Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeos...Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.展开更多
目的分析胎儿超声心动图联合母体血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、同型半胱氨酸(homocysteine,Hcy)浓度对先天性心脏病(先心病)胎儿的诊断效能。方法选取2018年7月至2022年2月在十堰市妇幼保健院...目的分析胎儿超声心动图联合母体血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、同型半胱氨酸(homocysteine,Hcy)浓度对先天性心脏病(先心病)胎儿的诊断效能。方法选取2018年7月至2022年2月在十堰市妇幼保健院进行孕中期产前检查的孕妇2756例为研究对象,根据妊娠结局将孕妇分为先心病组(n=110),正常组(n=2646)。孕中期均行胎儿超声心动图检查。酶联免疫吸附法试验(enzymelinked immunosorbent assay,ELISA)检测母体血清SFRP5浓度,全自动生化分析仪检测Hcy浓度。Pearson法分析先心病组母体血清SFRP5浓度与Hcy浓度的相关性。以妊娠结局为“金标准”,分析胎儿超声心动图、母体血清SFRP5、Hcy浓度及三者联合对先心病胎儿的诊断效能。结果先心病组母体血清SFRP5浓度明显低于正常组(P<0.05),Hcy浓度明显高于正常组(P<0.05),两者浓度呈负相关(r=-0.575,P<0.05)。胎儿超声心动图、母体血清SFRP5、Hcy浓度诊断先天性心脏病胎儿的灵敏度分别为63.64%、64.55%、65.45%,特异度分别为81.52%、81.07%、80.35%,准确度分别为80.81%、80.41%、79.75%。胎儿超声心动图、母体血清SFRP5、Hcy浓度联合诊断先心病胎儿的灵敏度、准确度分别为96.36%、80.91%,均高于三者单独检测,且三者联合诊断的灵敏度显著高于三者单独诊断(P<0.05)。结论胎儿超声心动图联合母体血清SFRP5、Hcy浓度对先心病胎儿具有较高的诊断价值,三者联合诊断可提高灵敏度。展开更多
基金the National Natural Science Foundation of China(No.81902016).
文摘Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.
