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.

Untargeted lipidomics uncover hepatic lipid signatures induced by long-term exposure to polystyrene microplastics in Vivo.

OBJECTIVE: This study evaluated the effects of long-term polystyrene microplastics (PS-MPs) exposure on hepatic lipid metabolism in vivo by lipidomics. RESULTS: H&E staining showed long-term PS-MPs exposure could trigger the hepatic inflammatory cell infiltration and hepatic steatosis in SD rats, indicating long-term PS-MPs exposure caused hepatoxicity. Lipidomics revealed that the concentrations of 8 lipid metabolites in the liver were altered after exposure to PS-MPs for both 6 and 12 months, namely LdMePE (16:0), LPC (18:1), LPC (18:2), LPC (20:4), PC (17:0_20:4), PC (18:2_22:6), PC (22:6_13:0) and SM (d18:1_24:0), which were all statistically different from the control groups detected at both time points after PS-MPs exposure, suggesting the mainly metabolic pathway was glycerolipid metabolism. CONCLUSION: This study showed chronic exposure to PS-MPs could cause hepatotoxicity and induce hepatic lipidomics alterations in vivo, which could provide an essential clue for the safety assessment of PS-MPs.

Size-dependent toxicity of polystyrene microplastics on the gastrointestinal tract: Oxidative stress related-DNA damage and potential carcinogenicity.

Microplastics (MPs) and nanoplastics (NPs) have been generally regarded as emerging pollutants and received worldwide attention in recent years. Water and food consumption are the primary pathways for human exposure to MPs/NPs, thus gastrointestinal tracts may be susceptible to their toxicity. Although the recent report has indicated the presence of MPs/NPs in multiple human organs, little is known about their gastric effects. Therefore, this study focused on the adverse effects of polystyrene microplastics (PS-MPs) on gastric epithelium in vivo and in vitro. Surface-enhanced Raman spectroscopy (SERS) revealed the distribution of PS-MPs was associated with their particle sizes, and predominantly concentrated in gastric tissues. Gastric barrier injury and mitochondrial damage were observed in rats after exposure to PS-MPs. Compared with the larger ones, polystyrene nanoplastics (PS-NPs) more significantly reduced the activity of antioxidant enzymes while enhancing the level of MDA, 8-OhdG and γ-H2AX. Meanwhile, PS-MPs caused upregulation of ß-catenin/YAP through redox-dependent regulation of nucleoredoxin (NXN) and dishevelled (Dvl). These findings supported the size-dependent effects of PS-MPs on oxidative stress and DNA damage. Moreover, the redox-dependent activation of the ß-catenin/YAP cascade suggested a novel toxic mechanism for PS-MPs and implied the potential carcinogenic effects.