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*

To explore the therapeutic effect of honokiol on particulate matter 2.5 (PM2.5)-induced lung injury in asthmatic mice and the possible mechanisms.
 Methods: A total of 32 BALB/C mice were randomly divided into four groups: a normal saline group, a model group, a PM2.5 group and a honokiol group (n=8 in each group). The asthma mouse model was established by ovalbumin treatment. The mice were treated with physiological saline, ovalbumin, PM2.5 and honokiol, respectively. Lung tissues and serum were collected. The pathological changes of lung tissues were evaluated. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were measured and the expressions of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), retinoid-related orphan receptor gamma-t (RORγt) and forkhead box protein 3 (Foxp3) in lung tissues were detected.
 Results: 1) The lung tissues of mice in the asthma group showed obvious pathological changes and inflammatory state, suggesting that the asthma model was established successfully. PM2.5 could aggravate the pathological condition of inflammatory injury in lung tissues in asthmatic mice. 2) Compared to the PM2.5 group, the pathological symptoms in the lung tissues were alleviated in the honokiol group and the percentage of inflammatory cells in BALF and the levels of inflammatory cytokines in BALF and serum were significantly reduced (all P<0.05). 3) Compared to the PM2.5 group, the expressions of TLR4, NF-κB (p-p65) and RORγt in lung tissues were significantly decreased, while the expression of Foxp3 was increased; the ratio of RORγt/Foxp3 was also decreased in the honokiol group (all P<0.05).
 Conclusion: Honokiol can resist lung injury induced by PM2.5 in asthmatic mice. These effects are through inhibiting TLR4-NF-κB pathway-mediated inflammatory response or regulating the balance of Th17/Treg cells.
Animals ; Asthma ; chemically induced ; complications ; Biphenyl Compounds ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Cytokines ; analysis ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Inflammation Mediators ; analysis ; Lignans ; pharmacology ; Lung ; metabolism ; pathology ; Lung Injury ; drug therapy ; etiology ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; metabolism ; Ovalbumin ; Particulate Matter ; toxicity ; Random Allocation ; Toll-Like Receptor 4 ; metabolism

With the increasing occurrence of haze during the summer, the physicochemical characteristics and toxicity differences in PM_2.5 in different seasons are of great concern. Hangzhou is located in an area that has a subtropical monsoon climate where the humidity is very high during both the summer and winter. However, there are limited studies on the seasonal differences in PM_2.5 in these weather conditions. In this test, PM_2.5 samples were collected in the winter and summer, the morphology and chemical composition of PM_2.5 were analyzed, the toxicity of PM_2.5 to human bronchial cells BEAS-2B was compared, and the correlation between PM_2.5 toxicity and the chemical composition was discussed. The results showed that during both the winter and summer, the main compounds in the PM_2.5 samples were water-soluble ions, particularly SO₄^2-, NO₃^-, and NH₄⁺, followed by organic components, while heavy metals were present at lower levels. The higher the mass concentration of PM_2.5, the greater its impact on cell viability and ROS levels. However, when the mass concentration of PM_2.5 was similar, the water extraction from the summer samples showed a greater impact on BEAS-2B than that from the winter samples. The cytotoxicity of PM_2.5 was closely associated with heavy metals and organic pollutants but less related to water-soluble ions.
Air Pollutants/toxicity* ; Bronchi/metabolism* ; Carbon/chemistry* ; Environmental Monitoring ; Humans ; Ions ; Metals, Heavy ; Organic Chemicals ; Particle Size ; Particulate Matter/toxicity* ; Seasons ; Temperature ; Water

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p<0.01) and lower level of GSH-PS (p<0.01) in BALF, significantly higher levels of LDH and MDA (p<0.05) and lower level of GSH-PS (p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group (all P<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group (all P<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group (all P<0.05). Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.
Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Drugs, Chinese Herbal ; therapeutic use ; Lung ; metabolism ; pathology ; Lung Injury ; drug therapy ; etiology ; metabolism ; Male ; Particulate Matter ; toxicity ; Rats ; Rats, Wistar

Air Pollutants ; chemistry ; toxicity ; Cardiovascular Diseases ; epidemiology ; etiology ; Environmental Exposure ; Humans ; Particle Size ; Particulate Matter ; chemistry ; toxicity ; Respiratory Tract Diseases ; epidemiology ; etiology

