Cell Differentiation ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Particulate Matter/toxicity* ; Signal Transduction ; Toll-Like Receptor 4/metabolism* ; RAW 264.7 Cells

Humans ; Diabetes Mellitus, Type 2/epidemiology* ; Air Pollution/adverse effects* ; Air Pollutants/toxicity* ; Risk Assessment ; Particulate Matter ; Environmental Exposure

Ozone/toxicity* ; Air Pollution/analysis* ; Air Pollutants/analysis* ; China/epidemiology* ; Environmental Exposure/analysis* ; Mortality ; Particulate Matter/analysis*

Objective: To reveal the crucial toxic components of ambient fine particles (PM_2.5) that affect the maturation and differentiation of megakaryocytes. Methods: Human megakaryocytes were exposed to the organic fractions, metallic fractions and water-soluble fractions of PM_2.5 at two exposure doses (i.e. actual air proportion concentration or the same concentration), respectively. The cell viability was performed to screen the non-cytotoxic levels of toxic components of PM_2.5 using the CCK-8 assay. CellTiter-Blue assay, morphological observation, flow cytometry analysis and WGA staining assay were used to evaluate the cell morphological changes, occurrence of DNA ploidy, alteration in the expressions of biomarkers and platelet formation, which were key indicators of the maturation and differentiation of megakaryocytes. Results: Compared to the control group, both metallic and organic components of PM_2.5 resulted in a lag in megakaryocytes with an increase in cell volume and the onset of DNA ploidy. Flow cytometry analysis showed that CD33 (the marker of myeloid-specific) decreased and CD41a (a megakaryocyte maturation-associated antigen) increased in metallic and organic components of PM_2.5 treatment groups. Moreover, compared to the control group, budding protrusions increased in metallic and organic components of PM_2.5 treatment groups. The water-soluble components had no effect on the maturation and differentiation of macrophages. Conclusion: Metallic and organic components of PM_2.5 are the crucial toxic components that promote the maturation and differentiation of megakaryocytes.
Biomarkers ; DNA/pharmacology* ; Humans ; Megakaryocytes/chemistry* ; Particulate Matter/toxicity* ; Sincalide/pharmacology* ; Water/pharmacology*

Objective: Fine particulate matter (PM _2.5) is an air pollutant that has become of great concern in recent years. Numerous studies have found that PM _2.5 may contribute to lung cancer, but the pathogenesis has not yet been fully elucidated. In this study, we explored the roles of exosomes from bronchial epithelial cells in PM _2.5-promoted lung cancer metastasis. Methods: Exosomes were isolated from cell supernatants. An animal model of lung metastasis (established by tail vein injection of A549-luc) and in vitro studies with lung cancer cell lines were used to investigate the effects of exosomes derived from PM _2.5-treated human bronchial epithelial cells (PHBE-exo). Results: The animal experiments revealed that PHBE-exo-treated mice showed stronger luciferase activity and a larger relative metastatic region in the lungs, thus indicating that PHBE-exo promoted the metastatic potential of lung cancer. Additionally, PHBE-exo promoted the migration, invasion and epithelial-to-mesenchymal transition of lung cancer cells, in a manner mediated by activation of c-Jun N-terminal kinase. Conclusion These results implied that PM _2.5 may promote the development of lung cancer through exosomes derived from bronchial epithelial cells, thus providing a potential interventional target for lung cancer. These findings broadened our understanding of cancer-promoting mechanisms of environmental pollutants.
Animals ; Epithelial Cells/metabolism* ; Epithelial-Mesenchymal Transition ; Exosomes/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; Mice ; Particulate Matter/toxicity*

Epidermis ; Humans ; Hyperpigmentation ; Keratinocytes ; Particulate Matter/toxicity*

