Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential a...Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.展开更多
Objective: To study the effects of nuclear factor-κB(NF-κB) activation and tumor necrosis factor-α(TNF-α) expression on heart failure after myocardial infarction in rats. Methods: Male Wistar rats were divided in...Objective: To study the effects of nuclear factor-κB(NF-κB) activation and tumor necrosis factor-α(TNF-α) expression on heart failure after myocardial infarction in rats. Methods: Male Wistar rats were divided into the sham operation(SO) group and myocardial infarction(MI) group. The left anterior descending branch of the left coronary artery of the rats in MI group was ligated with a suture to induce MI. Sham operation was done in those of the SO group. All the rats were killed in the 4~ th,8~ th and 12~ th week after the arterial ligation respectively. The hemodynamic parameters and the wet weight of the right and left ventricles were recorded. The protein expression of TNF-α and the activity of NF-κB of the non-infarcted myocardium were determined with Western blot and electrophoretic motility shift assay(EMSA) respectively.Results: Significant lower mean arterial pressure(MAP) and maximal ascending and descending velocity of left ventricular pressure(+dp/dt max) and significant higher left ventricular end-diastolic pressure(LVEDP) were found in the rats of the MI group than in those of the SO group(P<0.05).Left ventricular relative weight(LVRW) and right ventricular relative weight(RVRW) were higher in the MI group than in the SO group(P<0.05) with an exception that LVRW showed no significant difference between the MI and SO groups in the 12~ th week after arterial ligation. The expression of TNF-α and the activity of NF-κB were increased in the non-infarcted myocardium after the arterial ligation. Conclusion: Overexpression of TNF-α and significant increase of the activity of NF-κB play an important role in the postinfarctional ventricular remodeling and progression of heart failure.展开更多
AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor α (TNF-α) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV)...AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor α (TNF-α) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).METHODS: Serum NTproBNP and TNF-α levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls. RESULTS: Cryoglobulinemic patients showed signifi cantly higher mean NTproBNP and TNF-α levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (χ2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (χ2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as thepatients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (χ2, P = 0.08).CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-α in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.展开更多
Objective: To investigate the intervention effect of Jianxin Decoction (健心汤, JXD) on the cytokine level in serum of patients with congestive heart failure (CHF). Methods; Sixty-six patients with CHF were randomly d...Objective: To investigate the intervention effect of Jianxin Decoction (健心汤, JXD) on the cytokine level in serum of patients with congestive heart failure (CHF). Methods; Sixty-six patients with CHF were randomly divided into the control group (n = 33) and the trial group (n = 33). The control group received conventional treatment, and the trial group was treated with conventional therapy plus JXD for 4 weeks. Before and after treatment, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitrogen monoxide (NO) in serum and cardiac function were determined. Results: After treatment, the levels of TNF-α, IL-6 and NO were significantly lower than those before treatment (P<0.05, or P<0.01) in the two groups, and the lowering degree of the indices in the trial group was more significantly reduced than that in the control group (P<0.05). And cardiac functions in both groups were improved significantly (P<0.05, or P< 0.01). Conclusion: JXD could prevent and reverse ventricular remodeling so as to ameliorate cardiac function through regulating the levels of cytokines.展开更多
OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of def...OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response.展开更多
目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130...目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130例老年慢性心力衰竭患者作为研究对象,根据是否于院内发生肺部感染分为感染组(32例)和未感染组(98例)。对TNIP1基因的两个SNP位点rs6889239(T>C)、rs17728338(A>G)进行基因分型,并检测外周血TNIP1基因的mRNA表达水平。结果TNIP1基因rs6889239位点在感染组和非感染组之间的基因型分布以及等位基因频率的差异均无统计学意义(P>0.05);两组的rs17728338位点AA、AG、GG基因型分布比较差异有统计学意义(P<0.05),且感染组等位基因G的频率显著高于未感染组(P<0.05)。相较于未感染组,感染组患者的外周血TNIP1基因mRNA表达水平显著增加,差异有统计学意义(P<0.001)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析结果显示外周血TNIP1基因表达水平预测慢性心力衰竭患者发生肺部感染的灵敏度和特异度分别为71.9%和95.9%。感染组和非感染组TNIP1基因rs6889239位点不同基因型患者的外周血TNIP1基因的表达水平比较差异均无统计学意义(P>0.05),而rs17728338位点不同基因型患者的外周血TNIP1基因表达水平比较差异有统计学意义(P<0.05)。结论TNIP1基因rs17728338表达水平与老年慢性心力衰竭患者发生肺部感染有关。展开更多
Tumor necrosis factor-a (TNF-a) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-a gene promoter region and secretion and release of TNF-a and its transformation by a series of signaling pathways ...Tumor necrosis factor-a (TNF-a) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-a gene promoter region and secretion and release of TNF-a and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-a antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-a and its mechanism as a mediator in MI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
文摘Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.
