Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model.

The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low­myricetin (1 mg/kg), medium­myricetin (5 mg/kg) and high­myricetin (25 mg/kg) groups. Neurological deficit scores were evaluated by an examiner blinded to the experimental groups. Brain infarct size was estimated macroscopically using 2,3,5­triphenyltetrazolium chloride staining. The levels of inflammatory factors tumor necrosis factor (TNF)­α, interleukin (IL)­6 and IL­1ß, and oxidative stress index superoxide dismutase (SOD), malondiadehyde (MDA), and the glutathione/glutathione disulfide (GSH/GSSG) ratio were measured by ELISA. The degree of brain cell apoptosis was determined using a terminal deoxynucleotidyl transferase dUTP nick­end labeling assay. Protein expression levels of total or phosphorylated p38 mitogen activated protein kinase (MAPK), nuclear factor (NF)­κB/p65 and protein kinase B (AKT) were determined using a western blotting assay. The neurological deficit score and infarct area induced by pMCAO decreased in a dose­dependent manner following myricetin treatment. Furthermore, myricetin reduced the expression levels of IL­1ß, IL­6, TNF­α, and MDA, and increased GSH/GSSG ratio and SOD activity. A significant decrease in cell apoptosis was observed in response to myricetin. In addition, myricetin significantly increased the level of phosphorylated AKT protein, and decreased the phosphorylation of p38 MAPK and the level of NF­κB/p65. Overall, the results of the present study suggested that myricetin exhibits a therapeutic effect by reducing ischemic cerebral injury, and the protective effect of myricetin may be associated with the p38 MAPK, NF­κB/p65 and AKT signaling pathways.

miR-143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma.

Despite evidence that the crucial role of NUAK family, SNF1-like kinase, 2 [NUAK2; also known as sucrose non-fermenting 1 (SNF1)-like kinase (SNARK)], has been highlighted in cancer development and in tumor progression, to the best of our knowledge, there are no studies available to date on the role of NUAK2 in glioblastoma. Thus, in this study, in order to determine the role of NUAK2 in glioblastoma, we performed western blot analysis to detect its expression in glioma. The results demonstrated that NUAK2 expression was upregulated in glioma tissues and that its expression was associated with the advanced stages of the disease. In vitro, NUAK2 overexpression promoted the proliferation, migration and invasion of A172 glioblastoma cells, whereas the silencing of NUAK2 with a plasmid carrying shRNA targeting NUAK2 inhibited the proliferation of A172 glioblastoma cells. Moreover, NUAK2 regulated cancer stem cell (CSC)-related gene expression in the glioblastoma cells. We performed an analysis of potential microRNA (miR or miRNA) target sites using 3 commonly used prediction algorithms, miRanda, TargetScan and PicTar. All 3 algorithms predicted that miR­143 targeted the 3'-untranslated region (3'UTR) of NUAK2. Subsequent experiments confirmed this prediction. Finally, we found that miR­143 inhibited the proliferation, migration and invasion of the glioblastoma cells. Thus, the findings of the present study demonstrate that miR­143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma.