Driscollpena7053

Membrane lipids change drastically in plants when they suffered from hypoxia (oxygen deficiency) stress. Overall, hypoxia stress lowers the contents of total lipids, inhabits lipid biosynthesis, and stimulates lipid degradation, leading to the accumulation of free fatty acids. Lipid alterations include changes in the contents of lipid classes, the extent of saturation, and the length of acyl chains. But the detail and systematic studies about lipid changes, as well as the function mechanism in hypoxia stress are poorly understood. Here, the major unanswered questions and suggestions on the study of the function of lipid in hypoxia stress were provided.Background Disability progression independent of relapses (PIRA) has been described as a frequent phenomenon in relapsing-remitting multiple sclerosis (RRMS). Objective To compare the occurrence of disability progression in relapse-free RRMS patients on interferon-beta/glatiramer acetate (IFN/GA) versus fingolimod. Methods This study is based on data from the Swiss association for joint tasks of health insurers. Time to relapse and 12-month confirmed disability progression were compared between treatment groups using multivariable Cox regression analysis with confounder adjustment. Inverse-probability weighting was applied to correct for the bias that patients on fingolimod have a higher chance to remain relapse-free than patients on IFN/GA. PD 0332991 Results We included 1640 patients (64% IFN/GA, 36% fingolimod, median total follow-up time = 4-5 years). Disease-modifying treatment (DMT) groups were well balanced with regard to potential confounders. Disability progression was observed in 155 patients (8.8%) on IFN/GA and 51 (7.6%) on fingolimod, of which 44 and 23 were relapse-free during the initial DMT, respectively. Adjusted standard regression analysis on all patients indicated that those on fingolimod experience less frequently disability progression compared with IFN/GA (hazard ratio = 0.53 (95% confidence interval = 0.37-0.76)). After bias correction, this was also true for patients without relapses (hazard ratio=0.56 (95% confidence interval = 0.32-0.98). Conclusion Our analysis indicates that fingolimod is superior to IFN/GA in preventing disability progression in both relapsing and relapse-free, young, newly diagnosed RRMS patients.Background - After massive small bowel resection (SBR), mice exhibit hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic b-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon like peptide-1 (GLP-1). Methods - C57Bl/6 mice underwent 50% SBR or sham operation. At 10 weeks, pancreatic insulin content and secretion was measured by ELISA. Immunohistochemistry was performed to determine alterations in pancreatic a- and b-cells. Western blot analysis was used to measure GLP-1R expression and immunoassay was used to measure plasma insulin and GLP-1. Results - After SBR, we identified pancreatic islet hypertrophy and impaired glucose tolerance. The proportion of a- and b-cells was not grossly altered. Whole pancreas and pancreatic islet insulin content was not significantly different; however, SBR pancreas demonstrated decreased insulin secretion in both static incubation and islet perfusion experiments. The expression of pancreatic GLP-1R was decreased approximately 2-fold after SBR and serum GLP-1 levels were decreased. Administration of a GLP-1 agonist mitigated the metabolic derangements. Conclusion Following massive SBR, there is significant hypertrophy of pancreatic islet cells with morphologically intact a- and b-cells. Significantly reduced pancreatic insulin release in both static and dynamic conditions demonstrate perturbed intrinsic b-cell function. GLP-1 is a key mediator of this amplification pathway. Decreased expression of serum GLP-1 and pancreatic GLP-1R in face of no change in insulin content offer a novel pathway for enteropancreatic glucose regulation following SBR.Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in non-cirrhotic livers in the setting of non-alcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply mechanical forces to the nucleus, functioning as mechanical stressors akin to stiffness. We investigated the effect of lipid droplets on cellular mechanosensing and found that primary human hepatocytes loaded with the fatty acids oleate and linoleate exhibited decreased stiffness-induced cell spreading and disrupted focal adhesions and stress fibers. The presence of large lipid droplets in hepatocytes resulted in increased nuclear localization of the mechano-sensor Yes-associated protein (YAP). In cirrhotic livers from patients with NAFLD, hepatocytes filled with large lipid droplets showed significantly higher nuclear localization of YAP as compared to cells with small lipid droplets. This work suggests that lipid droplets induce a mechanical signal that disrupts the ability of the hepatocyte to sense its underlying matrix stiffness, and that the presence of lipid droplets can induce intracellular mechanical stresses.Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In this context, we thus aimed to explore the mechanism of miR-382 in epithelial mesenchymal transition (EMT) and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. Gene expression datasets GSE16515, GSE71989 and GSE32676 were screened out with the findings showed the significance of miR-382 and Anxa3 in PC. A total of 115 PC patients was selected for determination of miR-382 and Anxa3 expression with lowly expressed miR-382 and highly expressed Anxa3 found via RT-qPCR and western blot analysis. Additionally, negative correlation was found between miR-382 and Anxa3 in PC. Dual-luciferase reporter gene assay and in situ hybridization results confirmed that miR-382 negatively regulated Anxa3. miR-382 targeted Anxa3 and suppressed PC progression by blocking the PI3K/Akt signaling pathway. After a series of gain- and loss-of function approaches, up-regulation of miR-382 or silencing of Anxa3 inhibited the EMT and lymph node metastasis as evidenced by increased level of E-cadherin and decreased level of N-cadherin, Vimentin, VEGFR-3, VEGF-C and VEGF-D.