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.

Associations between ambient air pollution and daily incidence of pediatric hand, foot and mouth disease in Ningbo, 2014-2016: a distributed lag nonlinear model.

Hand, foot and mouth disease (HFMD) has high prevalence around the world, with serious consequences for children. Due to the long survival period of HFMD virus in ambient air, air pollutants may play a critical role in HFMD epidemics. We collected data on daily cases of HFMD among children aged 0-14 years in Ningbo City between 2014 and 2016. Distributed lag nonlinear models were used to assess the effects of particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) on the daily incidence of HFMD among children, with analyses stratified by gender and age. Compared with moderate levels of air pollution, high SO2 levels had a relative risk (RR) of 2.32 (95% CI 1.42-3.79) and high NO2 levels had a RR of 2.01 (95% CI 1.22-3.31). The RR of O3 was 2.12 (95% CI 1.47-3.05) and that of PM2.5 was 0.77 (95% CI 0.64-0.92) at moderate levels of air pollution. Specifically, high levels of SO2 and NO2 had RRs of 2.39 (95% CI 1.44-3.96) and 2.02 (95% CI 1.21-3.39), respectively, among 0-4-year-old children, while high O3 had an RR of 2.31 (95% CI 1.09-4.89) among 5-14-year-old children. Our findings suggest significant associations of high SO2 and NO2 levels and moderate O3 levels in HFMD epidemics, and also indicate that air pollution causes lagged effects on HFMD epidemics. Our study provides practical and useful data for targeted prevention and control of HMFD based on environmental evidence.

Preparation of etoposide liposomes for enhancing antitumor efficacy on small cell lung cancer and reducing hematotoxicity of drugs.

Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential.

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.

The geno-toxicological impacts of microplastic (MP) exposure on health: mechanistic pathways and research trends from a Chinese perspective.

Due to their large-scale manufacture and widespread application, global concern regarding microplastics (MPs) has been increasing rapidly over the past decade, in particular their potential genotoxicity. The genome is constantly exposed to genotoxic insults that can lead to accumulation of reactive oxygen species (ROS), DNA damage, cell death, inflammation or genetic regulation which in turn can have consequences for health, such as the induction of carcinogenesis. In this review, we presented a comprehensive landscape of the effects of MPs on genotoxicity including the molecular mechanisms. Followed by the MP research trend analysis from a global viewpoint including the comparative research between China and USA and point out that scientists should continue to substantially contribute to the field of MPs through more extensive academic investigation, global cooperation, and the development of novel control methods. Challenges are also discussed. Overall, this review provides insights into the genotoxic effects of MPs on human health and related research trends in this field.

Preparation of PEGylated nedaplatin liposomes with sustained release behavior for enhancing the antitumor efficacy of non-small cell lung cancer.

Nedaplatin (NDP) plays an important role in the chemotherapies of non-small cell lung cancer (NSCLC). However, dose-limiting toxicities such as myelosuppression and drug resistance restrict its clinical application. Herein, we intended to overcome these defects by developing a PEGylated liposomal formulation encapsulated NDP (NDP-LPs). For the first time, we found the incompatibility between NDP and natural phospholipids such as egg phosphatidylcholine (EPC) using the high-performance liquid chromatography (HPLC) method. The orthogonal experimental design was applied to optimize the conditions for preparing NDP-LPs, with encapsulation efficiency (EE) as the evaluation indicator. The physicochemical properties of optimized NDP-LPs were further characterized, including particle size, zeta potential, EE, drug release profiles, and so on. Results showed that a significantly sustained-release profile of NDP-LPs was observed and the releasing time of NDP could reach as long as 8 days. At the cellular level, NDP encapsulated in the PEGylated liposomes enhanced its cellular uptake and possessed potent cytotoxic activity. After intravenous injection, NDP-LPs could accumulate at tumor sites and effectivelyinhibit tumor growth of mice without obvious adverse effects. In conclusion, our results demonstrated that PEGylated liposomes could serve as a promising carrier to enhance the therapeutic effects of NDP.

Impact of PM10 and meteorological factors on the incidence of hand, foot, and mouth disease in female children in Ningbo, China: a spatiotemporal and time-series study.

Hand, foot, and mouth disease (HFMD) is a viral illness that is considered a critical public health challenge worldwide. Previous studies have demonstrated that meteorological parameters are significantly related to the incidence of HFMD in children; however, few studies have focused only on female children. This study quantified the associations of HFMD incidence with meteorological parameters and PM10 (particulate matter with an aerodynamic diameter of 10 µm) among female children. Data were collected on daily HFMD cases, meteorological variables, and PM10 levels in Ningbo, China, from January 2012 to December 2016. Data were assessed using a distributed lag nonlinear model (DLNM) with Poisson distribution. A total of 59,809 female children aged 0-15 years with HFMD were enrolled. The results showed that highest relative risk (RR) of HFMD for temperature was 3 °C and the lag effect was 3 days. The highest RR for PM10 was 80 mg/m3 and the lag effect was 5 days. Spatial analysis showed that female HFMD incidence was mainly concentrated in the suburban of Ningbo city indicating that female children in this area should be more paid attention on avoiding this disease outbreak. Our findings suggest that HFMD prevention strategies should focus more attention on local meteorological parameters.

Effects of Meteorological Parameters and PM10 on the Incidence of Hand, Foot, and Mouth Disease in Children in China.

Hand, foot, and mouth disease (HFMD) is a globally-prevalent infectious disease. However, few data are available on prevention measures for HFMD. The purpose of this investigation was to evaluate the impacts of temperature, humidity, and air pollution, particularly levels of particulate matter with an aerodynamic diameter 10 micrometers (PM10), on the incidence of HFMD in a city in Eastern China. Daily morbidity, meteorological, and air pollution data for Ningbo City were collected for the period from January 2012 to December 2014. A total of 86,695 HFMD cases were enrolled in this study. We used a distributed lag nonlinear model (DLNM) with Poisson distribution to analyze the nonlinear lag effects of daily mean temperature, daily humidity, and found significant relationships with the incidence of HFMD; in contrast, PM10 level showed no relationship to the incidence of HFMD. Our findings will facilitate the development of effective preventive measures and early forecasting of HFMD outbreaks.