SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study...SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.展开更多
目的探讨加速康复外科(enhanced recovery after surgery,ERAS)下单孔加一孔(single-port plus one-port,SILS+1)腹腔镜与传统五孔腹腔镜在胃癌根治术后患者近期疗效与应激指标比较。方法回顾性收集本院普通外科接受腹腔镜胃癌根治术患...目的探讨加速康复外科(enhanced recovery after surgery,ERAS)下单孔加一孔(single-port plus one-port,SILS+1)腹腔镜与传统五孔腹腔镜在胃癌根治术后患者近期疗效与应激指标比较。方法回顾性收集本院普通外科接受腹腔镜胃癌根治术患者114例的临床资料,按患者采取的手术方式分为SILS+1腹腔镜组(n=66)和传统五孔腹腔镜组(n=48)。2组患者均按照加速康复外科理念进行围手术期相关处理,SILS+1腹腔镜组患者采用单孔术式进行相关操作,传统五孔腹腔镜组采用传统五孔腹腔镜进行操作。记录并比较2组患者术后1、3、5 d的应激指标,包括白细胞计数(WBC)、C-反应蛋白(CRP)、血沉(ESR)、降钙素原(PCT)及白细胞介素6(IL-6)的水平,并比较2组患者手术时间、切口长度、术中出血量、肿瘤类型及TNM分期,记录患者术后胃管拔除时间、首次进食时间、首次下床活动时间、肛门首次排气时间、首次排便时间及术后住院时间。结果①2组患者年龄、性别、体质量指数及肿瘤分期差异无统计学意义(P>0.05),2组患者术前1 d的WBC、CRP、ESR、PCT及IL-6水平比较差异均无统计学意义(P>0.05);②SILS+1腹腔镜组的手术时间较传统五孔腹腔镜组长,差异有统计学意义(P<0.05);③术后1、3、5 d,SILS+1腹腔镜组的WBC、CRP、ESR、PCT及IL-6水平均明显低于传统五孔腹腔镜组(P<0.05);④SILS+1腹腔镜组患者的切口长度、首次肛门排气时间、术后首次排便时间及总住院时间均明显短于传统五孔腹腔镜组(P<0.05),2组患者胃管拔除时间、首次进食时间、首次下床活动时间比较差异无统计学意义(P>0.05)。结论在ERAS理念下,SILS+1腹腔镜较传统五孔腹腔镜手术时间有所延长,但能获得更好的近期临床疗效,且SILS+1腹腔镜有助于降低胃癌根治术后患者的应激反应,促进患者术后康复。展开更多
基金National Natural Science Foundation of China(82230043,82293642)。
文摘SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.
文摘目的探讨加速康复外科(enhanced recovery after surgery,ERAS)下单孔加一孔(single-port plus one-port,SILS+1)腹腔镜与传统五孔腹腔镜在胃癌根治术后患者近期疗效与应激指标比较。方法回顾性收集本院普通外科接受腹腔镜胃癌根治术患者114例的临床资料,按患者采取的手术方式分为SILS+1腹腔镜组(n=66)和传统五孔腹腔镜组(n=48)。2组患者均按照加速康复外科理念进行围手术期相关处理,SILS+1腹腔镜组患者采用单孔术式进行相关操作,传统五孔腹腔镜组采用传统五孔腹腔镜进行操作。记录并比较2组患者术后1、3、5 d的应激指标,包括白细胞计数(WBC)、C-反应蛋白(CRP)、血沉(ESR)、降钙素原(PCT)及白细胞介素6(IL-6)的水平,并比较2组患者手术时间、切口长度、术中出血量、肿瘤类型及TNM分期,记录患者术后胃管拔除时间、首次进食时间、首次下床活动时间、肛门首次排气时间、首次排便时间及术后住院时间。结果①2组患者年龄、性别、体质量指数及肿瘤分期差异无统计学意义(P>0.05),2组患者术前1 d的WBC、CRP、ESR、PCT及IL-6水平比较差异均无统计学意义(P>0.05);②SILS+1腹腔镜组的手术时间较传统五孔腹腔镜组长,差异有统计学意义(P<0.05);③术后1、3、5 d,SILS+1腹腔镜组的WBC、CRP、ESR、PCT及IL-6水平均明显低于传统五孔腹腔镜组(P<0.05);④SILS+1腹腔镜组患者的切口长度、首次肛门排气时间、术后首次排便时间及总住院时间均明显短于传统五孔腹腔镜组(P<0.05),2组患者胃管拔除时间、首次进食时间、首次下床活动时间比较差异无统计学意义(P>0.05)。结论在ERAS理念下,SILS+1腹腔镜较传统五孔腹腔镜手术时间有所延长,但能获得更好的近期临床疗效,且SILS+1腹腔镜有助于降低胃癌根治术后患者的应激反应,促进患者术后康复。
