目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对...目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对幽门螺杆菌(Hp)感染相关高危胃癌患者的诊断价值。方法收集2017年2月-2019年1月胜利油田中心医院收治的47例萎缩性胃炎及59例胃癌患者胃黏膜组织标本;免疫组化染色测定组织CDX2、HNF4α、CAP2蛋白表达情况,快速银染法检测Hp感染情况,分析三者在Hp感染相关胃部炎症恶性转化过程中的作用,受试者工作曲线(Receiver operator characteristic curve,ROC)分析三者联合检测对Hp感染相关胃癌的诊断价值。结果胃癌患者组织标本CDX2阳性率低于萎缩性胃癌患者(P<0.05),HNF4α、CAP2阳性率高于萎缩性胃炎患者(P<0.05);胃癌患者Hp感染率为79.66%,高于萎缩性胃炎Hp感染率42.55%(P<0.05),Hp阳性胃癌、萎缩性胃炎组织标本CDX2、HNF4α、CAP2阳性率皆高于Hp阴性病例组织标本(P<0.05);胃癌患者组织CDX2、HNF4α、CAP2表达与Hp感染率呈正相关(P<0.05);HNF4α阳性染色评分>3分预测Hp相关高危胃癌价值最高,曲线下面积(Area under the curve,AUC)为0.870,敏感度、特异性分别为91.49%、75.00%;其次为CAP2,AUC为0.860,敏感度、特异性为89.36%、75.00%;三者联合预测Hp相关高危胃癌综合效能最高,AUC为0.891,敏感度、特异性分别为89.36%、91.67%。结论组织CDX2、HNF4α、CAP2异常表达与Hp感染有关,参与胃炎向胃癌恶性转化过程;联合检测组织CDX2、HNF4α、CAP2对Hp感染相关高危胃癌有较高的预测价值。展开更多
目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Gen...目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Genotyping系统进行rs1884614和rs2144908的基因型多态性分析。并分析它们与患者有关临床代谢指标的关系。结果:两组的基因型分布及等位基因频率差异无统计学意义(P>0.05);但在非肥胖(BMI<25 kg/m^2)患者的OGTT检测中,rs1884614 T/T基因型与较小的血浆胰岛素曲线下面积存在相关性(P<0.05)。结论:HNF-4α基因的P2启动子区的SNP rs1884614可能影响江苏地区非肥胖型2型糖尿病患者的胰岛素分泌。展开更多
Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein bet...Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.展开更多
文摘目的探讨组织尾侧型同源转录因子2(Caudal type homeobox transcription factor 2,CDX2)、肝细胞核因子4α(Hepatocyte nuclear factor 4 alpha,HNF4α)、腺苷酸环化酶相关蛋白2(Adenylate cyclase related protein 2,CAP2)联合检测对幽门螺杆菌(Hp)感染相关高危胃癌患者的诊断价值。方法收集2017年2月-2019年1月胜利油田中心医院收治的47例萎缩性胃炎及59例胃癌患者胃黏膜组织标本;免疫组化染色测定组织CDX2、HNF4α、CAP2蛋白表达情况,快速银染法检测Hp感染情况,分析三者在Hp感染相关胃部炎症恶性转化过程中的作用,受试者工作曲线(Receiver operator characteristic curve,ROC)分析三者联合检测对Hp感染相关胃癌的诊断价值。结果胃癌患者组织标本CDX2阳性率低于萎缩性胃癌患者(P<0.05),HNF4α、CAP2阳性率高于萎缩性胃炎患者(P<0.05);胃癌患者Hp感染率为79.66%,高于萎缩性胃炎Hp感染率42.55%(P<0.05),Hp阳性胃癌、萎缩性胃炎组织标本CDX2、HNF4α、CAP2阳性率皆高于Hp阴性病例组织标本(P<0.05);胃癌患者组织CDX2、HNF4α、CAP2表达与Hp感染率呈正相关(P<0.05);HNF4α阳性染色评分>3分预测Hp相关高危胃癌价值最高,曲线下面积(Area under the curve,AUC)为0.870,敏感度、特异性分别为91.49%、75.00%;其次为CAP2,AUC为0.860,敏感度、特异性为89.36%、75.00%;三者联合预测Hp相关高危胃癌综合效能最高,AUC为0.891,敏感度、特异性分别为89.36%、91.67%。结论组织CDX2、HNF4α、CAP2异常表达与Hp感染有关,参与胃炎向胃癌恶性转化过程;联合检测组织CDX2、HNF4α、CAP2对Hp感染相关高危胃癌有较高的预测价值。
文摘目的:研究肝细胞核因子-4α(hepatocyte nuclear factor-4α,HNF-4α)基因的P2启动子区域的2个单核苷酸多态性(SNP)位点rs1884614和rs2144908与2型糖尿病的相关性。方法:收集2型糖尿病患者328例和非糖尿病患者196例,应用Taq Man SNP Genotyping系统进行rs1884614和rs2144908的基因型多态性分析。并分析它们与患者有关临床代谢指标的关系。结果:两组的基因型分布及等位基因频率差异无统计学意义(P>0.05);但在非肥胖(BMI<25 kg/m^2)患者的OGTT检测中,rs1884614 T/T基因型与较小的血浆胰岛素曲线下面积存在相关性(P<0.05)。结论:HNF-4α基因的P2启动子区的SNP rs1884614可能影响江苏地区非肥胖型2型糖尿病患者的胰岛素分泌。
基金“Dawn”Program of Shanghai Education Commission,No.22SG37(to PY)the National Natural Science Foundation of China,Nos.82371313(to PY),82401536(to YongxinZ).
文摘Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.
