Publications by authors named "Tsun-Jen Cheng"

86 Publications

Lipid changes in extrapulmonary organs and serum of rats after chronic exposure to ambient fine particulate matter.

Sci Total Environ 2021 Aug 10;784:147018. Epub 2021 Apr 10.

Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.

Fine particulate matter (PM) is able to pass through the respiratory barrier to enter the circulatory system and can consequently spread to the whole body to cause toxicity. Although our previous studies have revealed significantly altered levels of phosphorylcholine-containing lipids in the lungs of rats after chronic inhalation exposure to PM, the effects of PM on phosphorylcholine-containing lipids in the extrapulmonary organs have not yet been elucidated. In this study, we examined the lipid effects of chronic PM exposure on various organs and serum by using a rat inhalation model followed by a mass spectrometry-based lipidomic approach. Male Sprague-Dawley rats were continuously exposed at the whole body level to nonfiltered and nonconcentrated ambient air from the outside environment of Taipei city for 8 months, while the control rats inhaled filtered air simultaneously. After exposure, serum samples and various organs, including the testis, pancreas, heart, liver, kidney, spleen, and epididymis, were collected for lipid extraction and analysis to examine the changes in phosphorylcholine-containing lipids after exposure. The results from the partial least squares discriminant analysis models demonstrated that the lipid profiles in the PM exposure group were different from those in the control group in the rat testis, pancreas, heart, liver, kidney and serum. The greatest PM-induced lipid effects were observed in the testes. Decreased lyso-phosphatidylcholines (PCs) as well as increased unsaturated diacyl-PCs and sphingomyelins in the testes may be related to maintaining the membrane integrity of spermatozoa, antioxidation, and cell signaling. Additionally, our results showed that decreased PC(16:0/18:1) was observed in both the serum and testes. In conclusion, exposure to chronic environmental concentrations of PM caused lipid perturbation, especially in the testes of rats. This study highlighted the susceptibility of the testes and suggested possible molecular events for future study.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147018DOI Listing
August 2021

Effect of particle morphology on performance of an electrostatic air-liquid interface cell exposure system for nanotoxicology studies.

Nanotoxicology 2021 May 30;15(4):433-445. Epub 2020 Dec 30.

Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, Taiwan.

Particle morphology can affect the performance of an electrostatic precipitator air-liquid interface (ESP-ALI) cell exposure system and the resulting cell toxicity. In this study, three types of monodisperse aerosols - spherical sucrose particles, nonspherical align soot aggregates, and nanosilver aggregates/agglomerates - were selected to evaluate the collection efficiency at flow rates ranging from 0.3 to 1.5 lpm. To quantify the particle morphology, the fractal dimensions () of the tested aerosols were characterized. The penetration of fine particles ( = 100-250nm) under different operating conditions was correlated with a characteristic exponential curve using the dimensionless drift velocity () as the scaling parameter. For nanoparticles (NPs, <100nm) with different particle morphologies, the particle penetrations in the ESP-ALI were similar, but their diffusion losses were not negligible. In contrast, for fine particles, the collection efficiency of soot nanoaggregates ( = 2.29) was higher than that of spherical sucrose particles. This difference might be due to the simultaneous influences of the electric field-induced and flow field-induced alignment. Furthermore, based on Zhibin and Guoquan's Deutsch model, a quadratic equation was applied to fit the experimental data and to predict the performance of the ESP-ALI.
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http://dx.doi.org/10.1080/17435390.2020.1863499DOI Listing
May 2021

Neuropathology changed by 3- and 6-months low-level PM inhalation exposure in spontaneously hypertensive rats.

Part Fibre Toxicol 2020 11 26;17(1):59. Epub 2020 Nov 26.

Institute of Environmental and Occupational Health Science, College of Public Health, National Taiwan University, 17 Xu-Zhou Road, Taipei, 100, Taiwan.

Background: Epidemiological evidence has linked fine particulate matter (PM) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM 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 PM in spontaneously hypertensive (SH) rats.

Results: SH rats were exposed to S-, K-, Si-, and Fe-dominated PM at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m 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 PM exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM exposure (p < 0.05). We observed that 3 months of exposure to PM caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM exposure, but significantly decreased in the cortex with 6 months exposure to PM. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM exposure.

Conclusions: Chronic exposure to low-level PM could accelerate the development of neurodegenerative pathologies in subjects with hypertension.
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http://dx.doi.org/10.1186/s12989-020-00388-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691081PMC
November 2020

Secure Health Care Workers' Health and Safety Methodically During COVID-19 Epidemic in Taiwan.

Asia Pac J Public Health 2020 Nov 16;32(8):485-488. Epub 2020 Oct 16.

Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

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http://dx.doi.org/10.1177/1010539520963629DOI Listing
November 2020

Simplest Way to Establish COVID-19 Quarantine Observation Wards Within 24 Hours.

Asia Pac J Public Health 2020 Sep-Oct;32(6-7):357-359. Epub 2020 Aug 14.

Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Reducing nosocomial transmission within health care facilities is important, but the number of negative-pressure airborne infection isolation rooms for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is limited. It is a daunting challenge to cope with a surge of suspected infectious patients in hospitals. We installed air exhaust fans on the windows to change the pressure direction within the wards rapidly. The best location for the fans was 90 cm from the floor and 90 cm from the edge of bed whether the indoor air conditioners were on or off. The noise level should be <60 dB(A) as per government regulations. General wards can be transformed into makeshift negative-pressure rooms easily and effectively within 24 hours, which is really the simple, fast, and effective way for the transformation being applied.
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http://dx.doi.org/10.1177/1010539520947874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521007PMC
September 2020

Brain lipid profiles in the spontaneously hypertensive rat after subchronic real-world exposure to ambient fine particulate matter.

Sci Total Environ 2020 Mar 18;707:135603. Epub 2019 Nov 18.

Institute of Environmental Health, College of Public Health, National Taiwan University, Taiwan; Department of Public Health, National Taiwan University, Taiwan. Electronic address:

Recent studies have illustrated an association between ambient fine particulate matter (PM) exposure and neuronal toxicity in epidemiological studies and animal models. However, the possible molecular effects on brains under real-world exposure to PM remain unclear. In this pilot study, male spontaneously hypertensive rats were whole-bodily exposed to ambient air from the outdoor environment of Taipei City for 3 months, while the control rats inhaled HEPA-filtered air. The PM-induced phosphatidylcholine and sphingomyelin profiles in the hippocampus, cortex, medulla, cerebellum, and olfactory bulb were assessed by mass spectrometry (MS)-based lipidomics. Partial least squares discriminant analysis (PLS-DA) and the Wilcoxon rank sum test were used to examine the lipid changes between the exposed and control groups. The PLS-DA models showed that phosphatidylcholine and sphingomyelin profiles of the PM exposure group were different from those of the control group in each brain region except the cortex. More lipid changes were found in the hippocampus, while fewer lipid changes were observed in the olfactory bulb. The lipid alteration in the hippocampus may strengthen membrane integrity, modulate signaling pathways, and avoid accumulation of lipofuscin to counter the PM-induced stress. The lipid changes in the cortex and medulla may respond to PM-induced injury and inflammation; while the lipid changes in the cerebellum were associated with neuron protection. This study suggests that the MS-based lipidomics is a powerful approach to discriminate the brain lipid profiles even at the environmental level of ambient PM and has the potential to suggest possible adverse health effects in long-term PM exposure studies.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135603DOI Listing
March 2020

The effect of the inhalation of and topical exposure to zinc oxide nanoparticles on airway inflammation in mice.

Toxicol Appl Pharmacol 2019 12 24;384:114787. Epub 2019 Oct 24.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Zinc oxide nanoparticles (ZnONPs) are widely used in the manufacturing of many commercial products. Workers exposed to ZnO particles may develop metal fume fever. Our previous study suggested that the oropharyngeal aspiration of ZnONPs could cause eosinophilic airway inflammation and increase T helper 2 (Th2) cytokine expression in the absence of allergens in mice. ZnO has been used topically as a sunscreen and a therapeutic agent for dermatological conditions. To understand whether inhalation and topically applied ZnONPs might cause or exert an adjuvant effect on the development of allergic airway inflammation in mice, C57BL/6 J mice were exposed to filtered air or 2.5 mg/m ZnONPs via whole-body inhalation for 5 h a day over 5 days, and BALB/c mice were topically exposed to ZnONPs using modified mouse models of atopic dermatitis (AD) and asthma. Ovalbumin (OVA) solution was used as an allergen in the topical exposure experiments. A significantly increased eosinophil count and mixed Th1/Th2 cytokine expression were detected in the bronchoalveolar lavage fluid (BALF) after ZnONP inhalation. However, only mild eosinophilia and low Th2 cytokine expression were detected in the BALF after oropharyngeal OVA aspiration in the high-dose ZnONP topical treatment group. These results suggest that ZnONP inhalation might play a role in the development of allergic airway inflammation in mice. However, topically applied ZnONPs only play a limited role in the development of allergic airway inflammation in mice.
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http://dx.doi.org/10.1016/j.taap.2019.114787DOI Listing
December 2019

Microglial activation and inflammation caused by traffic-related particulate matter.

Chem Biol Interact 2019 Sep 23;311:108762. Epub 2019 Jul 23.

