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Fine particulate matter (PM2.5) has been linked to cardiopulmonary disease and systemic effects in humans. However, few studies have investigated the particle bioreactivity in Chinese megacities during haze episodes. The objective of this study was to determine the contributions of chemical components in PM2.5 to particle bioreactivity in Chinese megacities during haze episodes. PM2.5 samples were collected in 14 megacities across China from 23 December 2013 to 16 January 2014. Average PM2.5 concentrations ranged 88.92~199.67 μg/m3. Organic carbon (OC), elemental carbon (EC), anions, and cations per unit of PM2.5 were linked to cellular bioreactivity (i.e., reactive oxygen species (ROS) as assessed by dichlorodihydrofluorescein diacetate (DCFH) and inflammation as assessed by interleukin (IL)-6 in A549 cells). The contributions of chemicals in PM2.5 to ROS and inflammation were examined by the Pearson correlation coefficient and random forests. These results indicated that OC, Ca2+, SO42−, Cl−, F−, K+, and NO3− contributed to ROS production, whereas OC, Cl−, EC, K+, F−, Na+, and Ca2+ contributed to inflammation. In conclusion, PM2.5-contained OC and acidic ions are important in regulation of oxidative stress and inflammation during haze episodes. Our findings suggest that severe haze PM2.5 events cause deterioration in air quality and may adversely affect human health.

Background Exposure to air pollution exerts direct effects on respiratory organs; however, molecular alterations underlying air pollution-induced pulmonary injury remain unclear. In this study, we investigated the effect of air pollution on the lung tissues of Sprague-Dawley rats with whole-body exposure to traffic-related PM1 (particulate matter Results Rats in the 6-month PM1-exposed group exhibited a significant decline in lung function, as determined by decreased FEF25–75% and FEV20/FVC; however, histological analysis revealed earlier lung damage, as evidenced by increased congestion and macrophage infiltration in 3-month PM1-exposed rat lungs. The lung tissue proteomics analysis identified 2673 proteins that highlighted the differential dysregulation of proteins involved in oxidative stress, cellular metabolism, calcium signalling, inflammatory responses, and actin dynamics under exposures to PM1 and gaseous pollutants. The presence of PM1 specifically enhanced oxidative stress and inflammatory reactions under subchronic exposure to traffic-related PM1 and suppressed glucose metabolism and actin cytoskeleton signalling. These factors might lead to repair failure and thus to lung function decline after chronic exposure to traffic-related PM1. A detailed pathogenic mechanism was proposed to depict temporal and dynamic molecular regulations associated with PM1- and gaseous pollutants-induced lung injury. Conclusion This study explored several potential molecular features associated with early lung damage in response to traffic-related air pollution, which might be used to screen individuals more susceptible to air pollution.

Exposure to road dust particulate matter (PM) causes adverse health impacts on the human airway. However, the effects of road dust on the upper airway epithelium in humans remain unclear. We investigated the involvement of the epidermal growth factor receptor (EGFR) after PM with an aerodynamic diameter of < 2.5 μm (PM2.5)-induced E-cadherin disruption of human pharyngeal epithelial cells. First, we collected road dust PM2.5 from 10 Chinese cities, including Wuhan, Nanjing, Shanghai, Guangzhou, Chengdu, Beijing, Lanzhou, Tianjin, Harbin, and Xi'an. Human pharyngeal FaDu cells were exposed to road dust PM2.5 at 50 μg/mL for 24 h, cytotoxicity (cell viability and lactate dehydrogenase (LDH)) was assessed, and expressions of the proinflammatory interleukin (IL)-6 and high-mobility group box 1 (HMGB1) protein, receptor for advanced glycation end products (RAGE), occludin, E-cadherin, EGFR, and phosphorylated (p)-EGFR were determined. The E-cadherin gene was then knocked down to investigate EGFR activation in FaDu cells. Exposure to road dust PM2.5 resulted in a decrease in cell viability and increases in LDH and IL-6. Our data suggested that PM2.5 could decrease expressions of occludin and E-cadherin and increase expressions of EGFR and p-EGFR, which was confirmed by E-cadherin-knockdown. Our results showed a negative association between the alterations in E-cadherin and total elemental components in correlation analysis, especially S, Cl, K, Ti, Mn, Fe, Cu, Zn, and Pb. Exposure to metals in PM2.5 from road dust may lead to loss of the barrier function of the upper airway epithelium and activation of the EGFR. Our study showed the adverse effects of road dust PM2.5 on pharyngeal epithelial cells of the human upper airway.

Background Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats. Results SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p 2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p 2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure. Conclusions Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.

Introduction Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with COPD could have severe outcomes after SARS-CoV-2 infection. The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD. Methods Sprague Dawley rats were exposed to unconcentrated traffic-related air pollution for 3 and 6 months. We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure. Results Lung injury occurred due to an increase in permeability and lactate dehydrogenase cytotoxicity was observed after 6 months of exposure to fine particulate matter of, Short-term exposure to PM1 increases ACE2 overexpression in lungs. Long-term exposure to PM1 decreases the ACE2 overexpression in emphysema. Air pollution may be a risk for #SARSCoV2 adhesion during the development of COPD. https://bit.ly/2Vfykur

Quartz can increase oxidative stress, lipid peroxidation, and inflammation. The objective of this study was to explore the volatile biomarkers of quartz-induced lung injury using a lung alveolar cell model. We exposed the human alveolar A549 cell line to 0, 200, and 500 μg/mL quartz particles for 24 h and used gas chromatography–mass spectrometry to measure the volatile metabolites in the headspace air of cells. We identified ten volatile metabolites that had concentration–response relationships with particles exposure, including 1,2,4-oxadiazole, 5-(4-nitrophenyl)-3-phenyl- (CAS: 28825-12-9), 2,6-dimethyl-6-trifluoroacetoxyoctane (CAS: 61986-67-2), 3-buten-1-amine, N,N-dimethyl- (CAS: 55831-89-5), 2-propanol, 2-methyl- (CAS: 75-65-0), glycolaldehyde dimethyl acetal (CAS: 30934-97-5), propanoic acid, 2-oxo-, ethyl ester (CAS: 617-35-6), octane (CAS: 111-65-9), octane, 3,3-dimethyl- (CAS: 4110-44-5), heptane, 2,3-dimethyl- (CAS: 3074-71-3) and ethanedioic acid, bis(trimethylsilyl) ester (CAS: 18294-04-7). The volatile biomarkers are generated through the pathways of propanoate and nitrogen metabolism. The volatile biomarkers of the alkanes and methylated alkanes are related to oxidative and lipid peroxidation of the cell membrane. The lung alveolar cell model has the potential to explore the volatile biomarkers of particulate-induced lung injury.

