During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

Tungsten (W) is an emerging contaminant that can damage multiple systems in humans. However, studies of its effects on cardiovascular disease (CVD) are limited. The monocyte count to High-density lipoprotein cholesterol ratio (MHR) is a composite inflammatory index of great concern in recent years, derived from lipid and cell inflammation parameters, that is used to indicate the risk of CVD. This study aimed to investigate the association between urinary W and CVD in the general population and compare the mediating effects of lipids, cell inflammatory parameters, and MHR to find a better target for intervention. We analyzed data from 9137 (≥ 20 years) participants in the National Health and Nutrition Examination Survey (NHANES), from 2005 to 2018. Restricted cubic splines (RCS) and survey-weighted generalized linear models (SWGLM) were used to assess the relationship between W and CVD. Mediated analyses were used to explore lipids, cell inflammatory parameters, and MHR in the possible mediating pathways between W and CVD. In SWGLM, we found that W enhances the risk of CVD, especially congestive heart failure (CHF), coronary heart disease (CHD), and angina pectoris (AP). Women, higher age groups (≥ 55 years), and those with hypertension were vulnerable to W in the subgroup analysis. Mediation analysis showed that monocyte count (MC), white blood cell count (WBC), high-density lipoprotein cholesterol (HDL), and MHR played a mediating role between W and CVD in proportions of 8.49%, 3.70%, 5.18%, and 12.95%, respectively. In conclusion, our study shows that urinary W can increase the risk of CVD, especially for CHF, CHD, and AP. Women, older age groups, and people with hypertension seem to be more vulnerable to W. In addition, MC, WBC, HDL, and MHR mediated the association between W and CVD, especially MHR, which suggests that we should consider it as a priority intervention target in the future.

Tungsten (W) is an emerging contaminant that can damage multiple systems in humans. However, studies of its effects on cardiovascular disease (CVD) are limited. The monocyte count to High-density lipoprotein cholesterol ratio (MHR) is a composite in ammatory index of great concern in recent years, derived from lipid and cell in ammation parameters, that is used to indicate the risk of CVD. This study aimed to investigate the association between urinary W and CVD in the general population and compare the mediating effects of lipids, cell in ammatory parameters, and MHR to nd a better target for intervention. We analyzed data from 9137 (≥ 20 years) participants in the National Health and Nutrition Examination Survey (NHANES), from 2005 to 2018. Restricted cubic splines (RCS) and survey-weighted generalized linear models (SWGLM) were used to assess the relationship between W and CVD. Mediated analyses were used to explore lipids, cell in ammatory parameters, and MHR in the possible mediating pathways between W and CVD. In SWGLM, we found that W enhances the risk of CVD, especially congestive heart failure (CHF), coronary heart disease (CHD), and angina pectoris (AP). Women, higher age groups (≥ 55 years), and those with hypertension were vulnerable to W in the subgroup analysis. Mediation analysis showed that monocyte count (MC), white blood cell count (WBC), high-density lipoprotein cholesterol (HDL), and MHR played a mediating role between W and CVD in proportions of 8.49%, 3.70%, 5.18%, and 12.95%, respectively. In conclusion, our study shows that urinary W can increase the risk of CVD, especially for CHF, CHD, and AP. Women, older age groups, and people with hypertension seem to be more vulnerable to W. In addition, MC, WBC, HDL, and MHR mediated the association between W and CVD, especially MHR, which suggests that we should consider it as a priority intervention target in the future.