School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Electronic address:

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 PM (PM with an aerodynamic diameter of <1 μm) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.
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http://dx.doi.org/10.1016/j.cbi.2019.108762DOI Listing
September 2019

Correction to: Particle toxicology and health - where are we?

Part Fibre Toxicol 2019 Jun 27;16(1):26. Epub 2019 Jun 27.

National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

After the publication of this article [1] it was hihglighted that the number of deaths related to natural disasters was incorrectly reported in the second paragraph of the Hazards from Natural particulates and the evolution of the biosphere section. This correction article shows the correct and incorrect statement. This correction does not change the idea presented in the article that from an evolutionary view point, natural disasters account only for a small fraction of the people on the planet. The original article has been updated.
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http://dx.doi.org/10.1186/s12989-019-0308-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595670PMC
June 2019

Particle toxicology and health - where are we?

Part Fibre Toxicol 2019 04 23;16(1):19. Epub 2019 Apr 23.

National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Background: Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles' and fibres' risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios.

Conclusions: Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.
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http://dx.doi.org/10.1186/s12989-019-0302-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480662PMC
April 2019

Chronic pulmonary exposure to traffic-related fine particulate matter causes brain impairment in adult rats.

Part Fibre Toxicol 2018 11 9;15(1):44. Epub 2018 Nov 9.

School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 μm (PM), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats.

Results: The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) μg/m of PM during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM exposure. A short-term memory deficiency occurred with 3 months of exposure to PM as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM exposure.

Conclusions: Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.
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http://dx.doi.org/10.1186/s12989-018-0281-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234801PMC
November 2018

LC-MS-based lipidomics to examine acute rat pulmonary responses after nano- and fine-sized ZnO particle inhalation exposure.

Nanotoxicology 2018 06 11;12(5):439-452. Epub 2018 Apr 11.

a Institute of Environmental Health, College of Public Health , National Taiwan University , Taipei , Taiwan.

Zinc oxide (ZnO) nano- and fine-sized particles are associated with respiratory toxicity in humans, but the underlying molecular mechanisms remain unclear. Our previous nuclear magnetic resonance-based metabolomic study demonstrated that changes in phosphorylcholine-containing lipids (PC-CLs) in the respiratory system were associated with ZnO particle-induced respiratory toxicity. However, the details of the lipid species associated with adverse effects and possible biomarker signatures have not been identified. Thus, a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics platform was applied to examine the alterations of PC-CL species in the lungs of rats treated with a series of concentrations of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles via inhalation. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and the Mann-Whitney U (MWU) test with false discovery rate (FDR) control were conducted to explore the perturbed lipid species and to discriminate a potential pulmonary biomarker signature after ZnO particle exposure. The PCA and PLS-DA models revealed that the fine-sized ZnO particle-treated groups and the high-concentration nano-sized group were separated from the control groups as well as from the low and moderate nano-sized groups. The results from the MWU test further suggested that after FDR adjustment, numerous PC-CL species were altered in the high-concentration and moderate-concentration fine-sized groups. Furthermore, our results suggested that lipids involved in anti-oxidation, membrane conformation, and cellular signal transduction were altered in response to ZnO-induced oxidative stress and inflammation. One lipid, PC(18:0/18:1), exhibited good performance (AUC > 0.8) of discriminative ability in distinguishing ZnO particle exposure from the control. These findings not only provide a foundation for the exploration of possible ZnO particle-mediated mechanisms but also suggest a lipid biomarker for ZnO particle exposure.
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http://dx.doi.org/10.1080/17435390.2018.1458918DOI Listing
June 2018

Association of ultrafine particles with cardiopulmonary health among adult subjects in the urban areas of northern Taiwan.

Sci Total Environ 2018 Jun 3;627:211-215. Epub 2018 Feb 3.

Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

The association between short-term exposure to particulate air pollution, especially fine particles, and cardiopulmonary health has been well-established in previous studies. However, previous findings regarding the effect of ultrafine particles (UFPs) on cardiopulmonary health are inconsistent. We repeatedly measured the mass concentrations of UFPs using a Micro-Orifice Uniform Deposit Impactor (MOUDI) in the apartments of 100 adult participants and collected the participants' health data from the pulmonary outpatient unit of Shuang-Ho Hospital to investigate the association between short-term exposure to UFPs and cardiopulmonary health using mixed-effects models from January 1, 2014 to August 31, 2017. We also collected ambient air pollution monitoring data from the Taiwan Environmental Protection Administration for data analysis. We observed that an interquartile range increase in the 24-hour mean UFPs (0.97 μg/m) was associated with a 6.3% [95% confidence interval (CI) = 2.9, 9.7], 5.6% (95% CI = 4.1, 7.1) and 8.5% (95% CI = 3.9, 13.1) increase in systolic blood pressure, diastolic blood pressure and high sensitivity-C-reactive protein, respectively. We also observed the association of particulate matter less than or equal to 2.5 μm in diameter and nitrogen dioxide with increased blood pressure and ozone with decreased lung function. A negative trend between UFPs and forced expiratory volume in the first second was observed. We concluded that short-term exposure to UFPs was associated with cardiovascular health in adult subjects in the urban areas of northern Taiwan.
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http://dx.doi.org/10.1016/j.scitotenv.2018.01.218DOI Listing
June 2018

