Exhaled VOC Biomarkers from Rats Injected with PMs from Thirty-One Major Cities in China.

Particulate matter (PMs) of different origins can cause diverse health effects. Here, a homemade box was used to facilitate real-time measurements of breath-borne volatile organic compounds (VOCs) by gas chromatography-ion mobility spectrometry. We have tracked exhaled VOC changes in 228 Wistar rats that were injected with water-soluble PM suspension filtrates (after 0.45 µm) from 31 China cities for 1 h to up to 1-6 days during the experiments. Rats exposed to the filtrates exhibited significant changes in breath-borne VOCs within hours, featuring dynamic fluctuations in the levels of acetone, butan-2-one, heptan-2-one-M, acetic acid-M, and ethanol. Subsequently, on the fifth to sixth day after the injection, there was a notable increase in the proportion of aldehydes (including hexanal-M, hexanal-D, pentanal, heptanal-M, and (E)-2-hexenal). The 10 dynamic VOC fingerprint patterns mentioned earlier showcased the capability to indirectly differentiate urban PM toxicity and categorize the 31 cities into four distinct groups based on their health effects. This study provides valuable insights into the mechanisms of exhaled VOCs and underscores their critical role as biomarkers for differentiating the toxicity of different PMs and detecting the early signs of potential diseases. The results from this work also provide a scientific basis for city-specific air pollution control and policy development.

Effects of differential regional PM2.5 induced hepatic steatosis and underlying mechanism.

Emerging evidence suggests that exposure to PM2.5 is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM2.5-induced hepatic steatosis remain to be elucidated. In this study, ten-month-old C57BL/6 female mice were exposed to PM2.5 from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM2.5 was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM2.5 from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM2.5 exposure. Moreover, Guangzhou PM2.5-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM2.5 significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM2.5 exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM2.5. This study provides critical information regarding the components of PM2.5, which cause hepatic steatosis.

Biochemical evidence of PM2.5 critical components for inducing myocardial fibrosis in vivo and in vitro.

PM2.5 constituents are tightly linked to the initiation of many cardiovascular diseases (CVDs). Little is known, however, about the events which critical components of PM2.5 can induce the initiating events in CVDs. C57BL/6 female mice were exposed to PM2.5 (3 mg/kg b.w.) from four different cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) by oropharyngeal aspiration every other day. PM2.5 from Taiyuan increased the diastolic function of the hearts and induced myocardial fibrosis with increased areas of interstitial fibrosis through the NOX4/TGF-ß1/Smad 3/Col1a1 pathways. Pb, Cr, Mn, Zn, and most of the polycyclic aromatic hydrocarbons (PAHs) were positively associated with the related indicators of cardiac diastolic function and myocardial fibrosis by using Pearson correlation (R2 = 0.9085-0.9897). To determine the critical components in PM2.5 that can induce the occurrence of myocardial fibrosis, BEAS-2b cells were treated with one or more of five candidate components with/without Guangzhou PM2.5, and then the conditioned medium of BEAS-2b was used to culture AC16 cells. The results showed that Zn + Pb + Mn + BaP with PM2.5 from Guangzhou exposure significantly increased reactive oxygen species production of BEAS-2b cells and induced a dramatic increase of myocardial fiber-related gene expression (Col1a1 and TGF-ß) in AC16 cells. It indicated that the different mass concentrations of Zn, Pb, Mn, and ΣPAHs in PM2.5 might be the critical factors that modulated myocardial fibrosis induction by targeted. Our study provided a novel avenue for further elucidation of molecular mechanisms of PM2.5 components-induced myocardial fibrosis.

Suppression of NADPH oxidase 4 inhibits PM2.5-induced cardiac fibrosis through ROS-P38 MAPK pathway.

Fine particulate matter (PM2.5) has been consistently linked to cardiovascular diseases, and cardiac fibrosis plays a crucial role in the occurrence and development of heart diseases. It is reported that NOX4-dependent redox signaling are responsible for TGFß-mediated profibrotic responses. The current study was designed to explore the possible mechanisms of cardiac fibrosis by PM2.5 both in vitro and in vivo. Female C57BL/6 mice received PM2.5 (3 mg/kg b.w.) exposure with/without NOX4 inhibitor (apocynin, 25 mg/kg b.w.) or ROS scavenger (NALC, 50 mg/kg b.w.), every other day, for 4 weeks. H9C2 cells were incubated with PM2.5 (3 µg/mL) with/without 5 mM NALC, TGFß inhibitor (SB431542, 10 µM), or siRNA-NOX4 for 24 h. The results demonstrated that PM2.5 induced evident collagen deposition and elevated expression of fibrosis biomarkers (Col1a1 & Col3a1). Significant systemic inflammatory response and cardiac oxidative stress were triggered by PM2.5. PM2.5 increased the protein expression of TGFß1, NOX4, and P38 MAPK. Notably, the increased effects of PM2.5 could be suppressed by SB431542, siRNA-NOX4 in vitro or apocynin in vivo, and NALC. The reverse verification experiments further supported the involvement of the TGFß/NOX4/ROS/P38 MAPK signaling pathway in the myocardial fibrosis induced by PM2.5. In summary, the current study provided evidence that PM2.5 challenge led to cardiac fibrosis through oxidative stress, systemic inflammation, and subsequent TGFß/NOX4/ROS/P38 MAPK pathway and may offer new therapeutic targets in cardiac fibrosis.

Comparative studies on regional variations in PM2.5 in the induction of myocardial hypertrophy in mice.

Exposure to fine particulate matter (PM2.5) has been indicated to be related to an increased risk of cardiovascular diseases (CVDs) in sensitive people. However, the underlying mechanisms of PM2.5-induced CVDs are poorly understood. In the present study, PM2.5 samples were collected during winter from four cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) in China. Ten-month-old C57BL/6 female mice were exposed to PM2.5 suspension at a dosage of 3 mg·kg-1 (b. w.) every other day for 4 weeks by oropharyngeal aspiration. PM2.5 from Taiyuan increased the blood pressure and the thicknesses of the left ventricular anterior and posterior walls, decreased the ratio of nucleus to cytoplasm in cardiomyocytes and reduced the systolic function of the heart in mice. Further investigation revealed that PM2.5 from Taiyuan induced lung inflammatory cytokines with up-regulated expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The mRNA expression levels of myocardial hypertrophy markers atrial natriuretic peptide and the ß isoform of myosin heavy chain (ANP and ß-MHC), matrix metalloproteinase 2 (MMP2), MMP9, and inflammatory cytokines TNF-α and IL-6 in the myocardium were significantly increased after exposure to PM2.5 of Taiyuan. Furthermore, PM2.5 from Taiyuan activated the IL-6/JAK2/STAT3/ß-MHC signaling pathway in the myocardium. The correlation between the PM2.5 components and myocardial hypertrophy markers suggested that Zinc (Zn) and acenaphthene (AC) are related to the changes in ANP and ß-MHC at the transcriptional level, respectively. The above results indicated that PM2.5 exposure induced myocardial hypertrophy in older mice, which might be related to the critical contributions of Zn and AC in PM2.5. The present study provides new insights into the mechanism of myocardial hypertrophy after PM2.5 exposure.