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
AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells.
目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232...目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232例)和验证集(116例)。所有患者均接受随访,将发生复发的患者纳入复发组,未发生复发的患者纳入未复发组。比较训练集复发组、未复发组血清IL-6、PGE2、TNF-α水平及一般资料;用Logistic回归模型分析训练集膀胱癌术后复发的影响因素,并建立回归方程;用ROC曲线分析术前IL-6、PGE2、TNF-α单独及联合预测膀胱癌术后复发的效能;建立膀胱癌术后复发的风险预测列线图模型,并验证其效能。结果与未复发组比较,复发组血清IL-6、PGE2、TNF-α水平升高,肿瘤直径增大,多发性肿瘤、肿瘤分期T 2~T 4、肿瘤WHO病理学分级Ⅱ~Ⅲ级的构成比升高,术后规律膀胱灌注的构成比降低(P<0.05)。Logistic回归分析显示,术前血清IL-6、PGE2、TNF-α、肿瘤分期、肿瘤WHO病理学分级是膀胱癌术后复发的影响因素(P<0.05),并建立Logistic回归方程:Y=1.718 X 1+2.081 X 2+1.815 X 3+2.319 X 4+1.868 X 5。ROC曲线显示,术前IL-6、PGE2、TNF-α预测膀胱癌术后复发的最佳截断点分别为0.60 ng/L、57.13 pg/mL、2.10 ng/mL,三者单独及联合预测膀胱癌的ROC曲线下面积(AUC ROC)分别为0.729、0.743、0.733和0.825。基于训练集Logistic回归分析结构建立膀胱癌术后复发的风险预测列线图模型,该模型预测训练集、验证集的敏感性分别为94.12%、90.20%,特异性分别为90.06%、87.29%,AUC ROC分别为0.940、0.914;Bootstrap法内部验证结果显示,训练集、验证集的C-index分别为0.918(95%CI:0.824~0.987)、0.901(95%CI:0.835~0.957)。结论术前血清IL-6、PGE2、TNF-α水平是膀胱癌术后复发的影响因素,据此建立的风险预测列线图模型具有良好的预测效能。展开更多
背景:目前已有针对miRNA/mRNA轴调节骨关节炎疾病进程的分子机制研究。先前生物信息学研究发现具有临床预测价值的mRNA(磷脂酶Cδ3:phospholipase C delta 3,PLCD3)及其靶向miRNA(miR-34a-5p),尚缺实验验证其调控骨关节炎的具体作用及...背景:目前已有针对miRNA/mRNA轴调节骨关节炎疾病进程的分子机制研究。先前生物信息学研究发现具有临床预测价值的mRNA(磷脂酶Cδ3:phospholipase C delta 3,PLCD3)及其靶向miRNA(miR-34a-5p),尚缺实验验证其调控骨关节炎的具体作用及机制。目的:探讨miR-34a-5p/PLCD3轴对骨关节炎进展的调控作用及机制。方法:选择15例膝骨关节炎患者的滑膜为骨关节炎组,同时选择同期因创伤致髌骨骨折行内固定术的15例年轻患者的健康滑膜为对照组,Real-time PCR法检测滑膜中PLCD3及miR-34a-5p的表达。通过细胞转染的方法,将人滑膜关节炎成纤维细胞(human fibroblast like synovial cells-osteoarthritis,HFLS-OA)进行处理,并分为miR-34a-5p模拟物组、pCDH-PLCD3组、miR-34a-5p模拟物+pCDH-PLCD3组、miR-34a-5p抑制剂组、si-PLCD3组、miR-34a-5p抑制剂+si-PLCD3组,通过Real-time PCR法检测PLCD3和miR-34a-5p表达的关系;通过CCK-8法、细胞划痕实验检测各组HFLS-OA细胞活力及细胞迁移的影响;使用Western Blot法检测凋亡标记蛋白表达水平;使用ELISA法检测炎症因子的表达。结果与结论:①PLCD3是miR-34a-5p的直接靶标,同时PLCD3和miR-34a-5p表达水平呈负相关。②PLCD3上调会促进HFLS-OA细胞的增殖并抑制细胞迁移,而miR-34a-5p上调会显著抑制HFLS-OA细胞的活性并增强细胞迁移;miR-34a-5p过表达使HFLS-OA细胞Casp3和Casp9蛋白水平显著升高,而PLCD3过表达则表现出相反趋势。③PLCD3过表达显著增加了HFLS-OA细胞白细胞介素6和肿瘤坏死因子α的表达,而miR-34a-5p模拟物则表现出保护活性。④结果说明,miR-34a-5p/PLCD3轴可能通过调节滑膜细胞的炎症过程或凋亡来影响骨关节炎的进展。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.
