamimai en-aut-mei=Sunao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 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=8 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Medical School 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 Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil= kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=methamphetamine kn-keyword=methamphetamine en-keyword=dopamine neuron kn-keyword=dopamine neuron en-keyword=high mobility group box-1 kn-keyword=high mobility group box-1 en-keyword=hyperthermia kn-keyword=hyperthermia en-keyword=inflammation kn-keyword=inflammation en-keyword=neurotoxicity kn-keyword=neurotoxicity END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=6 article-no= start-page=101180 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200626 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A en-subtitle= kn-subtitle= en-abstract= kn-abstract=High-mobility group box-1 (HMGB1) protein has been postulated to play a pathogenic role in severe sepsis. Histidine-rich glycoprotein (HRG), a 75 kDa plasma protein, was demonstrated to improve the survival rate of septic mice through the regulation of neutrophils and endothelium barrier function. As the relalionship of HRG and HMGB1 remains poorly understood, we investigated the effects of HRG on HMGB1-mediated pathway in endothelial cells, focusing on the involvement of specific receptors for HRG. HRC potently inhibited the HMGB1 mobilization and effectively suppressed rHMGB1-induced inflammatory responses and expression of all three HMGB1 receptors in endothelial cells. Moreover, we first clarified that these protective effects of HRG on endothelial cells were mediated through C-type lectin domain family 1 member A (CLEC-1A) receptor. Thus, current study elueiates protective effects of HRG on vascular endothelial cells through inhintion of HMGB1-mediated pathways may contribute to the therapeutic effects of HRG on severe sepsis. 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=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=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=TakahashiYouhei en-aut-sei=Takahashi en-aut-mei=Youhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 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=6 ORCID= en-aut-name=ZhongHui en-aut-sei=Zhong en-aut-mei=Hui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 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=8 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=9 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=10 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=11 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 Cell Biology,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 Pharmacology, School of Pharmacy, Shujitsu University kn-affil= affil-num=9 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacology, Faculty of Medicine, Kindai University kn-affil= affil-num=11 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions. 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=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=FukuyasuYusuke en-aut-sei=Fukuyasu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=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=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji 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, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Human Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=middle cerebral artery occlusion kn-keyword=middle cerebral artery occlusion en-keyword=high-mobility group box 1 kn-keyword=high-mobility group box 1 en-keyword=subcellular localization and subcellular organelle kn-keyword=subcellular localization and subcellular organelle END start-ver=1.4 cd-journal=joma no-vol=292 cd-vols= no-issue=20 article-no= start-page=8436 end-page=8446 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201705 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity en-subtitle= kn-subtitle= en-abstract= kn-abstract= Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation. en-copyright= kn-copyright= en-aut-name=HoriuchiTakahiro en-aut-sei=Horiuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SakataNatsumi en-aut-sei=Sakata en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NarumiYoshihiro en-aut-sei=Narumi en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraTomohiro en-aut-sei=Kimura en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiTakashi en-aut-sei=Hayashi en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NaganoKeisuke en-aut-sei=Nagano en-aut-mei=Keisuke 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=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukitaSohei en-aut-sei=Tsukita en-aut-mei=Sohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTetsuya en-aut-sei=Yamada en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KatagiriHideki en-aut-sei=Katagiri en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShirakawaRyutaro en-aut-sei=Shirakawa en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HoriuchiHisanori en-aut-sei=Horiuchi en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=2 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=3 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=4 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=5 en-affil= Biomedical Technology Research Center, Tokushima