Background: Air pollution has been linked to emphysema in chronic obstruction pulmonary disease (COPD). However, the underlying mechanisms in the development of emphysema due to air pollution remain unclear. The objective of this study was to investigate the role of components of the Hippo signaling pathway for E-cadherin-mediated contact inhibition of proliferation in the lungs after air pollution exposure. E-Cadherin-mediated contact inhibition of proliferation via the Hippo signaling pathway was investigated in Sprague-Dawley (SD) rats whole-body exposed to air pollution, and in alveolar epithelial A549 cells exposed to diesel exhaust particles (DEPs), E-cadherin-knockdown, and high-mobility group box 1 (HMGB1) treatment. Underlying epithelial differentiation, apoptosis, and senescence were also examined, and the interaction network among these proteins was examined. COPD lung sections were used to confirm the observations in rats. Results: Expressions of HMGB1 and E-cadherin were negatively regulated in the lungs and A549 cells by air pollution, and this was confirmed by knockdown of E-cadherin and by treating A549 cells with HMGB1. Depletion of phosphorylated (p)-Yap occurred after exposure to air pollution and E-cadherin-knockdown, which resulted in decreases of SPC and T1α. Exposure to air pollution and E-cadherin-knockdown respectively downregulated p-Sirt1 and increased p53 levels in the lungs and in A549 cells. Moreover, the protein interaction network suggested that E-cadherin is a key activator in regulating Sirt1 and p53, as well as alveolar epithelial cell differentiation by SPC and T1α. Consistently, downregulation of E-cadherin, p-Yap, SPC, and T1α was observed in COPD alveolar regions with particulate matter (PM) deposition. Conclusions: Our results indicated that E-cadherin-mediated cell-cell contact directly regulates the Hippo signaling pathway to control differentiation, cell proliferation, and senescence due to air pollution. Exposure to air pollution may initiate emphysema in COPD patients.

Organic components of fine particles, especially polycyclic aromatic hydrocarbons (PAHs), play an essential role in the toxicity of fine particulate matter (PM2.5). The chemical and bioreactive properties of PM2.5 in indoor environments were investigated from 2014 to 2016 in Hong Kong among 33 residential indoor environments. All analyzed components revealed higher concentrations in winter than in summer, except for organic carbon (OC). High molecular weight PAHs (4–6 rings) contributed higher total PAH compositions than low molecular weight PAHs (2–3 rings). The study results suggested that the major sources of indoor PM2.5 originated from outdoor vehicle emissions, indoor cooking activities, and incense burning. Cytotoxicity tests only revealed significant associations in winter. The cell viability demonstrated strong negative correlations between OC (r = − 0.8, p < 0.05), total PM2.5-bound PAHs (r = − 0.6, p < 0.05), and United States Environmental Protection Agency (US EPA) priority PAHs (r = − 0.7, p < 0.05). Cell lactate dehydrogenase (LDH) and 8-isoprostane were positively associated with OC (r = 0.8, p < 0.05; r = 0.7, p < 0.05), total PM2.5-bound PAH (r = 0.7, p < 0.05; r = 0.7, p < 0.05), and US EPA priority PAH (r = 0.6, p < 0.05; r = 0.5, p = 0.07) concentrations. IL-6 had the only positive association with OC (r = 0.5, p < 0.05). This study focused on indoor PM2.5 levels and the associated cytotoxicity in the absence of environmental tobacco smoke.

Traffic emission is responsible for most small-sized particulate matter (PM) air pollution in urban areas. Several recent studies have indicated that traffic-related PM may aggravate kidney disease. Furthermore, exposure to particulate air pollution may be related to the risk of chronic kidney disease (CKD). However, the underlying molecular mechanisms have not been adequately addressed. In the present study, we studied the mechanisms of renal damage that might be associated with exposure to PM. In a real world of whole-body exposure to traffic-related PM model for 3-6 months, PM in urban ambient air can affect kidney function and induce autophagy, endoplasmic reticulum (ER) stress and apoptosis in kidney tissues. Exposure to traffic-related diesel particulate matter (DPM) led to a reduction in cell viability in human kidney tubular epithelial cells HK-2. DPM increased mitochondrial reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Furthermore, DPM induced ER stress and activated the unfolded protein response (UPR) pathway. Eventually, DPM exposure induced caspase pathways and triggered apoptosis. In addition, DPM induced autophagy through the inhibition of the Akt/mTOR pathway. Autophagy inhibition resulted in significantly increased cytotoxicity and apoptosis. These findings suggest that air pollution in urban areas may cause nephrotoxicity and autophagy as a protective role in PM-induced cytotoxicity.

The association between houseplants and indoor air quality improvement has been reported in previous studies. However, the effect of houseplant-emitted isoprene on the association between ozone (O3) formation and respiratory health remains unclear. We recruited 60 adult subjects from 60 houses with or without houseplants (1:1) in Taipei; twelve house visits were conducted in each home throughout 2014. The indoor air pollutants that were measured consisted of particulate matter less than or equal to 2.5 μm in diameter (PM2.5), O3 and isoprene. Peak expiratory flow rate (PEFR) was measured in each study subject during each house visit. Household information was collected by a questionnaire. Mixed-effects models were used to explore the association between indoor air pollution levels and PEFR. We found that the concentrations of O3 and isoprene in houses with houseplants were higher than those in houses without houseplants. In contrast, PM2.5 levels and % predicted PEFR were higher in houses without houseplants than in those with houseplants. Moreover, increased levels of O3 and PM2.5 in houses with houseplants were associated with a decreased % predicted PEFR, especially in the summer. We concluded that increased levels of indoor O3 and PM2.5 were associated with decreased PEFR. The presence of houseplants was associated with indoor O3, isoprene and PEFR variations in the summer. Keywords: Houseplant, Indoor air, Ozone, Isoprene, Peak expiratory flow rate

Vinyl chloride (VC) is classified as a group 1 carcinogen to humans by the International Agency for Research on Cancer, and inhalation is considered to be an important route of occupational exposure. In addition, increasing numbers of studies have observed adverse health effects in people living in the vicinity of petrochemical complexes. The objective of this study was to investigate the adverse in vivo health effects on the lungs and liver caused by pulmonary exposure to low-level VC. BALB/c mice were repeatedly intranasally administrated 50 µL/mouse VC at 0, 1, and 200 ng/mL (5 days/week) for 1, 2, and 3 weeks. We observed that exposure to 1 and 200 ng/mL VC significantly increased the tidal volume (μL). Dynamic compliance (mL/cmH2O) significantly decreased after exposure to 200 ng/mL VC for 3 weeks. Total protein, lactate dehydrogenase (LDH), and interleukin (IL)-6 levels in bronchoalveolar lavage fluid (BALF) significantly increased after exposure to 200 ng/mL VC for 2 and/or 3 weeks. Significant decreases in 8-isoprostane and caspase-3 and an increase in IL-6 in the lungs were found after VC exposure for 2 and/or 3 weeks. We observed that aspartate aminotransferase (AST), alkaline phosphatase (ALKP), albumin (ALB), and globulin (GLOB) had significantly increased after three weeks of VC exposure, whereas the ALB/GLOB ratio had significantly decreased after 3 weeks of exposure to VC. IL-6 in the liver increased after exposure to 1 ng/mL VC, but decreased after exposure to 200 ng/mL. IL-1β in the liver significantly decreased following exposure to 200 ng/mL VC, whereas tumor necrosis factor (TNF)-α and caspase-3 significantly increased. Hepatic inflammatory infiltration was confirmed by histological observations. In conclusion, sub-chronic and repeated exposure to low levels of VC can cause lung and liver toxicity in vivo. Attention should be paid to all situations where humans are frequently exposed to elevated VC levels such as workplaces or residents living in the vicinity of petrochemical complexes.

