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STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury

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World Journal of Gastroenterology 2017年第37期23卷 6833-6844页

作者： Mitsuhiko Abe Takafumi Yoshida Jun Akiba Yu Ikezono Fumitaka Wada Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka hideki iwamoto Toru Nakamura Michio Sata Hironori Koga Akihiko Yoshimura Takuji Torimura Division of Gastroenterology Department of Medicine Kurume University School of Medi-cine Liver Cancer Division Research Center for Innovative Cancer Therapy Kurume University Kurume Clinical pharmacology Clinic Department of Diagnostic pathology Kurume University hospital Department of Microbiology Immun--ology Keio University School of Medicine

AIM To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. METHODS We investigated thioacetamide(TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma(HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAAinduced biliary ductular proliferation and analyzed the activation of sex determining region Y-box9(SOX9) and Yes-associated protein(YAP), which regulate the transdifferentiation of hepatocytes to *** Both compensatory hepatocyte proliferation and HCC formation were significantly decreased in hepatic STAT3-deficient mice as compared with control mice. STAT3 deficiency resulted in augmentation of hepatic necrosis and fibrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-deficient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-deficient *** STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.

关键词： Hepatocellular carcinoma Ductular reaction Signal transducer and activator of transcription 3 Yesassociated protein Sex determining region Y-box9 Transdifferentiation

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Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： hideki Kanamaru Hidenori Suzuki Department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

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Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki Suzuki hideki iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano Yihai Cao Hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

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Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism： a multicenter, randomized controlled trial in Japan （EARTH Study）

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Asian Journal of Andrology 2016年第1期18卷 25-34页

作者： Hiroyuki Konaka Kazuhiro Sugimoto hideki Orikasa Teruaki iwamoto Toshinari Takamura Yoshiyu Takeda Kazuyoshi Shigehara Masashi Iijima Eitetsu Koh Mikio Namiki Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan Division of Biostatistics and Clinical Epidemiology University of Toyama School of Medicine Toyama Toyama Japan Division of Male Infertility Center for Infertility and IVF International University of Health and Welfare Nasushiobara Tochigi Japan Department of Disease Control and Homeostasis Kanazawa University Graduate Schoofof Medical Science Kanazawa Ishikawa Japan Departrnent of Internal Medicine. Division of Endocrinology and Hypertension Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan.

Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG）（P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.

关键词： androgen replacement therapy health-related quality of life late-onset hypogonadism randomized controlled trial testosterone

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A Review of Contact Electrification at Diversified Interfaces and Related Applications on Triboelectric Nanogenerator

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Nano-Micro Letters 2024年第1期16卷 106-130页

作者： Jun Hu Mitsumasa iwamoto Xiangyu Chen CAS Center for Excellence in Nanoscience Beijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 100083People’s Republic of China School of Nanoscience and Engineering University of Chinese Academy of SciencesBeijing 100049People’s Republic of China Department of Physical Electronics Tokyo Institute of Technology2‑12‑1 S3‑33 O‑OkayamaMeguro‑KuTokyo 152‑8552Japan

The triboelectric nanogenerator(TENG)can effectively collect energy based on contact electrification(CE)at diverse interfaces,including solid–solid,liquid–solid,liquid–liquid,gas–solid,and gas–*** enables energy harvesting from sources such as water,wind,and *** this review,we provide an overview of the coexistence of electron and ion transfer in the CE *** elucidate the diverse dominant mechanisms observed at different interfaces and emphasize the interconnectedness and complementary nature of interface *** review also offers a comprehensive summary of the factors influencing charge transfer and the advancements in interfacial modification ***,we highlight the wide range of applications stemming from the distinctive characteristics of charge transfer at various ***,this review elucidates the future opportunities and challenges that interface CE may *** anticipate that this review can offer valuable insights for future research on interface CE and facilitate the continued development and industrialization of TENG.

关键词： Contact electrification Interfaces Triboelectric nanogenerators Diversified applications

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Optical second-harmonic generation measurement for probing organic device operation

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Light(Science & Applications) 2015年第1期4卷 99-108页

作者： Takaaki Manaka Mitsumasa iwamoto Department of Physical Electronics Tokyo Institute of Technology2-12-1 O-okayamaMeguro-kuTokyo 152-8552Japan

We give a brief overview of the electric-field induced optical second-harmonic generation(EFISHG)technique that has been used to study the complex behaviors of organic-based *** analyzing EFISHG images of organic field-effect transistors,the in-plane two-dimensional distribution of the electric field in the channel can be *** susceptibility tensor of the organic semiconductor layer and the polarization of the incident light are considered to determine the electric field *** imaging can effectively evaluate the distribution of the vectorial electric field in organic films by selecting a light *** the time-resolved technique,measurement of the electric field originating from the injected carriers allows direct probing of the carrier motion under device operation,because the transient change of the electric field distribution reflects the carrier *** applications of the EFISHG technique to organic electronic devices are reviewed.

