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Increased platelet P2Y12 expression in diabetes and the therapeutic implication of inverse agonist for antiplatelet therapy

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Increased platelet P2Y12 expression in diabetes and the ther...

第十一届海峡两岸心血管科学研讨会、2017年全国心脑血管药理学术会议、中国卒中学会第一次新药研讨会

作者： Hu Liang Chang Lin ding zhongren Fudan University Shanghai Medical College

Background-Platelets from patients with diabetes are hyperactive,which contributes to not only the increased prevalence of cardiovascular complications,but also the inadequate response to currently available antiplatelet agents leading to increased cardiovascular *** underlying mechanism is still not completely ***-We detected P2 Y expression level on platelets from patients with type 2 diabetes mellitus

关键词： Increased platelet P2Y12 expression in diabetes and the therapeutic implication of inverse agonist for antiplatelet therapy

STUDY OF THE REACTION MECHANISM OF CYCLOHEXENE HYDROGENATION CATALYZED BY RhCl(PPh_3)_3

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分子催化 1990年第S1期4卷 1-9页

作者： Li Guangnian, Liang Yixun, Zhang Liangfu, Zhou zhongren, ding Funjiang (Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, China)

The hydrogenation rate of styrene in benzene using RhCI（PPh3）3 as catalyst increases with the concentration of styrene. But the hydrogenation rate of cyclohexene is rather different, It shows a maximum. So we inquire into the reaction mechanism of cyclohexene hydrogenation catalyzed by RhCI（PPh3）3. The rate of hydrogenation was measured at 25±0.15℃, as a function. of catalyst concentration, olefin concentration, triphenylphosphine concentration and hydrogen pressure. The maximum of the reaction rate is interpreted by the formation of RhClL2S2. The rate determining step is considered to be the reaction of olefin insertion into one of the Rh-H bonds formed by hydrogenation of RhClL3 to H2RhClL3. The hydrogenation rate of the substrate can be described by a third order equation in terms of concentration of H2RhClL3. Average error between the results evaluated by this equation and experimental results is about 4.9％. The quantum chemistry calculation gives support to the present mechanism.

关键词： hydrogenation styrene catalyzed benzene olefin bonds insertion determining explained dimer

Membrane Akt Phosphorylation Regulates Platelet Aggregation downstream of Gi and G12/13 Pathways

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Membrane Akt Phosphorylation Regulates Platelet Aggregation ...

首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Yan Zhang Shuang Zheng Lin Chang Zhiling Zhang Jianjun Zhang Liang Hu Si Zhang Junling Liu zhongren ding Key Laboratory of Metabolism and Molecular Medicine Ministry of Educationand Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesFudan University Institutes of Medical Sciences School of MedicineShanghai Jiao Tong University

Platelet activation plays a pivotal role in physiological hemostasis and pathological *** activation triggered by atherosclerotic plaque disruption or endothelium injury caused by percutaneous coronary intervention（PCI）and the consequent intravascular arterial thrombogenesis is the common pathological basis of heart attack and ischemic stroke.G protein coupled receptors（GPCRs）,the largest family of membrane receptors and also the targets of about 50% clinically used drugs,sense molecules outside the cells and activate inside signal transduction pathways and,ultimately,cellular *** platelet agonists,such as adenosine diphosphate（ADP）,thrombin,thromboxane A2,epinephrine,protease-activated receptor（PAR）-1 activating peptide SFLLRN,PAR-4 activating peptide AYPGKF,collagen,activate platelets directly or indirectly through the activation of GPCR coupled to different G proteins,including Gq,Gi,and *** studies suggest that simultaneous activation of Gi and G signaling pathway is sufficient to cause platelet *** Gq knockout mice and Gq specific inhibitor,in this study we found that platelet aggregation downstream of coactivation of Gi and G depends on agonist concentrations;coactivation of Gi and G pathways only induces platelet aggregation under higher concentrations of *** demonstrated that Akt and PAK（p21-activated kinase） membrane translocation and phosphorylation is the convergence point regulating platelet aggregation downstream of Gi and ***,we found that PI3 K/Akt/PAK pathway mediates platelet aggregation downstream of Gi and G.

关键词： platelets Gi G12/13 Akt PI3k PAK

TAZ negatively regulates platelet activation and thrombosis by inhibiting MEK-ERK pathway

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TAZ negatively regulates platelet activation and thrombosis ...

