Silica nanoparticles induce pulmonary autophagy dysfunction and epithelial-to-mesenchymal transition via p62/NF-κB signaling pathway.

It has been reported that silica nanoparticles (SiNPs) could cause epithelial-to-mesenchymal transition (EMT), but the specific mechanism is still unclear. Thus, the purpose of this study was to investigate the underlying mechanisms of pulmonary EMT after subacute exposure to SiNPs. The results showed intratracheal instillation of SiNPs increased the pulmonary MDA content, while decreased the activity of SOD and GSH-Px in rats. Western blot analysis demonstrated that SiNPs induced autophagy dysfunction via the upregulation of p62. Meanwhile, the inflammation cytokines (TNF-α, IL-18, IL-1ß) were released in rat lung. Immunohistochemistry and western blot assays both showed that SiNPs could regulate the related protein biomarkers of EMT through decreasing E-cadherin and increasing vimentin in a dose-dependent manner. Besides, SiNPs activated the proteins expression involved in p62/NF-κB signaling pathway, whereas the pulmonary EMT induced by SiNPs was significantly dampened after the knock down of p62. In this study, we illustrated that subacute exposure to SiNPs could trigger the autophagy dysfunction and pulmonary inflammation, further lead to EMT via activating the p62/NF-κB signaling pathway. Our findings provide new molecular evidence for SiNPs-induced pulmonary toxicity.

New insight into air pollution-related cardiovascular disease: an adverse outcome pathway framework of PM2.5-associated vascular calcification.

Despite the air quality has been generally improved in recent years, ambient fine particulate matter (PM2.5), a major contributor to air pollution, remains one of the major threats to public health. Vascular calcification is a systematic pathology associated with an increased risk of cardiovascular disease. Although the epidemiological evidence has uncovered the association between PM2.5 exposure and vascular calcification, little is known about the underlying mechanisms. The adverse outcome pathway (AOP) concept offers a comprehensive interpretation of all of the findings obtained by toxicological and epidemiological studies. In this review, reactive oxygen species generation was identified as the molecular initiating event (MIE), which targeted subsequent key events (KEs) such as oxidative stress, inflammation, endoplasmic reticulum stress, and autophagy, from the cellular to the tissue/organ level. These KEs eventually led to the adverse outcome, namely increased incidence of vascular calcification and atherosclerosis morbidity. To the best of our knowledge, this is the first AOP framework devoted to PM2.5-associated vascular calcification, which benefits future investigations by identifying current limitations and latent biomarkers.

Associations of organophosphate metabolites with thyroid hormone and antibody levels: findings from U.S. National Health and Nutrition Examination Survey (NHANES).

Studies have shown that organophosphate pesticides (OPs) exposure may disrupt thyroid endocrine functions in animal models, agricultural population, occupational workers, and work-related population. However, the relationships between OPs exposure and thyroid hormone levels in the general population are unclear. This study aimed to explore the relationships of OPs exposure with thyroid hormone and antibody levels in the general population. We analyzed a sample of 1089 US adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2002. OPs exposure was estimated using measures of six non-specific dialkyl phosphate metabolites (DAPs), e.g., dimethylphosphate (DMP). Multiple linear regression models were used to examine the associations of OPs exposure with thyroid hormone and antibody levels. The medians of urinary ∑DAPs detected in males and females were 32.98 nmol/g creatinine and 40.77 nmol/g creatinine, with statistical significance (p = 0.001). After controlling for sociodemographic factors, we found that concentrations of urinary OPs metabolites were positively associated with the serum thyroid stimulating hormone (TSH) in the general US population, particularly in males; OPs metabolites were associated with the serum TgAb, tT3, fT3, and TSH. These findings showed that thyroid hormone and antibody disruption are probably associated with OPs exposure in the general population; more studies are needed to confirm our findings.