CircRIMS promotes cerebral ischemia-reperfusion injury through increasing apoptosis and targeting the miR-96-5p/JAK/STAT1 axis.

OBJECTIVE: This study aims to explore the function of circRIMS in cerebral ischemia/reperfusion (CIR) and its regulatory mechanism. METHOD: The expression of the circRIMS was examined in GEO chip data and validated by qRT-PCR analysis. A middle cerebral artery occlusion/repression (MCAO/R) model was developed using C57BL/6J mice. Starbase and circinteractome were employed to identify the target miRNA and mRNA. The result was confirmed by dual-luciferase reporter assay, and biotinylated RNA-pulldown assay. The cell viability and apoptosis were confirmed through CCK-8 and flow cytometry assay. RESULTS: This study revealed that circRIMS expression was upregulated in MCAO mice model and OGD/RX-simulated cell model. Knockdown circRIMS demonstrated the functional of circRIMS in increasing cell viability, reducing apoptosis, LDH activity and inflammatory factors secretion in OGD/RX-simulated CIR injury in vitro. Additionally, miR-96-5p was identified as a target of circRIMS, while the STAT1 gene is a downstream gene of miR-96-5p, and JAK was also considered to be a downstream gene of the JAK-STAT pathway. Furthermore, inhibition of miR-96-5p or overexpression of STAT1 promoted the progression of CIR injury by elevating apoptosis, reducing cell viability, and increasing the secretion of inflammatory cytokines. CONCLUSION: CircRIMS contributes to the progression of CIR injury via regulating miR-96-5p/JAK/STAT1 axis.

Lycium barbarum polysaccharide alleviates oxygen glucose deprivation-induced PC-12 cells damage by up-regulating miR-24.

Objective: This research was aimed to detect the functions of Lycium barbarum polysaccharides (LBPs) on oxygen and glucose deprivation (OGD) injury and potential mechanisms at PC-12 cells. Methods: CCK-8, flow cytometry and reactive oxygen species (ROS) assays were used to detect OGD, LBPs and miR-24 effects on cell viability, apoptosis, and oxidative stress. MiR-24 was transfected and texted by transfection and qRT-PCR. Moreover, the related-protein levels of apoptosis, autophagy and pathways were tested by Western blotting. Results: LBPs significantly enhanced cell viability , inhibited cell apoptosis, autophagy and ROS level in OGD injury. In addition, miR-24 expression was declined in OGD-treated cells, while it was elevated when added LBPs. The preventive effects of LBPs on PC-12 cell damage induced by OGD were reversed by down-regulating miR-24. Furthermore, miR-24 inhibitor declined LBPs-induced change in Wnt/ß-catenin and JAK1/STAT3 pathways in OGD-injuried cells. Conclusions: LBPs exhibited preventive effects via up-regulating miR-122 and activating Wnt/ß-catenin and JAK1/STAT3 pathways in OGD-induced PC-12 cells.

Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494.

Cerebral stroke is a leading cause of death and permanent disability. The current therapeutic outcome of ischemic stroke (>85% of all strokes) is very poor, thus novel therapeutic drug is urgently needed. In vitro cell model of ischemia was established by oxygen-glucose deprivation (OGD) and in vivo animal model of ischemia was established by middle cerebral artery occlusion (MCAO). The effects of Spatholobus suberctus Dunn extract (SSCE) on OGD-induced cell injury, MCAO-induced neural injury and miR-494 level were all evaluated. The possible target genes were virtually screened utilizing bioinformatics and verified by luciferase assay. Subsequently, the effects of abnormally expressed miR-494 on OGD-induced cell injury and target gene expression were determined. Additionally, whether SSCE affected target gene expression through modulation of miR-494 was studied. Finally, the effects of aberrantly expressed Sox8 on OGD-induced injury and signaling pathways were estimated. SSCE reduced OGD-induced cell injury and ameliorated MCAO-induced neuronal injury, along with down-regulation of miR-494. Then, OGD-induced cell injury was increased by miR-494 overexpression but decreased by miR-494 silence. Sox8 was a target gene of miR-494, and SSCE could up-regulate Sox8 expression via down-regulating miR-494. Afterwards, OGD-induced cell injury was proved to be increased by Sox8 inhibition but reduced by Sox8 overexpression. Finally, OGD-induced inhibition of PI3K/AKT/mTOR and MAPK pathways was further inhibited by Sox8 silence but activated by Sox8 overexpression. SSCE ameliorates ischemia-induced injury both in vitro and in vivo by miR-494-mediated modulation of Sox8, involving activations of PI3K/AKT/mTOR and MAPK pathways.

Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. Galectin-3 (Gal-3) is characterized by a conserved sequence within the carbohydrate recognition domain. The effect of Gal-3 in AD is presently unknown. In this study, we found significantly increased Gal-3 serum levels in patients with AD compared to control participants (P=.017). There was no significant difference between patients with mild cognitive impairment (MCI) and healthy controls (P=.143) or between patients with AD and MCI (P=.688). The degree of cognitive impairment, as measured by the Mini-Mental Status Examination score, was found to have a significant correlation with the Gal-3 serum levels in all patients and healthy controls. These data suggest that Gal-3 potentially plays a role in the neuropathogenesis of AD. The Gal-3 found in serum could be a potential candidate for a biomarker panel for AD diagnosis.