目的探讨HDL脂质转运蛋白ATP结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)、载脂蛋白A1(apolipoprotein A1,ApoA1)和吸收蛋白B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)是否在Ⅰ型子宫内膜样癌(endomet...目的探讨HDL脂质转运蛋白ATP结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)、载脂蛋白A1(apolipoprotein A1,ApoA1)和吸收蛋白B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)是否在Ⅰ型子宫内膜样癌(endometrial carcinoma,EC)中存在表达失衡。方法选取80例Ⅰ型EC和47例对照增生改变子宫内膜组织,采用免疫组化EnVision两步法检测ABCA1和ApoA1的表达;分析Ⅰ型EC中ABCA1、ApoA1与SR-B1、ER、PR蛋白表达的相关性及与临床病理特征的关系。结果(1)Ⅰ型EC中ABCA1阳性率为86.1%(62/72),低于对照增生改变子宫内膜组织(95.5%,42/44),差异有统计学意义(P<0.05);Ⅰ型EC组织中ApoA1阳性率为63.8%(44/69),高于对照增生改变子宫内膜组织(53.3%,23/43),差异无统计学意义(P>0.05);(2)在Ⅰ型EC中,ABCA1与SR-B1、ApoA1、ER之间呈负相关;ApoA1与PR之间呈正相关;(3)Ⅰ型EC中ABCA1和ApoA1蛋白表达与临床病理特征无明显相关性(P>0.05)。结论与对照增生改变子宫内膜组织相比,Ⅰ型EC中可能存在HDL转运蛋白ABCA1和HDL吸收蛋白SR-B1的表达失衡。展开更多
Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and scalab...Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and scalability.Of them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of action.Using chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against HCoV-OC43.Furthermore,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane fusion.Accordingly,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).展开更多
目的观察尿毒症毒素硫酸吲哚酚(IS)是否促进巨噬泡沫细胞脂滴的蓄积,以及对细胞内B类1型清道夫受体(SR-B1)表达和核因子NF-κB活化的影响。方法体外佛波酯(PMA)诱导人源单核细胞系THP-1分化为巨噬细胞,加入氧化低密度脂蛋白(ox-LDL)培...目的观察尿毒症毒素硫酸吲哚酚(IS)是否促进巨噬泡沫细胞脂滴的蓄积,以及对细胞内B类1型清道夫受体(SR-B1)表达和核因子NF-κB活化的影响。方法体外佛波酯(PMA)诱导人源单核细胞系THP-1分化为巨噬细胞,加入氧化低密度脂蛋白(ox-LDL)培养促进巨噬细胞泡沫化,随后以不同浓度的IS干预巨噬泡沫细胞,油红O染色观察细胞内脂滴变化,实时PCR和Western blotting检测SR-B1 m RNA和蛋白表达的水平,ELISA法检测NF-κB活化情况;经NF-κB抑制剂四氢化吡咯二硫代氨基甲酸酯(PDTC)预处理后IS再干预,实时PCR检测巨噬泡沫细胞内SR-B1 m RNA表达的变化。结果与对照组(IS 0μmol/L)比较,IS干预后巨噬泡沫细胞内脂滴明显增加,随着IS浓度的升高,细胞内脂滴逐渐增加;IS干预后巨噬泡沫细胞的NF-κB活化程度增高,差异有统计学意义(P<0.05)。与对照组比较,细胞在不同浓度的IS(2.5、25、250μmol/L)处理下,SR-B1 m RNA和蛋白的表达下降,随着IS浓度的增加,SR-B1和蛋白逐渐减少,呈现浓度依赖性,差异有统计学意义(P<0.05)。PDTC预处理后SR-B1m RNA表达增加,差异有统计学意义(P<0.05)。结论 IS抑制SR-B1 m RNA和蛋白的表达,增加THP-1源性巨噬泡沫细胞胆固醇的蓄积,促进巨噬细胞泡沫化,从而促进动脉粥样硬化。NF-κB活化可能是IS抑制SR-B1 m RNA表达的可能机制之一。展开更多
Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes ...Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.展开更多
目的 :越来越多的文献显示脂质代谢参与肿瘤的发生发展,但在口腔鳞癌的关系中尚未见报道,故本文拟通过检测脂质代谢转运相关蛋白ATP结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)和载脂蛋白A(apolipoprotein A-I,Apo A...目的 :越来越多的文献显示脂质代谢参与肿瘤的发生发展,但在口腔鳞癌的关系中尚未见报道,故本文拟通过检测脂质代谢转运相关蛋白ATP结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)和载脂蛋白A(apolipoprotein A-I,Apo A I)及脂质代谢吸收蛋白B类1型清道夫受体(Scavenger receptor class B type I,SR-B1)在口腔鳞癌组织中的差异性表达,探讨脂质转运蛋白和吸收蛋白是否在口腔鳞癌中存在失衡表达,及其与临床病理参数之间的关系及意义。方法:收集石河子大学医学院第一附属医院2004-2016年有完整临床病理资料的口腔鳞癌患者24例及正常口腔黏膜患者35例,制备组织芯片2张,应用免疫组织化学检测ABCA1,Apo A I和SR-B1的表达水平,并结合患者临床病理特征进行分析。结果:(1)ABCA1蛋白在口腔鳞癌(37.50%,9/24)中较正常鳞状上皮(0%,0/25)高表达,差异具有统计学意义(χ2=11.484,P=0.001);Apo A I蛋白在两者之间均高表达(100%,24/24),SR-B1蛋白在两者中均不表达或低表达(0%,0/18),差异均无统计学意义;(2)在口腔鳞癌中ABCA1和SR-B1存在负相关(r=-0.452,P=0.003),Apo A I和SR-B1存在负相关(r=-1.000,P<0.01),ABCA1和Apo A I存在正相关(r=0.674,P<0.01);(3)ABCA1蛋白的表达与口腔鳞癌患者年龄相关,差异有统计学意义。结论:ABCA1蛋白的高表达可能参与了口腔鳞癌脂质代谢的失衡。展开更多
