Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines’ levels are associated with the severity of CAD. We have recently repor...Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines’ levels are associated with the severity of CAD. We have recently reported on the association of resistin, a relatively novel cytokine with the pathogenesis of cardiovascular disease (CVD). Although the inflammatory cytokines’ impact on atherosclerosis is widely accepted, yet some controversy exists regarding the involvement of these factors in atherogenesis. The current review highlights the potential association of TNF-alpha, IL-6 and resistin SNPs (single nucleotide polymorphisms) with CAD. Molecular genetics data along with the intracellular signaling cascade mechanisms may have important clinical implications in the treatment of CAD.展开更多
目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑...目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑州大学第二附属医院门诊产检的孕10~13周孕妇,收集孕妇的年龄、身高、体质量、末次月经时间,检测孕早期总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、CTRP6水平,计算孕前体质量指数(body mass index,BMI)、基线BMI、产前BMI和胰岛素抵抗指数(亦称胰岛素抵抗的稳态模型评估,homeostatic model assessment of insulin resistance,HOMA-IR)。所有孕妇均于孕24~28周行75g口服葡萄糖耐量试验,根据试验结果分为GDM组和糖耐量正常(normal glucose tolerance,NGT)组。比较两组孕妇孕早期的临床资料及实验室指标,分析孕早期血清CTRP6与各指标的相关性及其与GDM的关系。结果共纳入孕妇213例,完整随访203例,其中52例孕妇被诊断为GDM,GDM发病率25.62%。GDM组孕妇的孕早期血清CTRP6、年龄、孕前BMI、基线BMI、产前BMI、TC、LDL、FPG、HbA1c、FINS、HOMA-IR均较NGT组升高,差异有统计学意义(P<0.05)。孕早期CTRP6与年龄、孕前BMI、基线BMI、产前BMI、TG、LDL、FPG、HbA1c、FINS、HOMA-IR呈正相关,与HDL呈负相关(P<0.05)。校正年龄、BMI、糖脂代谢指标及HOMA-IR后,孕早期CTRP6为GDM发病的独立影响因素。结论孕早期血清CTRP6升高与GDM相关,是GDM的独立危险因素。展开更多
目的:检测急性心肌梗死(acute myocardial infarction,AMI)患者血清C1q/肿瘤坏死因子相关蛋白-6(C1q/tumor necrosis factor related protein 6,CTRP6)表达水平与病情和预后的相关性。方法:选取河南科技大学第一附属医院2021年1月至2022...目的:检测急性心肌梗死(acute myocardial infarction,AMI)患者血清C1q/肿瘤坏死因子相关蛋白-6(C1q/tumor necrosis factor related protein 6,CTRP6)表达水平与病情和预后的相关性。方法:选取河南科技大学第一附属医院2021年1月至2022年1月收治的144例AMI患者为研究对象,检测血清CTRP6的表达含量,并分析及评估CTRP6表达与AMI患者的临床特征和MACE的相关性。结果:AMI组患者外周血CTRP6含量为119.32(78.4,165.8)μg/L,显著低于对照组的372.3(303.6,454.2)μg/L(P<0.05);与高表达组比较,低表达组患者血清CK-MB、NT-proBNP、Gensini评分和SYNTAX II评分明显升高(P<0.05),而LVEF明显降低(P<0.05);此外,CTRP6低表达组患者MACE的累积发生率显著高于CTRP6高表达组(P<0.05);CTRP6预测AMI患者发生MACE事件的ROC曲线下面积为0.851。当最佳截断值为当88.423μg/L时,此时的敏感性为75.3%,特异性87.4%。结论:AMI患者血清CTRP6的表达明显降低,且CTRP6低表达可能是识别AMI高危患者和优化治疗策略的重要靶点。展开更多
Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clini...Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.展开更多
Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether ...Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase （MAPK）-activated protein kinase 2 （MK2） and HuR participate in the tumor necrosis factor （TNF）-induced expression of interleukin-6 （IL-6）. Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.展开更多
文摘Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines’ levels are associated with the severity of CAD. We have recently reported on the association of resistin, a relatively novel cytokine with the pathogenesis of cardiovascular disease (CVD). Although the inflammatory cytokines’ impact on atherosclerosis is widely accepted, yet some controversy exists regarding the involvement of these factors in atherogenesis. The current review highlights the potential association of TNF-alpha, IL-6 and resistin SNPs (single nucleotide polymorphisms) with CAD. Molecular genetics data along with the intracellular signaling cascade mechanisms may have important clinical implications in the treatment of CAD.
