Microglia are the tissue resident macrophages of the brain and represent the sole immune population located in the parenchyma of the central nervous system （CNS）. These cells are hidden be-tween neurons, astrocytes ...Microglia are the tissue resident macrophages of the brain and represent the sole immune population located in the parenchyma of the central nervous system （CNS）. These cells are hidden be-tween neurons, astrocytes as well as oligodendrocytes and account for only 5-10% of CNS cells. Even though microglia were already identified in 1913 by the Spanish neuroanatomist Ramon y Cajal and further seminally investigated by his student Pio del Rio Hortega,展开更多
目的:系统评价基因检测指导的个体化抗血小板治疗与常规治疗比较在急性冠状动脉综合征(ACS)或接受经皮冠状动脉介入治疗(PCI)患者中的有效性和安全性。方法:计算机检索PubMed、Cochrane Library、Embase、Web of Science、CNKI、WanFang...目的:系统评价基因检测指导的个体化抗血小板治疗与常规治疗比较在急性冠状动脉综合征(ACS)或接受经皮冠状动脉介入治疗(PCI)患者中的有效性和安全性。方法:计算机检索PubMed、Cochrane Library、Embase、Web of Science、CNKI、WanFang Data、SinoMed数据库及中国临床试验注册中心(ChiCTR),搜集有关ACS或行PCI术的患者基因检测指导的个体化抗血小板治疗与常规抗血小板治疗比较的随机对照试验(RCT),检索时限均为从建库至2021年5月10日。由两位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入5个RCT,累计6329例患者。Meta分析结果显示,与常规抗血小板治疗相比,基因检测指导的个体化抗血小板治疗可降低心肌梗死发生率[RR=0.57,95%CI(0.42,0.78),P<0.01]和支架内血栓形成发生率[RR=0.45,95%CI(0.25,0.80),P<0.01],两组的主要不良心血管事件(MACE)发生率[RR=0.73,95%CI(0.50,1.07),P=0.11]、全因死亡发生率[RR=0.82,95%CI(0.41,1.63),P=0.57]、任意出血发生率[RR=0.84,95%CI(0.58,1.23),P=0.37]、心血管死亡率[RR=0.78,95%CI(0.54,1.13),P=0.19]和卒中发生率[RR=0.70,95%CI(0.38,1.27),P=0.23]差异均无统计学意义;在安全性方面,两组大出血发生率差异无统计学意义[RR=0.88,95%CI(0.64,1.23),P=0.46],但基因指导治疗组可降低小出血发生率[RR=0.74,95%CI(0.59,0.94),P=0.01]。结论:基因检测指导的个体化抗血小板治疗相比于常规治疗虽未明显降低患者MACE、全因死亡、心血管死亡、卒中和任意出血、大出血等风险,但在降低患者心肌梗死、支架内血栓、小出血风险方面更有优势。基因检测指导的个体化抗血小板治疗方案可能更适合高危冠心病患者。展开更多
Ticagrelor is the first reversibly binding oralP2Y_(12) receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At pre...Ticagrelor is the first reversibly binding oralP2Y_(12) receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At present, the other pharmacological functions of ticagrelor remain poorly understood. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a critical role in the innate immune system, but its excessive activation also contributes to the pathogenesis of complex diseases. In this study, we systematically examined the effects of ticagrelor on the NLRP3 inflammasome and found that ticagrelor inhibits NLRP3 inflammasome activation in macrophages independent of its classic inhibitory effect on theP2Y_(12) signaling pathway. Further mechanistic studies demonstrate that ticagrelor attenuates the oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) by blocking chloride efflux, an effect achieved through the degradation of chloride intracellular channel proteins (CLICs) and blockade of the translocation of CLICs to the plasma membrane. Moreover, experiments on lipopolysaccharide-induced sepsis and alum-induced peritonitis in mice confirmed that ticagrelor mitigates the severity of systemic inflammation independent ofP2Y_(12) receptor antagonism. Importantly, oral administration of ticagrelor rapidly and strongly inhibited NLRP3 inflammasome activation in peripheral blood mononuclear cells from patients with acute coronary syndrome. Overall, our study reveals a novel pharmacological function of ticagrelor in addition to its classic antiplatelet properties, which suggests that ticagrelor may serve as a potential therapeutic agent for use in NLRP3-associated diseases.展开更多
Two series of novel derivatives of4,5,6,7-tetrahydrothieno [3,2-c]pyridine were synthesized and structurally characterized by 1^H NMR and MS. Their in vivo antiplatelet aggregation activities were evaluated.
基金supported by the Deutsche Forschungsgemeinschaft(DFGMI1328)
文摘Microglia are the tissue resident macrophages of the brain and represent the sole immune population located in the parenchyma of the central nervous system （CNS）. These cells are hidden be-tween neurons, astrocytes as well as oligodendrocytes and account for only 5-10% of CNS cells. Even though microglia were already identified in 1913 by the Spanish neuroanatomist Ramon y Cajal and further seminally investigated by his student Pio del Rio Hortega,
基金supported by the National Natural Science Foundation of China(Grant Nos.81773016,21976155,and 31471297)Zhejiang Provincial Natural Science Foundation of China(No.LY18C060001)+1 种基金WeiJian Special Foundation(Zhejiang University School of Public Health)Fundamental Research Funds for the Central Universities.
文摘Ticagrelor is the first reversibly binding oralP2Y_(12) receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At present, the other pharmacological functions of ticagrelor remain poorly understood. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a critical role in the innate immune system, but its excessive activation also contributes to the pathogenesis of complex diseases. In this study, we systematically examined the effects of ticagrelor on the NLRP3 inflammasome and found that ticagrelor inhibits NLRP3 inflammasome activation in macrophages independent of its classic inhibitory effect on theP2Y_(12) signaling pathway. Further mechanistic studies demonstrate that ticagrelor attenuates the oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) by blocking chloride efflux, an effect achieved through the degradation of chloride intracellular channel proteins (CLICs) and blockade of the translocation of CLICs to the plasma membrane. Moreover, experiments on lipopolysaccharide-induced sepsis and alum-induced peritonitis in mice confirmed that ticagrelor mitigates the severity of systemic inflammation independent ofP2Y_(12) receptor antagonism. Importantly, oral administration of ticagrelor rapidly and strongly inhibited NLRP3 inflammasome activation in peripheral blood mononuclear cells from patients with acute coronary syndrome. Overall, our study reveals a novel pharmacological function of ticagrelor in addition to its classic antiplatelet properties, which suggests that ticagrelor may serve as a potential therapeutic agent for use in NLRP3-associated diseases.
文摘Two series of novel derivatives of4,5,6,7-tetrahydrothieno [3,2-c]pyridine were synthesized and structurally characterized by 1^H NMR and MS. Their in vivo antiplatelet aggregation activities were evaluated.
