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Air pollution is a significant concern for human health, particularly in relation to cardiovascular damage. Currently, the precise mechanisms underlying myocardial tissue injury induced by air pollution remain to be fully elucidated. Oil mist particulate matter (OMPM) is a key environmental factor that has been linked to increased mortality from cardiovascular diseases. The research aims to explore the detrimental effects and underlying molecular mechanisms of OMPM exposure on myocardial tissue. In this study, we established exposure models with different concentrations of OMPM both in vivo and in vitro to assess their deleterious effects on myocardial tissue. The results indicated that OMPM exposure induced alterations in myocardial enzymes and large accumulation of lipid droplets in rat myocardial tissue, with a dose-dependent increase in cell apoptosis, oxidative stress, and inflammatory responses, accompanied by mitochondrial structural damage and dysfunction. Proteomic analysis suggested that OMPM induced myocardial tissue damage is closely associated with changes in mitochondrial biological functions and fatty acid metabolism, possibly through inhibition of the PPAR signaling pathway. Further experiments using a PPARα agonist (WY-14643) and PPARα siRNA transfection cell model demonstrated that WY-14643 could mitigate abnormal fatty acid metabolism, mitochondrial dysfunction, and cell apoptosis caused by OMPM exposure. Overall, the study suggests that OMPM exposure disrupts myocardial fatty acid metabolism, contributes to mitochondrial damage and dysfunction through targeted inhibition of the PPAR signaling pathway, and ultimately results in cardiomyocyte apoptosis and myocardial tissue injury. [Display omitted] • OMPM systemic exposure induces cardiotoxic effects. • OMPM exposure interferes with fatty acid metabolism and mitochondrial function. • PPARα is a key target of OMPM induced myocardial tissue damage. [ABSTRACT FROM AUTHOR]

Moringa oleifera leaves are rich in bioactive substances. The purpose of this study was to evaluate the effects of Moringa oleifera leaf aqueous extract supplements on energy metabolism and antioxidant function in young male adults. Forty-four young male adults (26.3 ± 3.5 years) were randomly assigned to two groups: a supplement group (n = 23) receiving aqueous extract of Moringa oleifera leaves and a placebo group (n = 21). The supplementation period lasted for 30 days. Baseline measurements were taken at the beginning of the study, and further measurements were taken at the end of the supplementation period. Changes in upper- and lower-body strength, treadmill endurance, and certain blood biochemical parameters were evaluated. After 30 days of supplementation, participants in the supplement group exhibited enhanced performance in push-ups and treadmill exhaustion tests compared to the placebo group. Levels of glucose, urea, malondialdehyde, and glutathione peroxidase activity in serum were also improved in the supplement group. The findings suggest that Moringa oleifera leaf aqueous extracts have the potential to improve post-exercise energy metabolism and antioxidant function in young male adults. [Display omitted] [ABSTRACT FROM AUTHOR]

Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus. [Display omitted] • Nanoplastics selectively accumulate in brain regions of fetal rats, especially the cerebellum. • Nanoplastics reduce cerebellar medullary sheath thickness and related protein expression. • Nanoplastics cause oligodendrocyte apoptosis and impaired motor coordination in offspring. [ABSTRACT FROM AUTHOR]

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms. • Early postnatal PM2.5 exposure induced more pronounced ASD-like phenotype in male offspring rats than maternal exposure. • Early postnatal period may be a sensitive window for PM2.5 to trigger autism spectrum disorder development. • PM2.5 exposure caused neuroinflammation and reduced anti-inflammatory melatonin levels in offspring rat brains. • PI3K-AKT pathway activation may link developmental PM2.5 exposure and autism spectrum disorder pathogenesis. [ABSTRACT FROM AUTHOR]

