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3-甲基胆蒽对大鼠肝细胞细胞色素P4501A的诱导作用

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卫生毒理学杂志 2003年第3期17卷 152-154页

作者：王堃仲来福 SHINDOH Hideto-shi INOUE Tomoa-ki horii ikuo 大连医科大学药理教研室辽宁大连116027 大连医科大学卫生学教研室辽宁大连116027 日本罗氏研究所临床前科学部

目的　研究 3 甲基胆蒽 (3 methylcholanthrene,3 MC)对原代培养大鼠肝细胞细胞色素P450 1A(CYP 1A)酶活力的诱导作用 ,并探讨其时间效应和剂量效应关系。方法　原位 2步胶原酶灌流法分离大鼠肝细胞 ,无血清条件下培养细胞 ,并用不... 详细信息

目的　研究 3 甲基胆蒽 (3 methylcholanthrene,3 MC)对原代培养大鼠肝细胞细胞色素P450 1A(CYP 1A)酶活力的诱导作用 ,并探讨其时间效应和剂量效应关系。方法　原位 2步胶原酶灌流法分离大鼠肝细胞 ,无血清条件下培养细胞 ,并用不同剂量的 3 MC诱导肝细胞 2 4h或 48h。乙氧基试卤灵 (ethoxyresorufin,EOR)为CYP 1A酶活力探针药 ,高效液相色谱法 (HPLC)测定试卤灵 (resorufin,RSF)浓度。结果　实验条件下对照组和 3 MC诱导组的RSF均可被检测 ,与对照细胞相比 ,除 0 0 0 5μmol L的 3 MC对原代培养大鼠肝细胞EROD无显著诱导作用外 ,其余剂量 (0 0 5 ,0 5 ,5μmol L)的 3 MC均明显诱导酶活力 ,酶活力分别被上调至对照组的 5 0 8,2 3 3 ,33 6倍 (P <0 0 1 ) ,3 MC的诱导作用在 2 4h达最强 ,而其在 48h的诱导作用与 2 4h相似。3 MC对原代培养大鼠肝细胞CYP 1A酶活力的诱导作用呈明显的剂量依赖性。结论　 3 MC对大鼠原代培养肝细胞CYP

关键词： 3-甲基胆蒽大鼠细胞色素P4501A 诱导作用原代培养肝细胞高效液相色谱法剂量依赖性

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曲格列酮对大鼠肝细胞氧化性损伤的研究

中国新药杂志 2005年第6期14卷 701-705页

作者：王堃于学炜仲来福 Inoue Tomaki Shindoh Hidtoshi horii ikuo 大连医科大学药理教研室大连116027 大连市第三人民医院泌尿外科大连116021 大连医科大学卫生学教研室大连116027 Nippon Roche Research Center Japan

目的:研究曲格列酮的肝细胞毒性及其可能的机制。方法:在原代大鼠肝细胞模型和其他3种不同来源非肝细胞系,用WST-1法、乳酸脱氢酶释放法、荧光检测法、生物发光法等方法,观察曲格列酮对肝细胞的损伤作用。结果:不同剂量曲格列酮作用后,... 详细信息

目的:研究曲格列酮的肝细胞毒性及其可能的机制。方法:在原代大鼠肝细胞模型和其他3种不同来源非肝细胞系,用WST-1法、乳酸脱氢酶释放法、荧光检测法、生物发光法等方法,观察曲格列酮对肝细胞的损伤作用。结果:不同剂量曲格列酮作用后,其在原代培养大鼠肝细胞的IC_(50)值最低,即其对原代肝细胞毒性最大。曲格列酮诱导活性氧(ROS)生成,并引起还原型谷胱甘肽(GSH)和ATP水平比对照细胞显著降低。不同剂量的曲格列酮作用5h后诱发肝细胞凋亡、坏死。结论:曲格列酮对大鼠肝细胞的毒性作用强于对其他非肝细胞来源细胞的毒性作用。曲格列酮可以引起肝细胞氧化性损伤,肝细胞凋亡和坏死。

关键词：曲格列酮肝细胞毒性氧化性损伤凋亡

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曲格列酮对人肝微粒体CYP450氧化酶的抑制作用

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曲格列酮对人肝微粒体CYP450氧化酶的抑制作用

Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events

中国药理学会制药工业专业委员会第十一届学术会议

作者：王堃于学炜 Hidetoshi SHINDOH ikuo horii 大连医科大学药理教研室日本罗氏研究所临床前科学部日本大连市第三人民医院泌尿外科

目的:研究曲格列酮对人肝微粒体CYP450氧化酶的抑制作用并探讨其与肝毒性的关系。方法:应用高效液相色谱(high pressure liquid chromatography,HPLC)法测定曲格列酮和阳性抑制剂对人肝微粒体睾酮-6β-羟化酶、咪达唑仑-1’-羟化酶(CYP3...

