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Sixteen polycyclic aromatic hydrocarbons (PAHs) present in PM 2. 5 were analyzed in 2012 in Taiyuan (China) using high performance liquid chromatography (HPLC) with fluorescence and ultraviolet detectors. The average daily mass concentrations of ΣPAHs in different seasons ranged from 10.36 ng/m 3 to 215.93 ng/m 3 and had strong seasonal variation, with highest values in winter and lowest in summer. Over the whole year, PAHs appeared in the following order of frequency: 4-ring > 6-ring > 5-ring > 3-ring; in winter, the percentage of 4-ring PAHs was the highest (62.68%), while in summer, the percentages of 5-ring and 6-ring PAHs (cumulative total of 50.57%) were higher. The ratio method was employed to investigate potential source categories of PAHs in PM 2.5 in Taiyuan, with data suggesting that the main PAH sources are coal and wood combustion and vehicle emissions. Finally, a risk assessment of PAHs was performed based on benzo(a)pyrene equivalent (BaPeq) values and individual cancer risk ratios, with results suggesting that the toxicity of PAHs was high during winter and spring time in Taiyuan. The values of incremental lifetime cancer risk (ILCR) induced by whole year inhalation exposure(R i ) for all age groups were larger than 10 − 6 in spring and winter, while R i values for male and female adults in summer and autumn were also larger than 10 − 6 , indicating high potential carcinogenic risk. During the same season, the ILCR of adults was greater than that of other age groups and that of females was a little higher than of males. With respect to the season, the ranking of ILCR in decreasing order was as follows: winter, spring, autumn, and summer. [ABSTRACT FROM AUTHOR]

Inhibition of cell apoptosis is an increasingly important factor in modulating airway inflammation in asthma, which is related to environmental pollutants. To investigate the effects of sulfur dioxide (SO2) on the mRNA and protein expressions of apoptosis-related genes in lungs from asthmatic rats, male Wistar rats were challenged by ovalbumin (OVA) or SO2 (2 ppm) inhalation alone or together. Examinations were performed 24 h after the last treatment. The mRNA and protein levels of p53, bax, and bcl-2 were analyzed in lungs using real-time reverse transcription-polymerase chain reaction (RT-PCR) assay and Western blot analysis, respectively. The results indicated that increases of bcl-2 or decreases of p53 and bax mRNA and protein levels were not significant in lungs of rats exposed to SO2 alone, compared with controls, but elevated or reduced levels of these genes appeared in lungs of asthmatic rats exposed to SO2 plus OVA, compared with controls, suggesting that SO2 exposure could result in OVA-induced increases or decreases of transcription and translation levels of these apoptosis-related genes in rat lungs, and may have relations to airway inflammation in asthma. The regulation mechanism of apoptosis in asthma disease exposure to SO2 needs further study. [ABSTRACT FROM AUTHOR]

In this article, protein oxidative damage and DNA-protein crosslinks (DPC) induced by sulfur dioxide (SO2) in lungs, livers, and hearts of mice were studied. The protein carbonyl (PCO) content was measured using spectrophotometric DNPH assay to reflect the degree of protein oxidative damage, and the DPC coefficient was measured by using a KCl-sodium dodecyl sulfate (SDS) assay to show the degree of DNA damage in lungs, livers, and hearts from mice exposed to SO2 at various concentrations (0, 14, 28, and 56 mg-m- 3) for 6 h per day for 7 days. The results indicate that SO2 caused an increase of PCO and DPC level in all organs tested from mice in a concentration-dependent manner. The concentration-response relationships in all organs tested of both female and male mice could be fitted well with monolinear regression equations. The adjusted coefficient R squared of all equations is more than 0.9. These results lead to a conclusion that SO2 may cause an increase of protein oxidation damage and DNA-protein crosslinking in lungs, livers, and hearts from mice. The rank order of absolute increase in PCO contents and DPC coefficient in three organs from mice compared with controls was lung > liver > heart. Our results also indicated the regulation of PCO and that of DPC induced by SO2 were conformed to each other; this implies that the protein oxidative damage may be associated with the emergence of DPC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hypoxia-induced circWhsc1 in neonatal cardiac endothelial cells promotes cardiac regenerative repair by activating TRIM59/STAT3/cyclin B2 pathway. • CircWhsc1 was secreted by neonatal cardiac endothelial cells in an extracellular vesicle-dependent manner to promote cardiomyocyte proliferation. • Intercellular circWhsc1 delivery by extracellular vesicles might be a plausible alternative strategy for inducing cardiac regenerative repair. Extracellular vesicles (EVs)-mediated cell-to-cell communication is crucial for hypoxia-induced cell proliferation and tissue repair, but its function in endogenous cardiac regeneration is still unknown. Herein, we aimed to determine whether hypoxia-inducible circWhsc1 in endothelial EVs promoted cardiomyocyte (CM) proliferation and cardiac regeneration. RNA-sequence data was used to identify EV circRNAs that were involved into endogenous cardiac regeneration. Quantitative polymerase chain reactions were conducted to determine circRNA expression in tissue, cells and EVs. Gain- and loss-of-function assays were performed to explore the function of EV-derived circWhsc1 during cardiac regeneration. Western blotting and RNA pulldown assays were used to investigate its underlying mechanism. We found that circWhsc1 was enriched in neonatal mouse hearts, particularly in cardiac ECs, and was further upregulated both in ECs and EC-derived EVs under hypoxic conditions. When cocultured with hypoxia-preconditioned neonatal ECs or their secreted EVs, both neonatal and adult CMs exhibited an increased proliferation rate and G2/M ratio, which could be attenuated by knockdown of circWhsc1 in ECs. In vivo , EC-restricted overexpression of circWhsc1 and EV-mediated delivery of circWhsc1 induced CM proliferation, alleviated cardiac fibrosis and restored cardiac function following myocardial infarction in adult mice. Mechanistic studies revealed that EV-derived circWhsc1 activated TRIM59 by enhancing its phosphorylation, thereby reinforcing the binding of TRIM59 to STAT3, phosphorylating STAT3 and inducing CM proliferation. The current study demonstrated that hypoxia-inducible circWhsc1 in EC-derived EVs induces CM proliferation and heart regeneration. EC-CM communication mediated by EV-derived circWhsc1 might represent a prospective therapeutic target for inducing cardiac repair post-myocardial infarction. [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: Sulfur dioxide (SO2) is a common air pollutant, and inhaled SO2 in airway epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite), which are toxic to the respiratory system and related to the exacerbation of asthma. In order to study the possible asthmatic molecular mechanism of SO2 and its derivatives, the dose-response and time-response relationships of SO2 derivatives on gene expressions of some asthma-related genes in human bronchial epithelial cells (BEP2D) were investigated. The mRNA and protein levels of EGF, EGFR, ICAM-1 and COX-2 were analyzed in BEP2D cells using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay, radio-immunoassay (RIA) method and Western blot analysis, respectively. The results showed that SO2 derivatives caused the dose-dependent inductive expressions of four gene mRNA and protein in BEP2D cells. Moreover, SO2 derivatives significantly increased the mRNA and protein levels at 0, 0.5, 1, 4 and 24h post-exposure, along with the highest inductions at 0.5h post-exposure for EGFR and COX-2 and at 4h post-exposure for EGF and ICAM-1. It was suggested that SO2 derivatives could increase the expressions of EGF, EGFR, ICAM-1 and COX-2 on the transcription and translation levels in BEP2D cells, and result in mucus over-production and inflammation responses. This might be one of the possible mechanisms that SO2 aggravates asthma disease. [Copyright &y& Elsevier]