Sustained renal inflammation following 2 weeks of inhalation of occupationally relevant levels of zinc oxide nanoparticles in Sprague Dawley rats.

J Toxicol Pathol 2017 Oct 19;30(4):307-314. Epub 2017 Aug 19.

Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City 813, Taiwan.

Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure. A significant increase in microscopic inflammatory foci with pronounced periglomerular inflammation and interstitial lymphocytic infiltration was found in rats exposed to low and high doses of ZnONPs compared with rats exposed to HEPA-FA at the three time points following 2 weeks of exposure. Tubulitis featuring lymphocytic infiltrate within the tubular epithelium was found after 24 hours but had disappeared at 7 and 30 days in both the low- and high-dose exposure groups. Our findings demonstrate that inhaled ZnONPs cause sustained renal periglomerular and interstitial inflammation through lymphocytic infiltration. These findings provide histopathological evidence regarding sustained renal inflammation of nanoparticle exposure in rats and may provide some insight into the occupational health effects of ZnONPs on exposed workers.
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http://dx.doi.org/10.1293/tox.2017-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660952PMC
October 2017

Effects of physical characteristics of carbon black on metabolic regulation in mice.

Environ Pollut 2018 Jan 6;232:494-504. Epub 2017 Oct 6.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.envpol.2017.09.077DOI Listing
January 2018

Alterations in cardiovascular function by particulate matter in rats using a crossover design.

Environ Pollut 2017 Dec 31;231(Pt 1):812-820. Epub 2017 Aug 31.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

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 μm (PM) mass concentration, particle number concentration, and black carbon (BC) were monitored. Organic carbon (OC), elemental carbon (EC), and soluble ions of PM 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 mass concentration was associated with decreases in the SBP, DBP, MAP, and HR (p < 0.05), whereas no significant changes in the BP or HR occurred with the particle number or black carbon. For HRV, the ln 5-min standard deviation of the normal-to-normal (NN) interval (LnSDNN) and the ln root mean square of successive differences in adjacent NN intervals (LnRMSSD) were positively associated with the PM mass concentration (p < 0.05). There were no significant effects of the particle number concentration or BC on HRV. Alterations in the HR were associated with OC, EC, Na, Cl, and NO. Cl was associated with the DBP, MAP, HR, SDNN, and RMSSD. NO 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.
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http://dx.doi.org/10.1016/j.envpol.2017.08.082DOI Listing
December 2017

Characterization of titanium dioxide nanoparticle removal in simulated drinking water treatment processes.

Sci Total Environ 2017 Dec 2;601-602:886-894. Epub 2017 Jun 2.

Institute of Environmental Health, National Taiwan University, Taipei, Taiwan. Electronic address:

This study characterized the fate of nano-TiO in both powder (TiO(P)) and suspension (TiO(S)) forms in simulated drinking water treatments. Nano-TiO solutions of 0.1, 1.0, and 10mg/L were prepared with deionized water and raw waters from the Changxing and Fengshan Water Treatment Plants in Taiwan to assess the effects of water matrices on nano-TiO behavior during water treatment. After the laboratory simulated water treatment, including pre-chlorination, coagulation, sedimentation, filtration and post-chlorination, the residual Ti concentration ranged from 2.7 to 47.4% in different treatment units and overall removal efficiency was between 52.6% and 97.3% in all cases except for nano-TiO at concentration of 0.1mg/L. Overall removal efficiency for the TiO at 10mg/L concentration ranged from 9.3 to 53.5%. Sedimentation (after coagulation) and filtration were the most important processes for removing nano-TiO due in part to particle agglomeration, which was confirmed by size distribution and zeta potential measurements. The size of nano-TiO increased from 21-36nm to 4490nm in the supernatant after sedimentation, and subsequent filtration treatment further removed all agglomerates at size >1μm. Zeta potential revealed interactions between nano-TiO particles and anionic functional groups or negatively-charged natural organic matters, leading to a decrease in surface charge. After sedimentation and filtration, the zeta potential of supernatants and filtrates were close to zero, meaning the absence of nanoparticles. The highest Ti removal after sedimentation occurred in Fengshan raw water due to higher ionic strength and coagulant dosage applied. On the other hand, the surfactant additives in TiO(S) promoted dispersion of nano-TiO particles, which in turn led to lower particle removal. SEM images of nanoparticles after chlorination or coagulation revealed the coverage of nano-TiO particles by viscous substances and formation of colloidal structures.
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http://dx.doi.org/10.1016/j.scitotenv.2017.05.228DOI Listing
December 2017

Comparative Proteomic Analysis of Rat Bronchoalveolar Lavage Fluid after Exposure to Zinc Oxide Nanoparticles.

