目的系统评价ABCB1基因C3435T多态性对他汀类药物降脂疗效的影响。方法计算机检索PubMed、Web of Science、the Cochrane Library、中国知网和维普网,收集患者使用他汀类药物的队列研究,检索时限为建库至2023年11月1日。筛选文献、提取...目的系统评价ABCB1基因C3435T多态性对他汀类药物降脂疗效的影响。方法计算机检索PubMed、Web of Science、the Cochrane Library、中国知网和维普网,收集患者使用他汀类药物的队列研究,检索时限为建库至2023年11月1日。筛选文献、提取数据、评价质量后,采用RevMan 5.4软件进行Meta分析。结果共纳入11项文献,共计1575例患者。Meta分析结果显示,显性遗传模型下,CT+TT型患者的低密度脂蛋白胆固醇(LDL-C)降低程度[MD=-1.87,95%CI(-3.62,-0.13),P=0.04]、总胆固醇(TC)降低程度[MD=-1.42,95%CI(-2.80,-0.04),P=0.04]均显著高于CC型;CT+TT型患者的高密度脂蛋白胆固醇(HDL-C)升高程度[MD=-0.65,95%CI(-2.48,1.18),P=0.49]、甘油三酯(TG)降低程度[MD=-0.05,95%CI(-2.94,2.84),P=0.97]与CC型比较,差异均无统计学意义。隐性遗传模型下,TT型患者的TC降低程度[MD=2.26,95%CI(0.97,3.56),P=0.0006]、HDL-C升高程度[MD=2.38,95%CI(0.42,4.35),P=0.02]均显著高于CC+CT型;CC+CT型患者的LDL-C降低程度[MD=1.53,95%CI(-0.10,3.15),P=0.07]、TG降低程度[MD=0.06,95%CI(-2.98,3.10),P=0.97]与TT型比较,差异均无统计学意义。加性遗传模型下,TT型患者的TC降低程度[MD=2.98,95%CI(1.27,4.69),P=0.0006]、LDL-C降低程度[MD=2.84,95%CI(0.67,5.01),P=0.01]均显著高于CC型;TT型患者的HDL-C升高程度[MD=2.40,95%CI(-0.17,4.97),P=0.07]、TG降低程度[MD=0.97,95%CI(-2.93,4.87),P=0.63]与CC型比较,差异均无统计学意义。结论血脂异常患者接受他汀类药物治疗时,LDL-C、TC降低效果可能与ABCB1基因C3435T杂合和纯合突变有关,即与CC型患者比较,CT或TT型患者的LDL-C、TC降低效果可能更明显;HDL-C升高效果可能与纯合突变有关,即与CC+CT型患者比较,TT型患者的HDL-C升高效果可能更明显;而TG变化可能与ABCB1基因C3435T多态性无关。展开更多
The identification of functional midgut receptors for pesticidal proteins produced by Bacillus thuringiensis(Bt)is critical for deciphering the molecular mechanism of Bt resistance in insects.Reduced expression of the...The identification of functional midgut receptors for pesticidal proteins produced by Bacillus thuringiensis(Bt)is critical for deciphering the molecular mechanism of Bt resistance in insects.Reduced expression of the PxABCB1 gene was previously found to be associated with Cry1Ac resistance in the diamondback moth,Plutella xylostella(L.).To directly validate the potential receptor role of PxABCB1 and its contribution to Bt Cry1Ac toxicity in P.xylostella,we used CRISPR/Cas9 to generate a homozygous knockout ABCB1KO strain with a 5-bp deletion in exon 3 of its gene.The ABCB1KO strain exhibited a 63-fold resistance to Cry1Ac toxin compared to the parental DBM1Ac-S strain.Intriguingly,the ABCB1KO strain also exhibited significant increases in susceptibility to abamectin and emamectin benzoate.No changes in susceptibility to various other Bt Cry proteins or synthetic insecticides were observed.The knockout strain exhibited no significant fitness costs.Overall,our study indicates that PxABCB1 can protect the insect against avermectin insecticides on one hand,while on the other hand it facilitates the toxic effect of the Bt Cry1Ac toxin.The results of this study will help to inform integrated pest management approaches against this destructive pest.展开更多
目的:在小鼠胚胎成纤维细胞(mouse embryonic fibroblast,MEF)中探讨动力相关蛋白1(dynamin related protein 1,Drp1)基因缺失激活线粒体未折叠蛋白反应(mitochondrial unfolded protein reaction,mtUPR)的分子机制。方法:采用不同浓度(...目的:在小鼠胚胎成纤维细胞(mouse embryonic fibroblast,MEF)中探讨动力相关蛋白1(dynamin related protein 1,Drp1)基因缺失激活线粒体未折叠蛋白反应(mitochondrial unfolded protein reaction,mtUPR)的分子机制。方法:采用不同浓度(0、2.5、5.0、10.0mmol/L)3-硝基丙酸(3-nitropropionic acid,3-NP)处理Drp1敲除或敲低的MEF细胞、Drp1抑制剂Mdivi-1或选择性阻断Drp1与下游蛋白相互作用的小分子多肽P110处理的MEF细胞以及相应对照,随后进行Western blot检测CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)、ATP结合盒B亚家族成员10(ATP binding cassette subfamily B member 10,ABCB10)、Lon肽酶1(Lon peptidase 1,LONP1)以及热休克蛋白60(heat shock protein 60,Hsp60)的表达。