Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. We previously reported that opioids inhibit cell growth and trigger apoptosis in lymphocytes. However, the underlying mechanism by which microglia apoptosis in response to opioids is not yet known. In this study, we show that morphine induces microglia apoptosis and caspase-3 activation in an opioid-receptor dependent manner. Morphine decreased the levels of microglia phosphorylated Akt (p-Akt) and p-GSK-3β (glycogen synthase kinase 3 beta) in an opioid receptor dependent manner. More interestingly, GSK-3β inhibitor SB216763 significantly increases morphine-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. Moreover, co-treatment of microglia with SB216763 and morphine led to a significant synergistic effect on the level of phospho-p38 mitogen-activated protein kinase (MAPK). In addition, inhibition of p38 MAPK by its specific inhibitor SB203580 significantly inhibited morphine-induced apoptosis and caspase-3 activation. Taken together, our data clearly demonstrates that morphine induced apoptosis in microglial cells, which is mediated via GSK-3β and p38 MAPK pathways.
Our results demonstrated that SCH was significantly associated with a higher risk of MetS. Well-designed cohort studies were warranted to confirm our findings.
The relationship between abdominal aortic calcification (AAC) and bone fracture has been examined by some observational studies, but the results remain discordant. Therefore, we aimed to assess the link between them by conducting a meta-analysis of prospective studies. Relevant studies were identified by searching PubMed and EMBASE databases until the end of December 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between AAC and fracture risk were estimated with fixed- or random- effects models. Seven prospective studies were included in the final analysis. The summarized RRs of any type of fractures for the highest compared with the lowest category of AAC were 1.64 (95% CI 1.30-2.07, P = 0.000) with mild heterogeneity (I = 30.1%, P = 0.188). Subgroup analysis showed that the association between AAC and fracture was not significantly modified by gender and follow-up length. Risks were similar when analyses were restricted to the studies with adjustment for bone mineral density (BMD) (RR = 1.76, 95% CI 1.31-2.38, P = 0.000, I = 49.1%). For the specific type of fracture, severe AAC was significantly related with hip fracture (RR = 1.64, 95% CI 1.22-2.20, P = 0.001, n = 5), but not with vertebral (RR = 1.45, 95% CI 0.81-2.58, P = 0.213, n = 3) or non-vertebral fracture (RR = 1.35, 95% CI 0.96-1.88, P = 0.081, n = 3). There was no evidence of publication bias. Our findings demonstrated that AAC was significantly and independently associated with a higher fracture risk, especially for hip fracture.
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