Mass Spectrom (Tokyo) 2017 24;6(2):S0066. Epub 2017 Mar 24.

Institute of Molecular Biology, National Chung Hsing University.

Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in consumer products and industrial applications. As a result of all these uses, this has raised concerns regarding their potential toxicity. We previously found that candidate markers of idiopathic pulmonary fibrosis and lung cancer were significantly up-regulated in rat bronchoalveolar lavage fluid (BALF) following exposure to ZnO NPs by using a liquid chromatography (LC)-based proteomic approach. To achieve comprehensive protein identification analysis, we conducted the two-dimensional gel electrophosis (2-DE)-based proteomic workflow to analyze the differences in BALF proteins from rats that had been exposed to a high dose of 35 nm ZnO NPs. A total of 31 differentially expressed protein spots were excised from the gels and analyzed by nanoLC-tandem mass spectrometry (MS/MS). Gene ontology (GO) annotation of these proteins showed that most of the differentially expressed proteins were involved in response to stimulus and inflammatory response processes. Moreover, pulmonary surfactant-associated protein D and gelsolin, biomarkers of idiopathic pulmonary fibrosis, were significantly up-regulated in rat BALF after ZnO NPs exposure (2.42- and 2.84-fold, respectively). The results obtained from this present study could provide a complementary consequence with our previous study and contribute to a better understanding of the molecular mechanisms involved in ZnO NP-induced lung disorders.
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http://dx.doi.org/10.5702/massspectrometry.S0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448331PMC
March 2017

Pulmonary pathobiology induced by zinc oxide nanoparticles in mice: A 24-hour and 28-day follow-up study.

Toxicol Appl Pharmacol 2017 07 19;327:13-22. Epub 2017 Apr 19.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the alveolar region of the lungs; however, the adverse health effects of ZnONPs on the respiratory system are unclear. Herein, pathobiological responses of the respiratory system of mice that received intratracheal administration of ZnONPs were investigated by a combination of molecular and imaging (SPECT and CT) approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to confirm the results in mice. First, female BALB/c mice were administrated a series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered saline control for 24-h and 28-day follow-up observations. Field emission-scanning electron microscopy and an energy-dispersive X-ray microanalysis were first used to characterize ZnONPs. After 24h, instilled ZnONPs had caused significant increases in lactic dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and the p63 tumor marker in lung tissues (p<0.05). Airway inflammation was present in a dose-dependent manner from the upper to the lower airway as analyzed by SPECT. After 28days, p63 had significantly increased due to ZnONP exposure in lung tissues (p<0.05). Pulmonary inflammatory infiltration mainly occurred in the left and right subsegments of the secondary bronchial bifurcation as observed by CT. A significant increase in p63 and decrease in TTF1 levels were observed in BEAS-2B cells by ZnONP (p<0.05), but not in A549 cells. Our results demonstrated that regional lung inflammation occurred with ZnONP exposure. We also showed that p63 was consistently overexpressed due to ZnONP exposure in vivo and in vitro. This work provides unique findings on the p63 response and the pathobiology in response to ZnONPs, which could be important to the study of pulmonary toxicity and repair.
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http://dx.doi.org/10.1016/j.taap.2017.04.018DOI Listing
July 2017

The effect of size-segregated ambient particulate matter on Th1/Th2-like immune responses in mice.

PLoS One 2017 28;12(2):e0173158. Epub 2017 Feb 28.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.

Background: Particulate matter (PM) has been associated with increased pulmonary and cardiovascular mortality and morbidity. Additionally, PM is known to exacerbate asthma. However, whether ambient PM exposure contributes to the onset of asthma, especially in non-atopic children and adults, is less conclusive. The current study aimed to evaluate the effects of size-fractioned PM on lung immune responses in healthy BALB/c mice.