文摘目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑州大学第二附属医院门诊产检的孕10~13周孕妇,收集孕妇的年龄、身高、体质量、末次月经时间,检测孕早期总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、CTRP6水平,计算孕前体质量指数(body mass index,BMI)、基线BMI、产前BMI和胰岛素抵抗指数(亦称胰岛素抵抗的稳态模型评估,homeostatic model assessment of insulin resistance,HOMA-IR)。所有孕妇均于孕24~28周行75g口服葡萄糖耐量试验,根据试验结果分为GDM组和糖耐量正常(normal glucose tolerance,NGT)组。比较两组孕妇孕早期的临床资料及实验室指标,分析孕早期血清CTRP6与各指标的相关性及其与GDM的关系。结果共纳入孕妇213例,完整随访203例,其中52例孕妇被诊断为GDM,GDM发病率25.62%。GDM组孕妇的孕早期血清CTRP6、年龄、孕前BMI、基线BMI、产前BMI、TC、LDL、FPG、HbA1c、FINS、HOMA-IR均较NGT组升高,差异有统计学意义(P<0.05)。孕早期CTRP6与年龄、孕前BMI、基线BMI、产前BMI、TG、LDL、FPG、HbA1c、FINS、HOMA-IR呈正相关,与HDL呈负相关(P<0.05)。校正年龄、BMI、糖脂代谢指标及HOMA-IR后,孕早期CTRP6为GDM发病的独立影响因素。结论孕早期血清CTRP6升高与GDM相关,是GDM的独立危险因素。
文摘目的:检测急性心肌梗死(acute myocardial infarction,AMI)患者血清C1q/肿瘤坏死因子相关蛋白-6(C1q/tumor necrosis factor related protein 6,CTRP6)表达水平与病情和预后的相关性。方法:选取河南科技大学第一附属医院2021年1月至2022年1月收治的144例AMI患者为研究对象,检测血清CTRP6的表达含量,并分析及评估CTRP6表达与AMI患者的临床特征和MACE的相关性。结果:AMI组患者外周血CTRP6含量为119.32(78.4,165.8)μg/L,显著低于对照组的372.3(303.6,454.2)μg/L(P<0.05);与高表达组比较,低表达组患者血清CK-MB、NT-proBNP、Gensini评分和SYNTAX II评分明显升高(P<0.05),而LVEF明显降低(P<0.05);此外,CTRP6低表达组患者MACE的累积发生率显著高于CTRP6高表达组(P<0.05);CTRP6预测AMI患者发生MACE事件的ROC曲线下面积为0.851。当最佳截断值为当88.423μg/L时,此时的敏感性为75.3%,特异性87.4%。结论:AMI患者血清CTRP6的表达明显降低,且CTRP6低表达可能是识别AMI高危患者和优化治疗策略的重要靶点。
文摘Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.
基金This study was supported by the National Natural Science Foundation of China （No. 81270138）, the Natural Science Foundation of Jiangsu Province （No. BK2011657 and No. BK20130402）, and the Medical Technology Innovation Foundation of Nanjing Military Command （No. CWS 12J008）.
文摘Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase （MAPK）-activated protein kinase 2 （MK2） and HuR participate in the tumor necrosis factor （TNF）-induced expression of interleukin-6 （IL-6）. Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.