Indoor air pollution sources with emissions of fine particles (PM2.5), including environmental tobacco smoke (ETS) and incense smoke (IS) deteriorate indoor air quality and may cause respiratory diseases in humans. This study characterized the emission factors (EFs) of five types of tobacco and incense in Hong Kong using an environmental chamber. Human alveolar epithelial cells (A549) were exposed to PM2.5 collected from different indoor sources to determine their cytotoxicity. The PM2.5 EF of ETS (109.7±36.5 mg/g) was higher than IS (97.1±87.3 mg/g). The EFs of total polycyclic aromatic hydrocarbons (PAHs) and carbonyls for IS were higher than ETS, and these two combustion sources showed similar distributions of individual PAHs and carbonyls. Oxidative damage and inflammatory responses (i.e. DNA damage, 8-hydroxy-desoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6)) of A549 cells was triggered by exposure to PM2.5 generated from ETS and IS. Different indoor sources showed different responses to oxidative stress and inflammations due to the accumulation effects of mixed organic compounds. High molecular weight PAHs from incense combustion showed higher correlations with DNA damage markers, and most of the PAHs from indoor sources demonstrated significant correlations with inflammation. Exposure to anthropogenic produced combustion emissions such as ETS and IS results in significant risks (e.g. lung cancer) to the alveolar epithelium within the distal human respiratory tract, of which incense emissions posed a higher cytotoxicity.

Certain studies have reported various insulin resistance responses to ambient heavy metal pollution, but few have reported such responses to occupational heavy metal pollution. Even fewer have demonstrated a relationship between mixture effects of heavy metals and insulin resistance in welding workers. Overall, we recruited 53 welders and 48 administrative staff from a shipyard located in northern Taiwan. Personal exposure to heavy metals was monitored for PM2.5 and urine. Blood samples from each participant were collected from the antecubital vein after fasting. Urine samples from each participant were collected in the same period as blood samples. The geometric mean levels for chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), and cadmium (Cd) in the PM2.5 of the personal breathing zone and urinary Mn of welders were significantly higher than those in administrative staffs. Ambient Cr, Co, Ni, and Cu levels in the PM2.5 and urinary Cd were positively related to HOMA2-IR after adjusting for personal covariates (PM2.5-Cr: β=0.036, 95%C.I.: 0.002 to 0.070; PM2.5-Co: β=0.040, 95%C.I.: 0.002 to 0.077; PM2.5-Ni: β=0.054, 95%C.I.: 0.013 to 0.094; PM2.5-Cu: β=0.049, 95%C.I.: 0.010 to 0.088; U-Cd: β=0.209, 95%C.I.: 0.052 to 0.366, respectively). Our findings indicated the PM2.5 metal components and urinary metals were associated with increased insulin resistance in shipyard welders.

Toxicological studies have demonstrated the associations between fine particle (PM2.5) components and various cytotoxic endpoints. However, few studies have investigated the toxicological effects of source-specific PM2.5 at the individual level. To investigate the potential impact of source-specific PM2.5 on cytotoxic effects, we performed repeated personal PM2.5 monitoring of 48 adult participants in Hong Kong during the winter and summer of 2014–2015. Quartz filters were analyzed for carbonaceous aerosols and water-soluble ions in PM2.5. Teflon filters were collected to determine personal PM2.5 mass and metal concentrations. The toxicological effects of personal PM2.5 exposure—including cytotoxicity, inflammatory response, and reactive oxygen species (ROS) production—were measured using A549 cells in vitro. Personal PM2.5 samples collected in winter were more effective than those collected in summer at inducing cytotoxicity and the expression of proinflammation cytokine IL-6. By contrast, summer personal PM2.5 samples induced high ROS production. We performed a series of statistical analyses, Spearman correlation and a source apportionment approach with a multiple linear regression (MLR) model, to explore the sources contributing most significantly to personal PM2.5 bioreactivity. Secondary inorganic species and transition metals were discovered to be weak-to-moderately associated with cytotoxicity (rs: 0.26–0.55; p

Toxicity attributable to the particle charge remains unclear. The objective of this study was to investigate pulmonary effects of the electric charge of particles. We established a stably charged aerosol particle generation system for whole-body exposure in BALB/c mice, which produced positively, negatively, and neutrally charged soot particles in a wide range of numbers and mass concentrations. The charged soot particles on average carried 1.16~1.35 electric charges, and the mode sizes for particles under different charging statuses were all fixed at 69.6~71.8 nm. After inhalation, the positively and negatively charged soot particles arrested the body weight increase in mice. Pulmonary cytotoxicity of lactate dehydrogenase, oxidative stress 8-isoprostane, and the benzo(a)pyrene diolepoxide protein adduct occurred in dose-dependent manners by negatively charged soot particles. We further observed that positively and negatively charged soot particles induced systemic interleukin-6 production in dose-dependent responses in mice. Our findings suggest that inhalation of particles carrying negative electric ions could cause lung toxicity that should be of concern in terms of pulmonary health protection.

Background: Exposure to particulate matter (PM) pollution has direct impacts on the respiratory organs, yet the molecular alterations underlying PM-induced pulmonary injury remain unclear. In this study, we investigated the effect of PM on lung tissues from our previously reported rat model with whole-body exposure to traffic-related PM1 pollutants and compared it with rats exposed to high-efficiency particulate air-filtered gaseous pollutants and clean air control for 3 and 6 months. Lung function and histological examinations as well as quantitative proteomics analysis and functional validation were performed. Results: The rats in 6-month PM1-exposed group showed significant decline in lung function by decreased forced expiratory flow and forced expiratory volume, but the histological analysis revealed an earlier lung damage evidenced by increased congestion and macrophage infiltration in 3-month PM1-exposed rat lungs. The lung tissue proteomics analysis identified 2,673 proteins which highlighted dysregulations on proteins involved in oxidative stress, cellular metabolisms, calcium signaling, inflammatory responses, and actin dynamics. The presence of fine particles specifically enhanced the oxidative stress and inflammatory reactions under sub-chronic exposure of traffic-related PM1 and suppressed the glucose metabolism and actin cytoskeleton signaling which might lead to repair failure and thus lung function decline after chronic exposure of traffic-related PM1. A detailed pathogenic mechanism was proposed to depict the temporal and dynamic molecular regulations associated with PM1-induced lung injury.Conclusion: Our study explored the earlier lung injury prior to lung function decline and proposed several proteins as potential molecular features for traffic-related PM1-induced lung injury.

Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been found to be pivotal biomarkers to predict the risk of inflammation and oxidative stress. Limited evidence focuses on the influence of occupational exposure to polycyclic aromatic hydrocarbon (PAH) and metal fumes on AGE and RAGE in shipyard welders. Our aim was to determine the relationships among PAH, metal exposure, and inflammatory biomarkers. From September 1 to December 31, 2017, 53 welding workers (exposed group) and 29 office workers (control group) were enrolled in the study. Comprehensive workups included demographic characteristics, laboratory data, AGE, RAGE, Interleukin-6 (IL-6), tumor necrosis factor-α, PAH, and urinary metal concentrations. RAGE levels were measured by flow cytometric analysis. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to PAH. Several metals were elevated in the personal fine particulate matter (PM2.5) samples, including Mn, Fe, V, Co, Zn, and Cu. The exposed group had significantly higher exposure to PM2.5 (p = 0.015), RAGE (p = 0.020), IL-6 (p = 0.008) than the control group. After adjusting for pertinent variables, there was still a significant and positive association between Ni level and AGE (β = 0.101; 95% CI, 0.031–0.172). Significant relationship between Cr and Cd levels and RAGE was observed (β = 0.173; 95% CI, 0.017–0.329; β = 0.084; 95% CI, 0.011–0.157, respectively). Participants with elevated 1-OHP level had higher odds of high RAGE level in the model 1 (OR = 3.466, 95% CI, 1.053–11.412) and model 2 (OR = 3.454, 95% CI, 1.034–11.536). The RAGE expression of participants was significantly associated with IL-6 levels in the fully adjusted model (β = 0.294; 95% CI, 0.083–0.732). Our findings highlighted that urinary metal levels and PAH were associated with increased AGE and RAGE formation in shipyard workers. Elevated serum RAGE might induce the production of proinflammatory cytokines and trigger ensuing inflammatory cascades.

Adverse health effects have been observed in nearby residents due to exposure to petrochemical-derived chemicals. The objective of this study was to examine associations of soluble metals with lung and liver toxicity in fine particulate matter (PM2.5) in the vicinity of a petrochemical complex. PM2.5 was collected in the vicinity of a petrochemical complex of Mailiao Township (Yunlin County, Taiwan) to investigate lung and liver toxicity in BALB/c mice. The PM2.5 concentration was 30.2 ± 11.2 μg/m3, and the PM2.5 was clustered in major local emissions (19.1 μg/m3) and minor local emissions (14.1 μg/m3) using a k-means clustering model. The PM2.5 (50 and 150 μg/kg) and PM2.5-equivalent soluble nickel (Ni), vanadium (V), and lead (Pb) concentrations were intratracheally instilled into BALB/c mice. PM2.5 and V significantly decreased the tidal volume after exposure (p

Although the applications for zinc oxide nanoparticles (ZnONP) are continually increasing, the neurotoxicity of this material remains unclear. This study investigated the acute effects of pulmonary exposure to ZnONP on the brain in terms of behavioral changes, oxidative stress, inflammation, and tau and autophagy expressions using rat subjects. Based on the test subjects’ performance in a Morris water maze and an elevated-plus maze, respectively, no major alterations occurred in spatial cognition or learning ability, or anxiety. Following exposure to 10 mg kg–1 of ZnONP, we observed that the level of 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG)/dG significantly increased in the hippocampus, whereas those of interleukin (IL)-1β and IL-6 significantly decreased in the cerebellum and the cortex. Additionally, microglia were activated in the hippocampus. Tau protein expression was strong in the cerebellum and the hippocampus, but no significant expression of Beclin-1, light chain 3 (LC3) II/I, or ubiquitin was detected. Our results suggest that acute exposure to ZnONP induces oxidative stress, microglia activation, and tau protein expression in the brain, leading to neurotoxicity.

Particulate air pollution is recognized as a potential risk factor for neurological disorders; however, the underlying mechanisms of neurodegenerative diseases that occur due to particulate air pollution remain unclear. The objective of the present study was to evaluate the neurotoxic effects caused by diesel exhaust particles (DEPs). We determined the ability of DEPs and carbon black (CB) to induce neurotoxicity, oxidative stress and inflammation, and to disrupt the expression of tau and autophagy proteins in human neuroblastoma IMR-32 cells. Spherical CB (dominated by C, N, and S) and DEPs (dominated by C, N, and O) in aggregates were observed using a field emission-scanning electron microscope (FE-SEM) equipped with energy-dispersive x-ray (EDX) microanalysis. Cell viability was significantly decreased by CB and DEPs in IMR-32 cells, but neither particle altered malondialdehyde (MDA) production. We observed that exposure to DEPs significantly increased 8-isoprostane and tumor necrosis factor (TNF)-α levels. Significantly increased expression of tau was induced in IMR-32 cells by DEPs but not by CB. Expression of beclin 1 was increased by DEPs, whereas the light chain 3II (LC3II)/LC3I ratio was increased by CB. Results of the present study suggested that DEPs induced neuroinflammation, oxidative stress, and neurodegenerative-related tau overexpression and regulation by autophagy in IMR-32 cells. We demonstrated that DEPs are able to induce neurotoxicity, which could be associated with the development of neurodegenerative diseases.

Recent studies suggest that exposure to air pollution might be associated with severity of sleep-disordered breathing (SDB). However, the association between air pollution exposure, especially particulate matter with aerodynamic diameters

The direct air-liquid interface (ALI) in vitro exposure method are used for high-throughput screening of nanoparticle toxicity, due to the relatively low capital required and the low cost of labor compared to animal and in vivo experiments. In this study, a new ALI exposure chamber using an electrostatic precipitator (ESP–ALI) was designed to improve the nano- and submicron-sized particle collection efficiency on the air-liquid exposure interface. Particle penetration tests were performed to characterize the performance under different operating conditions. The effects of different geometric dimensions and operating conditions were explored, and the similarity-scaling process was applied to reveal the hidden effects underlying the experimental data. The penetration results show that the developed electrostatic precipitator is able to efficiently collect particles with a size of up to 300 nm under a DC electric field of 5.0 kV/cm and at a flow rate of up to 1.5 lpm. The electrospray charging technique was also tested with this ESP–ALI system and proved to enhance the ALI collection efficiency without ozone generation. In addition, the particles collected on the exposure interface are uniformly distributed under various operating conditions, as supported by consistent dimensionless precipitation densities.

Lung cancer, mostly non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths; however, efficient treatments for NSCLC remain insufficient. The objective of this study was to investigate the effects of an epidermal growth factor receptor (EGFR) mutation on autophagic cell death in human lung adenocarcinoma cells by 20-nm zinc oxide nanoparticles (ZnONP20) and aluminum-doped ZnONPs (Al-ZnONP20). Two types of human lung adenocarcinoma cells were used throughout the study: wild-type EGFR A549 cells and EGFR-mutated CL1-5 cells. We observed that a significant reduction in cell viability resulting from ZnONP20 and Al-ZnONP20 occurred in A549 and CL1-5 cells after 18 and 24 hr of exposure. A colony formation analysis showed that A549 cells re-grew after exposure to 20 μg/mL Al-ZnONP20. Levels of light chain 3 (LC3) II conversion were activated by ZnONP20 and Al-ZnONP20 in A549 cells, whereas LC3 II was inhibited by ZnONP20 and Al-ZnONP20 in CL1-5 cells. In conclusion, we have shown that human lung adenocarcinoma cells with an EGFR mutation are sensitive to ZnONP20 and Al-ZnONP20, which may have resulted in non-autophagic cell death. ZnONP20 and Al-ZnONP20 may have the potential for personalized therapeutics in NSCLC with an EGFR mutation.

Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM1 (PM with an aerodynamic diameter of

Vinyl chloride (VC) is a noninfective occupational risk factor. It is found in industrial chemicals, volatile organic compounds, cigarette smoke ingredients, etc. It is a kind of toxic gas that causes many diseases. VC exposure causes an increased risk of liver fibrosis and can result in angiosarcoma of the liver. Previous studies have shown that high-doses of VC exposure in mice resulted in acute death with marked tubular necrosis of the renal cortex. In this study, we assessed the nephrotoxicity of VC in vitro and in vivo. As a result, we demonstrated that VC induced fibrosis-associated protein expression, such as connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and collagen 1, and autophagy-associated protein expression, such as Beclin 1 and LC3-II, in kidney cells. The beclin1 siRNA experiments found that autophagy inhibited VC-induced fibrosis. Blood urea nitrogen (BUN) and creatinine levels were increased after VC treatment. Furthermore, VC caused glomerulosclerosis and tubular injury in mouse kidney tissues. Kidney tissue sections showed that VC induced fibrosis and autophagy in mouse kidney tissues. In summary, the results of VC-induced fibrosis suggest that autophagy plays an important role in kidney damage. VC may cause nephrotoxicity, and the results illustrate the importance of considering the toxicological hazards of VC in kidney cells.

The lung is the first target organ to interact with harmful particles, mists, vapors, or gases. Inhalation of the environmental pollutants is able to induce environmental lung diseases. Reactive oxygen species (ROS) are usually produced from pollutant itself (from the physicochemical characteristic) or disrupt the oxidative stress in normal biological system. The overload ROS is able to attack DNA and the surrounding protein, leading to DNA damage and protein adduct. Particulate matter (PM)-containing ROS interacts with sulfur-containing methionine (Met) to produce oxidized forms of methionine sulfoxide (MetO). An overload of ROS causes the MetO reductase (MSR) repair system to malfunction, leading to MetO accumulation in cells. Apoptosis pathways are activated due to self-defense mechanisms when oxidized proteins accumulate. Disruption of protein repairing system caused by air pollution may be a potential role of the pathogenesis of environmental lung disease. In this review of the literature on environmental lung diseases, the focus is on environmental oxidants and protein oxidation.

Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is a type II acute-phase protein; however, the role of pulmonary ITIH4 after exposure to air pollution remains unclear. In this study, we investigated the role of ITIH4 in the lungs in response to air pollution. ITIH4 expression in bronchoalveolar lavage fluid (BAL) of 47 healthy human subjects and of Sprague-Dawley rats whole-body exposed to air pollution was determined, and the underlying antiapoptotic and matrix-stabilizing pathways in alveolar epithelial A549 cells induced by diesel exhaust particles (DEPs) as well as ITIH4-knockdown were investigated. We found that an interquartile range (IQR) increase in PM2.5 was associated with a decrease of 2.673 ng/mL in ITIH4, an increase of 1.104 pg/mL of 8-isoprostane, and an increase of 6.918 pg/mL of interleukin (IL)-6 in human BAL. In rats, increases in 8-isoprostane, IL-6, and p53 and a decrease in sirtuin-1 (Sirt1) in the lungs and decreases in ITIH4 in the BAL, lungs, and serum were observed after PM2.5 and gaseous exposure. ITIH4 levels in lung lysates were correlated with levels in BAL samples (r = 0.377, p

Organic compounds in fine particles play major roles in cardiopulmonary diseases. A study was conducted to determine the characteristics and cytotoxicity of organic aerosols (OA) in an urban roadside area in Hong Kong. Chemical components in nonrefractory submicron aerosol (NR-PM1) were observed using a Quadrupole Aerosol Chemical Speciation Monitor (Q-ACSM), and the chemical profile of organic compounds in NR-PM1 was examined with filter-based approach. Associations between cytotoxicity and organic sources and compositions were evaluated. NR-PM1 contributed to 84% of the PM1 concentrations. The NR-PM1 was composed of organics (55 ± 15%), followed by sulfate (21 ± 9%), ammonium (13 ± 6%), nitrate (10 ± 6%) and chloride (1 ± 1%). Three major organic sources were identified using positive matrix factorization, namely primary organic aerosol (POA, 40 ± 19%), more-oxidized oxygenated OA (MO-OOA, 32 ± 22%) and less-oxidized oxygenated OA (LO-OOA, 28 ± 19%). Variations in organic groups, including alkanes, hopanes, steranes, polycyclic aromatic hydrocarbons (PAHs), oxy-PAHs (OPAHs), and fatty acids, demonstrated that traffic and cooking emissions were dominant pollution sources in this roadside station. Human lung alveolar epithelial (A549) cells were exposed to PM1, revealing increases in lactate dehydrogenase (LDH), reactive oxygen species (ROS), and interlukin-6 (IL-6), which indicated the occurrence of inflammatory and oxidative responses. POA was significantly associated with ROS and IL-6, and alkanes, hopanes, steranes, PAHs and OPAHs, and fatty acids presented medium to high correlations with LDH and IL-6, demonstrating the importance of primary emissions and organic compounds in cytotoxicity. This study demonstrated that organic compounds emitted from traffic and cooking play critical roles in PM-induced oxidative stress and inflammation in urban areas.

Abnormal activation of transforming growth factor (TGF)-β is a common cause of fibroblast activation and fibrosis. In bleomycin (BLM)-induced lung fibrosis, the marked expression of phospho-Src homology-2 domain-containing phosphatase (SHP) 2, phospho-signal transducer and activator of transcription (STAT) 3, and suppressor of cytokine signaling (SOCS) 3 was highly associated with pulmonary parenchymal lesions and collagen deposition. Human pulmonary fibroblasts differentiated into myofibroblasts exhibited activation of SHP2, SOCS3, protein inhibitor of activated STAT1, STAT3, interleukin (IL)-6, and IL-10. The significant retardation of interferon (IFN)-γ signaling in myofibroblasts was revealed by the decreased expression of phospho-STAT1, IFN-γ-associated genes, and IFN-γ-inducible protein (IP) 10. Microarray analysis showed an induction of fibrotic genes in TGF-β1-differentiated myofibroblasts, whereas IFN-γ-regulated anti-fibrotic genes were suppressed. Interestingly, BIBF 1120 treatment effectively inhibited both STAT3 and SHP2 phosphorylation in TGF-β1-differentiated myofibroblasts and BLM fibrotic lung tissues, which was accompanied by suppression of fibroblast-myofibroblast transition. Moreover, the combined treatment of BIBF 1120 plus IFN-γ or SHP2 inhibitor PHPS1 plus IFN-γ markedly reduced TGF-β1-induced α-smooth muscle actin and further ameliorated BLM lung fibrosis. Accordingly, myofibroblasts were hyporesponsiveness to IFN-γ, while blockade of SHP2 contributed to the anti-fibrotic efficacy of IFN-γ.

Chemical composition and bioreactivity of PM2.5 samples collected from Beijing (BJ), Xi'an (XA), Xiamen (XM) and Hong Kong (HK) in China during haze events were characterized. PM2.5 mass concentrations in BJ, XA, XM and HK in the episodes were found to be 258 ± 100 μg m−3, 233 ± 52 μg m−3, 46 ± 9 μg m−3 and 48 ± 13 μg m−3, respectively. Significant increase of sulfate, nitrate and ammonium concentrations in northern cities were observed. High contributions of biomass burning emissions to organic carbon (OC) in northern cities were estimated in this study implying frequent biomass burning during the haze periods. The urea concentrations in PM2.5 were 1855 ± 755 ng m−3 (BJ), 1124 ± 243 ng m−3 (XA), 543 ± 104 ng m−3 (XM) and 363 ± 61 ng m−3 (HK) suggesting higher or close to upper limits compared to other regions in the world. Dose-dependent alterations in oxidative potential, IL-6, IFN-γ and TNF-α levels were also investigated. The oxidative potential levels are BJ > XM > XA > HK, whereas levels of IL-6, IFN-γ and TNF-α were BJ > XA > XM > HK. The sulfate, nitrate, ammonium, OC, urea and levoglucosan are associated with oxidative-inflammatory responses. These experimental results are crucial for the policymakers to implement cost-effective abatement strategies for improving air quality.

