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The atmosphere's fine particulate matter (PM2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM2.5 with or without RES. The results showed that (1) PM2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM2.5 plus RES treatment group compared to the PM2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM2.5 compared to the PM2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM2.5. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is a common pollutant, and its health risk has attracted much attention. Studies have shown that PM2.5 exposure is associated with liver disease. The composition of PM2.5 is complex, and its hepatotoxic effects and lipid metabolism process are not well understood. In this study, we detected the concentrations of PM2.5 and its components (metals and polycyclic aromatic hydrocarbon (PAHs)) in the winter in Taiyuan, Shanxi Province, China, from 2017 to 2020 and then assessed the health risks. We also investigated the effects of different components (whole particles (WP), water-soluble particles (WSP), organic particles (OP)) of PM2.5 on the cytotoxicity and lipid metabolism in human liver cell line (HepG2) after 24 h of treatment. The changes in cytotoxicity indexes (LDH, IL-6, reactive oxygen species (ROS)) and lipids (triglyceride (TG), free fatty acid (FFA)) were measured after 24 h. The mRNA expression of lipid metabolism-related factors (SREBP1, CD36, MTTP) was determined by real-time quantitative RT-qPCR. Finally, the correlation between metals and PAHs with higher PM2.5 content in 4 years and biomarkers was analyzed. The results showed that: (1) The PM2.5 pollution was severe in Taiyuan during winter in 2017 and the subsequent four years. The calculation results of the metal enrichment factor (EF) value and PAHs characteristic ratio of PM2.5 showed that PM2.5 pollution sources differed in different years. (2) Exposure to metals and PAHs in PM2.5 did not cause a non-carcinogenic risk. Metals had no cancer risk, while PAHs inhaled in PM2.5 in 2017 and 2018 had a potential cancer risk. The atmospheric PM2.5 pollution in Taiyuan has had a downward trend, but the PAHs in the PM2.5 of 2017–18, when the pollution is relatively serious, have a potential carcinogenic risk. (3) WP, OP and WSP inhibited cell survival rate from 2017 to 2020, and OP had higher cytotoxicity at the same concentration. (4) WP, OP and WSP increased the levels of LDH, IL-6, TNF-α, ROS, MDA, TG and FFA, and inhibited SOD activity in a dose-effect relationship. The organic components in PM2.5 are more toxic to HepG2 cells and affect the expression of lipid metabolism-related factors at the transcriptional level. (5) The mRNA expressions of factors related to lipid synthesis, uptake, oxidation and output were up-regulated after treatment with PM2.5 and its components, suggesting a lipid metabolism disorder. (6) The biomarkers were associated with certain metals (Zn, Pb, Cu and Cr) and PAHs in PM2.5. These suggested that PM2.5- and PM2.5-bound organic matter caused HepG2 cytotoxicity and affected lipid metabolism. [ABSTRACT FROM AUTHOR]

Abstract A new method for the determination of 19 polyaromatic hydrocarbons (PAHs) and 12 hydroxy-polyaromatic hydrocarbons (OHPAHs) in fine particulate matter (PM 2.5) was developed using atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS). Better sensitivity was achieved by APGC-MS/MS than conventional liquid chromatography or gas chromatography coupled with mass spectrometry. The method detection limits (< 0.4 pg m−3 for PAHs and < 0.076 pg m−3 for OHPAHs), recoveries (67.7–120%), repeatability (RSD of 0.9–19.1%) and linearity (R2 > 0.99) were obtained for the analysis of PM 2.5 samples. The content profile of 19 PAHs and 12 OHPAHs were successfully obtained in 55 PM 2.5 samples collected from two major Chinese megacities, Taiyuan and Guangzhou, in both summer and winter by this method. Based on the concentrations, possible emission sources for the pollutants were also identified. Graphical abstract fx1 Highlights • APGC-MS/MS achieved lower LODs of 19 PAHs and 12 OHPAHs in PM 2.5 than previous method. • 19 PAHs and 12 OHPAHs in PM 2.5 all could be detected by APGC-MS/MS. • Pollution characteristics of PAHs/OHPAHs in PM 2.5 were obtained based on determined concentrations. