Regulation of PPAR-γ activity in lipid-laden hepatocytes affects macrophage polarization and inflammation in nonalcoholic fatty liver disease

BACKGROUNDLipid metabolism disorder and inflammatory-immune activation are vital triggers in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Various studies have shown that PPAR-γ exerts potent anti-inflammatory and immunomodulatory properties. However, little is known about the regulation of PPAR-γ activity in modulating cell crosstalk in NAFLD.AIMTo investigate whether the regulation of PPAR-γ activity in lipid-laden hepatocytes affects macrophage polarization and inflammation.METHODSPrimary hepatocytes were isolated from wild-type C57BL6/J mice or hepatocyte-specific PPAR-γ knockout mice and incubated with free fatty acids (FFAs). Macrophages were incubated with conditioned medium (CM) from lipid-laden hepatocytes with or without a PPAR-γ agonist. Wild-type C57BL/6J mice were fed a high-fat (HF) diet and administered rosiglitazone.RESULTSPrimary hepatocytes exhibited significant lipid deposition and increased ROS production after incubation with FFAs. CM from lipid-laden hepatocytes promoted macrophage polarization to the M1 type and activation of the TLR4/NF-κB pathway. A PPAR-γ agonist ameliorated oxidative stress and NLRP3 inflammasome activation in lipid-laden hepatocytes and subsequently prevented M1 macrophage polarization. Hepatocyte-specific PPAR-γ deficiency aggravated oxidative stress and NLRP3 inflammasome activation in lipid-laden hepatocytes, which further promoted M1 macrophage polarization. Rosiglitazone administration improved oxidative stress and NLRP3 inflammasome activation in HF diet-induced NAFLD mice in vivo.CONCLUSIONUpregulation of PPAR-γ activity in hepatocytes alleviated NAFLD by modulating the crosstalk between hepatocytes and macrophages via the reactive oxygen species-NLRP3-IL-1β pathway.     

天冬天精的合成

本文通过全新的合成路线,以L-苯丙氨酸为起始化合物,经过甲酯化、游离、成内酐、缩合、水解、精制等6步反应得到天冬天精,总收率达到45．85％,较文献收率提高了8％,质量符合标准。     

百令胶囊在肾移植术后早中期的应用研究

为研究百令胶囊在肾移植术后早,中期的免疫抑制作用,将肾移植患者分为３组,Ａ组为百令胶囊＋Ｐｒｅｄ＋ＣｓＡ,Ｂ组为百令胶囊＋Ｐｒｅｄ＋ＣｓＡ＋ＡｚａＣ组为Ｐｒｅｄ＋ＣｓＡ＋Ａｚａ。结果：１．急性排斥发生情况：Ａ组１６．５％（３３／２００）,Ｂ组１１．７９％（３３／２８０）,Ｃ组１６％（１６／１００）,２．肝功能损害情况;Ａ组１８．５％,Ｂ组为２１．０７％,Ｃ组２５％,３．白细胞下降,Ａ组无,Ｂ组１２     

非穿透性小梁手术超声生物显微镜检查

目的：应用超声生物显微镜（ＵＢＭ）检查技术,探讨非穿透性小梁手术联合透明质酸钠生物胶植入手术区域解剖特点和房水引汉机制。方法：对１４例１６只眼行非穿透性小梁手术联合透明质酸钠生物胶植入的患者,在术后１～３个月内进行手术区域ＵＢＭ检查。检查的指标（项目）包括：巩膜瓣下形成液间腔的大小（宽和高）、透明质酸钠生物胶吸收的情况、剩余角膜小梁膜的厚度以及滤过泡的形态,并对结果进行分析。结果：１６只眼术前平均     

18甲基炔诺酮阴道环的临床观察

本文介绍108例妇女使用释放左旋18甲基炔诺酮20微克/天阴道环一年的临床效果和副反应。每100例妇女使用一年的净累积率为:妊娠率3.7,脱落率4.6,与阴道环有关的停用率26.9,持续使用率71.2。副反应主要为月经紊乱,但随使用时间的延长而逐步改善。本文有20例首进行月经血量,血红蛋白和铁蛋白测定。使用阴道环后第一月,经血量略有增加,此后有下降趋势,血红蛋白浓度在放环后第6和第12月有明显增加(P<0.05)。     

不同发育天数囊胚冻融移植后妊娠结局分析

目的比较不同发育天数冻融囊胚移植后的妊娠结局。方法回顾性分析1 176例行冻融囊胚移植患者的临床资料,其中植入前遗传学诊断(preimplantation genetic diagnosis,PGD)周期135例,比较第5日单囊胚移植(single embryo transfer,SET)组、双囊胚移植(double embryo transfer,DET)组与第6日SET组和DET组的妊娠结局。结果同是优质囊胚级别的条件下,第5日DET组的生化妊娠率(56.91%)、临床妊娠率(53.25%)以及多胎妊娠率(1.20%)显著高于其他组(P0.05);第5日DET组与SET组的胚胎着床率无统计学差异(P0.05),但均显著高于第6日DET组和SET组(P0.05);同级别以及PGD周期中第5日和第6日SET组相比较,第5日组的生化妊娠率、胚胎着床率均显著高于第6日组(P0.05)。结论在同是优质囊胚的条件下,第5日SET、DET及经PGD诊断的SET妊娠结局均优于第6日。     

Risk of infections of biological and targeted drugs in patients with spondyloarthritis: meta-analysis of randomized clinical trials

Background: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in ...     

微小RNA在牙周炎龈沟液中的表达差异及对牙周炎的调控机制

牙周炎是一种以牙周袋形成和牙槽骨吸收为特征的炎症性疾病,是40岁以上成人牙齿脱落的主要原因之一。牙周组织产生的龈沟液可以一定程度的揭示牙周的状态,其中的微小RNA (miRNA)的表达水平会根据牙周炎症的发展发生改变,可以作为牙周诊断的指标之一。miR-146a及miR-223是牙周炎进展中表达水平显著变化的miRNA,它们是目前利用龈沟液miRNA对牙周炎诊断最有潜力的生物标志物。不同miRNA可以通过调控牙周炎信号通路的不同阶段发挥作用,如通过细菌脂多糖与Toll样受体的结合、核因子κB配体信号通路及炎症因子的释放等过程调控牙周炎症进程。本文就牙周炎龈沟液中miRNA的表达差异及调控机制作一综述,以期为龈沟液miRNA准确诊断牙周炎提供新思路和新进展。