Bioinformatics analysis of gene expression profiles of Inclusion body myositis.

Inclusion body myositis (IBM) is a disease with a poor prognosis and limited treatment options. This study aimed at exploring gene expression profile alterations, investigating the underlying mechanisms and identifying novel targets for IBM. We analysed two microarray datasets (GSE39454 and GSE128470) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between IBM and normal samples. Gene Ontology（GO）function and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Finally, protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, in order to identify hub genes. A total of 144 upregulated DEGs and one downregulated DEG were identified. The GO enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 22 significant pathways, the majority of which could be divided into the immune and infectious diseases. Following the construction of PPI networks, ten hub genes with high degrees of connectivity were picked out, namely PTPRC, IRF8, CCR5, VCAM1, HLA-DRA, TYROBP, C1QB, HLA-DRB1, CD74 and CXCL9. Our research hypothesizes that autoimmunity plays an irreplaceable role in the pathogenesis of IBM. The novel DEGs and pathways identified in this study may provide new insight into the underlying mechanisms of IBM at the molecular level.

Inhibitory Effects of Genistein on Vascular Smooth Muscle Cell Proliferation Induced by Ox-LDL: Role of BKCa Channels.

BACKGROUND: Oxidized low-density lipoprotein (Ox-LDL) is a crucial pathogenic factor for vascular diseases, which can induce the proliferation of vascular smooth muscle cells (VSMCs). Genistein is the main component of soybean isoflavone. Genistein has a variety of pharmacological properties in the treatment of vascular diseases and a promising clinical application. Large-conductance calcium-activated potassium (BKCa) channels are the primary type of potassium channels in VSMCs, which regulate various biological functions of VSMCs. However, whether genistein exerts an antiproliferation effect on Ox-LDL-stimulated VSMCs remains unclear. The current study is aimed at elucidating the effect of genistein on the Ox-LDL-stimulated proliferation of VSMCs and its possible molecular mechanism, especially the electrophysiological mechanism related to BKCa channels. METHODS: Monoculture VSMC was obtained by an acute enzyme-dispersing method. The proliferation of cells was measured by CCK-8, cell cycle, and proliferating cell nuclear antigen (PCNA) expression. The BKCa whole-cell currents were measured by patch-clamp. RESULTS: Ox-LDL treatment induced the proliferation of VSMCs, upregulated the BKCa protein expression, and increased the density of BKCa currents, while genistein significantly inhibited these effects caused by Ox-LDL. BKCa channels exerted a regulatory role in the proliferation of VSMCs in response to Ox-LDL. The inhibition of BKCa channels suppressed Ox-LDL-stimulated VSMC proliferation, while the activation of BKCa channels showed the opposite effect. Moreover, genistein suppressed the activity of BKCa, including protein expression and current density in a protein tyrosine kinase- (PTK-) dependent manner. CONCLUSION: This study demonstrated that genistein inhibited the Ox-LDL-mediated proliferation of VSMCs by blocking the cell cycle progression; the possible molecular mechanism may be related to PTK-dependent suppression of BKCa channels. Our results provided novel ideas for the application of genistein in the treatment of vascular diseases and proposed a unique insight into the antiproliferative molecular mechanism of genistein.

Cannabidiol improves cognitive impairment in dementia model rats by regulating the expression of AMPA receptor in the brain / 中风与神经疾病杂志

@#To observe the effects of cannabidiol（CBD）on cognitive function and AMPA receptor expression in sporadic Alzheimer’s disease（sAD）rats induced by bilateral intraventricular injection of streptozotocin（STZ）. MethodsForty adult male Sprague-Dawley（SD）rats were randomly divided into four groups：sham operation group（S），cannabidiol（CBD）+ sham operation group（CBD+S），model group（STZ），CBD+model group（CBD+STZ）. The cognitive function of rats was tested by Morris water maze（MWM）and step-down test. Western blot was used to detecte the expression of GluR1 and GluR2 in the cerebral cortex and hippocampus. ResultsIn the Morris water maze test，compared with the S group，the escape latency in the STZ group was significantly prolonged（P<0.01），and the escape latency in the CBD+STZ group was significantly shortened（P<0.01）. In the step-down test，compared with the latency and the number of errors in the S group，the latency in the STZ group was significantly shortened（P<0.01），and the number of errors was significantly increased（P<0.01）. Compared with the STZ group，the latency of CBD+STZ group was significantly prolonged（P<0.05），and the number of errors of CBD+STZ group was significantly reduced（P<0.05）. Compared with the STZ group，the contents of GluR1 in cortex and hippocampus of the CBD+STZ group were significantly（P<0.01）（P<0.05）decreased. Compared with STZ group，the contents of GluR2 in cortex and hippocampus of the CBD+STZ group were significantly（P<0.01）（P<0.01）decreased. ConclusionCannabidiol improves STZ-induced cognitive impairment in rats by regulating AMPA receptor expression in the brain.