Research Institute kn-affil= affil-num=6 en-affil=First Institute of New Drug Discovery, Otsuka Pharmaceutical Co 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 Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= affil-num=13 en-affil=Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University kn-affil= en-keyword=cytokine kn-keyword=cytokine en-keyword=inflammation kn-keyword=inflammation en-keyword=liver injury kn-keyword=liver injury en-keyword=metformin kn-keyword=metformin en-keyword=p38 MAPK kn-keyword=p38 MAPK END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=2 article-no= start-page=97 end-page=102 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anti?high mobility group box-1 antibody therapy for traumatic brain injury kn-title=ŠO«”]ŠQ‚ɑ΂·‚éRHMGB-1R‘ÌŽ¡—à en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OkumaYu en-aut-sei=Okuma en-aut-mei=Yu kn-aut-name=‘åŒF—C kn-aut-sei=‘åŒF kn-aut-mei=—C aut-affil-num=1 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name=—«Ž–ñ kn-aut-sei=—« kn-aut-mei=Ž–ñ aut-affil-num=2 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name=˜a‹CG“¿ kn-aut-sei=˜a‹C kn-aut-mei=G“¿ aut-affil-num=3 ORCID= en-aut-name=HarumaJun en-aut-sei=Haruma en-aut-mei=Jun kn-aut-name=tŠÔƒ kn-aut-sei=tŠÔ kn-aut-mei=ƒ aut-affil-num=4 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name=‹g–ì³ kn-aut-sei=‹g–ì kn-aut-mei=³ aut-affil-num=5 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name=‘å’ˈ¤“ñ kn-aut-sei=‘å’Ë kn-aut-mei=ˆ¤“ñ aut-affil-num=6 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name=‚‹´‰p•v kn-aut-sei=‚‹´ kn-aut-mei=‰p•v aut-affil-num=7 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name=XGŽ¡ kn-aut-sei=X kn-aut-mei=GŽ¡ aut-affil-num=8 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name=¼–x³—m kn-aut-sei=¼–x kn-aut-mei=³—m aut-affil-num=9 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name=ˆÉ’BŒM kn-aut-sei=ˆÉ’B kn-aut-mei=ŒM aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È ”]_ŒoŠO‰ÈŠw affil-num=2 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È –ò—Šw affil-num=3 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È –ò—Šw affil-num=4 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È ”]_ŒoŠO‰ÈŠw affil-num=5 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È •a—ŠwiŽîᇕa—j affil-num=6 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È l‘Ì\¬Šw affil-num=7 en-affil= kn-affil=‹ß‹E‘åŠwˆãŠw•” –ò—Šw affil-num=8 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È AŽÀ‘åŠw–òŠw•” affil-num=9 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È–ò—Šw affil-num=10 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È ”]_ŒoŠO‰ÈŠw en-keyword=HMGB-1 kn-keyword=HMGB-1 en-keyword=traumatic brain injury i“ª•”ŠOj kn-keyword=traumatic brain injury i“ª•”ŠOj en-keyword=secondary injury i“ñŽŸ“I‘¹j kn-keyword=secondary injury i“ñŽŸ“I‘¹j en-keyword=blood brain barrier iŒŒ‰t”]ŠÖ–åj kn-keyword=blood brain barrier iŒŒ‰t”]ŠÖ–åj END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=3 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20081201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats kn-title=ƒ‰ƒbƒg’†”]“®–¬•ÂÇEğ󗬃‚ƒfƒ‹‚É‚¨‚¯‚éR HMGB1 ’PƒNƒ[ƒ“R‘Ì‚ÌŽ¡—ÃŒø‰Ê en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name=—«Ž–ñ kn-aut-sei=—« kn-aut-mei=Ž–ñ aut-affil-num=1 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name=XGŽ¡ kn-aut-sei=X kn-aut-mei=GŽ¡ aut-affil-num=2 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name=‚‹´‰p•v kn-aut-sei=‚‹´ kn-aut-mei=‰p•v aut-affil-num=3 ORCID= en-aut-name=TomonoYasuko en-aut-sei=Tomono en-aut-mei=Yasuko kn-aut-name=—F–ì–õŽq kn-aut-sei=—F–ì kn-aut-mei=–õŽq aut-affil-num=4 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name=˜a‹CG“¿ kn-aut-sei=˜a‹C kn-aut-mei=G“¿ aut-affil-num=5 ORCID= en-aut-name=KankeToru en-aut-sei=Kanke en-aut-mei=Toru kn-aut-name=›‰Æ“O kn-aut-sei=›‰Æ kn-aut-mei=“O aut-affil-num=6 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name=²“¡N° kn-aut-sei=²“¡ kn-aut-mei=N° aut-affil-num=7 ORCID= en-aut-name=HiragaNorihito en-aut-sei=Hiraga en-aut-mei=Norihito kn-aut-name=•½‰êŒ›l kn-aut-sei=•½‰ê kn-aut-mei=Œ›l aut-affil-num=8 ORCID= en-aut-name=AdachiNaoto en-aut-sei=Adachi en-aut-mei=Naoto kn-aut-name=‘«—§®“o kn-aut-sei=‘«—§ kn-aut-mei=®“o aut-affil-num=9 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name=‹g–ì³ kn-aut-sei=‹g–ì kn-aut-mei=³ aut-affil-num=10 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name=¼–x³—m kn-aut-sei=¼–x kn-aut-mei=³—m aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw affil-num=2 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw affil-num=3 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw affil-num=4 en-affil= kn-affil=dˆäˆãŠwŒ¤‹†Š affil-num=5 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw affil-num=6 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw affil-num=7 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@•a—ŠwiŽîᇕa—j affil-num=8 en-affil= kn-affil=ˆ¤•Q‘åŠw‘åŠw‰@@–ƒŒ‘h¶Šw affil-num=9 en-affil= kn-affil=ˆ¤•Q‘åŠw‘åŠw‰@@–ƒŒ‘h¶Šw affil-num=10 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@•a—ŠwiŽîᇕa—j affil-num=11 en-affil= kn-affil=‰ªŽR‘åŠw‘åŠw‰@ˆãŽ•–òŠw‘‡Œ¤‹†‰È@–ò—Šw en-keyword=R‘̈ã–ò kn-keyword=R‘̈ã–ò en-keyword=‰ŠÇ kn-keyword=‰ŠÇ en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=”][Ç kn-keyword=”][Ç en-keyword=ŒŒ‰t”]ŠÖ–å kn-keyword=ŒŒ‰t”]ŠÖ–å END