Methods And Principal Findings: We collected PM10, PM2.5, PM1 and PM0.1 samples from October 2012 to August 2013 in the Taipei Basin. These PM samples were representative of urban traffic pollution. The samples were extracted and sonicated in phosphate-buffered saline (PBS). Female BALB/c mice were exposed to the samples via intratracheal instillation at three different doses: 1.75 mg/kg (35 μg/per mouse), 5 mg/kg (100 μg/per mouse), and 12.5 mg/kg (250 μg/per mouse). The mice were exposed on days 0 and 7, and PBS alone was used as a control. Following the exposures, the expression profiles of inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were assessed. Exposure to PM10 resulted in inflammatory responses, including the recruitment of neutrophils and the induction of T helper 1 (Th1) cell-related cytokine release, such as TNF-α and IFN-γ. Furthermore, an allergic immune response, including the recruitment of eosinophils and the up-regulation of T helper 2 (Th2) cell-related cytokine release, such as IL-5 and IL-13, was also observed in the BALF of mice exposed to PM10.

Conclusions: Our study showed that exposure to PM alone caused mixed Th1/Th2 inflammatory responses in healthy mice. These findings support the hypothesis that PM may contribute to the onset of asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173158PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330505PMC
August 2017

Association of temporal distribution of fine particulate matter with glucose homeostasis during pregnancy in women of Chiayi City, Taiwan.

Environ Res 2017 Jan 13;152:81-87. Epub 2016 Oct 13.

Department of Medical Research, Kuang Tien General Hospital, Taichung, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Nutrition and Institute of Biomedical Nutrition, Hung Kuang University, Taichung, Taiwan; Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan. Electronic address:

Background: To investigate the effects of fine particulate matter (PM) on the indicators of glucose homeostasis during pregnancy.

Methods: A total of 3589 non-diabetic pregnant women who underwent a 3-h 100-g oral glucose tolerance test (OGTT) were enrolled from a tertiary teaching hospital in Chiayi City, Taiwan between 2006 and 2014. Fasting, 1-h, 2-h, and 3-h glucose levels after an OGTT were used as indicators of glucose homeostasis. PM and other air pollution data were obtained from one fixed-site monitoring station (Chiayi City station) operated by Taiwan Environmental Protection Administration (EPA). We used mixed models for indicators of glucose homeostasis to estimate the effects of PM. The models were adjusted for individual-specific effects (nulliparous status, age, body mass index, season, and year) and the moving averages of temperature and relative humidity in the corresponding study period.

Results: There were significant relationships between PM and the glucose homeostasis indicators, including fasting, 1-h, 2-h, and 3-h glucose levels in the single-pollutant covariate-adjusted model. The pre-screening 1-month to 1-year moving averages of IQR increases in PM were significantly associated with elevated fasting OGTT glucose levels (1.32-5.87mg/dL). The two-pollutant covariate-adjusted models had similar results.

Conclusions: We found positive associations between PM and OGTT glucose levels during pregnancy. The association was especially pronounced for the fasting and 1-h glucose levels. PM exposure in the second trimester may enhance this effect. Exposure to PM was associated with glucose homeostasis during pregnancy.
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http://dx.doi.org/10.1016/j.envres.2016.09.023DOI Listing
January 2017

Concurrent quantification of multiple biomarkers indicative of oxidative stress status using liquid chromatography-tandem mass spectrometry.

Anal Biochem 2016 11 1;512:26-35. Epub 2016 Aug 1.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, No. 17, ShiuJou Rd., Taipei 10055, Taiwan. Electronic address:

8-Hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso-prostaglandin F2α (8-IsoPGF2α), and N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine (HNE-MA) are well-studied and representative biomarkers for oxidative DNA damage, inflammation, and lipid peroxidation; all of which have been associated with increases in risks of various diseases and cancers. A rapid and highly sensitive isotope-dilution liquid-chromatography tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify the aforementioned biomarkers in urine. Upon validation, this method shows excellent feasibility, sensitivity (0.008-0.03 ng/mL) and satisfactory recoveries (88.7-95.4%); the calibration curves displayed excellent linearity with coefficients of determination (R(2)) greater than 0.998. Additionally, low variations were observed in the relative standard deviation for intra- and inter-day measurements for the four analytes. The relative matrix effects for all four analytes ranged from 2.04 to 3.27%, which signaled that interferences from endogenous levels of the analytes were deemed statistically insignificant. This study successfully developed an analytical method capable to simultaneously quantify urinary 8-OHdG, 8-NO2Gua, 8-IsoPGF2α, and HNE-MA. This analytical protocol can be applied towards conducting epidemiological studies to reveal the mechanisms related to disease development, and thus evaluate the associated risks of diseases.
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http://dx.doi.org/10.1016/j.ab.2016.07.030DOI Listing
November 2016

NMR-based metabolomics to determine acute inhalation effects of nano- and fine-sized ZnO particles in the rat lung.

