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Mesenchymal stem cells (MSC) represent an impressive opportunity in term of regenerative medicine and immunosuppressive therapy. Although it is clear that upon transplantation MSC exert most of their therapeutic effects through the secretion of bioactive molecules, the effects of a pro-inflammatory recipient environment on MSC secretome have not been characterized. In this study, we used a label free mass spectrometry based quantitative proteomic approach to analyze how pro-inflammatory cytokines modulate the composition of the human MSC secretome. We found that pro-inflammatory cytokines have a strong impact on the secretome of human bone marrow-derived MSC and that the large majority of cytokine-induced proteins are involved in inflammation and/or angiogenesis. Comparative analyses with results recently obtained on mouse MSC secretome stimulated under the same conditions reveals both analogies and differences in the effect of pro-inflammatory cytokines on MSC secretome in the two organisms. In particular, functional analyses confirmed that tissue inhibitor of metalloproteinase-1 (TIMP1) is a key effector molecule responsible for the anti-angiogenic properties of both human and mouse MSC within an inflammatory microenvironment. Mass spectrometry data are available via ProteomeXchange with identifier PXD005746 SIGNIFICANCE: The secretion of a broad range of bioactive molecules is believed to be the main mechanism by which MSC exert specific therapeutic effects. MSC are very versatile and respond to specific environments by producing and releasing a variety of effector molecules. To the best of our knowledge this is the first study aimed at describing the secretome of human MSC primed using a mixture of cytokines, to mimic pro-inflammatory conditions encountered in vivo, by a quantitative high-resolution mass spectrometry based approach. The main output of the study concerns the identification of a list of specific proteins involved in inflammation and angiogenesis which are overrepresented in stimulated MSC secretome. The data complement a previous study on the secretome of mouse MSC stimulated under the same conditions. Comparative analyses reveal analogies and differences in the biological processes affected by overrepresented proteins in the two organisms. In particular, the key role of TIMP-1 for the anti-angiogenic properties of stimulated MSC secretome already observed in mouse is confirmed in human. Overall, these studies represent key steps necessary to characterize the different biology of MSC in the two organisms and design successful pre-clinical experiments as well as clinical trials., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Gastroesophageal reflux disease (GERD) with or without hiatal hernia (HH) is now recognized as an obesity-related co-morbidity. Roux-en-Y gastric bypass has been proved to be the most effective bariatric procedure for the treatment of morbidly obese patients with GERD and/or HH. In contrast, the indication for laparoscopic sleeve gastrectomy (SG) in these patients is still debated. Our objective was to report our experience with 97 patients who underwent SG and HH repair (HHR). The setting was a university hospital in Italy., Methods: From July 2009 to December 2011, 378 patients underwent a preoperative workup for SG. In 97 patients, SG was performed with HHR. The clinical outcome was evaluated considering GERD symptom resolution or improvement, interruption of antireflux medications, and radiographic evidence of HH recurrence., Results: Before surgery, symptomatic GERD was present in 60 patients (15.8%), and HH was diagnosed in 42 patients (11.1%). In 55 patients (14.5%), HH was diagnosed intraoperatively. The mean follow-up was 18 months. GERD remission occurred in 44 patients (73.3%). In the remaining 16 patients, antireflux medications were diminished, with complete control of symptoms in 5 patients. No HH recurrences developed. "De novo" GERD symptoms developed in 22.9% of the patients undergoing SG alone compared with 0% of patients undergoing SG plus HHR., Conclusion: SG with HHR is feasible and safe, providing good management of GERD in obese patients with reflux symptoms. Small hiatal defects could be underdiagnosed at preoperative endoscopy and/or upper gastrointestinal contrast study. Thus, a careful examination of the crura is always recommended intraoperatively., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have demonstrated a high rate of type 2 diabetes mellitus (T2DM) resolution after sleeve gastrectomy. Different prognostic factors have been hypothesized for T2DM remission after bariatric surgery. Our objectives were to analyze the role of T2DM duration as an independent prognostic factor for remission., Methods: From January 2008 to September 2010, 56 obese patients with T2DM underwent sleeve gastrectomy. Group A consisted of 16 patients who had lived with T2DM for >10 years (12 women and 4 men, mean body mass index 42.7 kg/m2). Group B included 40 obese patients who had lived with T2DM for <10 years (29 women and 11 men, mean body mass index 44.9 kg/m2)., Results: In group A, 43.7% were treated with oral hypoglycemics, 6.3% with insulin, and 50% with oral hypoglycemics and insulin. In group B, 87.5% were treated with oral hypoglycemics, 5% with dietary therapy, and 7.5% with insulin. The preoperative average glycemia, glycosylated hemoglobin, and C-peptide value was 206.2 mg/dL, 9.5%, and 2.8 μg/L in group A and 134 mg/dL, 7.1%, and 4.5 μg/L in group B, respectively (P < .05 for all). The T2DM remission rate in all 56 patients was 80.3%. However, in group B, the resolution rate was 100%, but in group A, the resolution rate was 31%. Patients without complete remission were more sensitive to lower doses of antidiabetic drugs., Conclusion: Sleeve gastrectomy is effective in the treatment of obese patients with T2DM. The duration of T2DM seems to be of paramount importance as a prognostic factor, with 10 years representing a cutoff between a 100% rate of remission and significantly lower rates of remission., (Copyright © 2011 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)