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Activation of extracellular signal-regulated kinase during silibinin-protected,isoproterenol-induced apoptosis in rat cardiac myocytes is tyrosine kinase pathway-mediated and protein kinase C-dependent

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Acta Pharmacologica Sinica 2007年第6期28卷 803-810页

作者： Shin-ichi TASHIRO Satoshi ONODERA fumiaki uchiumi Takashi IKEJIMA Department of Clinical and BiomedicalSciences Showa Pharmaceutical UniversityTokyo 194-8543Japan Department of Gene Regulation Faculty of Pharmaceutical SciencesTokyo University of ScienceChiba 278-8510Japan China-Japan Research Institute of Medieal and Pharmaceutical Sciences Shenyang Pharmaceutical UniversityShenyang 110016China

Aim:To investigate the mechanism of silibinin-protected isoproterenol-inducedapoptosis in rat cardiac ***:The viability of rat cardiac myocyteswas measured by MTT *** apoptotic ratio was measured by terminaldeoxynucleotidyl transferase-mediated dUTP nick *** kinase C(PKC) activity assay was carried out according to the instructions of the PepTagnon-radioactive protein kinase C assay *** blot analysis was used toevaluate the level of Ras,Raf-1 and mitogen-activated protein kinase (MAPK)***:The protective effects of silibinin were significantly sup-pressed by inhibitors,including genistein,manumycin A and GW5074 [inhibitorsfor protein tyrosine kinases (PTK),Ras and Raf-1,respectively].The exposure ofrat cardiac myocytes to isoproterenol alone caused decreased PKC activity,whichwas prevented by pretreatment with silibinin ***,the increased expression of Ras and Raf-1 activated by silibinin were blocked bythe PKC inhibitor,*** addition,the extracellularly responsive kinase(ERK) inhibitor,PD98059,suppressed silibinin-protected apoptosis,whereas thep38 MAPK inhibitor,SB203580,protected cardiac myocytes from isoproterenol-induced injury,and the c-Jun N-terminal kinase (JNK) inhibitor,SP600125 had noprotective ***,Western blot analysis showed that the expres-sion of phosphorylated ERK was increased by silibinin,the expression of phos-phorylated p38 MAPK was decreased and total ERK,p38,JNK and phosphory-lated JNK MAPK did not change after treatment with both isoproterenol ***,pretreatment of cardiac myocyte with PKC,Ras and Rafinhibitors significantly blocked ERK ***:Silibinin issuggested to protect isoproterenol-induced rat cardiac myocyte apoptosis byactivating the tyrosine kinase pathway,PKC and MAPK pathways.

关键词： silibinin rat cardiac myocytes tyrosine kinase: protein kinase C mitngen-activated protein kinases

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Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15

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Protein & Cell 2024年第7期15卷 547-552页

作者： fumiaki Ito Hanjing Yang Z.Hong Zhou Xiaojiang S.Chen Molecular and Computational Biology Department of Biological SciencesUniversity of Southern CaliforniaLos AngelesCA 90089United States Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095United States California NanoSystems Institute University of CaliforniaLos AngelesCA90095United States Genetic Molecular and Cellular Biology ProgramKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90089United States Norris Comprehensive Cancer Center University of Southern CaliforniaLos AngelesCA 90089United States Center of Excellence in NanoBiophysics University of Southern CaliforniaLos AngelesCA 90089United States

Dear Editor,Coronaviruses have evolved a wide array of tactics to evade host antiviral *** host cells detect invading foreign nucleic acids including viral genome and viral replication intermediates,they activate interferon(IFN)signaling via cytoplasmic pattern recognition receptors(Kang et al.,2002;Kato et al.,2006).Remarkable stealth activities exhibited by coronaviruses are facilitated by a series of non-structural proteins(Nsps),such as Nsp15(Deng and Baker,2018;Deng et al.,2019;Hackbart et al.,2020),which is a uridine-specific endoribonuclease that mediates evasion of host detection of viral double-stranded RNA(dsRNA)(Bhardwaj et al.,2004;Deng et al.,2017;Frazier et al.,2021;Ivanov et al.,2004).Nsp15 targets a polyuridine[poly(U)]tract on the coronavirus negative strand RNA(Hackbart et al.,2020).Nsp15 limits the abundance and length of poly(U)within the negative strand RNA 5ʹ-extension by trimming down the initially synthesized poly(U)lead sequence to the optimal length that can suppress dsRNA formation but still serves as a template for poly(A)tail of the positive strand genome of the coronaviruses(Hofmann and Brian,1991).

