[目的]本试验旨在探究PPARGC1A/NRF1/TFAM通路核心基因在湖羊性成熟前后的表达变化。[方法]选取体况良好和系谱清楚的雄性湖羊18只(3和9月龄,各9只),颈静脉采血后进行阉割处理。ELISA检测血样中睾酮(T)、瘦素、胰岛素及胰岛素样生长因子...[目的]本试验旨在探究PPARGC1A/NRF1/TFAM通路核心基因在湖羊性成熟前后的表达变化。[方法]选取体况良好和系谱清楚的雄性湖羊18只(3和9月龄,各9只),颈静脉采血后进行阉割处理。ELISA检测血样中睾酮(T)、瘦素、胰岛素及胰岛素样生长因子Ⅰ(IGF-Ⅰ)的浓度;免疫组化法检测睾丸组织中PPARGC1A/NRF1/TFAM通路相关蛋白的表达定位; RT-qPCR和Western blot检测睾丸组织中PPARGC1A/NRF1/TFAM通路相关基因与蛋白的表达变化。[结果]与3月龄湖羊相比,9月龄湖羊外周血中T、瘦素、胰岛素及IGF-Ⅰ的浓度显著升高(P<0.05)。免疫组化法检测发现PPARGC1A、NRF1和TFAM蛋白在3月龄和9月龄湖羊睾丸组织的多种细胞内均呈时空特异性表达。此外,与3月龄湖羊相比,9月龄湖羊睾丸组织中PPARGC1A、NRF1和TFAM m RNA和蛋白表达水平均显著升高(P<0.05)。[结论]PPARGC1A/RNF1/TFAM通路相关基因可能与湖羊睾丸发育和性成熟过程密切相关。展开更多
BACKGROUND The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease(NAFLD)requires further confirmation.In addition,it is still unknown whether PPARGC1A rs8192678 is associated with hepatic hist...BACKGROUND The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease(NAFLD)requires further confirmation.In addition,it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population.AIM To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis(NASH),and whether this polymorphism is associated with hepatic histological features.METHODS Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population.The SAF(steatosis,activity,and fibrosis)scoring system was used for hepatic histopathological evaluation.The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 were genotyped.The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction.RESULTS Thirty-seven patients with NAFLD had NASH,of which 12 were nonobese.The PPARGC1A rs8192678 risk A allele(carrying GA and AA genotypes)had the lowest P value in the dominant model;the odds ratio(OR)for NAFLD was 2.321[95%confidence interval(CI):1.121-4.806].After adjusting for age,sex,and the PNPLA3 rs738409 risk G allele,the PPARGC1A rs8192678 A allele was a risk factor for NAFLD(OR 2.202,95%CI:1.030-4.705,P=0.042).The genetic analysis showed that patients with NAFLD,moderate-to-severe steatosis(S2-3),and Activity 2-4(A≥2)were more likely to carry A in PPARGC1A rs8192678(OR 5.000,95%CI:1.343-18.620,P=0.012;and OR 4.071,95%CI:1.076-15.402,P=0.031).The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3,A≥2,and NASH(OR 6.190,95%CI:1.508-25.410,P=0.011;OR 4.506,95%CI 1.070-18.978,P=0.040;and OR 6.337,95%CI:1.135-35.392,P=0.035,respectively)after adjusting for age,sex,body mass index,and PNPLA3 rs738409 risk G allele.The results also showed that this polymorphism was associated with nonobese NASH(OR 22.000,95%CI:1.540-314.292,P=0.021).The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele(P=0.014).CONCLUSION The PPARGC1A rs8192678 risk A allele is associated with NAFLD,and with S2-3,A≥2 and NASH in NAFLD patients,independent of PNPLA3 rs738409,and may be associated with nonobese NASH.展开更多
Metastasis is the major cause of treatment failure in cancer patients and of cancer?related deaths.This editorial discusses how cancer metastasis may be better perceived and controlled.Based on big?data analyses,a col...Metastasis is the major cause of treatment failure in cancer patients and of cancer?related deaths.This editorial discusses how cancer metastasis may be better perceived and controlled.Based on big?data analyses,a collection of150 important pro?metastatic genes was studied.Using The Cancer Genome Atlas datasets to re?analyze the effect of some previously reported metastatic genes—e.g.,JAM2,PPARGC1A,SIK2,and TRAF6—on overall survival of patients with renal and liver cancers,we found that these genes are actually protective factors for patients with cancer.The role of epithelial–mesenchymal transition(EMT)in single?cell metastasis has been well?documented.However,in metastasis caused by cancer cell clusters,EMT may not be necessary.A novel role of epithelial marker E?cadherin,as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling,has been found.This editorial also discusses the obstacles for developing anti?metastatic drugs,including the lack of high?throughput technologies for identifying metastasis inhibitors,less application of animal models in the pre?clinical evaluation of the leading com?pounds,and the need for adjustments in clinical trial design to better reflect the anti?metastatic efficacy of new drugs.We are confident that by developing more effective high?throughput technologies to identify metastasis inhibitors,we can better predict,prevent,and treat cancer metastasis.展开更多