Abstract: Asthma is a chronic inflammatory disease characterized by infiltration and activation of various inflammatory cells and mucus secretion. To investigate the effects of SO2 on the expressions of asthma related-genes, male Wistar rats were challenged by ovalbumin (OVA) or SO2 (2ppm) inhalation alone or together. Bronchoalveolar lavage and histopathologic examination were performed 24h after the last treatment. The mRNA and protein levels of MUC5AC and ICAM-1 were analyzed in lungs and tracheas using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay, immunohistochemistry method and Western blot analysis, respectively. Exposure to OVA or to OVA plus inhaled SO2 significantly caused increases of the mRNA and protein levels of MUC5AC and ICAM-1 in lungs and tracheas of rats compared with the control (P <0.05 or P <0.01), but the increases of mRNA and protein levels after SO2 inhalation were not statistically significant. Exposure to OVA plus inhaled SO2 significantly not only induced the mRNA and protein expressions of these genes, but also induced the infiltration of inflammatory cells in lungs and tracheas and the increase of the numbers of inflammatory cells in bronchoalveolar lavage fluids (BALF), versus exposure to OVA alone. Meanwhile, a synergistic effect on the pathological changes between SO2 and OVA was observed in lungs after SO2 and OVA exposure. These results suggested that SO2 could increase the expressions of MUC5AC and ICAM-1 on the transcription and translation levels in the lungs and tracheas from asthmatic rats, which might be one of the possible mechanisms that SO2 pollution aggravates asthma disease. [Copyright &y& Elsevier]

Skeletal muscle fibers are primarily categorized into oxidative and glycolytic fibers, and the ratios of different myofiber types are important factors in determining livestock meat quality. However, the molecular mechanism for determining muscle fiber types in chickens was hardly understood. In this study, we used RNA sequencing to systematically compare mRNA and microRNA transcriptomes of the oxidative muscle sartorius (SART) and glycolytic muscle pectoralis major (PMM) of Chinese Qingyuan partridge chickens. Among the 44,705 identified mRNAs in the two types of muscles, 3,457 exhibited significantly different expression patterns, including 2,364 up-regulated and 1,093 down-regulated mRNAs in the SART. A total of 698 chicken miRNAs were identified, including 189 novel miRNAs, among which 67 differentially expressed miRNAs containing 42 up-regulated and 25 down-regulated miRNAs in the SART were identified. Furthermore, function enrichment showed that the differentially expressed mRNAs and miRNAs were involved in energy metabolism, muscle contraction, and calcium, peroxisome proliferator-activated receptor (PPAR), insulin and adipocytokine signaling. Using miRNA-mRNA integrated analysis, we identified several candidate miRNA-gene pairs that might affect muscle fiber performance, viz, gga-miR-499-5p/SOX6 and gga-miR-196-5p/CALM1, which were supported by target validation using the dual-luciferase reporter system. This study revealed a mass of candidate genes and miRNAs involved in muscle fiber type determination, which might help understand the molecular mechanism underlying meat quality traits in chickens. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures. To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated. The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA–protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer. [Copyright &y& Elsevier]