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) exposure increases the risk of asthma. However, the effect of PM 2.5 exposure on liver metabolism in mice with asthma symptoms remains unclear. We established an ovalbumin (OVA)-induced asthma model in mice and divided the animals into four groups: control group (C), PM 2.5 exposure group (P), OVA-induced asthma group (O) and OVA-induced asthma PM 2.5 exposure group (OP). Gas chromatography-mass spectrometry (GC-MS) was used to identify the metabolite markers and related perturbed metabolic pathways in mouse liver tissue after PM 2.5 exposure. Multivariate analysis showed 9 and 12 potential metabolite markers in the P and OP groups, respectively, after PM 2.5 exposure that were significantly correlated with lipid peroxidation indices. PM 2.5 exposure perturbed 5 and 7 metabolic pathways in the P and OP groups, respectively. These metabolic pathways mainly involve the lipid metabolism, amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism. These results highlight the potential to study PM 2.5 -triggered alterations via liver tissue in normal and OVA-induced asthmatic mice to gain a more realistic appraisal of the resulting early toxicity events. Additionally, these results revealed potential metabolite markers of early antioxidant defense events triggered by PM 2.5 and indicated that metabolite markers are more sensitive than antioxidant indicators. Image 1 • Metabolic disorders were observed in liver tissues of normal mice and OVA-induced asthma mice after PM 2.5 exposure. • After exposure to PM 2.5 , 9 and 12 metabolic markers were screened in normal mice and asthmatic mice, respectively. • Perturbed metabolic pathways mainly involved the metabolism of lipid, amino acid, carbohydrate, and nucleotide metabolism. • Metabolomics plays a significant role in exploring the toxicity mechanism of PM 2.5 in mouse liver. [ABSTRACT FROM AUTHOR]

Abstract The risk of development of asthma, a multi-faceted chronic disease, increases as a result of exposure to PM 2.5. However, the mechanism underlying asthma-related metabolic changes caused by PM 2.5 exposure is unclear. Here, we investigated the major metabolic changes, metabolic pathways involved, and underlying molecular mechanisms in mice with PM 2.5 exposure-induced asthma. Forty-eight adult female mice were randomly assigned to control (C), low concentration-PM 2.5 exposure: 0.50 mg kg−1 (L), medium concentration-PM 2.5 exposure: 1.58 mg kg−1 (M), and high concentration-PM 2.5 exposure: 4.98 mg kg−1 (H) groups. M and H groups presented significantly higher IL-4, IL-8, IL-1β, IL-5, IL-13, and OVA-specific IgE levels, and significantly lower IFN-γ levels, than the C group, as well as significantly increased eosinophil count and MUC5AC expression in the lung tissue. These findings indicate that exposure to medium and high concentrations of PM 2.5 induced asthma in mice. Statistical analyses identified 13 asthma-related major metabolites, which were analyzed by gas chromatography-mass spectrometry (GC-MS). Meta Mapp Software revealed 4 major metabolic pathways. PM 2.5 -induced ATP requirement and oxidative stress may perturb metabolic processes in asthma. The present findings increase our understanding of the toxic effect of PM 2.5 in the development of asthma and identify potentially useful biomarkers. Graphical abstract Image 1 Highlights • PM 2.5 induces asthma in mice. • GC-MS analysis identified 13 biomarkers in PM 2.5 -induced asthmatic mice. • Screening identified four metabolic pathways involved in the pathogenesis of asthma. • PM 2.5 regulates amino acid and purine metabolism by disrupting the TCA cycle. [ABSTRACT FROM AUTHOR]

