脂联素受体AdipoR1对肺癌PC9细胞增殖和迁移的影响

目的 检测过表达或敲低人脂联素受体1（AdipoR1）基因对PC9细胞增殖和迁移的影响，阐明AdipoR1基因对肺癌的调控作用。方法 通过PCR检测AdipoR1在PC9细胞及对照细胞HBEC中的表达量；利用分子克隆的方法构建AdipoR1的过表达和shRNA干扰载体，并采用PCR和western blot方法检测转染AdipoR1过表达和干扰载体PC9细胞中AdipoR1的表达情况。运用CCK-8方法和划痕愈合实验检测AdipoR1激动剂AdipoRon、AdipoR1过表达及AdipoR1敲低对PC9细胞的增殖和迁移活性的调控作用。结果 PCR结果显示AdipoR1在PC9细胞中的表达量明显降低（P < 0.05）。PCR和western blot结果显示AdipoR1 mRNA和蛋白在其过表达的PC9细胞中的表达量明显高于空载体细胞系（P 均 < 0.05），在其干扰RNA处理组表达量明显低于空载体细胞系（P 均 <0.05）。CCK-8和划痕愈合实验结果显示：在24h和48h时，与溶剂对照组相比，AdipoRon能显著降低PC9细胞的吸光度值和划痕愈合百分比（P均 < 0.05）。过表达AdipoR1 PC9细胞的吸光度值和划痕愈合百分比明显低于空载体细胞（P均 < 0.05）。AdipoR1敲低能明显促进PC9细胞的吸光度值和划痕愈合百分比（P均 < 0.05）。结论 成功构建了人AdipoR1的真核过表达和shRNA干扰载体，AdipoR1激动剂AdipoRon或AdipoR1过表达能抑制肺癌PC9细胞增殖和迁移活性，而AdipoR1敲低则能明显促进肺癌PC9细胞增殖和迁移的活性。     

Therapeutic effects of AdipoRon on liver inflammation and fibrosis induced by CCl4 in mice

ObjectiveThe present work aimed to investigate the effects of AdipoRon against acute hepatitis and liver fibrosis induced by carbon tetrachloride (CCl₄) in mice.MethodsC57BL/6 mice were randomly divided into five groups: control, model, AdipoRon groups (three different dosages), CCl₄ was administered to induce acute hepatitis or liver fibrosis except for control group. The liver function, inflammatory and fibrotic profiles were evaluated by histology, immunohistochemistry and expression analysis, respectively.ResultsAdipoRon pretreatment effectively attenuated oxidative stress and hepatocellular damage in acute CCl₄ intoxication, demonstrated by marked reduction in peroxidation indexes [hepatic malonaldehyde (MDA), total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS)] and serum transaminases [alanine aminotransferase (ALT), aspartate transaminase (AST)]. Moreover, AdipoRon attenuated the severity of fibrosis induced by sustaining CCl₄ challenge, with the alleviation of fibrous deposit and architecture distortion. The levels of canonical fibrosis markers (aminotransferases, hydroxyproline, hyaluronic acid, laminin) were also dose-dependently modulated by AdipoRon. Immunochemistry and expression analysis showed AdipoRon restrained the proinflammatory and profibrotic cytokines (TNF-α, TGF-β1, α-SMA, COL1A1), which somehow, ascribed the anti-fibrotic action to inhibiting hepatic stellate cells (HSCs) activation and quenching specific inflammation-fibrogenesis pathways.ConclusionsAdipoRon demonstrates a remedial capacity against hepatitis and fibrosis induced by CCl₄, potentially by inflammation restraint and HSC deactivation, which might pave the way for its therapeutical application in hepatic fibrosis.     

脂联素受体激动剂AdiopRon对胶质瘤细胞生物学行为的影响及其机制

探讨脂联素受体激动剂AdipoRon对胶质瘤细胞生物学行为的影响，阐明其可能的作用机制。     

Diacerein versus adipoRon as adiponectin modulators in experimentally-induced end-stage type 2 diabetes mellitus in rats

The objective of the present study is to evaluate and compare the possible anti-diabetic effects of adipoRon and diacerein in type 2 diabetes mellitus (T2DM) rats. T2DM is marked by impaired oxidative, inflammatory and metabolic signaling. Indeed, T2DM progression is associated with elevated HbA1C%, low adiponectin and insulin concentration. Moreover, in this study epididymal adipose tissue and soleus muscle MDA contents significantly escalated, while serum TAC and epididymal adipose Nrf2 significantly declined. Nevertheless, serum TNF-α, epididymal NLRP3, NF-κB, PPARγ and CD68 expression rose significantly with a parallel significant reduction in serum IL-10 and soleus muscle expression of IRS1. Both adipoRon and diacerein significantly improved adiponectin and insulin secretion with augmentation of anti-oxidant defenses and diminution of oxidative burden, with obvious anti-inflammatory consequences (p < 0.05). Thus, adipoRon and diacerein positively modulated adiponectin expression with down-regulation of NF-κB/NLRP3/PPARγ expression with subsequent improvement in glycemic control, inflammatory and oxidative signaling.