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Dual therapy with zinc acetate and rifaximin prevents from ethanolinduced liver fibrosis by maintaining intestinal barrier integrity

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World Journal of Gastroenterology 2021年第48期27卷 8323-8342页

作者： yuki fujimoto Kosuke Kaji Norihisa Nishimura Masahide Enomoto Koji Murata Soichi Takeda Hiroaki Takaya Hideto Kawaratani Kei Moriya Tadashi Namisaki Takemi Akahane Hitoshi yoshiji Department of Gastroenterology Nara Medical UniversityKashihara 6348521NaraJapan

BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease(ALD)by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 ***,targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of *** acetate and rifaximin,which is a nonabsorbable antibiotic,had been clinically used for patients with cirrhosis,particularly those with hepatic encephalopathy,and had been known to improve intestinal barrier ***,only few studies focused on their efficacies in preventing the ALD-related fibrosis *** To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD *** To induce ALD-related liver fibrosis,female C57BL/6J mice were fed a 2.5%(v/v)ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride(CCl4)injection twice weekly(1 mL/kg)for 8 *** acetate(100 mg/L)and/or rifaximin(100 mg/L)were orally administered during experimental *** steatosis,inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular ***,the direct effects of both agents on Caco-2 barrier function were assessed by in vitro *** the ethanol plus CCl4-treated mice,combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and *** combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB ***,liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2,-9,-13,and *** agents improved the atrophic changes and permeability in the ileum,with restoration of tight junction proteins(TJPs)

关键词： Liver fibrosis Intestinal permeability Alcoholic liver disease Lipopolysaccharide Toll-like receptor Tight junction protein

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日本现存高层钢管混凝土建筑的结构特性

建筑结构 2016年第18期46卷 58-61,70页

作者： Toshiaki fujimoto Shuhei Oka 日本大学生产工学部千叶275-8575 日本大学大学院千叶275-8575

高层建筑中广泛使用钢管混凝土柱作为结构构件。收集了日本1968～2013年间设计的159座高层钢管混凝土建筑的结构特性数据,分析了不同设计阶段现存高层钢管混凝土建筑的结构布置和抗震设计参数。得到以下结论：不同阶段,结构所用的混凝... 详细信息

高层建筑中广泛使用钢管混凝土柱作为结构构件。收集了日本1968～2013年间设计的159座高层钢管混凝土建筑的结构特性数据,分析了不同设计阶段现存高层钢管混凝土建筑的结构布置和抗震设计参数。得到以下结论：不同阶段,结构所用的混凝土强度等级不断提高,因此结构的楼层数和楼层高度不断增加;近几年,隔震结构和消能减震结构的数量大幅增加;高层钢管混凝土建筑倾向于使用和钢结构建筑几乎相同的设计基底剪力系数。

关键词：日本高层建筑钢管混凝土结构特性

MOLECULAR MACHINARy OF THE MAMMALIAN CIRCADIAN CLOCK:ROLES OF DEC1 AND DEC2 IN RHyTHM GENERATION AND ENTRAINMENT

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MOLECULAR MACHINARY OF THE MAMMALIAN CIRCADIAN CLOCK:ROLES O...

围生期柠檬素缺乏的影响:新生儿柠檬素缺乏普查可行性

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作者： Honma,S. Takagi,y. Kawamoto,T. fujimoto,K. Nosihro,M. Kato,y. Honma,K. Dept.of Physiology Hokkaido University Graduate School of MedicineSapporo 060-8638Japan Dept.of Physiology Hokkaido University Graduate School of MedicineSapporo 060-8638Japan Dept.of Dental and Medical Biochemistry Hiroshima University Graduate School of Biomedical SciencesHiroshima 734-8553Japan Dept.of Dental and Medical Biochemistry Hiroshima University Graduate School of Biomedical SciencesHiroshima 734-8553Japan Dept.of Dental and Medical Biochemistry Hiroshima University Graduate School of Biomedical SciencesHiroshima 734-8553Japan Dept.of Dental and Medical Biochemistry Hiroshima University Graduate School of Biomedical SciencesHiroshima 734-8553Japan Dept.of Physiology Hokkaido University Graduate School of MedicineSapporo 060-8638Japan

＜正＞The master circadian clock in the suprachiasmatic nucleus of the hypothalamus （SCN） generates circadian rhythms, entrains the intrinsic periodicity to external time cues, specifically to light, and drives rhythms in bodily functions, such as hormones, autonomic functions and behaviors. Among them, the most pronounced circadian rhythm we observe is the sleep- wake-fulness cycle. The molecular machinery for rhythm generation is considered to consist of a

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世界核心医学期刊文摘（儿科学分册） 2005年第2期1卷 61-62页

作者： Tamamori A fujimoto A. Okano y. 虎小毅 Dr.Department of PediatricsOsaka City University Graduate School of Medicine1-4-3 AsahimachiAbeno-kuOsaka 545-8585Japan