文摘Objective: To study the effects of nuclear factor-κB(NF-κB) activation and tumor necrosis factor-α(TNF-α) expression on heart failure after myocardial infarction in rats. Methods: Male Wistar rats were divided into the sham operation(SO) group and myocardial infarction(MI) group. The left anterior descending branch of the left coronary artery of the rats in MI group was ligated with a suture to induce MI. Sham operation was done in those of the SO group. All the rats were killed in the 4~ th,8~ th and 12~ th week after the arterial ligation respectively. The hemodynamic parameters and the wet weight of the right and left ventricles were recorded. The protein expression of TNF-α and the activity of NF-κB of the non-infarcted myocardium were determined with Western blot and electrophoretic motility shift assay(EMSA) respectively.Results: Significant lower mean arterial pressure(MAP) and maximal ascending and descending velocity of left ventricular pressure(+dp/dt max) and significant higher left ventricular end-diastolic pressure(LVEDP) were found in the rats of the MI group than in those of the SO group(P<0.05).Left ventricular relative weight(LVRW) and right ventricular relative weight(RVRW) were higher in the MI group than in the SO group(P<0.05) with an exception that LVRW showed no significant difference between the MI and SO groups in the 12~ th week after arterial ligation. The expression of TNF-α and the activity of NF-κB were increased in the non-infarcted myocardium after the arterial ligation. Conclusion: Overexpression of TNF-α and significant increase of the activity of NF-κB play an important role in the postinfarctional ventricular remodeling and progression of heart failure.
文摘AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor α (TNF-α) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).METHODS: Serum NTproBNP and TNF-α levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls. RESULTS: Cryoglobulinemic patients showed signifi cantly higher mean NTproBNP and TNF-α levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (χ2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (χ2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as thepatients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (χ2, P = 0.08).CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-α in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.
文摘Objective: To investigate the intervention effect of Jianxin Decoction (健心汤, JXD) on the cytokine level in serum of patients with congestive heart failure (CHF). Methods; Sixty-six patients with CHF were randomly divided into the control group (n = 33) and the trial group (n = 33). The control group received conventional treatment, and the trial group was treated with conventional therapy plus JXD for 4 weeks. Before and after treatment, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitrogen monoxide (NO) in serum and cardiac function were determined. Results: After treatment, the levels of TNF-α, IL-6 and NO were significantly lower than those before treatment (P<0.05, or P<0.01) in the two groups, and the lowering degree of the indices in the trial group was more significantly reduced than that in the control group (P<0.05). And cardiac functions in both groups were improved significantly (P<0.05, or P< 0.01). Conclusion: JXD could prevent and reverse ventricular remodeling so as to ameliorate cardiac function through regulating the levels of cytokines.
基金Supported by the Traditional Chinese Medicine Research Program of Zhejiang Province(No.2014ZB124)Scientific Research Projects of Shaoxing Science and Technology Bureau(No.2018C30128)
文摘OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response.
