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Metformin is a widely used antidiabetic drug for the management of type 2 diabetes mellitus. Recently, epidemiological studies demonstrate that metformin has anticancer effects on esophageal squamous cell carcinoma (ESCC) and other cancers. However, the effects and potential mechanisms of metformin on ESCC remain elusive. In this study, we used N -nitroso- N -methylbenzylamine (NMBzA), a special carcinogen for esophagi, to develop a rat ESCC model, in which the carcinogenesis progression of ESCC in rat was induced and promoted. We investigated the effects of metformin on carcinogenesis of ESCC in this model. Our results revealed that metformin significantly decreased the incidence and precancerous lesions of ESCC and inhibited proliferation and promoted apoptosis of esophageal epithelial cells in rat treated with NMBzA. Moreover, metformin also increased apoptosis and inhibited migration, colony formation and tumor sphere formation of human ESCC cells in vitro. Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6). Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro. Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC. [ABSTRACT FROM AUTHOR]

Objectives: Statin is the most widely used as HMG-CoA reductase inhibitor, and contributes to clinically significant vascular risk reduction. However, the role of statins in the rheumatoid arthritis (RA) immunomodulation is debatable. This meta-analysis aimed to determine the efficacy of statins therapy in RA patients., Methods: A structured literature search was undertaken to identify randomised controlled trials (RCTs) conducted in RA patients receiving either statins or control. A meta-analysis on standardised mean difference (SMD) with a 95% confidence interval (95%CI) was conducted., Results: We included 15 studies with a total of 992 patients (487 patients allocated to statins therapy). Our data revealed statins can attenuate disease activity markedly. Overall, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) declined significantly during the treatment (n=12, SMD: -2.222, 95%CI: -2.404, -2.040, p=0.000; n=14, SMD: -3.014, 95%CI: -3.207, -2.821, p=0.000), among which ESR and CRP decreased obviously at 12 months (n=5, SMD: -2.874, 95%CI: -3.224, -2.523, p=0.000; n=7, SMD: -3.970, 95%CI: -4.300, -3.641, p=0.000; respectively). As expected, the tender joint count (TJC) and swollen joint count (SJC) also fell (n=9, SMD: -2.005, 95% CI: -2.216, -1.794; p=0.000; n=10, SMD: -1.76, 95%CI: -1.948, -1.577; p=0.000; respectively). Besides, morning stiffness was attenuated (n=5, SMD: -1.242, 95%CI: -1.474, -1.011, p=0.000), and showed no significant differences between 12 months and 24 months (p=0.205). Notably, statins indeed potently down-regulate inflammatory factors TNF-α (n=7, SMD: -4.290, 95%CI: -4.659, -3.922; p=0.000), IL-1 (n=4, SMD: -1.324, 95%CI: -1.646, -1.003; p=0.000), and IL-6 (n=10, SMD: -1.652, 95%CI: -1.822, -1.482; p=0.000). No publication bias was observed across all studies based on the Begg and Egger test., Conclusions: This meta-analysis demonstrates the pleiotropic effects of statins on ameliorating RA activity and mediating clinically apparent anti-inflammatory effects in the context of RA autoimmune inflammation, which make it recommended as a potent treatment for RA patients.