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Macrophage inhibitory cytokine-1 induced by a high-fat diet promotes prostate cancer progression by stimulating tumor-promoting cytokine production from tumor stromal cells

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Cancer Communications 2021年第5期41卷 389-403页

作者： Mingguo Huang Shintaro Narita atsushi koizumi Taketoshi Nara Kazuyuki Numakura Shigeru Satoh Hiroshi Nanjo Tomonori Habuchi Department of Urology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan Department of Clinical Pathology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan

Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is *** study aimed to delineate the molecular mechanisms of PCa progression underHFDmilieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1(MIC-1)***:We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control ***,we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal *** patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also ***:HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin(IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa *** addition,periprostatic adipocytes directly stimulatedMIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid *** increased serum MIC-1 was significantly correlated with human PCa stroma activation,high serum IL-8,IL-6,and lipase activity,advanced PCa progression,and high body mass index of the ***-derived neurotrophic factor receptor α-like(GFRAL),a specific receptor of MIC-1,was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts,and the expression levelwas decreased by androgen deprivation therapy and ***:HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression.

关键词： macrophage inhibitory cytokine-1 tumor microenvironment high-fat diet prostate cancer metabolism

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Development of Performance-Based Tunnel Evaluation Methodology and Performance Evaluation of Existing Railway Tunnels

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Journal of Transportation Technologies 2012年第2期2卷 113-128页

作者： Sadao Kimura Takashi Kitani atsushi koizumi Department of Civil and Environmental Engineering Kanazawa Institute of Technology Ishikawa Japan

The concept of performance-based design, which mainly focuses on mechanical performance, has become the international standard, as in the case for ISO. The standardization of tunnel design has not been achieved because it requires integration of separate specialized fields, such as geotechnical engineering, structural engineering and concrete engineering. It is also required to clarify performance-based criteria for tunnel structures to suit specific use purposes (objectives), establish the concept of survey, planning, design, construction and maintenance based on such criteria, and develop proper management systems for operation and maintenance to suit specific tunnel use purposes. To this end, it is vital to develop a methodology for evaluating and verifying the performance of existing tunnels. This paper presents a new concept of performance requirements for tunnel structures and describes the method of quantitatively evaluating the total performance of existing tunnels in relation to the required performance, assuming the total performance to be based on the Analysis Hierarchy Process.

关键词： Tunnel Performance Criterion Life Cycle Design Performance-Based Design Asset Management Maintenance Analysis Hierarchy Process

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日本盾构隧道掘进技术(英文)

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重庆交通大学学报（自然科学版） 2011年第A2期30卷 1093-1098页

作者：小泉淳早稻田大学理工学术院创造理工学部日本东京

盾构隧道施工方法被广泛应用于世界各地的软土隧道施工中。论述了盾构隧道开挖技术的发展背景以及盾构隧道开挖技术的精华,并探讨了该方法在未来将会面临的主要问题。

关键词：盾构隧道施工法盾构机拼装

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高脂饮食诱导的巨噬细胞抑制因子-1通过激活肿瘤间质细胞产生促肿瘤细胞因子促进前列腺癌的进展

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癌症 2022年第2期41卷 65-79页

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macroph... 详细信息

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)活性为主的肿瘤间质微环境的特征。方法我们利用HFD或正常饮食的PC-3M-luc-C6 PCa小鼠模型,研究了HFD对PCa间质微环境和MIC-1信号活性的影响。我们分离了原发PCa患者来源的前列腺周围脂肪细胞,并研究了其对前列腺间质成纤维细胞活性及其分泌细胞因子的影响。进一步研究了MIC-1信号的表达模式及其对人PCa间质活性和肿瘤进展的影响。结果在PC-3M-luc-C6 PCa小鼠模型中,HFD通过上调前列腺间质成纤维的MIC-1信号通路活性,增加了白介素(interleukin,IL)-8和IL-6的分泌,促进了PCa细胞的生长和侵袭。另外,前列腺周围脂肪细胞通过增加脂肪分解和游离脂肪酸的释放,直接促进了PC-3细胞产生MIC-1和前列腺间质成纤维细胞分泌IL-8。前列腺癌患者血清MIC-1水平增高与人PCa间质活性、高血清IL-8、IL-6水平、脂肪酶高活性、PCa患者疾病进展及高体重指数具有显著相关性。胶质细胞源性神经营养因子受体α(glial-derived neurotrophic factor receptor α-like,GFL)是MIC-1的特异性受体,在PCa细胞和癌周间质成纤维细胞中都出现高表达,雄激素去势治疗和化疗都降低了其表达水平。结论 HFD通过增加游离脂肪酸水平,在代谢水平上调了MIC-1信号活性,从而激活了PCa间质微环境,这可能是HFD和/或脂肪诱导的PCa进展的关键机制。