Volatile organic chemical exposure resulting from surgical operations is common in operating room personnel. The potential risk of long-term exposure to these low-level chemicals is always a concern. This study was conducted in an area hospital located in northern Taiwan to investigate the internal exposure scenario for operating room personnel. Breath samples were collected before and after surgery, whereas area samples were collected during the surgeries in process. There were 18 volatile organic compounds identified in the samples with gas chromatography-mass spectrometry. The average concentrations of sevoflurane (P = 0.0082), dimethyl sulfide (P = 0.0550), and methyl methacrylate (P = 0.0606) in breath samples collected after surgical operations were significantly higher compared to those obtained before surgical operations, whereas only slight elevations were present for benzene and hexamethyldisiloxane (P < 0.100). In addition, electrosurgical smoke-related chemicals, such as benzene, toluene, ethylbenzene, and m/p-xylene, also presented higher levels in operating room samples compared to the control area. Specifically, the findings in this preliminary study suggested the associations of elevated exposure to sevoflurane across various surgeries to methyl methacrylate with orthopedic surgery and to hexamethyldisiloxane with conventional electrosurgical units. Future study is warranted to explore the short-term high-level chemical exposure in operating rooms and to propose effective preventive measures accordingly to keep any exposure to chemicals at the lowest practical level.

Background Protein oxidation is considered to be one of the main causes of cell death, and methionine is one of the primary targets of reactive oxygen species (ROS). However, the mechanisms by which nickel nanoparticles (NiNPs) cause oxidative damage to proteins remain unclear. Objectives The objective of this study is to investigate the effects of NiNPs on the methionine sulfoxide reductases (MSR) protein repairing system. Methods Two physically similar nickel-based nanoparticles, NiNPs and carbon-coated NiNP (C-NiNPs; control particles), were exposed to human epithelial A549 cells. Cell viability, benzo(a)pyrene diolepoxide (BPDE) protein adducts, methionine oxidation, MSRA and B3, microtubule-associated protein 1A/1B-light chain 3 (LC3) and extracellular signal-regulated kinase (ERK) phosphorylation were investigated. Results Exposure to NiNPs led to a dose-dependent reduction in cell viability and increased BPDE protein adduct production and methionine oxidation. The methionine repairing enzymatic MSRA and MSRB3 production were suppressed in response to NiNP exposure, suggesting the oxidation of methionine to MetO by NiNP was not reversed back to methionine. Additionally, LC3, an autophagy marker, was down-regulated by NiNPs. Both NiNP and C-NiNP caused ERK phosphorylation. LC3 was positively correlated with MSRA (r = 0.929, p Conclusions MSR was made aberrant by NiNP, which could lead to the dysfunction of autophagy and ERK phosphorylation. The toxicological consequences may be dependent on the chemical characteristics of the nanoparticles.

Air pollution might have a great impact on pulmonary health, but biological evidence in response to particulate matter less than 2.5 μm in size (PM2.5) has been lacking. Physicochemical characterization of haze PM2.5 collected from Beijing, Xian and Hong Kong was performed. Biological pathways were identified by proteomic profiling in mouse lungs, suggesting that WNT/β-catenin is important in the response to haze PM2.5. Suppression of β-catenin levels, activation of caspase-3 and alveolar destruction, as well as IL-6, TNF-α and IFN-γ production, were observed in the lungs. The inhibition of β-catenin, TCF4 and cyclin D1 was observed in vitro in response to haze PM2.5. The inhibition of WNT/β-catenin signaling, apoptosis-related results (caspase-3 and alveolar destruction), and inflammation, particularly including caspase-3 and alveolar destruction, were more highly associated with polycyclic aromatic hydrocarbons in haze PM2.5. In conclusion, decreased WNT/β-catenin expression modulated by haze PM2.5 could be involved in alveolar destruction and inflammation during haze episodes.

Combustion-derived nanoparticles are characterised by a high surface area (SA) per mass. SA is proposed to regulate the bioreactivity of nanoparticles; however, the dose metric for carbon black remains controversial. To determine the relationships between bioreactivity and SA, male spontaneously hypertensive rats were exposed to carbon black (CB) nanoparticles (15, 51 and 95 nm) via intratracheal instillation for 24 h. Pulmonary exposure to CB resulted in a significant increase in systemic 8-hydroxy-2′-deoxyguanosine (8-OHdG), DNA single-strand breakages in peripheral blood cells and pulmonary cell infiltration in rats. The oxidative potential and particularly the corresponding SA of CB were correlated with the level of 8-OHdG, DNA single-strand breakages and pulmonary cell infiltration in rats. We conclude that SA is an important dose metric for CB that can regulate oxidative stress and DNA damage in rats. Furthermore, this observation was more significant for smaller sized CB.

In recent years growing evidence has shown that organic nitrogen (ON) constitutes a significant fraction of the nitrogen budget in particulate matter (PM). However, the composition and sources of ON in Chinese PM are not clear to date due to the lack of field measurements and receptor modeling interpretations. In this study, water-soluble ON (WSON), free amino acids (FAAs) and primary amines, together with water-soluble ionic species and carbonaceous components, were quantified in PM2.5 collected in Xi'an, China from 2008 to 2009. The yearly average WSON concentration (300 nmol N m−3, ranging from 29 to 1250 nmol N m−3) was one order of magnitude higher than that reported in other urban and rural regions in U.S. A total of 24 organic nitrogen species were determined, with an average total concentration of 2180 pmol m−3, which account for 1.2% of the WSON in PM2.5. Glycine, β-alanine and methylamine were the most abundant protein type amino acid, non-protein type amino acid and primary amine, respectively, contributing to 21.1%, 5.2% and 20.6% of the total quantified organic nitrogen species (TONS). Strong linear correlations (Pearson's correlation) (r = .72, p NH 4 + , NO 3 − , and SO 4 2 − ) also suggests the important contribution to WSON from secondary formation processes. Moreover, both protein type amino acids and primary amines revealed good correlations with water-soluble ions in spring, which indicates that seasonal variability occurred in primary sources and secondary formation pathway of the organic nitrogen species were found in Xi'an.