目的:研究曲格列酮对人肝微粒体CYP450氧化酶的抑制作用并探讨其与肝毒性的关系。方法:应用高效液相色谱(high pressure liquid chromatography,HPLC)法测定曲格列酮和阳性抑制剂对人肝微粒体睾酮-6β-羟化酶、咪达唑仑-1’-羟化酶(CYP3A4)、7-乙氧基-试卤灵-0-脱乙基酶(CYP1A)、丁呋洛尔羟化酶(CYP2D)和甲苯磺丁脲羟化酶(CYP2C8/9)活性的抑制作用。结果:曲格列酮对人肝微粒体咪哒唑仑-1’-

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Stroke & Vascular Neurology 2024年第2期9卷 108-125,I0001-I0005页

作者： Miao Lin Liubing Hu Si Shen Jiyue Liu Yanyan Liu Yixian Xu Honglin Chen Kazuo Sugimoto Jianshuang Li ikuo Kamitsukasa Takaki Hiwasa Hao Wang Anding Xu Stroke Center The First Affiliated HospitalJinan UniversityGuangzhouChina Department of Anesthesiology The First Affiliated HospitalJinan UniversityGuangzhouChina The Biomedical Translational Research Institute Faculty of Medical ScienceJinan UniversityGuangzhouChina Department of Radiology Medical Imaging CenterThe First Affiliated HospitalJinan UniversityGuangzhouChina Department of Biochemistry and Genetics Graduate School of MedicineChiba UniversityChibaJapan Department of Neurology Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Department of Neurology Chiba Rosai HospitalChibaJapan Department of Neurology Chibaken Saiseikai Narashino HospitalChibaJapan Department of Neurological Surgery Graduate School of MedicineChiba UniversityChibaJapan

Background Atherosclerosis(AS)and tumours are the leading causes of death worldwide and share common risk factors,detection methods and molecular ***,searching for serum markers shared by AS and tumours is beneficial to the early diagnosis of *** The sera of 23 patients with AS-related transient ischaemic attack were screened by serological identification of antigens through recombinant cDNA expression cloning(SEREX),and cDNA clones were *** function enrichment analysis was performed on cDNA clones to identify their biological pathways and determine whether they were related to AS or ***,gene–gene and protein–protein interactions were performed and AS-associated markers would be *** expression of AS biomarkers in human normal organs and pan-cancer tumour tissues were ***,immune infiltration level and tumour mutation burden of various immune cells were *** curves analysis could show the expression of AS markers in *** AS-related sera were screened by SEREX,and 83 cDNA clones with high homology were *** functional enrichment analysis,it was found that their functions were closely related to AS and tumour *** multiple biological information interaction screening and the external cohort validating,poly(A)binding protein cytoplasmic 1(PABPC1)was found to be a potential AS *** assess whether PABPC1 was related to pan-cancer,its expression in different tumour pathological stages and ages was *** AS-associated proteins were closely related to cancer immune infiltration,we investigated and found that PABPC1 had the same role in ***,analysis of Kaplan-Meier survival curves revealed that high PABPC1 expression in pan-cancer was associated with high risk of *** Through the findings of SEREX and bioinformatics pan-cancer analysis,we concluded that PABPC1 might serve as a potential biomarker for the

关键词： diagnosis cancer organs

Pyronaridine combined with diminazene aceturate inhibits Babesia in vitro and in vivo

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 93-99页

作者： Shimaa Abd El-Salam El-Sayed Mohamed Z.Sayed-Ahmed Shaimaa Ahmed Awad Ali Nourah Alsadaan Nawazish Alam Mahmoud S.Alkhoudary ikuo Igarashi Mohamed Abdo Rizk National Research Center for Protozoan Diseases Obihiro University of Agriculture and Veterinary MedicineInada-ChoObihiroHokkaido 080-8555Japan Department of Biochemistry and Chemistry of Nutrition Faculty of Veterinary MedicineMansoura UniversityMansoura 35516Egypt Department of Clinical Pharmacy College of PharmacyJazan UniversityJazan 45142Saudi Arabia Medical-Surgical Department College of NursingJouf UniversitySakaka 72388Saudi Arabia Critical Care and Emergency Nursing Faculty of NursingMansoura UniversityEgypt College of Nursing Jouf UniversitySakaka 72388Saudi Arabia Faculty of Pharmacy Mansoura UniversityMansoura 35516DakahliaEgypt Department of Internal Medicine and Infectious Diseases Faculty of Veterinary MedicineMansoura UniversityMansoura 35516Egypt

Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in ***:Bioinformatic analysis was performed using atom pair *** in vitro combination test was performed against Babesia bovis and Theileria ***,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory ***:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular *** in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria *** addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post *** combination therapy also normalized the hematological parameters of infected ***:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.