关键词： electric field optical second-harmonic generation semiconductor device

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Computationally Efficient Large-Eddy Simulation of Periodic Unsteady Flow using Harmonic Balance Method

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Journal of Thermal Science 2022年第1期31卷 62-71页

作者： YUMA iwamoto SUSUMU Teramoto KOJI Okamoto Department of Aeronautics and Astronautics University of TokyoTokyo 113-8656Japan Department of Advanced Energy University of TokyoTokyo 113-8656Japan

To improve the efficiency and fidelity of the numerical analysis for cascade flutter, we propose an efficient scale-resolving simulation method dedicated to time-periodic flows by incorporating the harmonic balance approach into the large-eddy simulation. This method combined convergence calculations of the steady-state problem based on the harmonic balance method for periodic components, and the nonlinear time-marching method for turbulent fluctuations. Using the proposed method, deterministic periodic components and stochastic turbulent fluctuations were calculated simultaneously, and the effect of turbulent fluctuations on deterministic periodic components was directly calculated without using turbulence models. In this paper, we explain the algorithm and feature of this simulation technique and present the results of the computation for channel flow excited in the streamwise direction as an analysis example using the proposed method. In order to validate the proposed method, an analysis of sinusoidally pulsating channel flow at the central friction-velocity Reynolds numbers Rer = 180 was conducted, confirming that the amplitude and phase of the mean velocity oscillation computed by the proposed method were in good agreement with those of the conventional LES. The present calculation achieved an order of magnitude improvement in computational efficiency compared to conventional LES.

关键词： harmonic balance LES turbulent channel flow

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Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

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Neural Regeneration Research 2024年第4期19卷 711-712页

作者： Masakazu iwamoto Taito Matsuda Department of Stem Cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous *** adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

关键词： neural integrate continuously

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Effect of impact deformation on shape recovery behavior in Fe-Mn-Si shape memory alloy under shape memory training process with cyclic thermo-mechanical loading

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Science China(Technological Sciences) 2021年第7期64卷 1389-1400页

作者： SUN Qian CAO Bo iwamoto Takeshi SUO Tao Graduate School of Engineering Hiroshima UniversityHigashi-Hiroshima739-8527Japan Cluster of Excellence livMatS@FIT-Freiburg Center for Interactive Materials and Bioinspired Technologies University of FreiburgFreiburgD-79110Germany Academy of Science and Technology Hiroshima UniversityHigashi-Hiroshima739-8527Japan School of Aeronautics Northwestern Polytechnical UniversityXi’an710072China

In the past studies, it has been discovered that the shape memory effect(SME) in the Fe-Mn-Si shape memory alloy(Fe-SMA)can gradually be enhanced by a pre-process called as shape memory training process under cyclic thermo-mechanical *** the other hand, it has been shown that the SME of Fe-SMA can also be affected by changing the strain rate. Therefore, it is possible to improve the SME by combining the strain rate sensitivity and shape memory training process. However, the improvement of SME caused by the training process under impact condition is still unclear. For the training process under impact condition, it is difficult to interrupt the test at the desired strain level due to many reflections of stress waves, which reload the specimen from the free ends. In this paper, to obtain reliable experimental results of SME after the training process under impact condition, the stress waves after first loading are eliminated by the double momentum-trap structure introduced into the impact tensile testing apparatus based on the split Hopkinson pressure bar method. In order to achieve an optimum design of the structure used in experiments, the finite element simulation of the structure is performed. Then, tensile tests in the training process of Fe-28Mn-6Si-5Cr alloy at different strain rates including the impact level are conducted and temperature change of the specimen is measured during training and heating process. As a result, the improvement of SME in the alloy after the training process under quasi-static and impact loading is compared with that under quasi-static loading through verification processes.

关键词： Fe-Mn-Si shape memory alloy training cyclic thermo-mechanical process split Hopkinson pressure bar momentumtrap impact deformation

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Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

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Cellular & Molecular Immunology 2021年第3期18卷 523-527页

作者： Hiroyuki Yoshitomi hideki Ueno Department of Immunology Graduate School of MedicineKyoto UniversitySakyo-kuf Kyoto 606-8501Japan lnstitute for the Advanced Study of Human Biology Kyoto UniversitySakyo-kuKyoto 606-8501Japan Department of Microbiology Icahn School of Medicine at Mount SinaiNew York 10029 NYUSA Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount SinaiNew York 10029 NYUSA

The interactions of CD4^(+)T cells and B cells are fundamental for the generation of protective antibody responses,as well as for the development of harmful autoimmune *** studies of human tissues and blood samples have established a new subset of CD4^(+)B helper T cells named peripheral helper T(Tph)*** T follicular helper(Tfh)cells,which interact with B cells within lymphoid organs,Tph cells provide help to B cells within inflamed *** cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing *** differentiation mechanism is also partly shared between Tph and Tfh cells in humans,and both Tfh and Tph cells can be found within the same tissues,including cancer ***,Tph cells display features distinct from those of Tfh cells,such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bd-6/Blimp1 *** that of Tfh cells,current evidence shows that the target of Tph cells is limited to memory B *** this review,we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

关键词： peripheral helper T cells T follicular helper cells CXCL13,Autoantibodies autoimmune diseases

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