Combined exposure to benzo(a)pyrene and dibutyl phthalate aggravates pro-inflammatory macrophage polarization in spleen via pyroptosis involving cathepsin B.

Humans are often simultaneously exposed to benzo(a)pyrene (BaP) and dibutyl phthalate (DBP) through consumption of food and water. Yet, direct evidence of the link between BaP and DBP co-exposure and the risk of splenic injury is lacking. In the present study, we established the rats and primary splenic macrophages models to evaluate the effects of BaP or/and DBP exposure on spleen and underlying mechanisms. Compared to the single exposure or control groups, the co-exposure group showed more severe spleen damage and higher production of pro-inflammatory cytokines. Co-exposure to BaP and DBP resulted in a 1.79-fold, 2.11-fold and 1.9-fold increase in the M1 macrophage markers iNOS, NLRP3 (pyroptosis marker protein) and cathepsin B (CTSB), respectively, and a 0.8-fold decrease in the M2 macrophage marker Arg1 in vivo. The more prominent effects in perturbation of imbalance in M1/M2 polarization (iNOS, 2.25-fold; Arg1, 0.55-fold), pyroptosis (NLRP3, 1.43-fold), and excess CTSB (1.07-fold) in macrophages caused by BaP and DBP co-exposure in vitro were also found. Notably, MCC950 (the NLRP3-specific inhibitor) treatment attenuated the pro-inflammatory macrophage polarization and following pro-inflammatory cytokine production triggered by BaP and DBP co-exposure. Furthermore, CA-074Me (the CTSB-specific inhibitor) suppressed the macrophages pyroptosis, pro-inflammatory macrophage polarization, and secretion of pro-inflammatory cytokine induced by BaP and DBP co-exposure. In conclusion, this study indicates co-exposure to BaP and DBP poses a higher risk of spleen injury. Pro-inflammatory macrophage polarization regulated by pyroptosis involving CTSB underlies the spleen injury caused by BaP and DBP co-exposure.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

Visceral adiposity measures are strongly associated with cardiovascular disease among female participants in Southwest China: A population-based prospective study.

Background and aims: Controversy remains regarding the prediction effects of different adiposity measure indicators for the risk of cardiovascular disease (CVD). Our study aimed to assess the associations of three traditional anthropometric indicators, namely, waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) as well as three non-traditional anthropometric indicators, namely, the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and body shape index (ABSI), with the risk of CVD among Southwest Chinese population. Methods: Our study was based on the Guizhou Population Health Cohort Study (GPHCS) conducted from 2010 to 2020. A total of 9,280 participants were recruited from 12 areas in Guizhou Province, China, from November 2010 to December 2012, and followed up for major chronic diseases until December 2020. A total of 7,837 individuals with valid data were included in this analysis. The gender-specific associations of WC, WHtR, BMI, CVAI, LAP, and ABSI with CVD were evaluated using Cox proportional hazards models. Receiver operating characteristic (ROC) curve analysis was used to estimate the prediction powers of different indicators for CVD. Results: No association of six indicators with CVD was observed among male participants. Female participants with either WC-based central obesity (HR: 1.82, 95% CI: 1.12-2.97) or WHtR-based central obesity (HR: 1.68, 95% CI: 1.07-2.64) had a higher risk of CVD, after adjusted for age, area, ethnic group, smoking, alcohol drinking, MET, previous history of diabetes, hypertension and dyslipidemia, medication use, and nutraceutical intake. Compared with female participants in the lowest quartile (Q1), those in the highest quartile (Q4) of WHtR (HR: 2.24, 95% CI: 1.17-4.27), CVAI (HR: 3.98, 95% CI: 1.87-8.49), and ABSI (HR: 1.94, 95% CI: 1.06-3.52) had an increased risk for incident CVD. CAVI showed the maximum predictive power of CVD with the biggest AUC of 0.687 (95% CI: 0.654-0.720) compared to other indicators in female participants. Conclusions: Visceral adiposity measures, especially CVAI, are stronger predictive indicators of CVD among female and not male participants in Southwest China. Different anthropometric indexes need to be combined to comprehensively assess health risks.

[Analysis of colliery migrant workers quality of life and its influential factors].

OBJECTIVE: To study colliery migrant workers' quality of life and related influential factors. METHODS: By multi-stage random sampling, 1161 colliery migrant workers were collected and assessed with the SF-36 and the self-made questionnaires. Multiple covariance and optimal scaling regression statistical methods were used to analyze the data. RESULTS: Physiological and mental health filed of colliery migrant workers, the physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) and vitality (VT) score of those colliery migrant workers whose working age was less than 5 years higher than those over 10 years. The PF, RP, BP, GH, mental health (MH), VT and SF based within the health group, resulted in a higher score, compared to those who suffer from chronic diseases. The RP, GH and social functioning (SF) based within the mild labor intensity, resulted in a higher score, compared to those who severe labor intensity. The PF and RE based within the non-initial coal mine work, resulted in a higher score, compared to those who initial coal mine work. The PF, BP and VT based within the pre-employment physical examination, resulted in a higher score, compared to those who non pre-employment physical examination. The MH based within the smoking, resulted in a higher score, compared to those who no smoking. These differences were statistical significance (P < 0.05). Multiple factors analysis showed that working age (F = 19.26, P < 0.01), chronic diseases (F = 13.89, P < 0.01) and initial coal mine work (F = 8.48, P < 0.01) were the influential factors of physical component summary (PCS). Labor intensity (F = 5.90, P < 0.01), smoking (F = 10.45, P < 0.01) and chronic diseases (F = 7.91, P < 0.01) were the influential factors of mental component summary (MCS). CONCLUSION: There are some difference in individual characteristics (e. g. working age). Working age, chronic diseases, initial coal mine work, labor intensity, smoking are the influential factors for quality of life.

[Analysis of occupational burnout and its influencing factors of colliery migrant workers in Guizhou Province].

OBJECTIVE: To understand the status of occupational burnout of colliery migrant workers and its influencing factors. METHODS: The occupational burnout of 1161 colliery migrant workers in Jinsha County, Guizhou Province was measured with MBI-GS and the self-made questionnaire. RESULTS: All dimensions of MBI-GS Cronbach's α coefficient was in the range of 0.86-0.88, all 15 items of MBI-GS were subjected to factor analysis, and three latent factors were identified, which explained 68.86% of the total variance and consisted with the theory model. The score of occupational burnout of each dimension, differences in different individual characteristics (physical examination, sleep, et al) were statistically significant (P <0.05). The influence factors of occupational burnout of colliery migrant workers were physical examination, chronic disease, smoking, physical exercise, sleep, initial work in coal mine, production post and labor intensity. CONCLUSION: MBI-GS can be used to study the occupational burnout of colliery migrant workers. Different individual characteristics effect the occurrence of occupational burnout.