关键词：巨噬细胞抑制因子-1 肿瘤微环境高脂饮食前列腺癌代谢

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Proposal of a Method to Easily Understand Rainfall Infiltration in Railway Embankments

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Journal of Civil Engineering and Architecture 2024年第6期18卷 261-268页

作者： Takashi Nakayama Tadashi Hara Keigo koizumi C.S.Inspector Co. Ltd.2-7-2 Nambanaka Naniwa-Ku Osaka-ShiOsaka-Fu 556-0011Japan Research and Education Faculty Kochi University2-5-1 Akebonocho Kochi-ShiKochi-Ken 780-8072Japan Earth Watch Institute Inc.8-10 Toyotsucho Suita-ShiOsaka-Fu 564-0051Japan

Slope failures due to heavy or prolonged rain have been occurring frequently in Japan in recent *** railway embankments,even small-scale surface collapse can result in track ***,train operation during rainy periods is regulated according to empirical rules based on rainfall and disaster ***,the validity of operation regulations is lacking because the rainfall infiltration circumstances inside the slope are *** have been attempting to understand rainfall infiltration in railway embankments by applying a method of predicting surface collapse from observations of volumetric water content in the *** used previous field monitoring and model experiments to propose a method for easily understanding the state of rainfall infiltration in the surface layer of an embankment using the relative history of volumetric water content at different *** this study,we applied this simple determination method to railway embankments with different topography and geological environments to demonstrate the versatility of the method.

关键词： Railway embankments field monitoring volumetric water content

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Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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World Journal of Gastroenterology 2024年第28期30卷 3428-3446页

作者： Aritoshi koizumi Kosuke Kaji Norihisa Nishimura Shohei Asada Takuya Matsuda Misako Tanaka Nobuyuki Yorioka Yuki Tsuji Koh Kitagawa Shinya Sato Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji Department of Gastroenterology Nara Medical UniversityKashihara 634-8521Japan

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver *** proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ***,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary ***,the benefits of EFN for ALD treatment is *** To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse *** ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 ***(3 and 10 mg/kg/day)was orally administered during the experimental *** and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier *** EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based *** The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN *** promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARα***,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)*** improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory *** protective effect on intestinal bar

关键词： Liver fibrosis Ethanol Gut barrier function Apoptosis Autophagy Peroxisome proliferator activated receptor

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水底盾构掘进泥水喷发现象研究

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岩石力学与工程学报 2007年第11期26卷 2296-2301页

作者：袁大军黄清飞小泉淳王梦恕北京交通大学隧道及地下工程教育部工程研究中心北京100044 早稻田大学土木工程系

泥水式盾构工法是水底软土隧道施工的首选工法,施工时泥水压力过大可导致开挖面前方地层劈裂,引发泥水喷发、河(海)水倒灌事故。以此类现象为研究对象,研究地层劈裂发生、伸展机制及不同泥水压力对地层劈裂的影响。研究结果表明:水底隧... 详细信息

泥水式盾构工法是水底软土隧道施工的首选工法,施工时泥水压力过大可导致开挖面前方地层劈裂,引发泥水喷发、河(海)水倒灌事故。以此类现象为研究对象,研究地层劈裂发生、伸展机制及不同泥水压力对地层劈裂的影响。研究结果表明:水底隧道泥水式盾构施工时,开挖面前方地层微小劈裂纹不可避免,但泥水喷发现象能否发生与盾构掘进参数、泥水性质、地层特性及盾构覆土厚度密切相关,通过理论分析和盾构掘进模型试验,得出了泥水喷发半经验公式,在此基础上提出了防止泥水喷发现象发生的相关措施。

关键词：隧道工程泥水式盾构水力劈裂劈裂伸展速度黏土地层盾构模型试验

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日本铁路隧道病害和运维管理现状及对我国隧道运维技术发展的建议