关键词： p15 interferon template

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水飞蓟宾对异丙肾上腺素引起的大鼠乳鼠心肌细胞损伤的保护作用及其机制

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药学学报 2007年第3期42卷 263-268页

作者：周蓓吴立军田代真一小野寺敏内海文彰池岛乔沈阳药科大学中日医药研究所沈阳药科大学天然药物研究室辽宁沈阳110016 沈阳药科大学昭和药科大学病态科学研究室东京理科大学药学部遗传子制御学教研室

水飞蓟宾(silibinin)为从菊科植物水飞蓟(Silybum marianum)的种子和果实中提取得到的黄酮类单体成分。本研究观察水飞蓟宾对β-肾上腺素受体激动剂异丙肾上腺素对培养乳鼠心肌细胞损伤的影响,并对其机制进行研究。采用MTT法测定细胞存... 详细信息

水飞蓟宾(silibinin)为从菊科植物水飞蓟(Silybum marianum)的种子和果实中提取得到的黄酮类单体成分。本研究观察水飞蓟宾对β-肾上腺素受体激动剂异丙肾上腺素对培养乳鼠心肌细胞损伤的影响,并对其机制进行研究。采用MTT法测定细胞存活率,酶联法测定细胞丙二醛(maleic dialdehyde,MDA)和细胞培养液中乳酸脱氢酶(lactate dehydrogenase,LDH)的含量以及超氧化物歧化酶(superoxide dismutase,SOD)的活性,流式细胞仪测定线粒体膜电位(ΔΨ),以及Western blotting检测与线粒体相关蛋白的表达。与模型组相比,水飞蓟宾使细胞受损伤的程度降低,并且增加SOD的活性,抑制了细胞膜电位的降低,并且改善Bcl-2家族蛋白中Bax/Bcl-2的表达比率,上调Bax上游去乙酰化酶SIRT1蛋白的表达。水飞蓟宾通过上调线粒体上游Bax/Bcl-2的表达比率与SIRT1蛋白的表达,改善了线粒体的功能,从而对由异丙肾上腺素引起的培养乳鼠心肌细胞损伤有明显的保护作用。

关键词：水飞蓟宾心肌细胞损伤线粒体膜电位 Bcl-2家族蛋白 SIRTI

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Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations

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Plant Communications 2024年第8期5卷 1-17页

作者： Xiaotong Liu Daisuke Igarashi Rachel A.Hillmer Thomas Stoddard You Lu Kenichi Tsuda Chad L.Myers fumiaki Katagiri Department of Plant and Microbial Biology University of Minnesota-Twin CitiesSt PaulMN 55108USA Department of Computer Science and Engineering University of Minnesota-Twin CitiesMinneapolisMN 55455USA Bioinformatics and Computational Biology Graduate Program University of Minnesota-Twin CitiesMinneapolisMN 55455USA Institute for Innovation Ajinomoto Co.Inc.KawasakiJapan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryHubei Key Lab of Plant PathologyCollege of Plant Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Present address:225 S 6th St MinneapolisMN 55402USA Present address:Biotalys Inc.2520 Meridian Parkway Suite 480DurhamNC 27713USA Present address:Life Sciences Institute and Department of Cell and Developmental Biology University of Michigan Medical SchoolAnn ArborMI 48109USA

Rapid plant immune responses in the appropriate cells are needed for effective defense against *** transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is *** reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in ***-peak time-course patterns are prevalent among thousands of upregulated *** implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each *** decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated *** demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to ***,the peak decomposition has extracted spatial information from the time-course *** echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered *** of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor *** discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.

关键词： Arabidopsis Pseudomonas syringae plant immune response multi-compartment model WRKY transcription factors resilient immune signaling network

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水飞蓟素在紫外线照射诱导A375-S2细胞凋亡中发挥抑制作用

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中国病理生理杂志 2005年第10期21卷 1873-1878页

作者：李林昊吴立军田代真一小野寺敏内海文彰池岛乔沈阳药科大学中日医药研究所天然药物研究室辽宁沈阳110016 沈阳药科大学天然药物研究室辽宁沈阳110016 昭和药科大学病态科学教研室东京理科大学药学部遗传子制御学教研室沈阳药科大学中日医药研究所辽宁沈阳110016

目的:从天然药物中筛选出抑制紫外线照射诱导人黑色素瘤细胞A375-S2凋亡的有效单体。方法:MTT法测定细胞生长抑制率;形态学观察,DNA凝胶电泳及LDH法;用半胱天冬酶活力检测试剂盒测定半胱天冬酶活力;用免疫印记法检测Bcl-2家族成员(Bcl... 详细信息