RT-qPCR检测Drp1敲低或Mdivi-1处理后MEF细胞的ABCB10的mRNA水平。同时敲低Drp1和ABCB10,Western blot检测CHOP蛋白的表达,试剂盒检测培养液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量,流式细胞术检测线粒体活性氧和线粒体膜电位水平。结果:3-NP处理后,Drp1敲除或敲低的MEF细胞以及Mdivi-1或P110处理的MEF细胞中CHOP表达呈现倍数上调。Drp1敲除或敲低的MEF细胞以及Mdivi-1或P110处理的MEF细胞中ABCB10蛋白表达上调,mtUPR效应蛋白LONP1和Hsp60表达上调。Drp1敲低的MEF细胞和Mdivi-1处理的MEF细胞中ABCB10 mRNA水平上调。同时敲低Drp1和ABCB10后,与Drp1敲低组相比,CHOP表达下调,LDH含量降低,线粒体活性氧水平降低,线粒体膜电位水平增加。结论:在MEF细胞中,Drp1表达下调可引起ABCB10表达量增加,导致mtUPR关键蛋白CHOP、LONP1和Hsp60蛋白表达上调,进而激活mtUPR。展开更多
基金the Laboratory of Lingnan Modern Agriculture Project,China(NT2021003)National Natural Science Foundation of China(32022074,32221004 and 32172458)Beijing Key Laboratory for Pest Control and Sustainable Cultivation of Vegetables,Chinese Academy of Agricultural Sciences,and the Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-CSCB-202303)。
文摘The identification of functional midgut receptors for pesticidal proteins produced by Bacillus thuringiensis(Bt)is critical for deciphering the molecular mechanism of Bt resistance in insects.Reduced expression of the PxABCB1 gene was previously found to be associated with Cry1Ac resistance in the diamondback moth,Plutella xylostella(L.).To directly validate the potential receptor role of PxABCB1 and its contribution to Bt Cry1Ac toxicity in P.xylostella,we used CRISPR/Cas9 to generate a homozygous knockout ABCB1KO strain with a 5-bp deletion in exon 3 of its gene.The ABCB1KO strain exhibited a 63-fold resistance to Cry1Ac toxin compared to the parental DBM1Ac-S strain.Intriguingly,the ABCB1KO strain also exhibited significant increases in susceptibility to abamectin and emamectin benzoate.No changes in susceptibility to various other Bt Cry proteins or synthetic insecticides were observed.The knockout strain exhibited no significant fitness costs.Overall,our study indicates that PxABCB1 can protect the insect against avermectin insecticides on one hand,while on the other hand it facilitates the toxic effect of the Bt Cry1Ac toxin.The results of this study will help to inform integrated pest management approaches against this destructive pest.
文摘目的:在小鼠胚胎成纤维细胞(mouse embryonic fibroblast,MEF)中探讨动力相关蛋白1(dynamin related protein 1,Drp1)基因缺失激活线粒体未折叠蛋白反应(mitochondrial unfolded protein reaction,mtUPR)的分子机制。方法:采用不同浓度(0、2.5、5.0、10.0mmol/L)3-硝基丙酸(3-nitropropionic acid,3-NP)处理Drp1敲除或敲低的MEF细胞、Drp1抑制剂Mdivi-1或选择性阻断Drp1与下游蛋白相互作用的小分子多肽P110处理的MEF细胞以及相应对照,随后进行Western blot检测CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)、ATP结合盒B亚家族成员10(ATP binding cassette subfamily B member 10,ABCB10)、Lon肽酶1(Lon peptidase 1,LONP1)以及热休克蛋白60(heat shock protein 60,Hsp60)的表达。RT-qPCR检测Drp1敲低或Mdivi-1处理后MEF细胞的ABCB10的mRNA水平。同时敲低Drp1和ABCB10,Western blot检测CHOP蛋白的表达,试剂盒检测培养液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量,流式细胞术检测线粒体活性氧和线粒体膜电位水平。结果:3-NP处理后,Drp1敲除或敲低的MEF细胞以及Mdivi-1或P110处理的MEF细胞中CHOP表达呈现倍数上调。Drp1敲除或敲低的MEF细胞以及Mdivi-1或P110处理的MEF细胞中ABCB10蛋白表达上调,mtUPR效应蛋白LONP1和Hsp60表达上调。Drp1敲低的MEF细胞和Mdivi-1处理的MEF细胞中ABCB10 mRNA水平上调。同时敲低Drp1和ABCB10后,与Drp1敲低组相比,CHOP表达下调,LDH含量降低,线粒体活性氧水平降低,线粒体膜电位水平增加。结论:在MEF细胞中,Drp1表达下调可引起ABCB10表达量增加,导致mtUPR关键蛋白CHOP、LONP1和Hsp60蛋白表达上调,进而激活mtUPR。
