目的红景天苷(Sal)是藏药红景天的主要活性成分,具有良好的抗凋亡潜能。目前,关于Sal的抗凋亡机制研究存在一些相互矛盾的结果。我们以Sal在缺氧缺血性脑损伤(HICD)中的作用为例,进行了系统综述和荟萃分析,以提供Sal在预防和治疗HICD中...目的红景天苷(Sal)是藏药红景天的主要活性成分,具有良好的抗凋亡潜能。目前,关于Sal的抗凋亡机制研究存在一些相互矛盾的结果。我们以Sal在缺氧缺血性脑损伤(HICD)中的作用为例,进行了系统综述和荟萃分析,以提供Sal在预防和治疗HICD中的临床前证据和抗凋亡特性。方法利用中文数据库中国知网(CNKI)、维普(VIP)、万方以及英文数据库PubMed和Web of Science在线检索1980年1月1日至2021年11月9日的有关Sal抗凋亡潜能治疗HICD的文献。采用Cochrane协作网偏倚风险评估标准评价纳入文献的质量,并利用RevMan 5.3软件进行Meta分析。结果最终纳入研究的文献有40篇。40篇文献中,动物实验30篇,体外细胞实验17篇,其中7篇既包含动物实验又包含细胞实验。经统计发现,Sal对HICD的脑梗死面积、脑含水量等疾病相关指标有明显改善作用(P<0.05)。在体内研究中,Sal主要通过抗炎、抗氧化、调节补体通路、信号转导和自噬等途径影响凋亡因子的表达,从而在治疗HICD疾病中发挥抗凋亡潜能。在体外研究中,Sal在HICD疾病模型中主要通过抗氧化、抗炎、改善Ca^(2+)超载、调节线粒体功能、信号转导和C3补体等途径发挥抗凋亡作用。结论Sal可通过抗炎、抗氧化、改善自噬、补体和信号转导、调节线粒体膜电位和改善Ca^(2+)过载等途径发挥抗凋亡作用,预防和治疗HICD疾病。展开更多
Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limit...Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limited by the efficiency of local catalytic reaction.Herein,we report a novel type of core–shell hybrid nanoparticles(CaCO_(3)@MS),consisting of CaCO_(3)and MnSiO_(x),for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload.In this system,MnSiO_(x)serves as catalysts with glutathione(GSH)responsive Mn^(2+)ions release functionality.CaCO_(3)nanoparticles play three important roles,including carbon dioxide(CO_(2))donor,pH modulator,and Ca^(2+)overload agent.It is found that the CaCO_(3)nanoparticles can induce CO_(2)production and pH increase in acidic tumor environment,both of which promote Mn^(2+)mediated ROS generation.And simultaneous release of Ca^(2+)ions from CaCO_(3)triggers calcium overload in tumor,which functions collaboratively with excessive ROS to induce cancer cell apoptosis.The results demonstrate that after treatment with CaCO_(3)@MS,a remarkable tumor inhibition was achieved both in vitro and in vivo,while no clear toxic effect was observed.This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an“exogenous CO_(2)delivery”strategy for combinational tumor therapy.展开更多
基金supported by the National Natural Science Foundation of China(82104533 and 81973569)Xinglin Scholar Research Promotion Project of Chengdu University of TCM(XKTD2022013).
文摘目的红景天苷(Sal)是藏药红景天的主要活性成分,具有良好的抗凋亡潜能。目前,关于Sal的抗凋亡机制研究存在一些相互矛盾的结果。我们以Sal在缺氧缺血性脑损伤(HICD)中的作用为例,进行了系统综述和荟萃分析,以提供Sal在预防和治疗HICD中的临床前证据和抗凋亡特性。方法利用中文数据库中国知网(CNKI)、维普(VIP)、万方以及英文数据库PubMed和Web of Science在线检索1980年1月1日至2021年11月9日的有关Sal抗凋亡潜能治疗HICD的文献。采用Cochrane协作网偏倚风险评估标准评价纳入文献的质量,并利用RevMan 5.3软件进行Meta分析。结果最终纳入研究的文献有40篇。40篇文献中,动物实验30篇,体外细胞实验17篇,其中7篇既包含动物实验又包含细胞实验。经统计发现,Sal对HICD的脑梗死面积、脑含水量等疾病相关指标有明显改善作用(P<0.05)。在体内研究中,Sal主要通过抗炎、抗氧化、调节补体通路、信号转导和自噬等途径影响凋亡因子的表达,从而在治疗HICD疾病中发挥抗凋亡潜能。在体外研究中,Sal在HICD疾病模型中主要通过抗氧化、抗炎、改善Ca^(2+)超载、调节线粒体功能、信号转导和C3补体等途径发挥抗凋亡作用。结论Sal可通过抗炎、抗氧化、改善自噬、补体和信号转导、调节线粒体膜电位和改善Ca^(2+)过载等途径发挥抗凋亡作用,预防和治疗HICD疾病。
基金National Natural Science Foundation of China(Nos.52172289 and 51902288)Provincial Key research program of Zhejiang Province(No.2020C04005)Fundamental Research Funds for the Central Universities.