OBJECTIVES: The deleterious effects of air pollution on various health outcomes have been demonstrated. However, few studies have examined the effects of air pollution on liver enzyme levels. METHODS: Blood samples were drawn up to three times between 2008 and 2010 from 545 elderly individuals who regularly visited a community welfare center in Seoul, Korea. Data regarding ambient air pollutants (particulate matter < or =2.5 mum [PM2.5], nitrogen dioxide [NO2], ozone [O3], carbon monoxide, and sulfur dioxide) from monitoring stations were used to estimate air pollution exposure. The effects of the air pollutants on the concentrations of three liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyltranspeptidase [gamma-GTP)]) were evaluated using generalized additive and linear mixed models. RESULTS: Interquartile range increases in the concentrations of the pollutants showed significant associations of PM2.5 with AST (3.0% increase, p=0.0052), ALT (3.2% increase, p=0.0313), and gamma-GTP (5.0% increase, p=0.0051) levels; NO2 with AST (3.5% increase, p=0.0060) and ALT (3.8% increase, p=0.0179) levels; and O3 with gamma-GTP (5.3% increase, p=0.0324) levels. Significant modification of these effects by exercise and alcohol consumption was found (p for interaction <0.05). The effects of air pollutants were greater in non-exercisers and heavy drinkers. CONCLUSIONS: Short-term exposure to air pollutants such as PM2.5, NO2, and O3 is associated with increased liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol.
Aged ; Aged, 80 and over ; Air Pollutants/analysis/*toxicity ; Alanine Transaminase/blood ; *Alcohol Drinking ; Aspartate Aminotransferases/blood ; Environmental Exposure ; *Exercise ; Female ; Humans ; Linear Models ; Liver/*drug effects/enzymology ; Male ; Nitrogen Dioxide/chemistry/toxicity ; Ozone/chemistry/toxicity ; Particulate Matter/analysis/toxicity ; Sulfur Dioxide/chemistry/toxicity ; gamma-Glutamyltransferase/blood

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.
Arsenic/*analysis ; Cosmetics/chemistry ; Drinking Water/chemistry ; *Environmental Exposure ; Humans ; Particulate Matter/chemistry ; Smoking ; Water Pollutants, Chemical/*analysis

Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.
Arsenic/*analysis ; Cosmetics/chemistry ; Drinking Water/chemistry ; *Environmental Exposure ; Humans ; Particulate Matter/chemistry ; Smoking ; Water Pollutants, Chemical/*analysis

The contribution of particles to cardiovascular mortality and morbidity has been enlightened by epidemiologic and experimental studies. However, adverse biological effects of the particles with different sizes on cardiovascular cells have not been well recognized. In this study, sub-cultured human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of pure quartz particles (DQ) of three sizes (DQPM1, <1 μm; DQPM3-5, 3-5 μm; DQPM5, 5 μm) and carbon black particles of two sizes (CB0.1, <0.1 μm; CB1, <1 μm) for 24 h. Cytotoxicity was estimated by measuring the activity of lactate dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and cytokines (TNF-α and IL-1β) releases were analyzed by using NO assay and enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both particles induced adverse biological effects on HUVECs in a dose-dependent manner. The size of particle directly influenced the biological activity. For quartz, the smaller particles induced stronger cytotoxicity and higher levels of cytokine responses than those particles of big size. For carbon black particles, CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at lower particle concentrations, in contrast to those at higher concentrations. Meanwhile, our data also revealed that quartz particles performed stronger cell damage and produced higher levels of TNF-α than carbon black particles, even if particles size was similar. In conclusion, particle size as well as particle composition should be both considered in assessing vascular endothelial cells injury and inflammation responses induced by particles.
Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Interleukin-1beta ; secretion ; L-Lactate Dehydrogenase ; metabolism ; Nitric Oxide ; biosynthesis ; Particle Size ; Particulate Matter ; chemistry ; pharmacology ; Quartz ; chemistry ; Soot ; chemistry ; Time Factors ; Tumor Necrosis Factor-alpha ; secretion

OBJECTIVES: We investigated the association between particulate matter less than 10 microm in aerodynamic diameter (PM10) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis. METHODS: Among the 819 published studies searched from PubMed and EMBASE using key words related to PM10 exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 microg/m3 increase of daily PM10 from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test. RESULTS: Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 microg/m3 increase of daily PM10 for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias. CONCLUSIONS: We found a significant positive association between PM10 exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.
Air Pollutants/*chemistry ; Asian Continental Ancestry Group ; Cross-Over Studies ; Databases, Factual ; *Environmental Exposure ; Humans ; Models, Theoretical ; *Mortality ; Particulate Matter/*chemistry ; Time Factors