Nuclear protein 1 promotes unfolded protein response during endoplasmic reticulum stress, and alleviates apoptosis induced by cisplatin in non-small cell lung cancer cells

Purpose: To investigate the role of nuclear protein 1 (NUPR1) in the drug resistance of non-small cell lung cancer (NSCLC) and its regulatory mechanisms. Methods: Quantitative polymerase chain reaction (qPCR) and immunoblot assays were conducted to determine NUPR1 expression in A549 cells. Cisplatin sensitivity and cisplatin-induced apoptosis were investigated in NUPR1 knockdown or overexpressed cells via 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and flow cytometry. The potential association between unfolded protein response (UPR) and NUPR1 levels in response to cisplatin were explored. The effect of endoplasmic reticulum (ER) stress on apoptosis was examined using flow cytometry. Results: Cisplatin treatment promoted the expression of NUPR1 in NSCLC cells. NUPR1 regulated cisplatin resistance in NSCLC and also regulated UPR in ER stress induced by cisplatin. The results show NUPR1 regulated apoptosis induced by ER stress following tunicamycin treatment. Conclusion: NSCLC cells may promote the UPR in ER stress by promoting the expression of NUPR1, thereby reducing the ER stress induced by cisplatin

Association between homocysteine, vitamin B₁₂, folic acid and erectile dysfunction:a cross-sectional study in China

Abstract Objectives: Erectile dysfunction (ED) affects up to 53.4% of men aged 30–80 years. In this study, we aimed to examine the association between homocysteine (HCY), vitamin B₁₂ (B12), folic acid (FA) and ED. Design: Cross-sectional study. Setting: Guangxi, China. Participants: A total of 1381 participants who completed questionnaires were included, between September 2009 and December 2009. Measures: ED was evaluated by the International Index of Erectile Function scores. Also, the values of HCY, B12 and FA were acquired. Then, regression and between-group analyses were performed. Results: No association between FA and ED was found. Significant correlations between HCY and ED were found—the relationships between these two parameters were most notable in men aged over 60 years and in men living alone (bachelors or bachelorhood). B12 levels were higher in men with ED (718.53±234.37 pg/mL vs 688.74±229.68, p=0.015). Using multinomial logistic regression analyses, B12 levels were related to mild ED (multivariate adjusted analysis: OR 1.620, 95% CI 1.141 to 2.300, p=0.007), especially among men aged 40–49 years (OR 2.907, 95% CI 1.402 to 6.026, p=0.004). Conclusions: We report, for the first time, a relationship between B12 levels and ED. We also found specific cohorts of men for whom the relationship between HCY levels and ED is most prominent. Further studies are required to elucidate the mechanisms underlying these relationships—these may ultimately result in new therapies for ED