Ambient fine particulate matters (PM_2.5) refer to particulate matters with an aerodynamic diameter less than or equal to 2.5 μm. PM_2.5 enter the body through the target organ-lung, and can induce a variety of adverse health effects (such as cardiovascular diseases, diabetes, respiratory diseases, neurodegenerative diseases and adverse birth outcomes). PM_2.5 are known to have complex compositions (including water-soluble/-insoluble components and biological components), diverse sources and capacity of secondary transformation. Numerous epidemiological and toxicological studies indicated that different components of PM_2.5 may induce adverse health effects through different biological mechanisms. In adddition, co-exposure of different components and their interaction should also be considered. Thus here we have systematically reviewed studies in recent years about the toxicological effects and underlying mechanisms of different components of ambient fine particulate matters, including inflammatory response, oxidative stress, endoplasmic reticulum stress, activation of the NF-κB signaling pathway and so on. The information may give some insights into the prevention and treatment of adverse health effects caused by exposure to different components of PM_2.5.
Air Pollutants/toxicity* ; Cardiovascular Diseases/chemically induced* ; Humans ; Lung ; Oxidative Stress ; Particulate Matter/toxicity*

Objective: To screen the differential methylation sites, genes and pathways of air pollution fine particles (PM(2.5)) on human bronchial epithelial (HBE) cells by methylation chip and bioinformation technology, so as to provide scientific basis for further study of the toxicological mechanism of PM(2.5) on HBE cells. Methods: In August 2020, HBE cells were infected with 10 μg/ml and 50 μg/ml PM(2.5) aqueous solution for 24 h, namely PM(2.5) 10 μg/ml exposure group (low dose group) and PM(2.5) 50 μg/ml exposure group (high dose group) ; uninfected HBE cells were used as control group. The DNA fragments were hybridized with the chip, the chip scanned and read the data, analyzed the data, screened the differential methylation sites, carried out GO analysis and KEGG analysis of the differential methylation sites, and analyzed the interaction relationship of the overall differential methylation sites by functional epigenetic modules (FEMs). Results: Compared with the control group, 127 differential methylation sites were screened in the low-dose group, including 89 genes, including 55 sites with increased methylation level and 72 sites with decreased methylation level. The differential methylation sites were mainly concentrated in the Body region and UTR region. Compared with the control group, 238 differential methylation sites were screened in the high-dose group, including 168 genes, of which 127 sites had increased methylation level and 111 sites had decreased methylation level. The differential heterotopic sites were mainly concentrated in the Body region and UTR region. Through FEMs analysis, 8 genes with the most interaction were screened, of which 6 genes had significant changes in methylation level. MALT1 gene related to apoptosis was found in the heterotopic site of methylation difference in low-dose group; PIK3CA and ARID1A genes related to carcinogenesis were found in the heterotopic sites of methylation difference in high-dose group; TNF genes related to tumor inhibition were found in the results of FEMs analysis. Conclusion: After PM(2.5) exposure to HBE cells, the DNA methylation level is significantly changed, and genes related to apoptosis and carcinogenesis are screened out, suggesting that the carcinogenic mutagenic effect of PM(2.5) may be related to DNA methylation.
Air Pollutants/toxicity* ; Basic Helix-Loop-Helix Transcription Factors/analysis* ; Carcinogenesis ; DNA Methylation ; Humans ; Particulate Matter/toxicity* ; Technology

Objective: To investigate the effects of PM_2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM_2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM_2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.
Animals ; Female ; Interleukin-1/pharmacology* ; Interleukin-6 ; Male ; Neurotransmitter Agents ; Particulate Matter/toxicity* ; Prefrontal Cortex ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; Superoxide Dismutase ; Tumor Necrosis Factor-alpha/pharmacology*

Objective To quantitatively evaluate the associations of PM
Air Pollutants/toxicity* ; Air Pollution/adverse effects* ; Child, Preschool ; China ; Dermatitis, Atopic/epidemiology* ; Female ; Humans ; Male ; Outpatients ; Particulate Matter/analysis*