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隧道建设（中英文） 2020年第12期40卷 1824-1833页

作者：王剑宏解全一刘健小泉淳山东大学齐鲁交通学院山东济南250002

日本铁路隧道(包括城市轨道交通)经过100余年的发展,产生了隧道老龄化严重、剥落掉块、开裂、劣化以及渗漏水等病害。通过调研日本铁路隧道建设情况、性能要求、病害类型与原因,得出日本铁路隧道约40%的病害与设计施工有关,27%的病害与... 详细信息

日本铁路隧道(包括城市轨道交通)经过100余年的发展,产生了隧道老龄化严重、剥落掉块、开裂、劣化以及渗漏水等病害。通过调研日本铁路隧道建设情况、性能要求、病害类型与原因,得出日本铁路隧道约40%的病害与设计施工有关,27%的病害与运行环境有关,23%的病害与所用材料有关,10%的病害与外力变化有关。介绍日本铁路隧道维护管理体系(隧道检查、健康诊断、措施对策、记录存档)、自动检测技术和智能化技术等新技术的发展应用及存在的问题(相同条件下同类隧道的运维无法统一;自动化检测技术因成本过高或未达到标准要求,只能作为辅助检查手段服务于部分隧道;很多信息因保密无法实现资源共享;运维技术人员、隧道专业人才不足及人才老龄化严重等)。指出这些问题不仅阻碍了运维技术的高质量发展,也影响了整个运维成本和质量。针对我国隧道运维技术的发展,提出以降低隧道设施的全生命周期成本与延长服役寿命为目标,构建基于结构性能与成本的"预测型"运维体系,建议发展一体化运维技术、研发快速维修加固技术、开发智慧运维管理系统等,通过多学科融合交叉,构建系统性的运维管理体系。

关键词：铁路隧道城市轨道交通隧道病害维护管理运维体系运维技术维修加固技术智慧运维管理系统

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Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 136-147页

作者： Takeshi Onda Osamu Goto Toshiaki Otsuka Yoshiaki Hayasaka Shun Nakagome Tsugumi Habu Yumiko Ishikawa Kumiko Kirita Eriko koizumi Hiroto Noda Kazutoshi Higuchi Jun Omori Naohiko Akimoto Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolGraduate School of MedicineBunkyo-ku 113-8603TokyoJapan Endoscopy Center Nippon Medical School HospitalBunkyo-ku 113-8603TokyoJapan Department of Hygiene and Public Health Nippon Medical SchoolBunkyoku 113-8603TokyoJapan Center for Medical Education Nippon Medical SchoolBunkyo-ku 113-8603TokyoJapan

BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological *** influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable *** This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were *** first assessed the difference in size with an absolute per-centage of the scaling ***,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),*** secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling ***,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate *** The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in *** incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimate

关键词： Endoscopic submucosal dissection Colorectal tumor Tumor size Size estimation Size discrepancy

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水下盾构隧道耐久性与全生命周期设计

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隧道与地下工程灾害防治 2020年第2期2卷 1-13页

作者：王剑宏常洪雷刘健小泉淳山东大学齐鲁交通学院山东济南250002 早稻田大学东京169-8555

随着国家的大规模基础设施发展,水下隧道建设需求日益增大,但水下隧道的建设与运维难度较大,需要综合考虑设施的耐久性、进行全生命周期设计。通过分析东京湾横断公路隧道的防水及耐久性措施,为水下大直径隧道建设提出"多重防水、多方... 详细信息

随着国家的大规模基础设施发展,水下隧道建设需求日益增大,但水下隧道的建设与运维难度较大,需要综合考虑设施的耐久性、进行全生命周期设计。通过分析东京湾横断公路隧道的防水及耐久性措施,为水下大直径隧道建设提出"多重防水、多方防腐、全生命周期设计"的综合耐久性对策;建立以性能和成本为评估指标的全生命周期设计方法,并通过计算评价某海底隧道的不同方案,揭示建设初期充分考虑耐久性、实施全生命周期设计的方案最有利,验证了全生命周期设计方法的有效性。通过构建兼顾经济、安全及环境的全生命周期设计理论体系,可为水下隧道的合理规划设计、科学建造养护提供有力的基础支撑。

关键词：水下隧道耐久性多重防水多方防腐全生命周期设计

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