Pancreatic beta-cell specific BAG3 knockout results in chronic hyperinsulinemia inducing insulin resistance.

BACKGROUND: Insulin, secreted from pancreatic islets of Langerhans, is of critical importance in regulating glucose homeostasis. Defective insulin secretion and/or the inability of tissues to respond to insulin results in insulin resistance and to several metabolic and organ alterations. We have previously demonstrated that BAG3 regulates insulin secretion. Herein we explored the consequences of beta-cells specific BAG3 deficiency in an animal model. METHODS: We generated a beta-cells specific BAG3 knockout mouse model. Glucose and insulin tolerance tests, proteomics, metabolomics, and immunohistochemical analysis were used to investigate the role of BAG3 in regulating insulin secretion and the effects of chronic exposure to excessive insulin release in vivo. RESULTS: Beta-cells specific BAG3 knockout results in primary hyperinsulinism due to excessive insulin exocytosis finally leading to insulin resistance. We demonstrate that resistance is mainly muscle-dependent while the liver remains insulin sensitive. The chronically altered metabolic condition leads in time to histopathological alterations in different organs. We observe elevated glycogen and lipid accumulation in the liver reminiscent of non-alcoholic fatty liver disease as well as mesangial matrix expansion and thickening of the glomerular basement membrane, resembling the histology of chronic kidney disease. CONCLUSION: Altogether, this study shows that BAG3 plays a role in insulin secretion and provides a model for the study of hyperinsulinemia and insulin resistance.

A proteomic insight reveals the role of food-associated Lactiplantibacillus plantarum C9O4 in reverting intestinal inflammation.

Nowadays, Western diets and lifestyle lead to an increasing occurrence of chronic gut inflammation that represents an emerging health concern with still a lack of successful therapies. Fermented foods, and their associated lactic acid bacteria, have recently regained popularity for their probiotic potential including the maintenance of gut homeostasis by modulating the immune and inflammatory response. Our study aims to investigate the crosstalk between the food-borne strain Lactiplantibacillus plantarum C9O4 and intestinal epithelial cells in an in vitro inflammation model. Cytokines profile shows the ability of C9O4 to significantly reduce levels of IL-2, IL-5, IL-6, and IFN-γ. Proteomic functional analysis reveals an immunoregulatory role of C9O4, able to revert the detrimental effects of IFN-γ through the JAK/STAT pathway in inflamed intestinal cells. These results suggest a promising therapeutic role of fermented food-associated microbes for the management of gastrointestinal inflammatory diseases. Data are available via ProteomeXchange with identifier PXD042175.

Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination.

COVID-19 pandemic has hit people's health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration.

Efficacy of the Laparoendoscopic "Rendezvous" to Treat Cholecystocholedocholithiasis in 210 Consecutive Patients: A Single Center Experience.

OBJECTIVE: The simultaneous laparoendoscopic "rendezvous" (LERV) represents an alternative to sequential or totally laparoscopic approaches for patients affected by cholecystocholedocholithiasis. The aim of this study was to analyze the results in a large series of 210 consecutive patients. MATERIALS AND METHODS: From 2002 to 2016 all patients affected by cholecystocholedocholithiasis were treated with a standardized "tailored" LERV. The relevant technical features of the procedure were recorded. An analysis of feasibility, effectiveness in stone clearance, and safety was performed. RESULTS: Among 214 patients with common bile duct stones, 210 were treated with LERV and 4 with open rendezvous approach. Intraoperative cholangiography confirmed common bile duct stones in 179 patients (85.2%) or sludge in 18 (8.5%) and in 98.9% stone clearance was obtained endoscopically. Endoscopic papilla cannulation was feasible in 161 patients (76.7%), whereas in 49 (23.3%) a transcystic guidewire was needed. The overall LERV feasibility was 96.6%. The conversion rate to open surgery was 3.3%. Minor morbidity was observed in 1.9% of cases, mortality in 0.47%, and the mean hospital stay was 4.3 days. CONCLUSIONS: These results confirm the high effectiveness of LERV. This approach to treat cholecystocholedocholithiasis should be preferred and therefore implemented where a strong collaboration between surgeons and endoscopists is possible.

Laparo-endoscopic rendez-vous versus sequential "delayed" approach in patients with choledocholithiasis.

BACKGROUND: The aim of this study was to compare the efficacy and safety of synchronous laparoscopic cholecystectomy with laparo-endoscopic rendez-vous (LRV) technique vs. sequential "delayed" approach with the main goal to compare the conversion rate and postoperative complications. METHODS: Patients diagnosed as having gallstones and CBD stones or sludge were enrolled in this study. From January 2013 to June 2015, 43 consecutive patients were submitted to the sequential treatment (ERCP prior to laparoscopic cholecystectomy) and the next consecutive 46 patients were submitted to undergo the rendez-vous technique. All endoscopic procedures in both groups were performed by the same endoscopist with the same technique. Data were collected on patient age, gender, latency operation time, duration of surgery, bilio-pancreatic events, hospital stay, mortality, conversion rate and postoperative complications. RESULTS: The overall mean age was 58 years-old (25-84 years) with 43 males (48.3%) and 46 females (51.7%). The conversion rate to open surgery was 11.6% in the "sequential group" vs. 2.2% in the LRV group with a P value 0.10. The reasons for conversion included in the first group unclear anatomy (in 2 patients) and severe adhesions (in the remnant 3 patient), and in the second group unclear anatomy (in one patient). No bilio-pancreatic events occurred in the waiting period for LC in the first group. No mortality was recorded in either group. Postoperative complications were seen in 7% of patients in the "sequential group" vs. 2.2% in the rendez-vous group (P value 0.35). CONCLUSIONS: LRV does not present real advantages in comparison to delayed sequential approach in terms of conversion rate and postoperative complications. However, these results require further elaboration in studies on large numbers of patients undergoing LRV approach.

Wilkie's syndrome An uncommon cause of small bowel obstruction in a young patient.

UNLABELLED: Superior mesenteric artery (SMA) syndrome, also named as Wilkie's syndrome, is a rare, potentially life-threatening gastro- vascular disorder and an uncommon cause of proximal bowel obstruction characterized by a compression of the third and final portion of the duodenum by the abdominal aorta and the overlying superior mesenteric artery. There isn't a consensus regarding to the optimal treatment of this condition. We describe a case of Wilkie's syndrome in a young female with characteristic symptoms of upper intestinal obstruction, whose diagnosis was delayed for 2 years. KEY WORDS: Superior mesenteric artery, Upper intestinal occlusion, Young female.