Sevoflurane anesthesia is reported to repress neurogenesis of neural stem cells (NSCs), thereby affecting the brain development, but the underlying mechanism of sevoflurane on the proliferation of NSCs remains unclear. Thus, this study aims to discern the relationship between sevoflurane and NSC proliferation. Bioinformatics tools were employed to predict the expression of microRNA-18a (miR-18a) in 9-day-old neonatal rat hippocampal tissues after sevoflurane treatment and the downstream genes of miR-18a, followed by a series of assays to explore the relationship among miR-18a, runt related transcription factor 1 (RUNX1), and β-catenin in the hippocampal tissues. NSCs were isolated from the hippocampal tissues and subjected to gain-/loss-of-function assays to investigate the interactions among miR-18a, RUNX1, and β-catenin in NSCs and their roles in NSC development. Bioinformatics analysis and experimental results confirmed high expression of miR-18a in rat hippocampal tissues and NSCs after sevoflurane treatment. Next, we found that miR-18a downregulated RUNX1 expression, while RUNX1 promoted NSC proliferation by activating the Wnt/β-catenin signaling pathway. The behavioral experiments also showed that sevoflurane caused nerve injury in rats, whilst RUNX1 overexpression protected rat neurodevelopment. Our findings uncovered that sevoflurane attenuated NSC proliferation via the miR-18a-meidated RUNX1/Wnt/β-catenin pathway, thereby impairing rat neurodevelopment.
Abnormal expression of miR-499 is related to progression of acute myocardial infarction (MI). This study aimed to explore the effect of liposomal nanoparticles carrying miR-499 antagonist on proliferation of cardiomyocytes and myocardial injury, to provide evidence for in-depth analysis of pathogenesis. With 10 sham-operated rats as control group, 10 rats were induced MI. The cardiac function and myocardial tissue morphology were detected. Myocardial cells were transfected with liposomal nanoparticles (blank group), miR-499 agonist (agonist group), liposomal nanoparticles carrying miR-499 agonist (carrier+antagonist group), or CDC25A activator and inhibitor. CDC25A, Akt, and mTOR expressions were determined in the myocardial cells upon treatments, as targeting relationships between miR-499 and CDC25A were detected by dualluciferase reporter gene assay. Myocardial cell proliferation and apoptosis were detected by flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarction (MI) rats exhibited myocardial damage and had irregular cardiac function indexes, and oxidative stress indexes with inflammatory cell infiltration and disordered myocardial architecture. miR-499 antagonist-loaded liposomal nanoparticles significantly elevated the ratio of viable cells, while cell viability was not altered in the other groups (P < 0.05). The miRNA-loaded nanomaterials induced decreased cell apoptosis, and overexpression of miR-499 increased apoptosis (P < 0.05). The expressions of CDC25A, Akt and mTOR proteins were increased by presence of miR-499 antagonist-loaded liposomal nanoparticles. However, silencing of CDC25A induced decreased viability, while the ratio of viable cells was increased in the CDC25A activator group (P < 0.05). There was a direct targeting relationship between miR-499 and CDC25A. It was found that Liposomal nanoparticles carrying miR-499 antagonist down-regulated the expression of CDC25A by down-regulating the expression of miR-499 to activate the Akt/mTOR signaling pathway, and enhanced the cardiomyocyte proliferation following MI.
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