The objective of this study was to investigate associations between cardiovascular effects and urban ambient particle constituents using an in vivo crossover experimental design. Ambient particles were introduced to an exposure chamber for whole-body exposure of WKY rats, where the particulate matter with an aerodynamic diameter of 2.5 ) mass concentration, particle number concentration, and black carbon (BC) were monitored. Organic carbon (OC), elemental carbon (EC), and soluble ions of PM 2.5 were determined. In a crossover design, rats were exposed to ambient particles or high-efficiency particle arrestance (HEPA)-filtered control air for 7 days following a 7-day washout interval. The crossover exposure between particles and HEPA-filtered air was repeated 4 times. Radiotelemetric data on blood pressure (BP) [systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP)], heart rate (HR), and heart rate viability (HRV) were subsequently obtained during the entire study. Exposure to the PM 2.5 mass concentration was associated with decreases in the SBP, DBP, MAP, and HR ( p 2.5 mass concentration ( p + , Cl − , and NO 3 − . Cl − was associated with the DBP, MAP, HR, SDNN, and RMSSD. NO 3 − was correlated with the SBP, MAP, HR, SDNN, and RMSSD. In conclusion, we observed cardiovascular responses to ambient particles in vivo using a crossover design which can reduce animal use in future environmental studies.

Potential adverse effects of human exposure to carbon black (CB) have been reported, but limited knowledge regarding CB-regulated metabolism is currently available. To evaluate how physical parameters of CB influence metabolism, we investigated CB and diesel exhaust particles (DEPs) and attempted to relate various physical parameters, including the hydrodynamic diameter, zeta potential, and particle number concentrations, to lung energy metabolism in female BALB/c mice. A body weight increase was arrested by 3 months of exposure to CB of smaller-size fractions, which was negatively correlated with pyruvate in plasma. There were no significant differences in cytotoxic lactate dehydrogenase (LDH) or total protein in bronchoalveolar lavage fluid (BALF) after 3 months of CB exposure. However, we observed alterations in acetyl CoA and the NADP/NADPH ratio in lung tissues with CB exposure. Additionally, the NADP/NADPH ratio was associated with the zeta potential of CB. Mild peribronchiovascular and interstitial inflammation and multinucleated giant cells (macrophages) with a transparent and rhomboid appearance and containing foreign bodies were observed in lung sections. We suggest that physical characteristics of CB, such as the zeta potential, may disrupt metabolism after pulmonary exposure. These results, therefore, provide the first evidence of a link between pulmonary exposure to CB and metabolism.

The city of Lanzhou in northwestern China experiences serious air pollution episodes in the form of PM10 that is characterized by having high levels of heavy metals. The Xigu District represents the industrial core area of Lanzhou City and is denoted by having the largest petrochemical bases in western China. This study investigates heavy metal compositions and oxidative potential of airborne PM10 (particulate matter with aerodynamic diameter of 10 μm or less) collected in Xigu District in the summer and winter of 2010. An in vitro plasmid scission assay (PSA) was employed to study the oxidative potential of airborne PM10 and inductively coupled plasma-mass spectrometry (ICP-MS) was used to examine heavy metal compositions. Transmission electron microscopy coupled with energy-dispersive X-ray spectrometry (TEM/EDX) was used to investigate elemental compositions and mixing states of PM10. The average mass concentrations of PM10 collected in Xigu District were generally higher than the national standard for daily PM10 (150 μg/m3). Cr, Zn, Pb and Mn were the most abundant metals in the intact whole particles of PM10. Zn, Mn and As was the most abundant metal in the water-soluble fraction, while Cr, Pb, and V existed primarily in insoluble forms. TD20 values (i.e. toxic dosage of PM10 causing 20% of plasmid DNA damage) varied considerably in both winter and summer (from 19 μg/mL to >1000 μg/mL) but were typically higher in summer, suggesting that the winter PM10 exhibited greater bioreactivity. In addition, the PM10 collected during a dust storm episode had a highest TD20 value and thus the least oxidative damage to supercoiled plasmid DNA, while the particles collected on a hazy day had a lowest TD20 value and thus the highest oxidative damage to supercoiled plasmid DNA. The particles collected on the first day after snow fall and on a day of cold air intrusion exhibited minor oxidative potential (i.e. caused limited DNA damage). The water-soluble Zn, Mn, As, and Cu displayed a significant negative correlation with TD20 values, suggesting that these heavy metals were responsible for the increase of oxidative potential. The high mass concentration of PM10 and resulting high oxidative potential in Xigu District may be due to the constant low wind speed and high relative humidity, particularly in winter. Finally, TEM analysis suggested that the oxidative potential of PM10 may be associated with its degree of internal mixing, whereby the heterogeneous assortment of soot, mineral and metals created a highly reactive moiety.

The chemical and bioreactivity properties of fine particulate matter (PM2.5) in indoor and outdoor environments in Xi'an were characterized, and the lung function of various participants was investigated. The concentrations of polycyclic aromatic hydrocarbons (PAHs), oxygenated polycyclic aromatic hydrocarbons, and nitrated polycyclic aromatic hydrocarbons were higher in outdoor environments than in indoor environments; in addition, urban areas had higher concentrations of these compounds than did suburban areas, with fossil fuel combustion likely being the primary source. Moreover, PM2.5-induced inflammation was higher in urban areas than in suburban areas. Indoor environments with coal combustion emissions showed relatively higher oxidative potential and inflammation. Moderate (phenanthrene) to strong (acenaphthylene and benzo(a)pyrene) correlations were observed between selected PAHs against interleukin 6 (IL-6), 8-hydroxy-desoxyguanosine (8-OHdG), and necrosis factor-α (TNF-α). Moreover, 9-fluorenone, 9,10-anthraquinone, and 5,12-naphthacenequinone exhibited higher oxidative stress and inflammation than did their parent PAHs. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were negatively correlated with 8-OHdG, and FEV1/FVC was negatively correlated with TNF-α and IL-6. These findings—which integrates PM2.5 with lung function and bioreactivity analyses—suggest that coal burning, especially indoors, could elevate the cytotoxicity of PM2.5 to the occupants and that chronic exposure may lead to a decline in lung function.

Considerable evidence shows a key role for protein modification in the adverse effects of chemicals; however, the interaction of diesel exhaust particles (DEP) with proteins and the resulting biological activity remains unclear. DEP and carbon black (CB) suspensions with and without bovine serum albumin (BSA) were used to elucidate the biological effects of air pollutants. The DEP and CB samples were then divided into suspensions and supernatants. Two important goals of the interaction of DEP with BSA were as follows: (1) understanding BSA modification by particles and (2) investigating the effects of particles bound with BSA and the corresponding supernatants on cellular oxidative stress and inflammation. We observed significant free amino groups production was caused by DEP. Using liquid chromatography–mass spectrometry (LC−MS), we observed that BSA was significantly oxidised by DEP in the supernatants and that the peptides ETYGDMADCCEK, MPCTEDYLSLILNR and TVMENFVAFVDK, derived BSA-DEP conjugates, were also oxidised. In A549 cells, DEP-BSA suspensions and the corresponding supernatants reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) production and increased interleukin-6 (IL-6) levels when compared to DEP solutions without BSA. Our findings suggest that oxidatively modified forms of BSA caused by DEP could lead to oxidative stress and the activation of inflammation.