文摘Nanocatalysts mediated reactive oxygen species(ROS)based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects.However,the treatment outcome is limited by the efficiency of local catalytic reaction.Herein,we report a novel type of core–shell hybrid nanoparticles(CaCO_(3)@MS),consisting of CaCO_(3)and MnSiO_(x),for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload.In this system,MnSiO_(x)serves as catalysts with glutathione(GSH)responsive Mn^(2+)ions release functionality.CaCO_(3)nanoparticles play three important roles,including carbon dioxide(CO_(2))donor,pH modulator,and Ca^(2+)overload agent.It is found that the CaCO_(3)nanoparticles can induce CO_(2)production and pH increase in acidic tumor environment,both of which promote Mn^(2+)mediated ROS generation.And simultaneous release of Ca^(2+)ions from CaCO_(3)triggers calcium overload in tumor,which functions collaboratively with excessive ROS to induce cancer cell apoptosis.The results demonstrate that after treatment with CaCO_(3)@MS,a remarkable tumor inhibition was achieved both in vitro and in vivo,while no clear toxic effect was observed.This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an“exogenous CO_(2)delivery”strategy for combinational tumor therapy.
基金This work was supported by the Educational Department of Jiangsu Province, China (No. 04KJA180110)the Personnel Department of Jiangsu Province, China (No. 06-B-040)the Nantong Municipality of Jiangsu Province, China (No. S40057 and S5040).
文摘近来研究发现,细胞因子白介素-6(interleukin-6,IL-6)不仪是重要的免疫调节因子,而且也是重要的神经调节因子。中枢神经系统中IL-6的作用是复杂的,尤其是对脑损伤时IL-6所发挥的作用及其作用机制尚不十分清楚。为此,我们利用N-甲基-D-天门冬氨酸(N-methyl-D-aspartate,NMDA)处理小脑颗粒神经元引起急性损伤的细胞模型,探讨IL-6对神经元损伤的保护及其作用机制。取出生后8 d幼鼠的小脑,进行小脑颗粒神经元培养。将IL-6(5或10 ng/mL)加入到小脑颗粒神经元的培养液中孵育8 d,然后用NMDA(100μmol／L)刺激小脑颗粒神经元30 min以造成神经元损伤。用噻唑兰(methyl-thiazole tetrazolium,MTT)比色法检测神经元的活性;用末端脱氧核苷酸转移酶介导的原位缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测神经元的凋亡;用激光扫描共聚焦显微镜(confocal laser scanning microscope,CLSM)观察神经元内游离Ca2+浓度的动态变化。用抗gp130单克隆抗体(75 ng／mL)抑制IL-6的活性,然后观察IL-6抗NMDA神经毒性作用的变化;并利用Western blot法检测IL-6对小脑颗粒神经元表达IL-6的细胞内信号转导蛋白——信号转导子和转录激活子3(signal transducer and activator of transcription 3,STAT3)和细胞外信号调节激酶(extracellular signal regulated kinase 1／2,ERK1／2)磷酸化水平的影响。NMDA刺激未经IL-6处理的小脑颗粒神经元,导致神经元活性降低、神经元凋亡增加和神经元内Ca2+超载。NMDA刺激经IL-6慢性预处理的小脑颗粒神经元,其损伤程度与未经IL-6处理的神经元相比明显减轻,包括神经元活性明显增强、神经元凋亡显著减少和神经元内Ca2+超载减轻。抗gp130抗体可阻断IL-6减轻NMDA激发的神经元内Ca2+超载的作用;经IL-6慢性处理的小脑颗粒神经元,其细胞内STAT3和ERK1／2的磷酸化水平显著增加。结果表明,IL-6能保护神�
