MicroRNAs are small noncoding RNAs that regulate gene expression post-transcriptionally. Here we applied microRNA profiling to 17 human lymphocyte subsets to identify microRNA signatures that were distinct among various subsets and different from those of mouse lymphocytes. One of the signature microRNAs of naive CD4+ T cells, miR-125b, regulated the expression of genes encoding molecules involved in T cell differentiation, including IFNG, IL2RB, IL10RA and PRDM1. The expression of synthetic miR-125b and lentiviral vectors encoding the precursor to miR-125b in naive lymphocytes inhibited differentiation to effector cells. Our data provide an 'atlas' of microRNA expression in human lymphocytes, define subset-specific signatures and their target genes and indicate that the naive state of T cells is enforced by microRNA.
Objective: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. Design: Double blind controlled study. Subjects: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.174.89 kg, mean body mass index (BMI) 43.671.09 kg/m 2 ) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. Measurements: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). Results: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (1171.09 vs 5.771.1 kg, Po0.001) and BMI reduction (470.36 vs 270.58 kg/m 2 , Po0.001) and a higher satiety score on a visual analogic scale (7.6370.38 vs 4.7270.44, Po0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6748 vs 139731, Po0.001) and a greater prolongation in gastric emptying time ( þ 18.9378 vs À2.276.9 min, Po0.05). No significant side effects or neurophysiologic changes were found. Conclusions: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.
Endoscopist's experience is an important independent prognostic factor for non-variceal acute upper GI bleeding. Urgent endoscopy should be undertaken preferentially by a skilled endoscopist as less expert staff tends to underestimate some risk lesions with a negative influence on hemostasis.
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