Metabolites produced by the human gut microbiota play an important role in fighting and intervening in inflammatory diseases. It remains unknown whether immune homeostasis is influenced by increasing concentrations of air pollutants such as oil mist particulate matters (OMPM). Herein, we report that OMPM exposure induces a hyperlipidemia-related phenotype through microbiota dysregulation-mediated downregulation of the anti-inflammatory short-chain fatty acid (SCFA)–GPR43 axis and activation of the inflammatory pathway. A rat model showed that exposure to OMPM promoted visceral and serum lipid accumulation and inflammatory cytokine upregulation. Furthermore, our research indicated a reduction in both the "healthy" microbiome and the production of SCFAs in the intestinal contents following exposure to OMPM. The SCFA receptor GPR43 was downregulated in both the ileum and white adipose tissues (WATs). The OMPM treatment mechanism was as follows: the gut barrier was compromised, leading to increased levels of lipopolysaccharide (LPS). This increase activated the Toll-like receptor 4 Nuclear Factor-κB (TLR4-NF-κB) signaling pathway in WATs, consequently fueling hyperlipidemia-related inflammation through a positive-feedback circuit. Our findings thus imply that OMPM pollution leads to hyperlipemia-related inflammation through impairing the microbiota-SCFAs-GPR43 pathway and activating the LSP-induced TLR4-NF-κB cascade; our findings also suggest that OMPM pollution is a potential threat to humanmicrobiota dysregulation and the occurrence of inflammatory diseases. [Display omitted] • OMPM can induce hyperlipidaemia-related inflammation and macrophage infiltration. • OMPM can disturb gut microbiota to inhibit anti-inflammatory SCFAs-GPR43 signaling. • OMPM can impair the intestinal barrier to release LPS into serum. • OMPM can activate the LPS-TLR4/NF-κB pathway to induce body inflammation. [ABSTRACT FROM AUTHOR]

Our study determined the toxic effects of zinc oxide (ZnO) particles with different diameters on dopaminergic (DA) neurons, the role of ubiquitin C-terminal hydrolase L1 (UCH-L1) for ZnO particles−induced neurotoxicity, and corresponding molecular mechanisms. We constructed an in vitro cell injury model for DA neurons to analyze the cytotoxicity of ZnO particles using SH-SY5Y cells. Following cell viability assays and flow cytometry, we found that the cytotoxicity of ZnO particles was affected by particle size, time, and dose of exposure. For example, the toxicity of ZnO particles with 50 nm or 100 nm diameter was stronger than that of ZnO particles with 1000 nm diameter. Furthermore, ZnO particles exposure resulted in a significant decrease in UCH-L1 expression in SH-SY5Y; whereas UCH-L1 overexpression led to a significant increase in cell viability and a sharp decrease in ROS level. Western blotting and adenovirus transfection found that exposure to ZnO particles with different diameters all activate the NF-κB signaling in SH-SY5Y cells; whereas UCH-L1 over-expression resulted in increased levels of IκBα, an endogenous inhibitor of NF-κB signaling pathway. ZnO particles with different diameters all induced cytotoxicity in DA neurons, which may be related to the free Zn2+ in the suspension. Regarding the neurotoxic effect of ZnO particles, UCH-L1 protects against and/or alleviates neuronal damage, possibly by deubiquitination of the endogenous inhibitor, IκBα, which leads to activation of NF-κB signaling. Therefore, one possible mechanism for ZnO particle−induced neurotoxicity may be mediated via the down-regulation of UCH-L1 expression in DA cells. • The cytotoxicity of micron and nanometer diameter ZnO NP in neurons was compared. • ZnO particle exposure down-regulates the abundance of UCH-L1 in DA neurons. • UCH-L1 plays a protective role against neurotoxic effect of ZnO particles. • UCH-L1 inhibits the activation of the NF- B pathway through IκBα. [ABSTRACT FROM AUTHOR]

