Objectives:This study is to investigate the effects of new anti-tumor formular(NAF)on expression of PCNA,P21 ras and NF-KB P65 in liver precancerous lesions of HBV large envelope transgenic mice injected by aflatoxin ...Objectives:This study is to investigate the effects of new anti-tumor formular(NAF)on expression of PCNA,P21 ras and NF-KB P65 in liver precancerous lesions of HBV large envelope transgenic mice injected by aflatoxin B1(AFB1).Methods:The precancerous HBV large envelope transgenic mouse injected by AFB1 liver model was used.Mice was given water,NAF concentrated water solution throughout the whole experiment(48 weeks).PCNA,P21 ras and NF-KB P65 protein expression were detected by immunohistochemical method.Results: PCNA,P21 ras and NF-KB P65 expressions were significantly inhibited by NAF treatment.Conclusion NAF inhibited PCNA,P21 ras and NF-KB P65 protein expressions,therefore,NAF could show obvious effects on protecting against synergistic hepatoearcinogenesis of HBV and AFB1.展开更多
目的探讨沉默信息调节因子1(SIRT1)在异烟肼致人肝细胞损伤中的作用。方法培养人正常肝细胞HL-7702,实验分为6组:空白对照组、异烟肼组、异烟肼+SIRT1激动剂组、SIRT1激动剂对照组、异烟肼+SIRT1抑制剂组、SIRT1抑制剂对照组。取各组细...目的探讨沉默信息调节因子1(SIRT1)在异烟肼致人肝细胞损伤中的作用。方法培养人正常肝细胞HL-7702,实验分为6组:空白对照组、异烟肼组、异烟肼+SIRT1激动剂组、SIRT1激动剂对照组、异烟肼+SIRT1抑制剂组、SIRT1抑制剂对照组。取各组细胞上清液测定丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)含量;实时荧光定量聚合酶链反应(q RT-PCR)检测肝细胞SIRT1、NF-k B p65 mRNA表达水平;酶联免疫吸附法(ELISA)检测SIRT1、核转录因子k B(NF-k B p65)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)蛋白表达水平。结果与空白对照组比较,异烟肼组细胞SIRT1的mRNA和蛋白表达下降(P<0.05),其下游靶基因NF-k B p65的mRNA和蛋白表达升高(P<0.05),炎症因子IL-6、TNF-α蛋白表达水平升高(P<0.05)。加入SIRT1激动剂可减轻异烟肼引起的炎症反应,加入SIRT1抑制剂可使NF-k B p65、IL-6、TNF-α表达水平进一步升高从而加重细胞的炎症损伤。结论异烟肼诱导肝细胞损伤过程中,降低SIRT1水平,增加炎症因子的表达。SIRT1的激活可以通过降低NF-k B p65表达进而减轻肝细胞损伤的发生。展开更多
Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in ...Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.展开更多
文摘Objectives:This study is to investigate the effects of new anti-tumor formular(NAF)on expression of PCNA,P21 ras and NF-KB P65 in liver precancerous lesions of HBV large envelope transgenic mice injected by aflatoxin B1(AFB1).Methods:The precancerous HBV large envelope transgenic mouse injected by AFB1 liver model was used.Mice was given water,NAF concentrated water solution throughout the whole experiment(48 weeks).PCNA,P21 ras and NF-KB P65 protein expression were detected by immunohistochemical method.Results: PCNA,P21 ras and NF-KB P65 expressions were significantly inhibited by NAF treatment.Conclusion NAF inhibited PCNA,P21 ras and NF-KB P65 protein expressions,therefore,NAF could show obvious effects on protecting against synergistic hepatoearcinogenesis of HBV and AFB1.
文摘目的探讨沉默信息调节因子1(SIRT1)在异烟肼致人肝细胞损伤中的作用。方法培养人正常肝细胞HL-7702,实验分为6组:空白对照组、异烟肼组、异烟肼+SIRT1激动剂组、SIRT1激动剂对照组、异烟肼+SIRT1抑制剂组、SIRT1抑制剂对照组。取各组细胞上清液测定丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)含量;实时荧光定量聚合酶链反应(q RT-PCR)检测肝细胞SIRT1、NF-k B p65 mRNA表达水平;酶联免疫吸附法(ELISA)检测SIRT1、核转录因子k B(NF-k B p65)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)蛋白表达水平。结果与空白对照组比较,异烟肼组细胞SIRT1的mRNA和蛋白表达下降(P<0.05),其下游靶基因NF-k B p65的mRNA和蛋白表达升高(P<0.05),炎症因子IL-6、TNF-α蛋白表达水平升高(P<0.05)。加入SIRT1激动剂可减轻异烟肼引起的炎症反应,加入SIRT1抑制剂可使NF-k B p65、IL-6、TNF-α表达水平进一步升高从而加重细胞的炎症损伤。结论异烟肼诱导肝细胞损伤过程中,降低SIRT1水平,增加炎症因子的表达。SIRT1的激活可以通过降低NF-k B p65表达进而减轻肝细胞损伤的发生。
基金supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。
文摘Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.
