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• PM 2.5 triggers mitochondrial morphological and function damage of H9c2 cells. • MiR-421/SIRT3 pathway regulates cardiac mitochondrial dynamics imbalance after PM 2.5 treatment. • MiR-421 inhibitor and resveratrol protect PM 2.5 -induced mitochondrial damage. Fine particulate matter (PM 2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM 2.5 , and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM 2.5 -triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM 2.5. Results illustrated that PM 2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM 2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM 2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM 2.5 and that miR-421i and resveratrol exert protective effects against PM 2.5 -incurred cardiotoxicity. [Display omitted] [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]

Exposure to fine particulate matter (PM 2.5 ) has a close association with respiratory damage. Vitamin c and quercetin have been documented to possess antioxidant and anti-inflammation properties. However, their potential protective effects against PM 2.5 -induced respiratory damage have not been evaluated yet. Hence, the study was aimed to investigate their protective effects and delineate the possible mechanisms. The results indicated that PM 2.5 depleted the cell viability of 16HBE cells, elevated reactive oxygen species (ROS) generation, and inhibited mitochondrial genes expressions, including fusion proteins Mfn1 and OPA1 , along with biogenesis markers SIRT1 and p53R2 . Additionally, the damage of mitochondrial morphology was observed upon PM 2.5 exposure using both JC-1 and MitoTracker Red staining. Expressions of mitochondrial respiratory chain genes including NDUFS2 and UQCRI1 were also attenuated by PM 2.5 exposure. Furthermore, PM 2.5 promoted the mRNA levels of NADPH oxidase and inflammation cytokines. However, the addition of vitamin c or quercetin strikingly antagonized the PM 2.5 -induced toxic effects. Collectively, these findings suggest that vitamin c and quercetin have repressive roles in respiratory oxidative damage incurred by PM 2.5 , which provide the theoretical basis about intervention and control of food nutrients on PM 2.5 -induced human adverse health. [ABSTRACT FROM AUTHOR]

Simulation of fine particulate matter (PM 2.5) exposure is essential for evaluating adverse health effects. In this work, an ambient exposure system that mimicked real atmospheric conditions was installed in Taiyuan, China to study impacts of chronic PM 2.5 exposure on adult and aged mice as well as Sirtuin3 knockout (Sirt3 KO) mice and wild-type (WT) mice. The real-ambient exposure system eliminated the possible artificial effects caused from exposure experiments and maintained the physiochemical characteristics of PM 2.5. The case studies indicated that aged mice exhibited apparent heart dysfunction involving increased heart rate and decreased blood pressure after 17-week of real-ambient PM 2.5 exposure. Meanwhile, 15-week of real-ambient PM 2.5 exposure decreased the heart rate and amounts of associated catecholamines to induce heart failure in Sirt3 KO mice. Additionally, the increased pro-inflammatory cytokines and decreased platelet related indices suggested that inflammation occurred. The changes of biomarkers detected by targeted metabolomics confirmed metabolic disorder in WT and Sirt3 KO mice after exposed to real-ambient PM 2.5. These results indicated that the real-ambient PM 2.5 exposure system could evaluate the risks of certain diseases associated with air pollution and have great potential for supporting the investigations of PM 2.5 effects on other types of rodent models. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Gestational exposure to PM 2.5 is associated with adverse postnatal outcomes. PM 2.5 can enter alveoli by using intratracheal instillation, even penetrate through lung cells into the blood circulation. Subsequently, they are transferred across the placenta and fetal blood brain barrier, causing the adverse birth outcomes of offspring. This study demonstrated that the gestational exposure resulted in cognitive and emotional disorders in female offspring although the offspring were not exposed to PM 2.5. Placental metabolic pathways modulated fetal brain development and played a pivotal role for maternal-placental-fetal interactions in the fetal programming of adult behavioral and mental disorders. Samples of fetus, offspring hippocampus and placenta from the mice exposed to PM 2.5 were investigated using a comprehensive approach including mass spectrometry-based lipidomics and three-dimensional imaging. The exposure induced the neuro-degeneration in hippocampus, impairment of placental cytoarchitecture, and reprogramming of lipidome, which might affect the modulation of maternal-fetal cross-talk and result in the behavior disorders of offspring. The variation of spatial distribution of lipids was profoundly affected in dorsal pallium and hippocampal formation regions of fetal brain, offspring hippocampus, as well as labyrinth and junctional zones of placenta. The abundance alteration of lipid markers associated with neurodegenerative diseases was validated in transgenic mouse model with Alzheimer's disease and human cerebrospinal fluid from patients with Parkinson's disease. The finding could help with the selection of more suitable heterogeneous-related substructures targeting PM 2.5 exposure and the exploration of PM 2.5 -induced toxicological effects on neurodegenerative diseases. [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 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]

Abstract Exposure to ambient fine particulate matter (PM 2.5) is associated with neurodegenerative diseases. Mitochondrion is key to brain degeneration. However, the underlying mechanism of PM 2.5 -induced brain injury, especially mitochondrial damage, is still unclear. In this study, changes in mitochondrial dynamics, mitochondrial permeability transition pore (mPTP), mitochondrial DNA (mtDNA) and oxidative stress in human SH-SY5Y cells exposed to PM 2.5 at different concentrations (0, 25, 100, and 250 μg mL−1) were investigated. The results showed that PM 2.5 caused more mitochondrial swell, accompanied by the opening of mPTP and the decrease of ATP levels, mitochondrial membrane potential and mtDNA copy number in SH-SY5Y cells. PM 2.5 significantly enhanced the expression of mitochondrial fission/fusion genes (Drp1 and OPA1) and affected the gene expression of CypD, SIRT3, and COX Ⅳ in SH-SY5Y cells. Besides, PM 2.5 triggered the increase of cellular ROS, Ca2+ and Aβ-42 levels, inhibition of manganese-superoxide dismutase (SOD 2) activities, reduction of GSH levels GSH/GSSG ratio, and elevation of mitochondrial malondialdehyde contents. It suggests that mitochondrial dysfunction and oxidative stress are the potential mechanisms underlying PM 2.5 -induced brain nerve cell injury, which may be related to neurological diseases. Additionally, our study elucidated that PM 2.5 components trigger different cytotoxicity. Graphical abstract Image 1 Highlights • PM 2.5 induces mitochondrial morphological damage of SH-SY5Y cells. • PM 2.5 triggers mitochondrion permeability transition pore opening. • PM 2.5 reduces ATP, mitochondrial membrane potential and mtDNA copy number. • PM 2.5 -caused oxidative stress related to enhancement of ROS, SIRT3 and Aβ-42 levels. [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]