Some basic research has shown that nanomaterials can aggravate allergic asthma. However, its potential mechanism is insufficient. Based on the research that alumina nanopowder (nAl 2 O 3) has been reported to cause lung tissue damage, the purpose of this study was to explore the relationship between nAl 2 O 3 and allergic asthma as well as its molecular mechanism. In this study, Balb/c mice were sensitized with ovalbumin (OVA) to construct the allergic asthma model while intratracheally administered 0.5, 5 or 50 mg kg−1·day−1 nAl 2 O 3 for 3 weeks. It was observed that exposure to nAl 2 O 3 exacerbated airway hyperresponsiveness (AHR), airway remodeling, and inflammation cell infiltration, leading to lung function damage in mice. Results revealed that nAl 2 O 3 could increase ROS levels and decrease GSH levels in lung tissue, promote the increases of the T-IgE, TGF-β, IL-1β and IL-6 levels, stimulate the overexpression of transcription factors GATA-3 and RORγt, decrease the levels of IFN-γ and IL-10 and increase the levels of IL-4 and IL-17A, resulting in the imbalance of Th1/Th2 and Treg/Th17 immune responses. In addition, antioxidant Vitamin E (Vit E) could alleviate asthma-like symptoms through blocking oxidative stress. The study displayed that exposure of nAl 2 O 3 deteriorated allergic asthma through promoting the imbalances of Th1/Th2 and Treg/Th17. Image 1 • Evaluated the effect of nAl 2 O 3 on allergic asthma mice. • Revealed that exposure to nAl 2 O 3 via intratracheal instillation could exacerbate AHR in mice. • It was the imbalance between Th2 and Th17 type immune responses induced by oxidative stress that aggravated asthma symptoms. Intratracheal instillation of nAl 2 O 3 aggravated the imbalance of th2-type th17-type immune, induced airway hyperresponsiveness and subsequently deteriorated allergic asthma in mice. [ABSTRACT FROM AUTHOR]

Ambient ozone (O 3) pollution can induce respiratory and cardiovascular toxicity. However, its impact on the metabolome and the underlying mechanisms remain unclear. This study first investigated the serum metabolite changes in rats exposed to 0.5 ppm O 3 for 3 months using untargeted metabolomic approach. Results showed chronic ozone exposure significantly altered the serum levels of 34 metabolites with potential increased risk of digestive, respiratory and cardiovascular disease. Moreover, bile acid synthesis and secretion, and arachidonic acid (AA) metabolism became the most prominent affected metabolic pathways after O 3 exposure. Further studies on the mechanisms found that the elevated serum toxic bile acid was not due to the increased biosynthesis in the liver, but the reduced reuptake from the portal vein to hepatocytes owing to repressed Ntcp and Oatp1a1 , and the decreased bile acid efflux in hepatocytes as a results of inhibited Bsep , Ostalpha and Ostbeta. Meanwhile, decreased expressions of detoxification enzyme of SULT2A1 and the important regulators of FXR, PXR and HNF4α also contributed to the abnormal bile acids. In addition, O 3 promoted the conversion of AA into thromboxane A2 (TXA2) and 20-hydroxyarachidonic acid (20-HETE) in the liver by up-regulation of Fads2 , Cyp4a and Tbxas1 which resulting in decreased AA and linoleic acid (LA), and increased thromboxane B2 (TXB2) and 20-HETE in the serum. Furthermore, apparent hepatic chronic inflammation, fibrosis and abnormal function were found in ozone-exposed rats. These results indicated chronic ozone exposure could alter serum metabolites by interfering their metabolism in the liver, and inducing liver injury to aggravate metabolic disorders. [Display omitted] • Subchronic O 3 induces characteristic changes in serum metabolites of rats especially bile acids and arachidonic acid. • O 3 reduces reuptake of bile acids from the portal vein to hepatocytes by repressing Ntcp and Oatp1a1. • O 3 decreases bile acid efflux in hepatocytes by inhibiting Bsep, Ostalpha and Ostbeta. • O 3 promotes the conversion of AA into TXA2 and 20-HETE by up-regulating Fads2 , Cyp4a and Tbxas1 in liver. • O 3 induces hepatic inflammation, fibrosis and function disturbance which may mutually reinforce with abnormal metabolites. [ABSTRACT FROM AUTHOR]

