Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of maternally expressed gene 3 (MEG3), microRNA-378 (miR-378), and growth factor receptor-bound protein 2 (GRB2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded (MCAO)-induced ischemic stroke and an in vitro model of oxygen-glucose deprivation (OGD)-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blot analysis and neuron death was evaluated using LDH leakage rate test. Firstly, it was found that the GRB2 gene, up-regulated in MCAO-operated mice and OGD-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment, and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.
Alpha-thalassemia occurs with high frenquency in China. Four common α-globin gene deletion mutations (–SEA, -α3.7, and -α4.2, Haemoglobin Constant Spring (CS) mutation) were identified in Chinese patients. Individuals with alpha-thalassemia syndrome are more often of children. However report on endocrinal complications in children with alpha thalassemia in China are still absent. The present study aimed to investigate the impact of genotype on endocrinal complications in Chinese children. Association analysis between genotype and endocrinal compliaction development was conducted on 200 patients with 200 healthy controls. Hypogonadism was found to be the most prominent endocrinal complications (84.0%) leading to the growth retardation, hypogonadism, diabetes mellitus, hypothyroidism and hypoparathyroidism whose incidence were significantly higher in pateints. (αCSα/–SEA) was the main genotype of Alpha thalassemia identified in the patients (37.5%), and patients with the (-α4.2/–SEA) genotype had a higher prevalence of hypogonadism, diabetes mellitus and hypoparathyroidism (P = 0.001, P = 0.001, P < 0.001, respectively).
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