2023年全国心血管药理学学术会议

作者： Xiaowen Wu Guanxing Pan Yulong Zhang Zhiling Zhang Qingyuan Yang Meina Jin Zhiqiang Zhao Fa-Xing Yu zhongren ding School of Pharmacy Tianjin Medical University Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Department of Cardiology 5Department of GeriatricsThe Second Hospital of Tianjin Medical University Institutes of Biomedical Sciences Shanghai Medical CollegeFudan University Department of Pharmacy the First Affiliated Hospital of Fujian Medical University

Objective:Arterial thrombotic events,such as myocardial infarction(MI) and stroke,causes more death than all tumors *** activation and intravascular thrombosis that blocks blood vessels causes serious adverse cardiovascular *** Hippo signaling pathway is highly conserved in mammalian evolution and plays important roles in regulating organ size,tissue regeneration,cell metabolism,and ***,the expression and function of TAZ,the main effector of Hippo signaling pathway,is completely unknown in non-nucleated cells including *** study is aimed to investigate the role and mechanism of TAZ in platelet activation and ***:The peripheral blood of healthy volunteers and wild type mice was collected,washed platelets were separated by two-step ***-PCR and Western blot were used to detect the expression of TAZ in platelets,and laser confocal microscopy was used to observe the localization of *** also successfully constructed platelet-specific TAZ knockout *** blood cell parameters of mice are measured using a *** effects of TAZ on platelet function were analyzed by aggregation,ATP release,spreading,and clot retraction assay using platelets from TAZ knockout and wild type *** effects of TAZ on hemostasis and thrombosis were detected by measuring mouse bleeding time and mesenteric artery thrombosis induced by FeCl3 injury using TAZ-knockout and wild type *** blot was used to detect the phosphorylation level of signaling molecules downstream of TAZ including MEK1/2 and ERK1/2 during platelet *** further elucidate the potential molecular mechanisms of the role of TAZ in platelet activation,the TAZ-interacting proteins were characterized using *** further investigated whether TAZ mediates activation of platelet function via MEK-ERK signaling using ERK inhibitor ***,we studied the effect of TAZ deficiency on αIIbβ3-mediated out

关键词： TAZ platelet MEK-ERK signaling pathway outside-in signaling

Receptor-interacting protein kinase 2(RIP2),a negative regulator of platelet activation and thrombosis

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Receptor-interacting protein kinase 2(RIP2),a negative regul...

首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Jianjun Zhang Zhiling Zhang Guanxing Pan Carol Dangelmaier Lin Chang Liang Hu Yan Zhang Jianlin Qiao Taei Matsui Xiaodong Xi Satya P.Kunapuli Si Zhang zhongren ding Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Department of Physiology and Sol Sherry Thrombosis Research Center Temple University School of Medicine Department of Hematology the affiliated hospitalXuzhou Medical University Department of Biology Faculty of Medical TechnologyFujta Health University School of Health Sciences Shanghai Institute of Hematology Ruijin HospitalShanghai Jiaotong University School of Medicine

Receptor-interacting protein 2 (RIP2) is an essential mediator of inflammation and innate ***,RIP2 has been shown to play a role in regulation of lipid metabolism in macrophages and be highly expressed in platelets,but its role in the platelet activation,thrombosis and hemostasis has not been ***,we show that RIP2 knockout (RIP2-/-) mice exhibit short bleeding time and impaired

关键词： Receptor-interacting protein kinase 2 a negative regulator of platelet activation and thrombosis

Effects of benactyzine on action potentials and contractile force of guinea pig papillary muscles

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郑州大学学报(医学版) 2000年第2期35卷 124-127页

作者： ding zhongren 1)△ , ZHANG Yan 2) , ZHANG Guiqing 2) , KE Jun 2) , HU Xiangjie 2) 1)Department of Hematology,Peking Union Medical Hospital,Chinese Academy of Medical Sciences,Beijing 100730 2)Department of Pharmacology, Henan Medica Department of Hematology Peking Union Medical HospitalChinese Academy of Medical SciencesBeijing 100730 Department of Pharmacology Henan Medical UniversityZhengzhou 450052

Aim: To explore the effects of benactyzine (BEN) on the action potential and contractile force in guinea pig papillary muscles. Methods: Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) of guinea pig papillary muscles. Results: Benactyzine 5, 10, 50 μmol·L -1 suppressed the maximal upstroke velocity ( v max ) of FAP and contractile force (Fc) concentration dependently while prolonged the action potential duration at 50%, 90% repolarization (APD 50 , APD 90 ) and effective refractory period (ERP) of FAP. The suppression on the v max was frequency dependent. Benactyzine 5, 10,50 μmol·L -1 lengthened the APD50, APD90 of SAP induced by isoprenaline or histamine when perfused with KCl 22 mmol·L -1 Tyrode’s solution. The v max of the SAP was not decreased by benactyzine 5, 10 μmol·L -1 but by 50 μmol·L -1 . The effects on the SAP were antagonized by elevation of the extracellular calcium from 2.0 to 5.6 mmol·L -1 . The effects of benactyzine on SAP elicited by tetrodotoxin resembled that by isoprenaline or histamine except the more pronounced suppression on v max and action potential amplitude (APA). The persistent rapid spontaneous activity and triggered tachyarrhythmia induced by ouabain were also abolished immediately by benactyzine 5 μmol·L -1 . Conclusion: Benactyzine can inhibit Na +, K +, Ca 2+ transmembrane movement and intracellular Ca 2+ mobilization in the myocardium, and this may be the electrophysiological basis of its effects against experimental arrhythmias.