Exposure to PM 2.5 can aggravate the occurrence and development of bronchial asthma and fibrosis. Here, we investigated the differences in bronchial injury caused by different exposure modes of PM 2.5 (high concentration intermittent exposure and low concentration continuous exposure), and the mechanism of macrophage activation and respiratory immune imbalance induced by PM 2.5 , leading to bronchial asthma and airway fibrosis using animal and cell models. A "PM 2.5 real-time online concentrated animal whole-body exposure system" was used to conduct PM 2.5 respiratory exposure of Wistar rats for 12 weeks, which can enhance oxidative stress in rat bronchus, activate epithelial cells and macrophages, release chemokines, recruit inflammatory cells, release inflammatory factors and extracellular matrix, promote bronchial mucus hypersecretion, inhibit the expression of epithelial cytoskeletal proteins, destroy airway barrier, and induce asthma. Furthermore, PM 2.5 induced M2 polarization in lung bronchial macrophages through JAK/STAT and PI3K/Akt signaling pathways, and compared with low concentration continuous exposure, high concentration intermittent exposure of PM 2.5 could regulate significantly higher expression of TIPE2 protein through promoter methylation of TIPE2 DNA, thereby activating PI3K/Akt signaling pathway and more effectively inducing M2 polarization of macrophages. Additionally, activated macrophages release IL-23, and activated epithelial cells and macrophages released TGF-β1, which promoted the differentiation of Th17 cells, triggered the Th17 dominant immune response, and activated the TGF-β1/Smad2 signaling pathway, finally causing bronchial fibrosis. Moreover, when the total amount of PM 2.5 exposure was equal, high concentration-intermittent exposure was more serious than low concentration-continuous exposure. In vitro experiments, the co-culture models of PM 2.5 with BEAS-2B, WL-38 and rat primary alveolar macrophages further confirmed that PM 2.5 could induce the macrophage activation through oxidative stress and TIPE2 DNA methylation, and activate the TGF-β1/Smad2 signaling pathway, leading to the occurrence of bronchial fibrosis. [Display omitted] • PM 2.5 exposure activated macrophages and epithelial cells to induce airway fibrosis. • PM 2.5 exposure triggered respiratory immune imbalance through Th17 cells activation. • PM 2.5 -induced above toxic effects was induced by oxidative stress mechanism. • PM 2.5 High-dose intermittent exposure is more harm than low-dose continuous exposure. • The difference between different exposure modes was related to TIPE2 DNA methylation. [ABSTRACT FROM AUTHOR]

Thiazole–Zn is a newly created Chinese systemic fungicide that is a thiadiazole compound. The toxicity of thiazole–Zn was examined in Sprague-Dawley rats fed diets containing 0, 4, 20 and 100 mg/kg thiazole–Zn for one year. Lower body weight gains were noted in both males and females of the 100 mg/kg diet group. Moreover, we show that the toxicity of thiazole–Zn was low, as evidenced by the absence of toxicologically significant changes in the general condition and appearance, hematology and clinical chemistry parameters, organ weights and necropsy findings of the rats. Thyroid follicular cell hyperplasia was the only finding of potential significance. The incidence of thyroid follicular cell hyperplasia significantly increased in high-dose males (4/10) and females (3/10) at the 26-week interim examination; one follicular adenoma in the thyroid was observed in high-dose males. At 52 weeks, the incidence of thyroid follicular cell hyperplasia was significantly higher in high-dose males (4/10) and females (4/10) than in the controls. Two thyroid follicular adenomas were observed in high-dose males. Other treatment-related effects and tumors at other sites were not observed. This study suggests that thiazole–Zn is a thyroid disrupter and likely a rat thyroid carcinogen. [ABSTRACT FROM AUTHOR]

