ABSTRACT
Rheumatoid arthritis (RA) represents a common systemic autoimmune disease which lays chronic and persistent pain on patients. The purpose of our study is to identify novel RA-related genes and biological processes/pathways. All the datasets of this study, including gene expression and DNA methylation datasets of RA and OA samples, were obtained from the free available database, i.e. Gene Expression Omnibus (GEO). We firstly identified the differentially expressed genes (DEGs) between RA and OA samples through the limma package of R programming software followed by the functional enrichment analysis in the Database for Annotation, Visualization and Integrated Discovery (DAVID) for the exploring of potential involved biological processes/pathways of DEGs. For DNA methylation datasets, we used the IMA package for their normalization and identification of differential methylation genes (DMGs) in RA compared with OA samples. Comprehensive analysis of DEGs and DMGs was also conducted for the identification of valuable RA-related biomarkers. As a result, we obtained 394 DEGs and 363 DMGs in RA samples with the thresholds of |log2fold change|> 1 and p-value < 0.05, and |delta beta|> 0.2 and p-value < 0.05 respectively. Functional analysis of DEGs obtained immune and inflammation associated biological processes/pathways. Besides, several valuable biomarkers of RA, including BCL11B, CCDC88C, FCRLA and APOL6, were identified through the integrated analysis of gene expression and DNA methylation datasets. Our study should be helpful for the development of novel drugs and therapeutic methods for RA.
ABSTRACT
Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively. mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.