文摘目的探讨HDL脂质转运蛋白ATP结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)、载脂蛋白A1(apolipoprotein A1,ApoA1)和吸收蛋白B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)是否在Ⅰ型子宫内膜样癌(endometrial carcinoma,EC)中存在表达失衡。方法选取80例Ⅰ型EC和47例对照增生改变子宫内膜组织,采用免疫组化EnVision两步法检测ABCA1和ApoA1的表达;分析Ⅰ型EC中ABCA1、ApoA1与SR-B1、ER、PR蛋白表达的相关性及与临床病理特征的关系。结果(1)Ⅰ型EC中ABCA1阳性率为86.1%(62/72),低于对照增生改变子宫内膜组织(95.5%,42/44),差异有统计学意义(P<0.05);Ⅰ型EC组织中ApoA1阳性率为63.8%(44/69),高于对照增生改变子宫内膜组织(53.3%,23/43),差异无统计学意义(P>0.05);(2)在Ⅰ型EC中,ABCA1与SR-B1、ApoA1、ER之间呈负相关;ApoA1与PR之间呈正相关;(3)Ⅰ型EC中ABCA1和ApoA1蛋白表达与临床病理特征无明显相关性(P>0.05)。结论与对照增生改变子宫内膜组织相比,Ⅰ型EC中可能存在HDL转运蛋白ABCA1和HDL吸收蛋白SR-B1的表达失衡。
基金supported by the National Natural Science Foundation of China(No.81974494)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-070).
文摘Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and scalability.Of them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of action.Using chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against HCoV-OC43.Furthermore,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane fusion.Accordingly,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).
文摘目的观察尿毒症毒素硫酸吲哚酚(IS)是否促进巨噬泡沫细胞脂滴的蓄积,以及对细胞内B类1型清道夫受体(SR-B1)表达和核因子NF-κB活化的影响。方法体外佛波酯(PMA)诱导人源单核细胞系THP-1分化为巨噬细胞,加入氧化低密度脂蛋白(ox-LDL)培养促进巨噬细胞泡沫化,随后以不同浓度的IS干预巨噬泡沫细胞,油红O染色观察细胞内脂滴变化,实时PCR和Western blotting检测SR-B1 m RNA和蛋白表达的水平,ELISA法检测NF-κB活化情况;经NF-κB抑制剂四氢化吡咯二硫代氨基甲酸酯(PDTC)预处理后IS再干预,实时PCR检测巨噬泡沫细胞内SR-B1 m RNA表达的变化。结果与对照组(IS 0μmol/L)比较,IS干预后巨噬泡沫细胞内脂滴明显增加,随着IS浓度的升高,细胞内脂滴逐渐增加;IS干预后巨噬泡沫细胞的NF-κB活化程度增高,差异有统计学意义(P<0.05)。与对照组比较,细胞在不同浓度的IS(2.5、25、250μmol/L)处理下,SR-B1 m RNA和蛋白的表达下降,随着IS浓度的增加,SR-B1和蛋白逐渐减少,呈现浓度依赖性,差异有统计学意义(P<0.05)。PDTC预处理后SR-B1m RNA表达增加,差异有统计学意义(P<0.05)。结论 IS抑制SR-B1 m RNA和蛋白的表达,增加THP-1源性巨噬泡沫细胞胆固醇的蓄积,促进巨噬细胞泡沫化,从而促进动脉粥样硬化。NF-κB活化可能是IS抑制SR-B1 m RNA表达的可能机制之一。
文摘Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.
文摘目的 :越来越多的文献显示脂质代谢参与肿瘤的发生发展,但在口腔鳞癌的关系中尚未见报道,故本文拟通过检测脂质代谢转运相关蛋白ATP结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)和载脂蛋白A(apolipoprotein A-I,Apo A I)及脂质代谢吸收蛋白B类1型清道夫受体(Scavenger receptor class B type I,SR-B1)在口腔鳞癌组织中的差异性表达,探讨脂质转运蛋白和吸收蛋白是否在口腔鳞癌中存在失衡表达,及其与临床病理参数之间的关系及意义。方法:收集石河子大学医学院第一附属医院2004-2016年有完整临床病理资料的口腔鳞癌患者24例及正常口腔黏膜患者35例,制备组织芯片2张,应用免疫组织化学检测ABCA1,Apo A I和SR-B1的表达水平,并结合患者临床病理特征进行分析。结果:(1)ABCA1蛋白在口腔鳞癌(37.50%,9/24)中较正常鳞状上皮(0%,0/25)高表达,差异具有统计学意义(χ2=11.484,P=0.001);Apo A I蛋白在两者之间均高表达(100%,24/24),SR-B1蛋白在两者中均不表达或低表达(0%,0/18),差异均无统计学意义;(2)在口腔鳞癌中ABCA1和SR-B1存在负相关(r=-0.452,P=0.003),Apo A I和SR-B1存在负相关(r=-1.000,P<0.01),ABCA1和Apo A I存在正相关(r=0.674,P<0.01);(3)ABCA1蛋白的表达与口腔鳞癌患者年龄相关,差异有统计学意义。结论:ABCA1蛋白的高表达可能参与了口腔鳞癌脂质代谢的失衡。