People spend generally 90 percent of their time indoors, yet toxicity of household particles has not been thoroughly investigated before. The objective of this study is to examine particle size and components effects of household particles on human coronary artery endothelial cells (HCAEC). We used two micro-orifice uniform deposit impactors to collect 60 sets of indoor particulate matters (PM) from 30 houses in Taipei, Taiwan. Polycyclic aromatic hydrocarbons (PAHs) effects of household particles were determined by high-resolution gas chromatograph/high-resolution mass spectrometer, respectively. HCAEC were exposed to household particles extracts in three size ranges: PM0.1 (diameters less than 0.1 μm), PM1.0–0.1 (diameters between 1.0 and 0.1 μm), and PM10-1.0 (diameters between 10 and 1.0 μm) at 50 μg mL−1 for 4 h, and interleukin-6 (IL-6), endothelin-1 (ET-1), and nitric oxide (NO) concentrations in the medium were measured. We found that household PM1.0–0.1 was associated with increased IL-6 and ET-1 production and decreased NO synthesis. Naphthalene of PM1.0–0.1 was highly correlated with IL-6 and ET-1 production and NO reduction. We concluded that size and compositions of household particles were both important factors on inflammation and endothelial dysfunction in HCAEC.

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of 2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m3 increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation.

Neutrophil elastase (NE) suppresses IL-8/CXCL8 in human airway smooth muscle cells (hASM) while stimulating its production in respiratory epithelial cells. This differential effect is mediated by the selective induction of NKRF and dysregulation in chronic inflammatory diseases. We hypothesized that the differential activation of NF-κB subunits confer the opposite effect of NKRF on IL-8/CXCL8 in primary hASM and A549 cells stimulated with NE. The events occurring at the promoters of NKRF and IL-8/CXCL8 were observed by ChIP assays, and the functional role of RelB was confirmed by knockdown and overexpression. Although p65 was stimulated in both cell types, RelB was only activated in NE-treated hASM, as confirmed by NF-κB DNA binding ELISA, Western blotting and confocal microscopy. Knockdown of RelB abolished the induction of NKRF and converted the suppression of IL-8/CXCL8 to stimulation. The forced expression of RelB induced NKRF production in hASM and A549 cells. NE activated the NIK/IKK1/RelB non-canonical NF-κB pathway in hASM but not in A549. The nuclear-translocated RelB was recruited to the NKRF promoter around the putative κB site, accompanied by p52 and RNA polymerase II. In conclusion, NFRF is a novel RelB-response gene, and NE is a stimulator of the non-canonical RelB/NF-κB pathway in hASM.

This study investigated the effects of particle-bound polycyclic aromatic hydrocarbons (PAHs) produced from burning three incense types on and their bioreactivity in the RAW 264.7 murine macrophage cell line. Gas chromatography/mass spectrometry was used to determine the levels of 16 identified PAHs. Macrophages were exposed to incense particle extracts at concentrations of 0, 3.125, 6.25, 12.5, 25, 50, and 100 μg/mL for 24 h. After exposure, cell viability and nitric oxide (NO) and inflammatory mediator [tumor necrosis factor (TNF)-α] production of the cells were examined. The mean atomic hydrogen (H) to carbon (C) ratios in the environmentally friendly, binchotan charcoal, and lao shan incenses were 0.69, 1.13, and 1.71, respectively. PAH and total toxic equivalent (TEQ) mass fraction in the incenses ranged from 137.84 to 231.00 and 6.73–26.30 pg/μg, respectively. The exposure of RAW 264.7 macrophages to incense particles significantly increased TNF-α and NO production and reduced cell viability. The cells treated with particles collected from smoldering the environmentally friendly incense produced more NO and TNF-α compared to other incenses. Additionally, the TEQ of fluoranthene (FL), pyrene (Pyr), benzo[a]anthracene (BaA), chrysene (Chr), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), indeno[1,2,3-cd]pyrene (INP), dibenz[a,h]anthracene (DBA), and benzo[g,h,i]perylene [B(ghi)P] had a significant correlation (R2 = 0.64–0.98, P

Particulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD) and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.

Induction of PM2.5-associated lung cancer in response to EGFR-tyrosine kinase inhibitors (EGFR-TKI) remains unclear. Polycyclic aromatic hydrocarbons (PAHs) and their polar derivatives (oxygenated PAHs: OPAHs and azaarenes: AZAs) were characterized in fine particulates (PM2.5) emitted from indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Human lung adenocarcinoma cells A549 (with wild-type EGFR) and HCC827 (with EGFR mutation) were exposed to the PM2.5, followed by treatment with EGFR-TKI. Two samples showed significant and dose-dependent reduction in the cell viability in A549. EGFR-TKI further demonstrated significantly decreased in cell viability in A549 after exposure to the coal emissions. Chrysene and triphenylene, dibenzo[a,h]anthracene, benzo[ghi]perylene, azaarenes and oxygenated polycyclic aromatic hydrocarbons (carbonyl-OPAHs) were all associated with EGFR-TKI-dependent reduced cell viability after 72-h exposure to the PM2.5. The findings suggest the coal emissions could influence the response of EGFR-TKI in lung cancer cells in Xuanwei.

The chemical and bioreactivity properties of fine particulate matter (PM2.5) emitted during controlled burning of different brands of incense were characterized. Incenses marketed as being environmentally friendly emitted lower mass of PM2.5 particulates than did traditional incenses. However, the environmentally friendly incenses produced higher total concentrations of non-volatile polycyclic aromatic hydrocarbons (PAHs) and some oxygenated polycyclic aromatic hydrocarbons (OPAHs). Human alveolar epithelial A549 cells were exposed to the collected PM2.5, followed by determining oxidative stress and inflammation. There was moderate to strong positive correlation (R > 0.60, p

Inhalation of zinc oxide (ZnO) metal fumes is known to cause metal fume fever and to have systemic effects; however, the effects of ZnO nanoparticles (ZnONPs) on the cardiovascular system remain unclear. The objective of this study was to investigate the cardiovascular toxicity of ZnONPs. Human coronary artery endothelial cells (HCAECs) were exposed to ZnONPs of different sizes to investigate the cell viability, 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, nitric oxide (NO), and regulation of cardiovascular disease-related genes. Exposure of HCAECs to ZnONPs resulted in decreased cell viability and increased levels of 8-OHdG, IL-6, and NO. Downregulation of cardiovascular-associated genes was observed in response to ZnONPs in HCAECs determined by qPCR, suggesting that the calcium signaling pathway, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy, and renin-angiotensin system are important affected pathways in response to ZnONPs. Furthermore, we observed a significant response of AGTR1 to ZnONP exposure in HCAECs. Our results suggest that ZnONPs cause toxicity to HCAECs, which could be associated with cardiovascular dysfunction.

Chih-Hong Pan,1,2,* Kai-Jen Chuang,3,4,* Jen-Kun Chen,5 Ta-Chih Hsiao,6 Ching-Huang Lai,2 Tim P Jones,7 Kelly A BéruBé,8 Gui-Bing Hong,9 Kin-FaiHo,10,11 Hsiao-Chi Chuang12,13 1Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, 2School of Public Health, National Defense Medical Center, 3School of Public Health, College of Public Health and Nutrition, 4Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, 6Graduate Institute of Environmental Engineering, National Central University, Taoyuan, Taiwan; 7School of Earth and Ocean Sciences, 8School of Biosciences, Cardiff University, Cardiff, Wales, UK; 9Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 10Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 11Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 12School of Respiratory Therapy, College of Medicine, 13Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP. Keywords: glycolysis, iTRAQ, metabolism, nanoparticles, S100-A9