Abstract Toxic chemicals such as flame retardants are associated with atmospheric fine particles (PM 2.5), which are an important pollutant in the world. In this study, a sensitive method using gas chromatography-tandem triple quadrupole mass spectrometry combined with ultrasonic-assisted extraction and multi-phase column purification was developed for simultaneously determination of 29 flame retardants including halogenated flame retardants (HFRs) and organophosphate flame retardants (OPFRs) in PM 2.5 samples. Extraction time, as well as the type and volume of elution solvent were optimized. The recoveries of all target flame retardants from PM 2.5 samples were in the range of 70%‒130%, with good repeatability and reproducibility (0.39%‒17.4%). The instrumental detection limits (IDLs) and method quantitation limits (MQLs) of HFRs were in the range of 0.004‒5.44 pg and 0.002‒2.52 pg m−3, while those of OPFRs were 0.003‒0.23 pg and 0.07‒5.41 pg m−3, respectively. The developed method has been successfully applied for analysis of target flame retardants in atmospheric PM 2.5 collected from the cities of Guangzhou and Taiyuan, China. HFRs were found at concentrations of 45.7‒1230 pg m−3 and 51.2‒82.3 pg m−3 in Guangzhou and Taiyuan. The concentrations of HFRs were lower than those of OPFRs, which were detected at concentrations of 6004‒49,800 pg m−3 and 16,741‒34,346 pg m−3 in Guangzhou and Taiyuan. Accordingly, the analytical method is robust and useful for further elucidating the contamination profiles of flame retardants in PM 2.5. Graphical abstract fx1 Highlights • A sensitive method for analysis of 17 HFRs and 12 OPFRs in PM 2.5 was developed. • MQLs of most OPFRs by GC-MS/MS were lower than the reported MQLs by GC-MS. • Good performance characteristics were obtained for all target flame retardants. • The method was successfully applied for analysis of PM 2.5 in different areas. [ABSTRACT FROM AUTHOR]

We reported the discovery and identification of emerging sulfur-containing polycyclic aromatic hydrocarbons, namely polycyclic aromatic sulfur heterocycles (PASHs), in PM 2.5 collected from two typical regions of China, Taiyuan and Guangzhou. Until now, there is no research on contamination status, sources and potential health risks of this unexpected group of organic contaminants in PM 2.5. High atmospheric concentrations (ng m−3) and significant time-dependent variations were determined in PM 2.5 of Taiyuan from 2017 to 2018. Coal combustion/secondary formation and traffic emission/secondary formation were apportioned as possible pollution sources for the PM 2.5 -bound PASHs in Taiyuan and Guangzhou, respectively. Dithiothreitol and cell viability assays were applied for evaluations of PASH-induced reactive oxygen species (ROS) production and cell toxicity based on the determined real exposure levels for adults. The results illustrated that PASHs in PM 2.5 possibly caused oxidative stress and inhibition of human bronchial epithelial cells in seriously polluted regions such as Taiyuan, suggesting that the pollutant-induced health concerns may need more investigations. This study provides new insights into PM 2.5 pollution, and is beneficial for the development of effective contamination control strategies and reduction of risks on public health. [Display omitted] • Detailed contamination levels of PM 2.5 -bound PASHs were firstly studied. • Different pollution sources were identified in Taiyuan and Guangzhou. • The PM 2.5 -bound PASHs possessed potential health risks for human inhalation. [ABSTRACT FROM AUTHOR]

• PM 2.5 caused inflammation, oxidative stress, and pathological damage in the hearts. • PM 2.5 induced heart histopathological and cardiac hypertrophy in rats. • PM 2.5 increased β-MHC and GATA4 expression and ratio of β-MHC/α-MHC expression. • MiR-208a/b associated with β-MHC/GATA4 expression in rats' hearts exposed to PM 2.5. Ambient air fine particulate matter (PM 2.5) may increase cardiovascular disease risks. In this study, we investigated the miR-208/GATA4/myosin heavy chain (MHC) regulation mechanisms on cardiac injury in rats after PM 2.5 exposure via an animal inhalation device. The results showed that PM 2.5 exposure for 2 months caused pathological heart injury, reduced nucleus-cytoplasm ratio, and increased the levels of CK-MB and cTnI, showing cardiac hypertrophy. Oxidative stress and inflammatory responses were also observed in rats' hearts exposed to PM 2.5. Of note, PM 2.5 exposure for 2-month significantly elevated GATA4 and β-MHC mRNA and protein expression compared with the corresponding controls, along with the high-expression of miR-208b. The ratios of β-MHC/α-MHC expression induced by PM 2.5 were remarkably raised in comparison to their controls. It suggested that the up-regulation of miR-208b/β-MHC and GATA4 and the conversion from α-MHC to β-MHC may be the important causes of cardiac hypertrophy in rats incurred by PM 2.5. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate matter (PM 2.5) is associated with decreased cardiac function, especially in high risk populations such as obese ones. In this study, impacts of PM 2.5 exposure on cardiac function were investigated by using the diet-induced obesity mice model. Mice were fed with normal diet or high-fat diet (HFD) for four weeks and then exposed to phosphate-buffered solution or Taiyuan winter PM 2.5 (0.25 mg/kg body/day) through intratracheal instillation for another four weeks. Among physiological indices recorded, heart rate and blood pressure were increased after PM 2.5 exposure in the heart of the obese mice. Metabolomics and lipidomics were applied to explore molecular alterations in response to the co-treatment of PM 2.5 and HFD. Our results demonstrated both direct impacts on cardiac function and indirect effects resulted from the injury of other organs. Inflammation of lung and hypothalamus may be responsible for the elevation of phenylalanine metabolism in serum and its downstream products: epinephrine and norepinephrine, the catecholamines involves in regulating cardiac system. In intracardiac system, the co-treatment led to imbalance of energy metabolism, in addition to oxidative stress and inflammation. In contrast to the upregulation of glucose and fatty acids uptake and CoA synthesis, levels of ATP, acetyl-CoA and the intermediates in glycolysis pathway decreased in the heart. The results indicated that energy metabolism disorder was possibly one of the important contributing factors to the more severe adverse effects of the combined treatment of HFD and PM 2.5. Unlabelled Image • PM 2.5 increased heart weight, heart rate and blood pressure in obese mice. • PM 2.5 activated phenylalanine metabolism by hypothalamus inflammation in obese mice. • PM 2.5 disturbed energy metabolism and caused lipotoxicity in hearts of obese mice. • PM 2.5 induced more severe cardiotoxicity in obese mice than normal mice. [ABSTRACT FROM AUTHOR]

• OPFRs were detected ubiquitously in PM 2.5 from Guangzhou and Taiyuan, China. • Cl-OPFRs such as TCEP and TCPP were the predominant contaminants in PM 2.5. • PM 2.5 -bound OPFRs could induce the death of BEAS-2B cells. • PM 2.5 in Taiyuan had strong redox activities for ROS production. • Minimum health risks to both toddlers and adults by PM 2.5 -bound OPFRs were found. Organophosphate flame retardants (OPFRs) are emerging contaminants in recent years. They can be present in the atmospheric fine particle (PM 2.5), leading to potential adverse effects on humans. In this study, the concentrations and in vitro toxicities of OPFRs in PM 2.5 samples were investigated for one year at Guangzhou and Taiyuan in China. Eleven OPFRs, including chloro-, aryl-, and alkyl-substituted OPFRs, were detected at total concentrations ranging from 3.10 to 544 ng m−3. Chloro-substituted OPFRs were the dominant contaminants. Based on the statistical analysis, the same contamination sources of all OPFRs were found except for tris(butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP), which may come from traffic emission. The results of cell viability and dithiothreitol assays indicated that OPFRs and PM 2.5 could induce the death of normal lung epithelial cells and the production of reactive oxygen species (ROS), respectively. According to the redundancy analysis, the distribution of OPFRs was significantly related to the PM 2.5 concentrations and indirectly associated with ROS production induced by PM 2.5 from Taiyuan. Exposure to PM 2.5 -bound OPFRs in Guangzhou and Taiyuan only posed minimum health risks to both toddlers and adults. These findings could provide important evidence to better clarify the contamination profiles and human health risks of OPFRs in atmospheric fine particles. [ABSTRACT FROM AUTHOR]