The molecular mechanisms of PM 2.5 exposure in the male reproductive system, have scarcely been studied. Here, we demonstrate the possible relationship and molecular mechanisms between endoplasmic reticulum stress (ERS), oxidative stress, and reproductive toxicity caused by PM 2.5. A "PM 2.5 real-time online concentrated animal whole-body exposure system" was employed to expose male Wistar rats to PM 2.5 for 12 weeks, which could induce sperm quality decline, apoptosis, inflammation, oxidative stress, ERS, and histopathological damage in the testis. In vitro study on cultured primary testicular spermatogonia and Leydig cells confirmed that treatment with PM 2.5 (0–320 μg/mL) for 24 h decreased cell survival rate, increased reactive oxygen species, lactate dehydrogenase and 8-hydroxydeoxyguanosine levels, induced DNA damage, ERS and apoptosis, and inhibit the secretion and synthesis of testosterone in Leydig cells. These results clarified that ERS pathways triggered by oxidative stress could significantly induce CHOP and caspase-12 activation, which are significantly associated with cell apoptosis. However, oxidative stress and ERS inhibitors significantly inhibited the occurrence of these injuries. In conclusion, PM 2.5 triggers the ERS pathway and induces DNA damage in rat testicular cells through oxidative stress, ultimately leading to cellular apoptosis. Furthermore, high-concentration intermittent inhalation was more harmful than low-concentration continuous inhalation when the total mass of PM 2.5 exposure was the same. [Display omitted] • PM 2.5 can cause reproductive toxicity in male Wistar rats. • PM 2.5 can cause DNA damage and ERS in male rat germ cells through oxidative stress. • PM 2.5 can activate ERS-mediated CHOP and Caspase-12 apoptosis pathways. • PM 2.5 can activate the DNA damage-mediated mitochondrial apoptosis pathway. • High-dose PM 2.5 intermittent exposure is more toxic than low-dose continuous exposure. [ABSTRACT FROM AUTHOR]

Oil mist particulate matter (OMPM) causes acute and chronic diseases and exacerbations. Owing to the characteristics of poor ventilation, high oil mist concentration, and a relatively closed working environment, the existence of OMPM in the cabin is inevitable, and its impact on the health of occupations on ships cannot be ignored. However, compared with several studies that summarized the health effects of OMPM from traditional sources, few studies have focused on the occupational exposure risk of OMPM from oil pollution sources in ships. In this study, we collected OMPM from oil pollution in cabins and assessed the exposure to OMPM from oil pollution and the corresponding health risks through acute exposure experiments in rats. OMPM exposure induces protein regulation in the extracellular matrix and immune responses, leading to severe inflammatory responses. The abundance and composition of the lung microbial community changed significantly. It interferes with the lung metabolite levels. However, more research is needed to fully understand the extent of health risks associated with OMPM exposure. Further research on vulnerable groups exposed to OMPM from ships is needed to inform public health interventions. [Display omitted] • 16S rRNA and metabolomics combined analysis were used to study the effects of oil mist particulate matter (OMPM) on rat lungs. • OMPM exposure caused significant damage to rat lung tissue. • OMPM exposure changed the microbial composition and structure of lung tissue. • Exposure to OMPM caused disturbances of various metabolic pathways in rats. • Altered lung metabolites were significantly associated with lung microbiota. [ABSTRACT FROM AUTHOR]

To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome. • Ozone exposure can lead to pulmonary mitochondrial dysfunction in vivo and in vitro. • Ozone exposure can lead to mitophagy in lung, and ROS is involved in this process. • ROS induce mitophagy through the activation of the PINK1/Parkin signaling pathway. • Mitophagy induced by ozone can induce pyroptosis through the activation of NLRP3 inflammasome in lung. [ABSTRACT FROM AUTHOR]