Nanotoxicology 2016 09 8;10(7):924-34. Epub 2016 Mar 8.

a Institute of Environmental Health, College of Public Health , National Taiwan University , Taipei , Taiwan and.

Zinc oxide (ZnO) particles induce acute occupational inhalation illness in humans and rats. However, the possible molecular mechanisms of ZnO particles on the respiratory system remain unclear. In this study, metabolic responses of the respiratory system of rats inhaled ZnO particles were investigated by a nuclear magnetic resonance (NMR)-based metabolomic approach. Male Sprague-Dawley rats were treated with a series of doses of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles. The corresponding control groups inhaled filtered air. After 24 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected, extracted and prepared for (1)H and J-resolved NMR analysis, followed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). PCA and PLSDA models from analysis of BALF and hydrophilic lung NMR spectra demonstrated that dose response trends were restricted to the 250 nm ZnO particle exposure group and were not observed in the 35 nm ZnO particle exposure group. Increased isoleucine and valine, as well as decreased acetate, trimethylamine n-oxide, taurine, glycine, formate, ascorbate and glycerophosphocholine, were recorded in the BALF of rats treated with moderate and high dose 250 nm ZnO exposures. Decreases in taurine and glucose, as well as an increase of phosphorylcholine-containing lipids and fatty acyl chains, were detected in the lung tissues from 250 nm ZnO-treated rats. These metabolic changes may be associated with cell anti-oxidation, energy metabolism, DNA damage and membrane stability. We also concluded that a metabolic approach provides more complete measurements and suggests potential molecular mechanisms of adverse effects.
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http://dx.doi.org/10.3109/17435390.2016.1144825DOI Listing
September 2016

The Associations Between Long Working Hours, Physical Inactivity, and Burnout.

J Occup Environ Med 2016 05;58(5):514-8

Department of Family Medicine, Shin Kong Wu Ho-Su Memorial Hospital (Dr Hu and Dr Chen); School of Medicine, Fu Jen Catholic University (Dr Chen); and Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University (Dr Cheng), Taiwan.

Objective: To examine the correlations between long working hours, physical activity, and burnout.

Methods: A cross-sectional survey was administered to 1560 full-time employees, who underwent periodic health examinations in the year 2013. The subjects were divided into upper, middle, and lower tertiles according to the Copenhagen Burnout Inventory (CBI) score.

Results: The comparison of the high- and low-burnout groups revealed that long working hours were significantly correlated with burnout in a dose-dependent manner. Long working hours were more significantly associated with burnout among individuals younger than 50 years, females, and physically inactive employees.

Conclusions: Long working hours are correlated with burnout when working over 40 hours per week and is even stronger when working over 60 hours per week. Limiting working hours to 40 weekly may be beneficial for the prevention of burnout. Physical activity helps reduce the risk of burnout.
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http://dx.doi.org/10.1097/JOM.0000000000000715DOI Listing
May 2016

Chronic exposure to particulate matter and risk of cardiovascular mortality: cohort study from Taiwan.

BMC Public Health 2015 Sep 21;15:936. Epub 2015 Sep 21.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, 17 Xu-Zhou Road, Rm706, Taipei, 100, Taiwan.

Background: Evidence on the association between long-term exposure to air pollution and cardiovascular mortality is limited in Asian populations.

Methods: We conducted a cohort study on the association between fine particulate matter (PM2.5) and cardiovascular mortality using 43,227 individuals in a civil servants health service in Taiwan. Each participant was assigned an exposure level of particulate matter based on their district of residence using air pollution data collected by the Taiwan Environmental Protection Agency and with modeling using geographic information systems. The participants were followed up from 1989 to 2008 and the vital status was ascertained from death records. Cox regression models were used to adjust for confounding factors.

Results: The district-level average of PM2.5 ranged from 22.8 to 32.9 μg/m(3) in the study area. After a median follow-up of 18 years, 1992 deaths from all causes including 230 cardiovascular deaths occurred. After adjustment for potential confounders, PM2.5 levels were not significantly associated with mortality from cardiovascular disease [Hazard Ratio (HR) 0.80; 95 % Confidence Interval (CI), 0.43 to 1.50 per 10 μg/m(3) increase in PM2.5] or all causes (HR 0.92; 95 % CI, 0.72 to 1.17 per 10 μg/m(3) increase in PM2.5). The results were similar when the analysis was restricted to the urban areas and when the PM2.5 measurement was changed from the period average (2000-2008) to annual average.

Discussion: Our findings are different from those in prior cohort studies conducted in Asia where ambient air pollutionwas associated with an increased risk of cardiovascular mortality. The high background level of air pollutionin our study area and the small number of event cases limited the power of this study.