由于SLC25A13基因突变而引起的柠檬素缺乏常导致成年人Ⅱ型瓜氨酸血症(CTLN2)和一种新生儿期肝内胆汁淤积(NICCD)。在新生儿普查(NMS)中,基于高半乳糖浓度、高苯丙氨酸浓度和(或)高蛋氨酸浓度,约有一半NICCD患者被发现。为了阐明围生期... 详细信息

由于SLC25A13基因突变而引起的柠檬素缺乏常导致成年人Ⅱ型瓜氨酸血症(CTLN2)和一种新生儿期肝内胆汁淤积(NICCD)。在新生儿普查(NMS)中,基于高半乳糖浓度、高苯丙氨酸浓度和(或)高蛋氨酸浓度,约有一半NICCD患者被发现。为了阐明围生期和新生儿期的影响及NMS不一致的结果。

关键词：围生期肝内胆汁淤积瓜氨酸血症基因突变血斑出生后氨基酸水平突变频率临床病程总氨基酸

The Cytomegalovirus Enhancer Induces an Immediate Response to the Myosin Light Chain 2v Promoter during P19CL6 Cell Differentiation

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American Journal of Molecular Biology 2017年第4期7卷 190-203页

作者： Takanari Wakayama Kazuaki Ohashi yasuyuki fujimoto Masatomo Maeda Laboratory of Biochemistry and Molecular Biology Graduate School of Pharmaceutical Sciences Osaka University Osaka Japan Department of Medical Biochemistry School of Pharmacy Iwate Medical University Shiwa-Gun Japan Department of Molecular Biology School of Pharmacy Iwate Medical University Shiwa-Gun Japan Laboratory of Gene Therapy Faculty of Pharmaceutical Sciences Niigata University of Pharmacy and Applied Life Sciences Niigata Japan

The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhancer and a 250 bp MLC-2v promoter in front of the GFP gene to further evaluate the role of the CMV enhancer. This plasmid (pCBVenh/MLC-2vpro/EGFP) was stably introduced into P19CL6 cells, and the transfectant differentiated into cardiomyocytes with DMSO. Upon DMSO addition, GFP was immediately transcribed (within 2 days) and the amount of the transcript increased with cultivation. Concomitantly, GFP fluorescence was detected in the cells under a microscope. However, native MLC-2v was transcribed later on day 4. This expression time course is different from that of GFP. Clearly the CMV enhancer responded immediately to DMSO. Since GATA DNA-binding proteins play crucial roles in the initiation of cardiomyocyte differentiation, such a response could be ascribed to the presence of multiple GATA motifs in the enhancer sequence but not in the native MLC-2v promoter. Thus the CMV enhancer may be not only useful for gene therapy and monitoring cell differentiation but also the study of the role of GATA transcription factors expressed in P19CL6 cells.

关键词： Cytomegalovirus Enhancer Differentiation GATA Transcription Factor Gene Expression Heart Muscle MLC-2v P19CL6 Cells Promoter

Effects of Cold Atmospheric Pressure Plasma on Accelerating Acute Wound Healing: A Comparative Study among 4 Different Treatment Groups

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Modern Plastic Surgery 2019年第1期9卷 18-31页

作者： Akio Nishijima Takahiro fujimoto Takamichi Hirata Junko Nishijima Department of Medical Engineering Faculty of Engineering Tokyo City University Tokyo Japan Department of Plastic and Reconstructive Surgery University of Tsukuba Ibaraki Japan Clinic F Tokyo Japan

Cold atmospheric pressure plasma (CAP) has been expected to be effective for wound healing among plasma medicines and has been attracting attention. The aim of this retrospective clinical study was to evaluate and compare the effects of CAP on acute wounds created by a fractional CO2 (FXCO2) laser on four treatment groups. Methods: This study was conducted between September 2017 and November 2018. Radiated surface wounds were created using a FXCO2 laser on four identically-sized regions on the medial side of the left forearm of 12 healthy volunteer subjects, for a total of 48 treatment regions. Each region was then randomly assigned to one of four groups: 1) no treatment (control group), 2) irradiated CAP for 60 seconds (plasma group), 3) topical application of ointment containing betamethasone valerate (steroid group), or 4) two to three sprays of basic fibroblast growth factor (bFGF group). The primary outcome of the skin was the change in absolute values of lightness index (L*), redness index (a*I) of L*a*b color space, arithmetical mean roughness (Ra), and mean melanin concentration. The secondary outcome was the clinical condition of the wounds, including inflammation, crust formation, and hyper/hypo-pigmentation on the recovering skin surface relative to the surrounding intact skin. Each item was evaluated at post-treatment 0, 1, 3, 7, 14, 28 days and 1 year. Results: Although no significant difference was observed among all groups, the CAP group exhibited more rapid recovery regarding a*I and Ra. No side-effects were observed in the CAP group. Conclusion: CAP is considered to accelerate healing of irradiated wounds via anti-inflammatory activity. Our study confirmed the effectiveness and safety of CAP which is devoid of side-effects of conventional therapies, and may aid in future development of medical plasma therapies.

