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Nedergaard Vasquez posted an update 6 days, 4 hours ago
Type-2 diabetes mellitus (T2DM) is a complex disease characterized by reduced pancreatic islets β-cell mass and impaired insulin release from these cells. Non-coding RNAs, including microRNAs (miRNA) and long non-coding RNAs (lncRNAs), play a role in the progression of T2DM. Decreased serum lncRNA GAS5 levels were reported to be associated with T2DM. However, the role of GAS5 in regulating islet cell functions remain unknown. In this study, we found that the serum levels of GAS5 were significantly lower in patients with T2DM compared with healthy control subjects, and the low serum GAS5 levels were associated with high levels of HbAlc and fasting glucose in patients with T2DM. In addition, we found that serum GAS5 levels were negatively correlated with the serum levels of miR-29a-3p, miR-96-3p, and miR-208a-3p in patients with T2DM. Consequently, using INS-1 832/13 rat β-cell line, we found that overexpression of GAS5 by lentivirus infection increased glucose-stimulated insulin secretion and insulin content compared with negative control, whereas knockdown of GAS5 expression reduced both them. Moreover, GAS5 interacted with miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells, as judged by pull-down assay and dual luciferase reporter assay. GAS5 overexpression caused the decrease in expression of miR-29a-3p, miR-96-3p, and miR-208a-3p in INS-1 832/13 cells and conversely caused the increase in expression of insulin receptor, insulin receptor substrate, and phosphoinositide-3-kinase regulatory subunit 1. Thus, these results reveal a novel mechanism whereby GAS5 is involved in maintaining insulin secretion and may represent a novel therapeutic target for T2DM.Scoring is a challenging step in protein-protein docking, where typically thousands of solutions are generated. In this study, we ought to investigate the contribution of consensus-rescoring, as introduced by Oliva et al. (2013) with the CONSRANK method, where the set of solutions is used to build statistics in order to identify recurrent solutions. We explore several ways to perform consensus-based rescoring on the ZDOCK decoy set for Benchmark 4. We show that the information of the interface size is critical for successful rescoring in this context, but that consensus rescoring in itself performs less well than traditional physics-based evaluation. The results of physics-based and consensus-based rescoring are partially overlapping, supporting the use of a combination of these approaches.In autohemotherapy, it is important to find a way to lower the effects of oxidation, especially at high concentrations of ozone. One of the parameters, other than ozone concentration, which can have a significant effect on the stability and rate of decomposition of ozone at high concentrations, is the presence of ions in water. A number of spectroscopic techniques including intrinsic fluorescence, circular dichroism and UV-VIS were used as well as SDS-PAGE, Native-PAGE dynamic light scattering and water ion analysis, in order to investigate the effects of two relatively high concentrations of ozone on purified human hemoglobin (Hb) in phosphate buffer and diluted versions with deionized, double distilled and tap water in vitro. Niraparib purchase Purified human Hb and not whole blood human Hb was used in this study, since the addition of water to the whole blood would have caused the RBCs to lyse, affecting the purification of Hb for further analysis. Therefore, using purified Hb, it was possible to investigate the effects of dap water, containing bicarbonate ions.
Molybdenum cofactor sulfurase (MOCOS) is an enzyme participating in purine metabolism. The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction.
This SNP was genotyped in 200 persons with methamphetamine addiction, 85 patients with bipolar disorder 1 (BP1), 78 patients with BP2, 33 patients with major depressive disorder (MDD) and 200 age-/sex-matched normal subjects using the tetra-primer amplification-refractory mutation system (ARMS)-PCR technique.
The rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C OR (95% CI) = 0.466 (0.252-0.864),
-value = 0.014; C/A vs C/C OR (95% CI) = 0.641 (0.418-0.981),
-value = 0.04]. This SNP was also associated with this trait in dominant model [OR (95% CI) = 0.591 (0.398-0.879),
-value = 0.009]. The A allele of rs594445 had a protective role against methamphetamine addiction [A vs C OR (95% CI) = 0.645 (0.48-0.866),
-value = 0.004]. The rs594445 was associated with BP1 in co-dominant model [C/A vs C/C OR (95% CI) = 0.423 (0.230-0.778),
-value = 0.005]. However, the associations were insignificant in other inheritance models.
Finally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.
Finally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.Cancer is a heterogeneous and complex disease and one of the leading causes of death worldwide. The high tumor heterogeneity between individuals affected by the same cancer type is accompanied by distinct molecular and phenotypic tumor profiles and variation in drug treatment response. In silico modeling of cancer as an aberrantly regulated system of interacting signaling molecules provides a basis to enhance our biological understanding of disease progression, and it offers the means to use computer simulations to test and optimize drug therapy designs on particular cancer types and subtypes. This sets the stage for precision medicine the design of treatments tailored to individuals or groups of patients based on their tumor-specific molecular cancer profiles. Here, we show how a relatively large manually curated logical model can be efficiently enhanced further by including components highlighted by a multi-omics data analysis of data from Consensus Molecular Subtypes covering colorectal cancer. The model expansion was performed in a pathway-centric manner, following a partitioning of the model into functional subsystems, named modules.