Identification of microRNA­363­3p as an essential regulator of chondrocyte apoptosis in osteoarthritis by targeting NRF1 through the p53­signaling pathway.

Osteoarthritis (OA) is a degenerative joint disease that affects the physical, and mental health of middle­aged and elderly people. The aims of the present study were to determine the biological function and molecular mechanisms of miR­363­3p in chondrocyte apoptosis. Exploration of the molecular mechanisms of OA may be helpful in the understand of the causes, and facilitating the prevention and treatment of OA. In the present study, the expression of nuclear respiratory factor1 (NRF1) was downregulated in the articular cartilage of OA rats in vivo and lipopolysaccharide (LPS)­treated chondrocytes in vitro. MicroRNAs (miRNA) are regulators of gene expression in the progression of OA. TargetScan software was used to predict that NRF1 was a potential target for miRNA (miR)­363, and this was confirmed in subsequent experiments. The expression of miR­363­3p was negatively correlated with the expression of NRF1, and its expression was significantly upregulated in OA model rats and in LPS­induced chondrocytes compared with the expression in the respective controls. In addition, the overexpression of miR­363­3p increased the levels of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α in vivo, and was demonstrated to promote chondrocyte injury and apoptosis by Safranin O staining and TUNEL. Moreover, the inhibition of miR­363­3p expression increased the expression of NRF1 and protected chondrocytes from apoptosis in vitro and in vivo, whereas the overexpression of miR­363­3p downregulated NRF1 expression and promoted LPS­induced chondrocyte apoptosis through the p53 pathway in vitro. The results of this study suggested that miR­363­3p­mediated inhibition of NRF1may be associated with chondrocyte apoptosis in OA.

Effect of Gastrodin on Early Brain Injury and Neurological Outcome After Subarachnoid Hemorrhage in Rats.

Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca2+ overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.