文摘[目的]本试验旨在探究PPARGC1A/NRF1/TFAM通路核心基因在湖羊性成熟前后的表达变化。[方法]选取体况良好和系谱清楚的雄性湖羊18只(3和9月龄,各9只),颈静脉采血后进行阉割处理。ELISA检测血样中睾酮(T)、瘦素、胰岛素及胰岛素样生长因子Ⅰ(IGF-Ⅰ)的浓度;免疫组化法检测睾丸组织中PPARGC1A/NRF1/TFAM通路相关蛋白的表达定位; RT-qPCR和Western blot检测睾丸组织中PPARGC1A/NRF1/TFAM通路相关基因与蛋白的表达变化。[结果]与3月龄湖羊相比,9月龄湖羊外周血中T、瘦素、胰岛素及IGF-Ⅰ的浓度显著升高(P<0.05)。免疫组化法检测发现PPARGC1A、NRF1和TFAM蛋白在3月龄和9月龄湖羊睾丸组织的多种细胞内均呈时空特异性表达。此外,与3月龄湖羊相比,9月龄湖羊睾丸组织中PPARGC1A、NRF1和TFAM m RNA和蛋白表达水平均显著升高(P<0.05)。[结论]PPARGC1A/RNF1/TFAM通路相关基因可能与湖羊睾丸发育和性成熟过程密切相关。
基金Supported by National Key R&D Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81700503,No.81873565,and No.81470840+1 种基金WBE Liver Fibrosis Foundation,No.CFHPC2020061Hospital Funded Clinical Research,Clinical Research Unit,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04.
文摘BACKGROUND The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease(NAFLD)requires further confirmation.In addition,it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population.AIM To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis(NASH),and whether this polymorphism is associated with hepatic histological features.METHODS Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population.The SAF(steatosis,activity,and fibrosis)scoring system was used for hepatic histopathological evaluation.The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 were genotyped.The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction.RESULTS Thirty-seven patients with NAFLD had NASH,of which 12 were nonobese.The PPARGC1A rs8192678 risk A allele(carrying GA and AA genotypes)had the lowest P value in the dominant model;the odds ratio(OR)for NAFLD was 2.321[95%confidence interval(CI):1.121-4.806].After adjusting for age,sex,and the PNPLA3 rs738409 risk G allele,the PPARGC1A rs8192678 A allele was a risk factor for NAFLD(OR 2.202,95%CI:1.030-4.705,P=0.042).The genetic analysis showed that patients with NAFLD,moderate-to-severe steatosis(S2-3),and Activity 2-4(A≥2)were more likely to carry A in PPARGC1A rs8192678(OR 5.000,95%CI:1.343-18.620,P=0.012;and OR 4.071,95%CI:1.076-15.402,P=0.031).The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3,A≥2,and NASH(OR 6.190,95%CI:1.508-25.410,P=0.011;OR 4.506,95%CI 1.070-18.978,P=0.040;and OR 6.337,95%CI:1.135-35.392,P=0.035,respectively)after adjusting for age,sex,body mass index,and PNPLA3 rs738409 risk G allele.The results also showed that this polymorphism was associated with nonobese NASH(OR 22.000,95%CI:1.540-314.292,P=0.021).The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele(P=0.014).CONCLUSION The PPARGC1A rs8192678 risk A allele is associated with NAFLD,and with S2-3,A≥2 and NASH in NAFLD patients,independent of PNPLA3 rs738409,and may be associated with nonobese NASH.
文摘Metastasis is the major cause of treatment failure in cancer patients and of cancer?related deaths.This editorial discusses how cancer metastasis may be better perceived and controlled.Based on big?data analyses,a collection of150 important pro?metastatic genes was studied.Using The Cancer Genome Atlas datasets to re?analyze the effect of some previously reported metastatic genes—e.g.,JAM2,PPARGC1A,SIK2,and TRAF6—on overall survival of patients with renal and liver cancers,we found that these genes are actually protective factors for patients with cancer.The role of epithelial–mesenchymal transition(EMT)in single?cell metastasis has been well?documented.However,in metastasis caused by cancer cell clusters,EMT may not be necessary.A novel role of epithelial marker E?cadherin,as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling,has been found.This editorial also discusses the obstacles for developing anti?metastatic drugs,including the lack of high?throughput technologies for identifying metastasis inhibitors,less application of animal models in the pre?clinical evaluation of the leading com?pounds,and the need for adjustments in clinical trial design to better reflect the anti?metastatic efficacy of new drugs.We are confident that by developing more effective high?throughput technologies to identify metastasis inhibitors,we can better predict,prevent,and treat cancer metastasis.