关键词： Babesia Pyronaridine tetraphosphate Diminazene aceturate Babesiosis Theileria

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

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World Journal of Gastroenterology 2014年第23期20卷 7298-7305页

作者： ikuo Nakamura Department of Gastroenterology Tokyo Medical UniversityTokyo 160-0023Japan Department of Gastroenterology Saitama Medical CenterJichi Medical UniversitySaitama 330-8503Japan

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

关键词： Branched-chain amino acids Liver cirrhosis Innate immunity Natural killer cell activity of lymphocytes Phagocytic function of neutrophils

Advances in diagnostic testing for gastroesophageal reflux disease

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World Journal of Gastroenterology 2010年第30期16卷 3750-3756页

作者： Andrew J Gawron ikuo Hirano Division of Gastroenterology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoIL 60611-2951United States

Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology.

关键词： Gastroesophageal reflux disease pH impedance pH monitoring Symptom association

A study on particle breakage behavior during pile penetration process using acoustic emission source location

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Geoscience Frontiers 2020年第2期11卷 413-427页

作者： Wuwei Mao Shogo Aoyama ikuo Towhata Department of Geotechnical Engineering College of Civil EngineeringTongji UniversityShanghai 200092China Key Laboratory of Geotechnical and Underground Engineering Ministry of EducationTongji UniversityShanghai 200092China Kiso-Jiban Consultants Co. Ltd.TokyoJapan Department of Civil Engineering University of TokyoTokyoJapan

Particle breakage is a common occurrence in granular systems when the external stress exceeds the individual particle strength.A large number of experimental evidences suggested that particle breakage may significantly influence the soil *** the case of pile foundations,the subsoil below the pile tip experiences considerable high stress and consequently prone to *** to the lack of sufficient understanding on particle breakage mechanism,there is currently no consentaneous theoretical background for particle breakage analysis during the pile penetration *** study aims to clarify the location of particle breakage and its evolving characteristics with the aid of acoustic emission(AE)source location *** spatial distribution of AE hypocenters is interpreted to be associated with the mechanism of particle *** showed that the AE sources were not uniformly distributed,but concentrated within certain zones below the pile *** AE concentration zone was pushed downward with the advancing pile tip,and its distance from the real time pile tip position decreased after certain depth of pile *** location of particle breakage interpreted from AE source location was verified with posttest excavations and the insights on the particle breakage evolution zone were further discussed.

关键词： Acoustic emission Source location Sand Particle breakage Pile

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On improving strigolactone mimics for induction of suicidal germination of the root parasitic plant Striga hermonthica

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aBIOTECH 2021年第1期2卷 1-13页

作者： ikuo Takahashi Kosuke Fukui Tadao Asami Graduate School of Agricultural and Life Sciences The University of TokyoTokyo 113-8657Japan

Strigolactones(SLs)are plant hormones that regulate the branching of plants and seed germination stimulants of root parasitic *** root parasites are a great threat to agricultural production,the use of SL agonists could be anticipated to provide an efficient method for regulating root parasites as suicidal germination inducers.A series of phenoxyfuranone-type SL mimics,termed debranones,has been reported to show potent bioactivities,including reduction of the tiller number on rice,and stimulation of seed germination in the root parasite Striga *** exert both activities,two substituents on the phenyl ring of the molecules were important but at least a substituent at the 2-position must be an electron-withdrawing ***,little is known about the effect of the properties of the substituents at the 2-position on ***,we found that different substituents at the 2-position give different preferences for *** debranones were more effective than the others and SL agonist GR24 for inhibiting rice tiller but far less effective in the induction of *** ***,nitrile and methyl derivatives clearly stimulated the germination of *** *** their IC_(50) values were 100 times higher than that of GR24 in the receptor competitive binding assay,their physiological activities were approximately 1/10 of *** differences could be due to their uptake in plants and/or their physicochemical stability under our experimental *** findings could support the design of more potent and selective SL agonists that could contribute to solving big agricultural issues.

关键词： Agonist Rice Root parasitic weed Seed germination Strigolactone Tillering