Hepatocellular carcinoma (HCC) is generally resistant to chemotherapy due to intrinsic or acquired drug resistances. Many molecules and signaling pathways are involved in chemo-resistance of HCC cells. However, the contribution of long noncoding RNA (lncRNA) to chemo-resistance of HCC cells is still largely unknown. In this study, we revealed the critical roles of long noncoding RNA lncARSR in chemo-resistance of HCC cells. lncARSR is upregulated in HCC, associated with large tumor size and advanced BCLC stage, and indicts poor prognosis. Functional assays showed that overexpression of lncARSR enhances doxorubicin resistance of HCC cells in vitro and in vivo. And while knockdown of lncARSR increases sensitivity of HCC cells to doxorubicin in vitro and in vivo. Mechanistically, we found that lncARSR physically associates with PTEN mRNA, promotes PTEN mRNA degradation, decreases PTEN expression, and activates PI3K/Akt pathway. PTEN is downregulated in HCC, and the expression of PTEN is negatively correlated with lncARSR in HCC tissues. Furthermore, the effects of lncARSR overexpression on doxorubicin resistance could be reversed by PI3K/Akt pathway inhibitor, and lncARSR knockdown-induced doxorubicin sensitivity could be reversed by PTEN depletion. Taken together, our results showed that upregulated lncARSR promotes doxorubicin resistance in HCC via modulating PTEN-PI3K/Akt pathway, and implied that lncARSR may serve as a promising prognostic biomarker and therapeutic target for HCC chemo-resistance. J. Cell. Biochem. 118: 4498-4507, 2017. © 2017 Wiley Periodicals, Inc.

No abstract

Tapentadol IR 75 mg might be an optimal dose for moderate to severe pain control with fewer side effects. All three doses of tapentadol IR could provide comparable efficacy to oxycodone HCL IR 10 mg.

Background The effect of inhaled corticosteroids (ICS) on risk of hyperglycemia in patients with chronic obstructive pulmonary disease (COPD) remains ambiguous. The aim of this study is to evaluate the association between ICS use and the incidence of hyperglycemia related adverse effects in COPD patients. Methods Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception to 25 May 2020. Randomized controlled trials (RCTs) of ICS versus control (non-ICS) treatment for COPD patients reporting on risk of hyperglycemia were included. The Mantel–Haenszel method with fixed-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Results Seventeen RCTs with 43,430 subjects were included in the meta-analysis. Pooled results suggested that there was no statistically significant difference in the risk of hyperglycemia between the ICS group and the control group (RR 1.02, 95% CI 0.90–1.16, P = 0.76). In addition, no significant difference was noted in the effect on glucose level (RR 1.20, 95% CI 0.79–1.82, P = 0.40), risk of diabetes progression (RR 0.84, 95% CI 0.20–3.51, P = 0.81) and new onset diabetes mellitus (RR 1.0, 95% CI 0.88–1.15, P = 0.95) between the ICS group and the control group. These findings also were consistent across all subgroup analyses. Conclusions Use of ICS does not have an effect on the blood glucose and is not associated with the risk of new onset diabetes mellitus and diabetes progression in patients with COPD. Further RCTs exploring the association between ICS use and risk of hyperglycemia in COPD patients are still needed to verify our results of this analysis.