Exposure to polystyrene nanoplastics induces abnormal activation of innate immunity via the cGAS-STING pathway.

Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.

Association between per- and polyfluoroalkyl substances (PFAS) and depression in U.S. adults: A cross-sectional study of NHANES from 2005 to 2018.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants (POPs) associated with diseases including osteoporosis, altered immune function and cancer. However, few studies have investigated the association between PFAS mixture exposure and Depression in general populations. METHODS: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) (2005-2018) were used to analyze the association between PFAS and Depression in U.S. adults. Total 12,239 adults aged 20 years or older who had serum PFAS measured and answered Patient Health Questionnaire-9 (PHQ-9) were enrolled in this study. PFAS monomers detected in all 7 investigation cycles were included in the study. Generalized additive model (GAM) was used to fit smooth curves and threshold effect analysis was carried out to find the turning point of smooth curves. Generalized linear model (GLM) was used to describe the non-linear relationship between PFAS and depression and unconditioned logistic regression was used to risk analysis. RESULTS: The median of total serum PFAS concentration was 14.54 ng/mL. The curve fitting results indicated a U-shaped relationship between total serum PFAS and depression: PFAS< 39.66 ng/mL, A negative correlation between PHQ-9 score and serum PFAS concentration was observed (ß 0.047,95%CI -0.059, -0.036). The depression PHQ-9 score decreased with the increase of serum PFAS concentration. PFAS ≥ 39.66 ng/mL, A positive correlation was observed between PFAS and PHQ-9 score (ß 0.010,95% CI 0.003, 0.017). The depression PHQ-9 score increased with the increase of serum PFAS concentration. CONCLUSIONS: Our study provides new clues to the association of PFAS with depression, and large population-based cohort studies that can validate the causal association as well as toxicological mechanism studies are needed for validation.

Predictive metabolomic signatures for safety assessment of three plastic nanoparticles using intestinal organoids.

Nanoplastic particles are pervasive environmental contaminants with potential health risks, while mouse intestinal organoids provide accurate in vitro models for studying these interactions. Metabolomics, especially through LC-MS, enables detailed cellular response studies, and there's a novel interest in comparing metabolic changes across nanoparticle species using gut organoids. This study used a mouse intestinal organoid combined with cell model to explore the differences in metabolites and toxicity mechanisms induced by exposure to three nanoplastics (PS, PTFE, and PMMA). The results showed that PS, PTFE, and PMMA exposure reduced mitochondrial membrane potential, intracellular ROS accumulation and oxidative stress, and inhibited the AKT/mTOR signaling pathway. Non-targeted metabolomics results confirmed that three types of nanoplastic particles regulate cellular status by regulating fatty acid metabolism, nucleotide metabolism, necroptosis and autophagy pathways. More importantly, these representative metabolites were further validated in model groups after mouse intestinal organoids and HCT116 cells were exposed to the respective NPs, indicating that organoid metabolomics results can be used to effectively predict toxicity. Untargeted metabolomics is sensitive enough to detect subtle metabolomic changes when functional cellular analysis shows no significant differences. Overall, our study reveals the underlying metabolic mechanism of NPs-induced intestinal organoid toxicity and provides new insights into the possible adverse consequences of NPs.

Metabolomics reveals that PS-NPs promote lung injury by regulating prostaglandin B1 through the cGAS-STING pathway.

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 µg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.