目的:从天然药物中筛选出抑制紫外线照射诱导人黑色素瘤细胞A375-S2凋亡的有效单体。方法:MTT法测定细胞生长抑制率;形态学观察,DNA凝胶电泳及LDH法;用半胱天冬酶活力检测试剂盒测定半胱天冬酶活力;用免疫印记法检测Bcl-2家族成员(Bcl-2,Bcl-xL和Bax)的表达。结果:紫外线照射(2．4 J／cm2,5 min)能显著诱导A375-S2细胞发生凋亡,其作用呈明显时间依赖性。形态学观察可见凋亡小体的形成,琼脂糖凝胶电泳可见凋亡典型的DNA梯带;水飞蓟素具有抑制紫外线照射(2．4 J／cm2,5 min)诱导A375-S2细胞凋亡的作用,水飞蓟素作用于紫外线照射(2．4 J／cm2,5 min)的A375-S2细胞,培养12 h,使紫外线照射诱导的半胱天冬酶 -9、半胱天冬酶-3的活力降低;免疫印记法检测发现水飞蓟素作用的A375-S2细胞(紫外线照射)中Bcl-2蛋白和Bcl-xL蛋白的表达增加。结论:水飞蓟素明显抑制紫外线照射诱导的A375-S2细胞的凋亡,其抑制凋亡作用与半胱天冬酶途径和线粒体途径相关。

关键词：紫外线 A375-S2细胞水飞蓟素细胞凋亡半胱氨酸天冬氨酸蛋白酶

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Malnutrition and Its Association with the Mortality of Patients with Femoral Intertrochanteric Fractures: A Retrospective Analysis of Japanese Patients

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Open Journal of Orthopedics 2024年第1期14卷 22-31页

作者： Taizo Kaneko Kyoko Matsudaira Kentaro Hayakawa fumiaki Tokimura Tsuyoshi Miyazaki Department of Orthopaedic Surgery Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan

Background: The incidence of femoral intertrochanteric fractures in older adults is higher than that of femoral neck fractures;however, both conditions are often analyzed together as proximal femoral fractures. Considering the difference in treatment, postoperative complication, and mortality risk, these two fractures should be analyzed separately. This study aimed to analyze 1-year mortality and its risk factors in patients with surgically treated femoral intertrochanteric fractures. Methods: Consecutive patients with intertrochanteric fractures who underwent surgical interventions at our institution between January 2017 and December 2021 were retrospectively reviewed. A total of 238 patients were eligible for inclusion in this study. Patients’ demographic and clinical information were retrospectively collected. Patients were divided into the 1-year mortality (n = 16) and survival (n = 222) groups. The incidence of 1-year mortality and its independent risk factors were investigated using univariate and multivariate logistic regression analyses. Results: The mean age of patients was 85.6 ± 8.5 years. The 1-year mortality rate was 6.7% (16/238). Preoperative albumin level, the Geriatric Nutritional Risk Index (GNRI), and malnutrition status (GNRI p = 0.02, p = 0.02, and p = 0.0011, respectively). Multivariate analysis showed that malnutrition status (GNRI p = 0.035) was an independent risk factor for 1-year mortality. Conclusion: Malnutrition status assessed using GNRI (GNRI < 92) was an independent risk factor for 1-year mortality. Our findings suggest that GNRI may be an effective screening tool for predicting postoperative 1-year mortality of patients with surgically treated femoral intertrochanteric fractures.

关键词： Intertrochanteric Fracture Mortality Geriatric Nutritional Risk Index Malnutrition Risk Factor

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木山英雄《〈野草〉论》的阅读(上)

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现代中文学刊 2024年第1期 4-20页

作者：尾崎文昭陈言(译) 东京大学首都师范大学大学外国语学院日语系

木山英雄的《〈野草〉论》通过对鲁迅《野草》进行解读,将《野草》中鲁迅的诗与哲学的关系加以勾连,由此进入鲁迅的内心世界与中国现代史,这在鲁迅研究史上获得了高度评价,是对“竹内鲁迅”的反拨和有力推进,然而,木山行文与立论的晦涩... 详细信息

木山英雄的《〈野草〉论》通过对鲁迅《野草》进行解读,将《野草》中鲁迅的诗与哲学的关系加以勾连,由此进入鲁迅的内心世界与中国现代史,这在鲁迅研究史上获得了高度评价,是对“竹内鲁迅”的反拨和有力推进,然而,木山行文与立论的晦涩同样在他与读者之间筑起了壁垒。本文对木山的《野草》论进行文本细读,从词语和概念的阐释、句子的释疑,到立论展开逻辑的阐发,以阐述、补注或者说明等多种方式,在消解木山文本的晦涩性的同时,探索木山论述展开的逻辑以及文本蕴含的可能性,以呈现木山的思维框架。在论文最后部分,以丸尾常喜和尾崎文昭的鲁迅论为例,阐明二者对木山英雄鲁迅论的自觉或者不自觉的继承以及与前者的不同,同时深化了木山鲁迅论与竹内鲁迅论的相通之处与不同之处。

