金黄色葡萄球菌(简称:金葡菌,Staphylococcus aureus)是细菌性感染的主要致病菌,主要通过其表面特异的弹性蛋白结合蛋白(elastin-binding protein of Staphylococcus aureus,EbpS)与宿主胞外基质结合引起宿主的感染。EbpS蛋白在不同的...金黄色葡萄球菌(简称:金葡菌,Staphylococcus aureus)是细菌性感染的主要致病菌,主要通过其表面特异的弹性蛋白结合蛋白(elastin-binding protein of Staphylococcus aureus,EbpS)与宿主胞外基质结合引起宿主的感染。EbpS蛋白在不同的环境中呈现不同的结构。这种结构的变化将会对进一步揭示金葡菌侵染宿主的机制产生极其重要的意义。展开更多
Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma...目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)以及癌旁组织中的表达差异,进一步研究这些表达与AEG患者的临床病理特点之间的联系。方法:从TCGA(The Cancer Genome Atlas)数据库中检索了XRCC1和EIF4EBP1在胃癌患者中的表达水平和临床数据,并从中筛选出AEG患者的相关数据。研究其在胃癌和AEG中的表达水平和相关性,以及AEG的表达水平与总生存期之间的联系。对我院128例2014年1月至2019年12月的AEG组织和癌旁组织石蜡包埋切片进行免疫组化(immunohistochemistry,IHC)染色,检测XRCC1和EIF4EBP1蛋白的表达水平,同时收集患者的相关临床资料。研究这两种蛋白质的表达水平和它们之间的相关性,以及它们的表达水平与临床病理特征之间的联系。结果:在TCGA数据库里,XRCC1和EIF4EBP1在412个胃癌组织样本中的表达水平明显超过了36个正常组织样本(P<0.001)。并且在这412个胃癌组织样本中,XRCC1和EIF4EBP1的表达之间呈正相关关系(r=0.349,P<0.001)。在其中的AEG患者中,XRCC1和EIF4EBP1在99例AEG组织样本中的表达水平明显超过了14例正常食管胃结合部组织样本(XRCC1:P=0.015,EIF4EBP1:P=0.046),但在这99例AEG组织中,XRCC1和EIF4EBP1的表达之间没有显著相关性(P=0.066)。在临床样本中,128例AEG组织样本中XRCC1和EIF4EBP1的高表达率分别为53.1%(68/128)和82%(105/128),超过了癌旁组织样本的高表达率33.6%(43/128)和54.7%(70/128),且在128例AEG组织样本中,XRCC1和EIF4EBP1的表达呈现出正相关性(r=0.245,P=0.005)。在AEG组织中,XRCC1和EIF4EBP1的表达与患者的大体类型、是否神经侵犯、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期以及总生存期之间,没有显示出具有统计学意义的相关性。在对AEG患者的总生存状况进行多因素分析时,脉管癌栓的形成(P=0.002)和临床分期(P=0.003)与患者的总生存率有着显著的关联。结论:在AEG组织中,XRCC1和EIF4EBP1的表达水平相对于癌旁组织更高,并且这两者表达之间存在正相关关系。在不同的XRCC1和EIF4EBP1表达水平的AEG患者中,无论是大体类型、是否侵犯神经、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期还是总生存期,都没有显著的差异。脉管癌栓及临床分期是决定AEG患者生存预后的关键因素。展开更多
文摘金黄色葡萄球菌(简称:金葡菌,Staphylococcus aureus)是细菌性感染的主要致病菌,主要通过其表面特异的弹性蛋白结合蛋白(elastin-binding protein of Staphylococcus aureus,EbpS)与宿主胞外基质结合引起宿主的感染。EbpS蛋白在不同的环境中呈现不同的结构。这种结构的变化将会对进一步揭示金葡菌侵染宿主的机制产生极其重要的意义。
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
文摘目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)以及癌旁组织中的表达差异,进一步研究这些表达与AEG患者的临床病理特点之间的联系。方法:从TCGA(The Cancer Genome Atlas)数据库中检索了XRCC1和EIF4EBP1在胃癌患者中的表达水平和临床数据,并从中筛选出AEG患者的相关数据。研究其在胃癌和AEG中的表达水平和相关性,以及AEG的表达水平与总生存期之间的联系。对我院128例2014年1月至2019年12月的AEG组织和癌旁组织石蜡包埋切片进行免疫组化(immunohistochemistry,IHC)染色,检测XRCC1和EIF4EBP1蛋白的表达水平,同时收集患者的相关临床资料。研究这两种蛋白质的表达水平和它们之间的相关性,以及它们的表达水平与临床病理特征之间的联系。结果:在TCGA数据库里,XRCC1和EIF4EBP1在412个胃癌组织样本中的表达水平明显超过了36个正常组织样本(P<0.001)。并且在这412个胃癌组织样本中,XRCC1和EIF4EBP1的表达之间呈正相关关系(r=0.349,P<0.001)。在其中的AEG患者中,XRCC1和EIF4EBP1在99例AEG组织样本中的表达水平明显超过了14例正常食管胃结合部组织样本(XRCC1:P=0.015,EIF4EBP1:P=0.046),但在这99例AEG组织中,XRCC1和EIF4EBP1的表达之间没有显著相关性(P=0.066)。在临床样本中,128例AEG组织样本中XRCC1和EIF4EBP1的高表达率分别为53.1%(68/128)和82%(105/128),超过了癌旁组织样本的高表达率33.6%(43/128)和54.7%(70/128),且在128例AEG组织样本中,XRCC1和EIF4EBP1的表达呈现出正相关性(r=0.245,P=0.005)。在AEG组织中,XRCC1和EIF4EBP1的表达与患者的大体类型、是否神经侵犯、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期以及总生存期之间,没有显示出具有统计学意义的相关性。在对AEG患者的总生存状况进行多因素分析时,脉管癌栓的形成(P=0.002)和临床分期(P=0.003)与患者的总生存率有着显著的关联。结论:在AEG组织中,XRCC1和EIF4EBP1的表达水平相对于癌旁组织更高,并且这两者表达之间存在正相关关系。在不同的XRCC1和EIF4EBP1表达水平的AEG患者中,无论是大体类型、是否侵犯神经、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期还是总生存期,都没有显著的差异。脉管癌栓及临床分期是决定AEG患者生存预后的关键因素。
