目的探讨血清铁调节蛋白2(iron regulatory protein 2,IRP2)、细胞周期蛋白依赖性激酶抑制剂1A(cyclin-dependent kinase inhibitor 1A,CDKN1A)、人Ⅱ型肺泡细胞表面抗原(human alveolar typeⅡcell surface antigen,KL-6)水平与慢性阻...目的探讨血清铁调节蛋白2(iron regulatory protein 2,IRP2)、细胞周期蛋白依赖性激酶抑制剂1A(cyclin-dependent kinase inhibitor 1A,CDKN1A)、人Ⅱ型肺泡细胞表面抗原(human alveolar typeⅡcell surface antigen,KL-6)水平与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者肺功能及临床预后的相关性。方法回顾性选取136例COPD患者为观察组,选取同期健康体检者136例为对照组。比较两组及不同预后患者血清IRP2、CDKN1A、KL6水平,并比较两组肺功能指标[第1秒用力呼气容积(forced expiratory volume in the first second,FEV_(1))与用力肺活量(forced vital capacity,FVC)的比值(FEV_(1)/FVC)、FEV_(1)占预计值百分比(forced expiratory volume in the first second as a percentage of the predicted value,FEV_(1)%_(pred))]。分析血清IRP2、CDKN1A、KL-6水平与FEV_(1)%_(pred)、FEV_(1)/FVC及预后的相关性,并分析各血清指标联合检测的预测价值。结果观察组血清IRP2、CDKN1A、KL-6水平明显高于对照组(均P<0.01);观察组FEV_(1)%_(pred)、FEV_(1)/FVC明显低于对照组(均P<0.01)。预后不良患者血清IRP2、CDKN1A、KL-6水平明显高于预后良好患者(均P<0.01)。血清IRP2、CDKN1A、KL-6水平与FEV_(1)%_(pred)、FEV_(1)/FVC呈负相关,与患者预后呈正相关(均P<0.01)。血清IRP2、CDKN1A、KL-6水平联合预测COPD患者预后不良的AUC值为0.937,约登指数为0.775,敏感性、特异性分别为94.12%、83.33%,且差异有统计学意义(均P<0.01)。结论血清IRP2、CDKN1A、KL-6水平随着COPD患者肺功能及临床预后的不同而改变,且存在较强相关性。各指标联合检测可为临床预测患者预后提供一定参考。展开更多
Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential r...Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.展开更多
文摘目的探讨血清铁调节蛋白2(iron regulatory protein 2,IRP2)、细胞周期蛋白依赖性激酶抑制剂1A(cyclin-dependent kinase inhibitor 1A,CDKN1A)、人Ⅱ型肺泡细胞表面抗原(human alveolar typeⅡcell surface antigen,KL-6)水平与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者肺功能及临床预后的相关性。方法回顾性选取136例COPD患者为观察组,选取同期健康体检者136例为对照组。比较两组及不同预后患者血清IRP2、CDKN1A、KL6水平,并比较两组肺功能指标[第1秒用力呼气容积(forced expiratory volume in the first second,FEV_(1))与用力肺活量(forced vital capacity,FVC)的比值(FEV_(1)/FVC)、FEV_(1)占预计值百分比(forced expiratory volume in the first second as a percentage of the predicted value,FEV_(1)%_(pred))]。分析血清IRP2、CDKN1A、KL-6水平与FEV_(1)%_(pred)、FEV_(1)/FVC及预后的相关性,并分析各血清指标联合检测的预测价值。结果观察组血清IRP2、CDKN1A、KL-6水平明显高于对照组(均P<0.01);观察组FEV_(1)%_(pred)、FEV_(1)/FVC明显低于对照组(均P<0.01)。预后不良患者血清IRP2、CDKN1A、KL-6水平明显高于预后良好患者(均P<0.01)。血清IRP2、CDKN1A、KL-6水平与FEV_(1)%_(pred)、FEV_(1)/FVC呈负相关,与患者预后呈正相关(均P<0.01)。血清IRP2、CDKN1A、KL-6水平联合预测COPD患者预后不良的AUC值为0.937,约登指数为0.775,敏感性、特异性分别为94.12%、83.33%,且差异有统计学意义(均P<0.01)。结论血清IRP2、CDKN1A、KL-6水平随着COPD患者肺功能及临床预后的不同而改变,且存在较强相关性。各指标联合检测可为临床预测患者预后提供一定参考。
基金Beijing Natural Science Foundation(Grant No.2171001)the National Natural Science Foundation of China(Grant No.31571403)the National High-tech R&D Program of China(Grant No.2014AA021103)
文摘Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.
