Bioinformatic analysis and validation of microRNA-508-3p as a protective predictor by targeting NR4A3/MEK axis in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) featured a debilitating progressive disorder. Here, we intend to determine diagnosis-valuable biomarkers for PAH and decode the fundamental mechanisms of the biological function of these markers. Two mRNA microarray profiles (GSE70456 and GSE117261) and two microRNA microarray profiles (GSE55427 and GSE67597) were mined from the Gene Expression Omnibus platform. Then, we identified the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. Besides, we investigated online miRNA prediction tools to screen the target gene of DEMs. In this study, 185 DEGs and three common DEMs were screened as well as 1266 target genes of the three DEMs were identified. Next, 16 overlapping dysregulated genes from 185 DEGs and 1266 target gene were obtained. Meanwhile, we constructed the miRNA gene regulatory network and determined miRNA-508-3p-NR4A3 pair for deeper exploring. Experiment methods verified the functional expression of miR-508-3p in PAH and its signalling cascade. We observed that ectopic miR-508-3p expression promotes proliferation and migration of pulmonary artery smooth muscle cell (PASMC). Bioinformatic, dual-luciferase assay showed NR4A3 represents directly targeted gene of miR-508-3p. Mechanistically, we demonstrated that down-regulation of miR-508-3p advances PASMC proliferation and migration via inducing NR4A3 to activate MAPK/ERK kinase signalling pathway. Altogether, our research provides a promising diagnosis of predictor and therapeutic avenues for patients in PAH.

[Analgesic effect of fentanyl in neonates during mechanical ventilation].

OBJECTIVE: To study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation. METHODS: Thirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age. RESULTS: The respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (P<0.05), and the PIPP scores in the drug intervention group was significantly lower than in the control group (P<0.05). The results of follow-up visits showed no significant differences in MDI and PDI at 3, 6, 9 and 12 months of age between the drug intervention and control groups (P>0.05). CONCLUSIONS: Fentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.

Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis.

Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.