434, respectively). However, differences in graft survival were found when GP subtypes and GP recurrence were analyzed. The predictors of graft loss were delayed graft function (hazard ratio [HR] = 2.226, P = .002), rejection episodes (HR = 1.904, P = .017), and recurrence or transplant GP (HR = 3.243, P = .006). The predictors of disease recurrence or transplant GP were age (HR = 0.945, P = .028) and cold ischemia time (HR = 1.117, P = .003). CONCLUSION Kidney transplantation could be a reasonable treatment for GP with end-stage renal disease. Despite the disease recurrence, which is a significant cause of graft loss in transplant recipients, graft survival remains satisfactory. BACKGROUND In simultaneous pancreas-kidney transplantation (SPKT), persistence or recurrence of pancreatic autoantibodies (PAs) has been associated with pancreas graft (PG) autoimmune-driven injury. Our aim was to analyze the impact of PAs on PG survival.  https://www.selleckchem.com/products/envonalkib.html  METHODS Between January 1, 2000, and December 31, 2017, we studied 139 patients with post-SPKT anti-glutamic acid decarboxylase (GAD) autoantibody. Alloimmune (ALI) events were defined as PG rejection and/or de novo donor-specific antibodies (DSA). Hence, 3 groups were defined patients without ALI events or anti-GAD (n = 42), those with ALI events (n = 14), or those only with autoimmune events (positive for anti-GAD and no ALI events; n = 83). RESULTS Male sex was predominant (n = 72, 52%). Median age was 35 years (interquartile range 31-39) and median follow-up was 6-7 years (interquartile range 4.1-9.2). Regarding anti-GAD positivity post-SPKT (n = 90, 65%), no differences were observed concerning age, sex, anti-HLA antibodies, HLA mismatch number and de novo DSA. ALI events were present in 10% (n = 14). PG survival 15 years post-SPKT was better in patients without immune events (96%) followed by those with ALI (69%) and autoimmune events (63%) (P = .025). Anti-GAD was associated to higher annualized mean Hb1AC (P = .006) and lower mean C-peptide (P = .013). According to pre- and post-SPKT anti-GAD status, conversion from negative to positive was associated to worse (63%) 10-year PG survival (P = .044), compared to persistence of negative (100%) or positive anti-GAD (88%). Anti-islet cell and anti-insulin autoantibodies had no impact. CONCLUSION Anti-GAD presence post-SPKT was associated to higher pancreas disfunction and lower PG survival. De novo anti-GAD seems to offer a particular risk of PG failure. The post-transcriptional regulation of gene expression plays an important role in many essential biological processes. The RNA decapping enzyme Dcp2 is a crucial enzyme involved in RNA degradation. Dcp2 proteins are highly expressed in the testis and brain in adult mice. This study aimed to investigate the in vivo functions of Dcp2. An inducible Dcp2 knockout mouse model was established. No obvious health abnormalities were observed after postnatal global deletion of Dcp2 in male mice. However, Dcp2-deleted male mice were infertile and showed Sertoli cell vacuolization and germ cell degeneration. Dcp2 deletion resulted in testicular atrophy, reduced number of epididymal sperm, and increased apoptosis in seminiferous tubules. However, spermatocyte-specific deletion of Dcp2 did not compromise the fertility. The findings of this study indicated that Dcp2 was important for spermatogenesis and male fertility. The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains unclear. Humanin (HN), a cytoprotective polypeptide, reportedly exhibits neuroprotective effects via suppression of inflammation and improvement of insulin resistance in neurons. This study aim was to investigate effects of HN on lipid accumulation in the hepatocytes and insulin signaling, and explore the underlying mechanisms. Protein expression levels were analyzed by Western blotting. Hepatic lipid accumulation was confirmed by Oil red-O staining. We found that HN-treatment ameliorated palmitate-induced lipid accumulation, expression of lipogenesis-associated genes (processed SREBP1, FAS, and SCD1), cell death, and caspase 3 activity in hepatocytes in a dose-dependent manner. Additionally, HN attenuated palmitate-induced impairment of insulin signaling. HN enhanced AMPK phosphorylation, whereas it suppressed palmitate-induced phosphorylation of mTOR. AMPK knockdown by siRNA neutralized the effects of HN on palmitic acid-treated hepatocytes. Collectively, HN prevents palmitate-induced hepatic lipid accumulation, apoptosis, and insulin resistance via AMPK-mediated suppression of the mTOR/SREBP1 pathway, suggesting that it may serve as a potential therapeutic agent in NAFLD treatment. A hyper-vesiculating Gram-negative bacterium, Shewanella vesiculosa HM13, secretes a protein of unknown function (P49) as a major cargo of the extracellular membrane vesicles (EMVs). Here, we analyzed the transport mechanism of P49 to EMVs. The P49 gene is found in a gene cluster containing the genes encoding homologs of surface glycolipid biosynthesis proteins (Wza, WecA, LptA, and Wzx), components of type II secretion system (T2SS), glycerophosphodiester phosphodiesterase (GdpD), and nitroreductase (NfnB). We disrupted the genes in this cluster and analyzed the productivity and morphology of EMVs and the localization of P49. EMV production and morphology were only moderately affected by gene disruption, demonstrating that these gene products are not essential for EMV synthesis. In contrast, the localization of P49 was significantly affected by gene disruption. The lack of homologs of the T2SS components resulted in deficiency in secretion of P49. When gdpD, wzx, lptA, and nfnB were disrupted, P49 was released to the extracellular space without being loaded to the EMVs. These results suggest that P49 is translocated across the outer membrane through the T2SS-like machinery and subsequently loaded onto EMVs through interaction with surface glycolipids of EMVs. The intestinal barrier dysfunction is closely implicated in low-grade chronic inflammation for insulin resistance in diet-induced obesity (DIO). It is generally believed that degradation of colon enterocytes contributes to intestinal barrier dysfunction in the pathological process of obesity. Sennoside A (SA) is reported to improve metabolic disorders, but the effect and mechanism of SA on colonic barrier function of DIO remains unknown. In this study, SA was found to restore colonic barrier function by protecting the continuity and integrity of colon enterocytes in DIO mice. An increase in mRNA expression of tight junction proteins Occludin, Claudin-2 and ZO-1 provides another mechanism of restoring colonic barrier function in SA-treated group. In the research of mechanism, mitophagy was inhibited by SA via a protection of mitochondrial structure and function in colon. A reduction was found in production of reactive oxygen species (ROS) in the colon, and the benefical effect was attributed to an inhibition of activity in complex I and III with a reduction of protein expression and an increase of Mn-SOD activity.