Abstract. The p53 protein is one of the best-known tumor suppressors. Recently discovered ASPP1 and ASPP2 are specific activators and iASPP is an inhibitor of p53. In the present study, we found that of 37 NSCLC patients, p53 alterations were detected in 20 tumors (54.1%), the mRNA expression of ASPP1 and ASPP2 was frequently dowregulated in tumor tissues, and this decreased significantly in samples expressing wild-type p53. The expression of ASPP1 and ASPP2 was downregulated and that of iASPP was upregulated in two NSCLC cell lines (the NCI-H157 cell line with altered p53 and the A549 cell line with wild-type p53). The NCI-H157 cell with higher ASPP1 and ASPP2 levels was more sensitive to cisplatin than the A549 cells with lower ASPP1 and ASPP2 levels. Downregulation of iASPP by siRNA stimulated apoptosis through p53 in two NSCLC cell lines. These findings provide new insights into the molecular mechanisms of action of the ASPP family in NSCLC and may have potent therapeutic applications.

Background:The association between the serum uric acid (sUA) to creatinine ratio (sUA/Cr) and non-alcoholic fatty liver disease (NAFLD) has not been sufficiently clarified. In this study, we investigated the relationship between sUA/Cr and NAFLD among participants in the United States. Methods:We performed a cross-sectional study based on data from the National Health and Nutrition examination Survey (NHANES) 2017-2018. A measured controlled attenuation parameter (CAP) value of ≥274 dB/m detected by Fibroscan was used to identify hepatic steatosis. SUA/Cr was calculated as sUA divided by serum creatinine. Multivariate logistic regression analysis was used to estimate the association between sUA/Cr and NAFLD. The adjusted odds ratio (OR) of sUA/Cr for NAFLD was estimated, and subgroup analysis stratified by sex was also conducted. The nonlinear relationship between sUA/Cr and NAFLD was further described using smooth curve fittings and threshold-effect analysis. Results:We found that sUA/Cr was positively correlated with NAFLD status after fully adjustment for confounding factors. In subgroup analysis stratified by sex, the positive interaction between sUA/Cr and NAFLD status only existed in women but not in men. Moreover, the nonlinear association between sUA/Cr and NAFLD status was an inverted U-shaped curve with an inflection point at 9.7 among men. Conclusions:Our study identified that sUA/Cr was positively associated with the risk of NAFLD among individuals in the United States. Moreover, the correlation between sUA/Cr and NAFLD differed according to sex.

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Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential. Sirt1 regulates cell differentiation and apoptosis. However, Sirt1’s effect on BMSCs osteogenic/adipogenic differentiation has not been fully elucidated. SD rats were randomly divided into Osteoporosis (OP) group and sham operation group. OP rat BMSCs were isolated and assigned into control group, NC group and Sirt1 siRNA group followed by analysis of Sirt1 level by Real-time PCR, cell proliferation by MTT assay, expression of OC, OPN and FABP4 level by real time PCR, and β-Catenin/TCF1/Runx2 protein expression by Western blot. In OP group, Sirt1 expression was significantly increased and BMSCs proliferation was decreased along with reduced OC and OPN mRNA expression, increased FABP4 expression and reduced β-Catenin/TCF1/Runx2 expression compared with sham operation group (P < 0.05). In Sirt1 siRNA group, Sirt1 expression was significantly reduced, BMSCs proliferation was increased, OC and OPN mRNA expression was increased, FABP4 expression was decreased, and β-Catenin/TCF1/Runx2 expression was increased compared to OP group (P < 0.05). Sirt1 is increased in osteoporosis. Down-regulating Sirt1 in osteoporotic BMSCs can regulate β-Catenin/TCF1/Runx2 signaling and promote BMSCs osteogenic differentiation and inhibit adipogenic differentiation.