关键词：木山英雄鲁迅《〈野草〉论》竹内好

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Urban climate in the Tokyo metropolitan area in Japan

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Journal of Environmental Sciences 2017年第9期29卷 54-62页

作者： Jun Matsumoto fumiaki Fujibe Hideo Takahashi Research Center for Climatology Department of Geography Tokyo Metropolitan University Department of Coupled Ocean-Atmosphere-Land Processes Research JAMSTEC

Long-term climate changes related with urbanization in Tokyo, Japan, and recent temperature and heavy rainfall distribution in the Tokyo metropolitan area are reviewed. A relatively high temperature increase in annual mean temperature at the rate of 3.0°C/century was detected in Tokyo for the period 1901–2015. Some observational evidence showed the existence of both thermal and mechanical effects of urbanization on recent heavy rainfall occurrences, and modeling studies also support precipitation enhancement. Urban influences were recognized in other climatological elements, such as number of fog days, relative humidity, and wind circulation.

关键词： Heat island Cool island Heavy rainfall Fog Humidity Sea breeze

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Bacterial communities in different locations, seasons and segments of a dairy wastewater treatment system consisting of six segments

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Journal of Environmental Sciences 2016年第8期28卷 109-115页

作者： Kikue Hirota Yuji Yokota Toru Sekimura Hiroshi uchiumi Yong Guo Hiroyuki Ohta Isao Yumoto Bioproduction Research Institute National Institute of Advanced Industrial Science and Technology (AIST) ACT Corporation Ibaraki University College of Agriculture Laboratory of Environmental Microbiology Graduate School of Agriculture Hokkaido University

A dairy wastewater treatment system composed of the 1st segment（no aeration） equipped with a facility for the destruction of milk fat particles, four successive aerobic treatment segments with activated sludge and a final sludge settlement segment was developed. The activated sludge is circulated through the six segments by settling sediments（activated sludge） in the 6th segment and sending the sediments beck to the 1st and 2nd *** was examined using samples from the non-aerated 1st and aerated 2nd segments obtained from two farms using the same system in summer or winter. Principal component analysis showed that the change in microbiota from the 1st to 2nd segments concomitant with effective wastewater treatment is affected by the concentrations of activated sludge and organic matter（biological oxygen demand [BOD]）, and dissolved oxygen（DO） content. Microbiota from five segments（1st and four successive aerobic segments） in one location was also examined. Although the activated sludge is circulating throughout all the segments, microbiota fluctuation was observed. The observed successive changes in microbiota reflected the changes in the concentrations of organic matter and other physicochemical conditions（such as DO）, suggesting that the microbiota is flexibly changeable depending on the environmental condition in the segments. The genera Dechloromonas, Zoogloea and Leptothrix are frequently observed in this wastewater treatment system throughout the analyses of microbiota in this study.

关键词： Dairy wastewater Dairy fat Activated sludge Bacterial community analysis

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Event detection and visualization of ocean eddies simulated by ocean general circulation model

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International Journal of Modeling, Simulation, and Scientific Computing 2019年第3期10卷 164-182页

作者： Daisuke Matsuoka fumiaki Araki Hideharu Sasaki Information Engineering Program Research Institute for Value-Added-Information Generation Japan Agency for Marine-Earth Science and Technology(JAMSTEC)3173-25 Showa-machi Kanazawa-kuYokohama 236-0001Japan Application Laboratory(APL)Research Institute for Value-Added-Information Generation Japan Agency for Marine-Earth Science and Technology(JAMSTEC)3173-25 Showa-machi Kanazawa-kuYokohama 236-0001Japan

Numerical study of ocean eddies has been carried out by using high-resolution ocean general circulation *** order to understand ocean eddies from the large volume data produced by simulations,visualizing only eddy distribution at each time step is insufficient;time-variations in eddy events and phenomena must also be ***,existing methods cannot precisely find and track eddy events such as amalgamation and *** this study,we propose an original approach for eddy detection,tracking,and event visualization based on an eddy classification *** proposed method detects streams and currents as well as eddies,and it classifies discovered eddies into several categories using the additional stream and current *** tracking how the classified eddies vary over time,detecting events such as eddy amalgamation and bifurcation as well as the interaction between eddies and ocean currents becomes *** adopt the proposed method for two ocean areas in which strong ocean currents exist as case *** visualize the detected eddies and events in a time series of images,allowing us to acquire an intuitive understanding of a region of interest concealed in a high-resolution data ***,our proposed method succeeded in clarifying the occurrence place and seasonality of each type of eddy event.

关键词： Ocean simulation ocean eddy ocean current visualization

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