关键词： benactyzine papillary muscle action potential myocardial contraction tetrodotoxin

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金昌城市居民区土壤重金属分布特征研究

干旱区资源与环境 2011年第1期25卷 180-184页

作者：胡小娜南忠仁刘晓文李媛丁海霞兰州大学西部环境教育部重点实验室资源环境学院兰州730000

通过对甘肃省金昌市居民区土壤重金属含量的调查分析,以国家土壤环境质量标准和区域土壤背景值为评价标准,利用单项和综合污染指数对金昌市居民区土壤重金属进行分析评价。结果表明:金昌市居民区五种重金属元素的平均含量均超过该地区... 详细信息

通过对甘肃省金昌市居民区土壤重金属含量的调查分析,以国家土壤环境质量标准和区域土壤背景值为评价标准,利用单项和综合污染指数对金昌市居民区土壤重金属进行分析评价。结果表明:金昌市居民区五种重金属元素的平均含量均超过该地区的背景值,90%以上研究区域的土壤重金属含量超过区域背景值,金昌市不同居民区土壤的重金属含量差异很大,土壤重金属含量的变异系数28.60-105.03%,变异系数相比较:Ni>Cu>Cd>Pb>Zn。对重金属含量进行相关性分析,Cu与Ni、Cd、Pb、Zn都达到显著性水平,Ni与Cu、Cd达到性显著水平。单项污染指数比较,污染程度是Cu>Ni>Cd>Zn>Pb,就平均值来看,Cu、Ni为轻度污染,Zn、Cd、Pb为非污染。综合污染指数最小值为0.82,最大值达到1.14,65%的研究区域为轻度污染。居民区土壤中重金属主要来源于该地区的矿业开采和金属冶炼等工业活动。

关键词：土壤重金属污染评价

绿洲农田土壤主要微量元素的影响因素及分布特征研究——以张掖甘州区和临泽县为例

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干旱区资源与环境 2010年第10期24卷 127-132页

作者：赵翠翠南忠仁刘晓文丁海霞晋王强兰州大学西部环境教育部重点实验室兰州大学资源环境学院兰州730000

运用传统统计学和地统计学方法,对张掖甘州区和临泽县农田土壤中Mn、Co、Cu、Zn、Ni全量的影响因素和空间分布特征进行了研究。结果显示:五种微量元素全量的平均值与全国土壤平均值相当;变异系数在9.27%～20.90%之间,属弱变异性或中等... 详细信息

运用传统统计学和地统计学方法,对张掖甘州区和临泽县农田土壤中Mn、Co、Cu、Zn、Ni全量的影响因素和空间分布特征进行了研究。结果显示:五种微量元素全量的平均值与全国土壤平均值相当;变异系数在9.27%～20.90%之间,属弱变异性或中等变异性。相关性分析表明,除Zn外,其余微量元素全量与pH成显著负相关;除Co和Zn,其余元素与OM成显著正相关,CaCO3、有效P和CEC与微量元素含量的相关性较小。运用克里格(Kriging)最优内插法得到土壤微量元素含量的空间分布图,图中显示除Ni外,其余元素的含量分布有一定规律性,说明Mn、Co、Cu、Zn种微量元素的分布主要取决于地形、成土母质等结构性因素。

关键词：绿洲农田土壤微量元素理化性质空间分布克里格(Kriging)插值

金昌城郊耕作土壤重金属Cu、Zn、Ni的分布规律

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干旱区资源与环境 2009年第8期23卷 164-170页

作者：李媛南忠仁刘晓文王胜利丁海霞兰州大学西部环境教育部重点实验室资源环境学院兰州730000

以干旱区绿洲金昌城郊耕作土壤为供试土壤,采用全量分析法和Tessier五步连续提取法研究了六个典型土壤剖面重金属Cu、Zn和Ni的总量以及形态纵向分布规律。结果表明:重金属Cu和Ni表聚现象明显,表层至下,其浓度先减少后稳定,两种元素在剖... 详细信息

以干旱区绿洲金昌城郊耕作土壤为供试土壤,采用全量分析法和Tessier五步连续提取法研究了六个典型土壤剖面重金属Cu、Zn和Ni的总量以及形态纵向分布规律。结果表明:重金属Cu和Ni表聚现象明显,表层至下,其浓度先减少后稳定,两种元素在剖面中的迁移距离相近,基本在45cm附近;Cu和Ni化学行为相似,反映了Cu和Ni来源相同;Zn的总量分布没有明显的规律性。在土壤剖面中,Cu、Ni有形态变化层位,0-45cm有机态Cu>残渣态Cu>铁-锰氧化态Cu,碳酸盐态Cu>可交换态Cu;Ni的铁-锰氧化态>有机态,残渣态,碳酸盐态>可交换态;45cm后Cu、Ni主要以残渣态存在;Zn在所有土层中均以残渣态为主要赋存形态。研究土壤Cu、Ni的总量及形态分布主要受人为活动影响,Zn主要受成土母岩影响。

关键词：重金属形态剖面分布