Berberine, a natural compound extracted from several Chinese herbs including Coptis chinensis, has been shown to have anti-obesity effects and prevents insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut microbiota; however, the molecular mechanisms underlying these activities remain unknown. We investigated the effects of berberine on obesity and insulin resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4)/tumor necrosis factor (TNF)-α signaling pathway in livers of HFD-fed obese rats. Our results showed that 8-week berberine (200 mg/kg) treatment significantly reduced fasting blood glucose, triglyceride, low-density lipoprotein-cholesterol and insulin resistance in HFD-fed obese rats. However, berberine had no significant effects on body weight, visceral fat mass or the visceral fat to body weight ratio. Berberine also attenuated HFD-induced hepatic steatosis. A prolonged HFD altered the gut microbiota composition by reducing protective bacteria like Bifidobacterium and increasing gram negative bacteria like Escherichia coli, which resulted in increased LPS release into plasma. Berberine reversed these effects and inhibited LPS-induced TLR4/TNF-α activation, resulting in increased insulin receptor and insulin receptor substrate-1 expression in the liver. These findings suggested that berberine may reduce insulin resistance, at least in part by modulating the gut microbiota along with inhibiting LPS/TLR4/TNF-α signaling in the liver.
TNF inhibitors have been used in ankylosing spondylitis (AS). The efficacy of TNF inhibitors was already evaluated by meta-analysis of randomized controlled trials (RCTs). However, the safety of TNF inhibitors is still unclear. Therefore, we aimed to evaluate and update the safety data from RCTs of TNF inhibitors in patients treated for AS. A systematic literature search was conducted from 1990 through May 31, 2016. All studies included were randomized, double-blind, controlled trials of patients with ankylosing spondylitis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The overall serious adverse events, the risk of serious infection events, and the risk of malignancy and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs). Fourteen randomized controlled trials involving 2032 subjects receiving TNF inhibitors and 1030 subjects receiving placebo and/or traditional disease-modifying anti-rheumatic drugs (DMARDs) were included. The overall serious adverse events (OR, 1.34; 95% CI, 0.87-2.05), the risk of serious infection events (OR, 1.59; 95% CI, 0.63-4.01), the risk of malignancy (OR, 0.98; 95% CI, 0.25-3.85), and discontinuation due to adverse events (OR, 1.55; 95% CI, 0.95-2.54) in patients treated with TNF inhibitors as a group were not significantly different from those treated with placebo in the control group. TNF inhibitors were generally safe for treatment of ankylosing spondylitis. These data may help guide clinical comparative decision making in the management of AS.
This is the first meta-analysis to evaluate the role that acarbose plays in the treatment of PCOS. The currently available data showed that acarbose can reduce testosterone, TG, and VLDL, and increase HDL. Acarbose caused a significantly higher incidence of gastrointestinal disturbance. Given the small RCTs and poor quality of RCTs included, these results are not conclusive. A large-scale, randomized controlled study is needed to ascertain this uncertainty.
Previous randomized controlled trials (RCTs) have reported conflicting results for the efficacy of sitagliptin and sulfonylurea therapy in patients with type 2 diabetes mellitus showing inadequate glycemic control with metformin monotherapy. To clarify these findings, a meta-analysis was conducted of the outcomes of all published RCTs comparing sitagliptin with sulfonylureas in the treatment of type 2 diabetes mellitus. Standard medical databases were searched to identify relevant English- and Chinese-language RCTs. RCT results were compared regarding the mean change in glycated hemoglobin (HbA1c) level; the proportion achieving <7% HbAlc; and a change in body weight. No significant differences were found between the metformin plus sitagliptin and metformin plus sulfonylurea groups regarding HbAlc or the proportion achieving <7% HbAlc, while the metformin plus sitagliptin group experienced fewer hypoglycemic events (P<0.00001) and a greater reduction in body weight (P<0.00001). Metformin plus sitagliptin therapy may decrease HbAlc values in patients with type 2 diabetes mellitus who are not achieving their glycemic targets with metformin monotherapy in a manner similar to metformin plus sulfonylurea therapy, whilst posing a lower risk of hypoglycemia, and yielding a more beneficial effect on body weight.
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