Objective: Immune-related mechanisms are involved in various neurological diseases and although mesenchymal stem cells (MSCs) have been shown to repair and replace injured neurons, it remains uncertain what the immune cells in the brain do during this process. Microglial cells are the representatives of immune cells in the brain. Microglial cells, injured neurons and stem cells often coexist in the same microenvironment. To investigate the effect of microglial cells on stem cells in such an environment, we tried to see how microglial cells affect the neurotrophicity of MSCs after being stimulated with injured neurons. Methods: Microglial cells (BV2) were stimulated by being cocultured with various sets of injured neurons (neuron cell pheochromocytoma, PC12), and we cocultured stimulated BV2 with MSCs whose supernatant was applied to injured PC12 to see if PC12 apoptosis was reduced. Neurotrophic factors in MSCs’ supernatant, including basic fibroblast growth factor, brain-derived neurotrophic factors and nerve growth factors, were detected. Results: We found that after coculturing with injured PC12, BV2 were able to promote the neurotrophic functions of MSCs. The supernatant of MSCs cocultured with stimulated BV2 reduced PC12 apoptosis significantly compared with control, and had the highest basic fibroblast growth factor concentration, which was also significantly different from the control. Conclusions: Our results showed that after being stimulated with injured neurons, microglial cells enhanced the neurotrophic functions of MSCs.

BackgroundAbnormal hypomethylation of oncogenes and hypermethylation of tumor suppressor genes play important roles in human tumorigenesis and cancer progression, including those of rectal cancer (RC). However, conjoint analysis of RC involving both gene expression and methylation profiling datasets remains rare. This study aimed to identify methylation-regulated differentially expressed genes (MeDEGs) and to evaluate their prognostic value in RC through bioinformatics analysis.MethodsGene expression (GSE20842 and GSE68204) and gene methylation (GSE75546) profiling datasets were obtained from the Gene Expression Omnibus database. GEO2R was adopted to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs). MeDEGs were obtained by overlapping the DEGs and DMGs and then subjected to protein–protein interaction (PPI) network analysis using STRING. Modules and hub genes within the network were identified using MCODE and CytoHubba, respectively. Prognostic MeDEGs were selected by univariate Cox regression. Finally, our findings were validated based on The Cancer Genome Atlas (TCGA) database.ResultsIn total, 243 upregulated-hypomethylated and 51 downregulated-hypermethylated genes were identified as MeDEGs. A PPI network of MeDEGs was constructed with 290 nodes and 578 edges. Three modules and three hub genes—COL3A1, FPR1, and PLK1—within the network were identified. Three MeDEGs—NFE2, COMP, and LAMA1—were found to be survival-related. Furthermore, the expression and methylation status of two hub genes (excluding FPR1) and the three prognostic MeDEGs were also significantly altered in TCGA and were consistent with our findings.ConclusionsWe identified novel MeDEGs and explored their relationship with survival in RC. Our methodology may provide an effective bioinformatics basis for further understanding of the methylation-mediated regulatory mechanisms in RC.