基金Supported by Grants-in-Aid for Young Scientists(B)No.22791295,No.23791557 and No.24791440Grant-in-Aid for Scientific Research(C)from the Japan Society for the Promotion of Science,No.22591464 and No.24591957
文摘AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells.
文摘胎儿生长受限(fetal growth restriction,FGR)是一种常见的产科疾病,其可导致新生儿低出生体质量和出生后肌肉量减少。这可能与肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)的调控密切相关。研究发现,这两种炎症因子在FGR胎儿中表达水平异常,可通过影响成肌细胞的增殖和分化,干扰正常骨骼肌的发育。此外,TNF-α与IL-6还可以激活特定的信号通路,如核因子κB(nuclear factor-κB,NF-κB)、Janus激酶/信号转导及转录活化因子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)、丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)等信号通路,调节肌细胞的代谢和功能。如使用特定的抗炎药物或生物制剂来降低TNF-α和IL-6的活性,可能有助于改善FGR胎儿的骨骼肌发育。总的来说,TNF-α和IL-6在FGR胎儿骨骼肌发育中的作用是一个多层面、复杂的过程,需要进一步的深入研究来阐明其具体机制,帮助理解FGR的病理生理学,并为治疗FGR胎儿提供新的思路。
文摘目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232例)和验证集(116例)。所有患者均接受随访,将发生复发的患者纳入复发组,未发生复发的患者纳入未复发组。比较训练集复发组、未复发组血清IL-6、PGE2、TNF-α水平及一般资料;用Logistic回归模型分析训练集膀胱癌术后复发的影响因素,并建立回归方程;用ROC曲线分析术前IL-6、PGE2、TNF-α单独及联合预测膀胱癌术后复发的效能;建立膀胱癌术后复发的风险预测列线图模型,并验证其效能。结果与未复发组比较,复发组血清IL-6、PGE2、TNF-α水平升高,肿瘤直径增大,多发性肿瘤、肿瘤分期T 2~T 4、肿瘤WHO病理学分级Ⅱ~Ⅲ级的构成比升高,术后规律膀胱灌注的构成比降低(P<0.05)。Logistic回归分析显示,术前血清IL-6、PGE2、TNF-α、肿瘤分期、肿瘤WHO病理学分级是膀胱癌术后复发的影响因素(P<0.05),并建立Logistic回归方程:Y=1.718 X 1+2.081 X 2+1.815 X 3+2.319 X 4+1.868 X 5。ROC曲线显示,术前IL-6、PGE2、TNF-α预测膀胱癌术后复发的最佳截断点分别为0.60 ng/L、57.13 pg/mL、2.10 ng/mL,三者单独及联合预测膀胱癌的ROC曲线下面积(AUC ROC)分别为0.729、0.743、0.733和0.825。基于训练集Logistic回归分析结构建立膀胱癌术后复发的风险预测列线图模型,该模型预测训练集、验证集的敏感性分别为94.12%、90.20%,特异性分别为90.06%、87.29%,AUC ROC分别为0.940、0.914;Bootstrap法内部验证结果显示,训练集、验证集的C-index分别为0.918(95%CI:0.824~0.987)、0.901(95%CI:0.835~0.957)。结论术前血清IL-6、PGE2、TNF-α水平是膀胱癌术后复发的影响因素,据此建立的风险预测列线图模型具有良好的预测效能。