This study comprises two sub-studies. Study I assessed the test-retest reliability of Family Affluence Scale (FAS II) items among 95 students aged 11 and 15 years old in Beijing. Study II investigated the completion rate of traditional indicators (parents' educational level, perceived family wealth, resident area, and school location) measuring socioeconomic status (SES) compared with FAS II, and examined the internal reliability, external and construct validity of the FAS II items in a population of 5876 schoolchildren aged 11, 13 and 15 years old in Beijing. Our study found that the FAS II items have high completion rates (> 99%) which are better than other SES indicators. Analyses of reliability showed a moderate internal reliability (Cronbach's alpha = 0.58) and at least substantial test-retest reliability (ICC > 0.75). Moderate external validity of FAS II was found by Spearman rank correlation between FAS II and other SES indicators (parental education level and perceived family wealth) (r s = 0.48-0.51, p < 0.001) and ordinal regressions. Graphical log-linear Rasch model (GLLRM) showed that FAS has adequate construct validity (few LD and weak DIF). In conclusion, the FAS II is a reliable and valid SES measure for adolescents in the Beijing area.
Background Neomorphic IDH1 mutations disrupt the redox balance by promoting reactive oxygen species (ROS) production. However, the mechanism by which IDH1-mutant cells maintain ROS homeostasis remains elusive. It is also not known whether reprogrammed ROS homeostasis establishes targetable vulnerability in IDH1-mutated cancers. Methods We investigated ROS homeostasis in wild-type (GSC827, GSC923, GSC627, and GSC711) and IDH1-mutated cells (IDH1R132C- and IDH1R132H-transduced U87, U251; MGG152, and TS603 cells). We analyzed the stability and transcriptional activity of NRF2 in IDH1-mutated cells. The oxidative DNA damage was analyzed using NRF2-targeting small interfering RNA. Moreover, we evaluated the effect of the NRF2 inhibitor brusatol in an IDH1-mutated subcutaneous xenograft nude mouse model (control group, n = 5; brusatol-treated group, n = 6). All statistical tests were two-sided. Results We showed that IDH1-mutated cells develop a dependency on the NRF2 antioxidative pathway. Genetic or pharmacologic blockade of NRF2 not only disrupted ROS homeostasis (mean [SD] ROS levels increased by 317 [42.1]%, P = .001, in IDH1R132C and by 286. 5 [48.7]%, P = .003, in IDH1R132H cells) but also enhanced oxidative DNA damage and decreased proliferation of IDH1-mutated cells. Brusatol selectively suppressed IDH1-mutated cancer progression in vivo (mean [SD] final tumor volume was 761.6 [391.6] mm3 in the control and 246.2 [215] mm3 in the brusatol-treated group, P = .02). Conclusions IDH1 mutation reprograms ROS homeostasis in cancer cells, which leads to dependency on the NRF2 antioxidant pathway for ROS scavenging. NRF2 blockade might be a novel therapeutic approach to treat malignancies with IDH1 mutation.
Scope Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. Methods and results Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow‐fed mice, thereby leading to the accumulation of tauro‐β‐muricholic acid (TβMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP‐induced suppression of enterohepatic FXR‐fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α‐hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. Conclusions CAP‐induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota‐BA‐enterohepatic FXR axis in db/db mice.
Chronic hepatitis B virus (HBV) infection is partly responsible for hepatitis, fatty liver disease and hepatocellular carcinoma (HCC). HBV core protein (HBc), encoded by the HBV genome, may play a significant role in HBV life cycle. However, the function of HBc in the occurrence and development of liver disease is still unclear. To investigate the underlying mechanisms, HBc-transfected HCC cells were characterized by multi-omics analyses. Combining proteomics and metabolomics analyses, our results showed that HBc promoted the expression of metabolic enzymes and the secretion of metabolites in HCC cells. In addition, glycolysis and amino acid metabolism were significantly up-regulated by HBc. Moreover, Max-like protein X (MLX) might be recruited and enriched by HBc in the nucleus to regulate glycolysis pathways. This study provides further insights into the function of HBc in the molecular pathogenesis of HBV-induced diseases and indicates that metabolic reprogramming appears to be a hallmark of HBc transfection.
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