文摘目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130例老年慢性心力衰竭患者作为研究对象,根据是否于院内发生肺部感染分为感染组(32例)和未感染组(98例)。对TNIP1基因的两个SNP位点rs6889239(T>C)、rs17728338(A>G)进行基因分型,并检测外周血TNIP1基因的mRNA表达水平。结果TNIP1基因rs6889239位点在感染组和非感染组之间的基因型分布以及等位基因频率的差异均无统计学意义(P>0.05);两组的rs17728338位点AA、AG、GG基因型分布比较差异有统计学意义(P<0.05),且感染组等位基因G的频率显著高于未感染组(P<0.05)。相较于未感染组,感染组患者的外周血TNIP1基因mRNA表达水平显著增加,差异有统计学意义(P<0.001)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析结果显示外周血TNIP1基因表达水平预测慢性心力衰竭患者发生肺部感染的灵敏度和特异度分别为71.9%和95.9%。感染组和非感染组TNIP1基因rs6889239位点不同基因型患者的外周血TNIP1基因的表达水平比较差异均无统计学意义(P>0.05),而rs17728338位点不同基因型患者的外周血TNIP1基因表达水平比较差异有统计学意义(P<0.05)。结论TNIP1基因rs17728338表达水平与老年慢性心力衰竭患者发生肺部感染有关。
基金the National Natural Science Foundation of China
文摘Tumor necrosis factor-a (TNF-a) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-a gene promoter region and secretion and release of TNF-a and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-a antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-a and its mechanism as a mediator in MI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
文摘目的 探究牛蒡子苷元(ATG)对慢性心力衰竭(CHF)大鼠心室重构和炎性反应的影响,并分析其潜在机制。方法 79只SD大鼠随机选取12只为假手术组,其余大鼠采用腹主动脉缩窄术建立CHF大鼠模型,成功造模60只大鼠随机分为CHF组、ATG低剂量组(ATG-L组,10 mg/kg)、ATG高剂量组(ATG-H组,20 mg/kg)、ATG+阴性对照(ATG+NC)组[20 mg/kg ATG+100μl高迁移率族蛋白B1(HMGB1)阴性对照质粒]、ATG+HMGB1组(20 mg/kg ATG+100μl HMGB1过表达质粒),每组12只。各组给予相应干预4周后,检测大鼠心功能、B型钠尿肽、N末端B型钠尿肽前体和炎性因子白细胞介素6、TNF-α水平、心脏质量指数和左心室质量指数、心肌组织病理变化、心肌细胞横截面积和心肌胶原体积分数、左心室心肌组织HMGB1/Toll样受体4(TLR4)/核转录因子κB(NF-κB)信号通路相关蛋白表达。结果 与假手术组比较,CHF组大鼠心肌组织HMGB1(0.42±0.05 vs 0.15±0.02)、TLR4(0.70±0.09 vs 0.21±0.04)蛋白水平和磷酸化NF-κB p65(p-NF-κB p65)/NF-κB p65(0.73±0.09 vs 0.26±0.05)蛋白比值显著升高,LVEF、左心室短轴缩短率(LVFS)显著降低(P<0.05);与CHF组比较,ATG-L组和ATG-H组大鼠心肌组织HMGB1(0.33±0.04、0.24±0.04 vs 0.42±0.05)、TLR4(0.56±0.06、0.41±0.05 vs 0.70±0.09)蛋白水平和p-NF-κB p65/NF-κB p65(0.61±0.08、0.49±0.06 vs 0.73±0.09)蛋白比值依次降低,LVEF、LVFS依次升高(P<0.05);HMGB1过表达能明显减弱ATG对HMGB1/TLR4/NF-κB信号通路和CHF大鼠心室重构、炎性反应的抑制作用(P<0.05)。结论 ATG可能通过抑制HMGB1/TLR4/NF-κB信号炎性通路,抑制了CHF大鼠的心室重构。
