Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

Apoptotic protease activating factor-1 gene and MicroRNA-484: A possible interplay in relapsing remitting multiple sclerosis.

BACKGROUND: Emerging evidence suggests that dysregulated apoptosis might be implicated in the pathogenesis of multiple sclerosis (MS). The aim of the current study was to evaluate the expression of Apoptotic protease activating factor-1 (APAF1) mRNA and its potential regulator miR-484 in relapsing remitting MS patients (RRMS) and to investigate their role as potential disease biomarkers. METHODS: After Bioinformatic analysis was conducted and revealed miR-484 involvement in the regulation of APAF-1 gene expression. Reverse Transcription-quantitative Real-Time PCR (RT-qPCR) was performed to detect the expression levels of APAF-1 and miR-484 in the peripheral blood mononuclear cells (PBMCs) of 34 RRMS patients recruited from the MS clinic of kasr al ainy hospital- faculty of medicine-Egypt and 34 healthy controls. RESULTS: APAF-1 mRNA was significantly downregulated in patients whereas miR-484 expression was upregulated compared to controls (p < 0.01). Sensitivity and specificity of APAF-1 and miR-484 to diagnose MS was (85.3%, 76.5%) and (88.2% and 86.7%) respectively. CONCLUSION: APAF-1 and miR-484 could play a role as potential MS diagnostic biomarkers. However, absence of a control group of patients with other inflammatory diseases in our study warrants further research to corroborate our findings.

Evaluation of the diagnostic and therapeutic roles of non-coding RNA and cell proliferation related gene association in hepatocellular carcinoma.

Micro RNA-34a-5p (miR-34a-5p) is an important molecule that can act as a modulator of tumor growth. It controls expression of a plenty of proteins controlling cell cycle, differentiation and apoptosis and opposing processes that favor viability of cancer cells, their metastasis and resistance to chemotherapy. Bioinformatics analysis indicated that minichromosome maintenance protein 2 (MCM2) is a target gene of miR-34a-p. In this study, RT-qPCR was employed to detect the expression of miR-34a-5p and MCM2 in 10 hepatocellular carcinoma (HCC) tissues. The functional role of miR-34a-5p in HCC was investigated and the interaction between miR-34a-5p and MCM2 was explored. Results showed miR-34a-5p expression in HCC tissues was significantly lower than in non HCC liver tissues (P < 0.05), but MCM2 expression in HCC tissues was markedly higher than in non HCC liver tissues (P < 0.05). In addition, miR-34a-5p expression was negatively related to MCM2 expression. To confirm effect of miR-34a-5p on tumor growth and its possible effect on MCM2, miR-34a-5p mimic and inhibitor was transfected into HCC cell lines (HepG2). MTS assay, showed miR-34a-5p over-expression could inhibit the proliferation of HCC cells. RT-qPCR was done to detect the expression of miR-34a-5p and MCM2 in HepG2 cells before and after transfection. Results showed that MCM2 expression in HCC tissues was markedly lower in mimic transfected group than in inhibitor transfected group and control group (P < 0.05) while miR-34a-5p expression in HepG2 cells was significantly higher in mimic transfected group than in inhibitor transfected group and control group (P < 0.05). Thus, miR-34a-5p may inhibit the proliferation of HCC cells via regulating MCM2 expression. These findings provide an evidence for the emerging role of microRNAs as diagnostic markers and therapeutic targets in HCC.