Current therapeutics options for viral myocarditis are unsatisfactory. Melatonin (MLT), a hormone secreted by the pineal gland and other organs, has protective effects on ischemic heart injury. However, the potential therapeutic effect of MLT on viral myocarditis is unknown. In this study, we investigated the protective effect of MLT on viral myocarditis in a mouse model of myocarditis infected with coxsackievirus B3 (CVB3) and explored the probable mechanisms. Mice with CVB3-induced myocarditis displayed inflammatory cell infiltration and interstitial edema. MLT treatment significantly ameliorated the myocardial injuries. In addition, the rate of autophagy changed, although apoptosis was inhibited in mouse hearts following treatment with MLT. These results suggest that MLT has a strong therapeutic effect on acute viral myocarditis, which is associated with changes in autophagy and apoptosis in the heart. Thus, MLT could be a promising novel therapeutic approach against viral myocarditis.
Embryo implantation and trophoblast invasion are principal limiting factors of pregnancy establishment. Aberrant embryo development or improper trophoblast differentiation and invasion may lead to various unfavorable pregnancy-related outcomes, including early pregnancy loss (EPL). Our clinical data show that the serum BMP2 levels were significantly increased during the first trimester of pregnancy and that the serum and BMP2 expression levels were lower in women with EPL than in women with normal early pregnancies. Moreover, we observed that BMP2 was expressed in oocytes and trophoblast cells of cleaved embryos and blastocysts prior to implantation in both humans and mice. Exogenous BMP2 promoted embryonic development by enhancing blastocyst formation and hatching in mice. LncRNA NR026833.1 was upregulated by BMP2 and promoted SNAIL expression by competitively binding to miR-502-5p. SNAIL induced MMP2 expression and promoted cell invasion in primary extravillous trophoblast cells. BMP2 promotes the invasive differentiation of mouse trophoblast stem cells by downregulating the expression of TS cell marker and upregulating the expression of trophoblast giant cell marker and labyrinthine/spongiotrophoblast marker. Our findings provide significant insights into the regulatory roles of BMP2 in the development of the placenta, which may give us a framework to explore new therapeutic strategies to pregnancy-related complications.
Background
Polycystic ovary syndrome (PCOS) is a common reproductive, neuroendocrine, and metabolic disorder in women of reproductive age that affects up to 5–10% of women of reproductive age. The aetiology of follicle development arrest and critical issues regarding the abnormal follicular development in PCOS remain unclear. The present study aims to systematically evaluate granulosa cell whole-transcriptome sequencing data to gain more insights into the transcriptomic landscape and molecular mechanism of PCOS in China.
Methods
In the present study, the microarray datasets GSE138518, GSE168404, GSE193123, GSE138572, GSE95728, and GSE145296 were downloaded from the Gene Expression Omnibus (GEO) database. Subsequently, differential expression analysis was performed on the PCOS and control groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in PCOS. Finally, hub genes and their associated ncRNAs were validated by qPCR in human-luteinized granulosa (hGL) cells and were correlated with the clinical characteristics of the patients.
Results
A total of 200 differentially expressed mRNAs, 3 differentially expressed miRNAs, 52 differentially expressed lncRNAs, and 66 differentially expressed circRNAs were found in PCOS samples compared with controls. GO and KEGG enrichment analyses indicated that the DEGs were mostly enriched in phospholipid metabolic processes, steroid biosynthesis and inflammation related pathways. In addition, the upregulated miRNA hsa-miR-205-5p was significantly enriched in the ceRNA network, and two hub genes, MVD and PNPLA3, were regulated by hsa-miR-205-5p, which means that hsa-miR-205-5p may play a fundamental role in the pathogenesis of PCOS. We also found that MVD and PNPLA3 were related to metabolic processes and ovarian steroidogenesis, which may be the cause of the follicle development arrest in PCOS patients.
Conclusions
In summary, we systematically constructed a ceRNA network depicting the interactions between the ncRNAs and the hub genes in PCOS and control subjects and correlated the hub genes with the clinical characteristics of the patients, which provides valuable insights into the granulosa cell whole-transcriptome landscape of PCOS in China.
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