ABSTRACT
BACKGROUND: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APOs). HCMV encodes multiple microRNAs (miRNAs) that have been reported to be partially related to host immune responses, cell cycle regulation, viral replication, and viral latency, and can be detected in human plasma. However, the relevance for HCMV-encoded miRNAs in maternal plasma as an indicator for APOs has never been evaluated. METHODS: Expression profiles of 22 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APOs and 28 normal controls using quantitative reverse-transcription polymerase chain reaction. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APOs and 27 control subjects. Markedly changed miRNAs were further assessed in the placenta tissues. HCMV DNA in peripheral blood leukocytes (PBLs) and anti-HCMV immunoglobulin M (IgM) and anti-HCMV immunoglobulin G (IgG) in plasma were also examined in both training and validation sets. Diagnostic value and risk factors were compared between APO cohorts and normal controls. RESULTS: Analysis of the training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were significantly increased in pregnant women with APOs compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (AUC) (0.735; 95% CI, 0.635-0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 correlated positively with APOs (P=0.029 and 0.035, respectively). Hcmv-miR-US25-1-5p in the placenta tissues were dramatically increased in APOs, and correlated with plasma hcmv-miR-US25-1-5p. Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and anti-HCMV IgG in plasma showed a statistically significant correlation with APOs. CONCLUSIONS: We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APOs that may be useful as a potential noninvasive biomarker for predicting and monitoring APOs during HCMV infection.
ABSTRACT
This study aims to investigate the effect of hesperidin on CORT-induced apoptosis and oxidative stress of mouse hippocampal nerve cells by up-regulating miR-146a-5p and related mechanism. Hesperidin was applied to CORT-induced HT-22 cells, or HT-22 cells whose expression of mir-146a-5p was up-regulated or down-regulated by CORT. The apoptosis rate was detected by flow cytometry. Expression of Cleaved-caspase-3 protein in cells was detected by Western blot. The levels of MDA, SOD and CAT in the cells were detected by enzyme-linked immunosorbent assay, and the expression of miR-146a-5p was detected by RT-qPCR. The application of hesperidin or up-regulation of miR-146a-5p can reduce the CORT-induced apoptosis rate of HT-22 cells, Cleaved caspase-3 protein expression and MAD content (p<0.05), and increase the activity of SOD and CAT and the expression of miR-146a-5p (p<0.05). In contrast, down-regulation ofmiR-146a-5p can increase the CORT-induced apoptosis rate of HT-22 cells, Cleaved caspase-3 protein expression and MAD content (p<0.05), and decrease the activity of SOD and CAT and the expression of miR-146a-5p (p<0.05). Down-regulation of miR-146a-5p expression can reverse the effects of hesperidin on CORT-induced HT-22 cell apoptosis and oxidative stress. Hesperidin may protect cells from being damaged by up-regulating miR-146a-5p to reduce CORT-induced HT-22 cell apoptosis and oxidative stress.