关键词： Cold Atmospheric Pressure Plasma Plasma Medicine New Energy Device Wound Healing Skin Activation

Acute renal failure associated with acute non-fulminant hepatitis B

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World Journal of Hepatology 2013年第2期5卷 82-85页

作者： Tomoya Kishi yuji Ikeda Tsuyoshi Takashima Shuichi Rikitake Motoaki Miyazono Shigehisa Aoki Takanobu Sakemi Toshihiko Mizuta Kazuma fujimoto Department of Internal Medicine Saga University Faculty of MedicineSaga 849-8501Japan Department of Pathology and Biodefense Center for ResearchSaga University Faculty of MedicineSaga 849-8501Japan Development in Higher Education Saga University Faculty of MedicineSaga 849-8501Japan

A 38-year-old female presenting with a high fever of 39 ℃ developed severe liver dysfunction and acute renal failure(ARF).In tests for a hepatitis associated virus,an Immunoglobulin M-anti-hepatitis B virus core antibody was the only positive ***,the progression of ARF coincided with the pole period of liver damage and all the other assumed causes for the ARF were ***,this case was diagnosed as ARF caused by acute hepatitis *** associated with non-fulminant hepatitis has been infrequently reported,usually in association with acute hepatitis *** case is considered to be an extremely rare and interesting case.

关键词： Acute hepatitis B Acute renal failure Nonfulminant hepatitis Acute tubular necrosis Hyperimmune response

Efficacy of Cognitive Remediation in Schizophrenia: A Short Review of Its Variable Effects According to Cognitive Domain

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Open Journal of Psychiatry 2015年第2期5卷 170-176页

作者： Akihiko Katsumi Hiroshi Hoshino Satoshi fujimoto Shin-Ichi Niwa Katsumi Clinic Niigata Japan Department of Neuropsychiatry School of Medicine Fukushima Medical University Fukushima Japan Department of Psychiatry Aizu Medical Center Fukushima Medical University Fukushima Japan

Cognitive impairment is a symptom of schizophrenia and strongly associated with impaired social function. In recent years, cognitive interventions (cognitive remediation therapies) have been implemented and their results have also been reported. Intervention studies have been conducted using a variety of methods that differ in terms of terminology, approach, and targeted cognitive domains. In this study, we examined trends in recent cognitive remediation research conducted subsequent to the meta-analyses of McGurk et al. (2007) and Wykes et al. (2011). We identified studies conducted between 2009 and 2013 to examine computer-assisted cognitive remediation and collated and analyzed the literature describing their major results and trends. Our results indicated improved cognitive performance subsequent to cognitive remediation therapy using computer programs. We found promising outcomes, particularly in reasoning and problem solving, verbal learning and memory, verbal working memory, and attention and vigilance, which replicated the findings of Wykes et al. (2011).

关键词： Schizophrenia Cognitive Deficit Cognitive Remediation Variance Cognitive Domain

The Adenosine Receptor Agonist 5’-N-Ethylcarboxamide-Adenosine Increases Mouse Serum Total Homocysteine Levels, Which Is a Risk Factor for Cardiovascular Diseases

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Pharmacology & Pharmacy 2015年第10期6卷 461-470页

作者： Shigeko fujimoto Sakata Koichi Matsuda yoko Horikawa yasuto Sasaki Faculty of Nutrition Kobe Gakuin University Kobe Japan

An increase in total homocysteine (Hcy) levels (protein-bound and free Hcy in the serum) has been identified as a risk factor for vascular diseases. Hcy is a product of the methionine cycle and is a precursor of glutathione in the transsulfuration pathway. The methionine cycle mainly occurs in the liver, with Hcy being exported out of the liver and subsequently bound to serum proteins. When the non-specific adenosine receptor agonist 5’-N-ethylcarboxamide-adenosine (NECA;0.1 or 0.3 mg/kg body weight) was intraperitoneally administered to mice that had been fasted for 16 h, total Hcy levels in the serum significantly increased 1 h after its administration. The NECA treatment may have inhibited transsulfuration because glutathione levels were significantly decreased in the liver. After the intraperitoneal administration of a high dose of NECA (0.3 mg/kg body weight), elevations in total Hcy levels in the serum continued for up to 10 h. The mRNA expression of methionine metabolic enzymes in the liver was significantly reduced 6 h after the administration of NECA. NECA-induced elevations in total serum Hcy levels may be maintained in the long term through the attenuated expression of methionine metabolic enzymes.

关键词： Adenosine 5’-N-Ethylcarboxamide-Adenosine Glutathione Homocysteine