Conclusions: In this population-based cohort study in Taiwan, we found no evidence of increased risk for all-cause or cardiovascular mortality with long-term exposure to PM2.5.
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http://dx.doi.org/10.1186/s12889-015-2272-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578246PMC
September 2015

Increased night duty loading of physicians caused elevated blood pressure and sympathetic tones in a dose-dependent manner.

Int Arch Occup Environ Health 2016 Apr 1;89(3):413-23. Epub 2015 Aug 1.

Institution of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.

Purpose: Night duty has been recognized as a significantly harmful stressor for physicians. However, the relationship between various levels of duty loading and stress response is unknown. This study examined whether duty load increases cardiovascular stress indicators in a dose-dependent manner.

Methods: An unallocated prospective observational study was conducted among physicians performing various levels of duties in a secondary referral medical center between 2011 and 2012. Heart rate variability (HRV), blood pressure (BP), and other stress markers of 12 attending physicians were compared during different duty loads: non-duty day (NDD), duty day with one duty area and three wards (1DD), and duty day with two duty areas and six wards (2DD).

Results: During the regular sleep time (i.e., 11 p.m. to 5 a.m.), the relative sympathetic modulations measured using the HRV were 59.0 ± 9.3, 61.6 ± 10.4, and 64.4 ± 8.9 for NDD, 1DD, and 2DD, respectively (p = 0.0012); those for relative parasympathetic modulations were 37.4 ± 9.4, 34.8 ± 9.8, and 32.0 ± 8.8 for NDD, 1DD, and 2DD, respectively (p = 0.0015). The percentages of abnormal systolic BPs were 9.7 ± 13.2 %, 25.3 ± 21.8 %, and 31.5 ± 21.0 % for NDD, 1DD, and 2DD, respectively (p = 0.003), and the percentages of abnormal diastolic BP were 6.7 ± 11.0 %, 18.3 ± 11.1 %, and 27.1 ± 30.9 % for NDD, 1DD, and 2DD, respectively (p = 0.002). Total sleep time was negatively associated with sympathetic/parasympathetic balance and the percentage of abnormal diastolic BP. Admitting new patients was positively associated with the percentages of abnormal systolic BP.

Conclusions: This observational analysis suggests that the dose-dependent stress responses of the cardiovascular system in physicians were caused by the duty load.
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http://dx.doi.org/10.1007/s00420-015-1080-8DOI Listing
April 2016

Effects of non-protein-type amino acids of fine particulate matter on E-cadherin and inflammatory responses in mice.

Toxicol Lett 2015 Sep 20;237(3):174-80. Epub 2015 Jun 20.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Exposure to particulate matter less than 2.5 μm (PM2.5) in size is an urgent issue for the protection of human health. Chemicals with PM2.5 collected during a period of intensive haze episodes in Beijing (BJ), Xian (XA) and Hong Kong (HK) were characterised for organic carbon (OC), elemental carbon (EC), total carbon (TC) and free amino acids. BALB/c mice underwent aspiration exposure of 50 or 150 μg of PM2.5/mouse (BJ, XA and HK) on days 1 and 7 and were euthanised on day 14. The effects of these exposures on E-cadherin and inflammatory responses in the mouse lungs were analysed. The PM2.5 chemicals consisted of significant amounts of OC: 36.6 ± 17.2 μg/m(3) for BJ, 38.8 ± 3.8 μg/m(3) for XA and 7.2 ± 1.4 μg/m(3) for HK. A total of 23 free amino compounds for the PM2.5 samples were analysed: 4075 ± 1578 pmol/m(3) for BJ, 4718 ± 2190 pmol/m(3) for XA and 1145 ± 213 pmol/m(3) for HK. Exposure to PM2.5 resulted in the suppression of E-cadherin levels in the lung tissues and increased IFN-γ, IL-2, IL-4, IL-6 and IL-10 in the bronchoalveolar lavage fluid. The alterations in E-cadherin, IFN-γ, IL-6 and IL-10 were associated with OC, TC and some amino acids, particularly non-protein-type amino acids. These data emphasised the deleterious health effects of PM2.5.
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http://dx.doi.org/10.1016/j.toxlet.2015.06.013DOI Listing
September 2015

Zinc oxide nanoparticles induce eosinophilic airway inflammation in mice.

J Hazard Mater 2015 Oct 16;297:304-12. Epub 2015 May 16.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Zinc oxide nanoparticles (ZnO NPs) have been widely used in industry. The metal composition of PM2.5 might contribute to the higher prevalence of asthma. To investigate the effects of ZnO NPs on allergic airway inflammation, mice were first exposed to different concentrations of ZnO NPs (0.1 mg/kg, 0.5 mg/kg) or to a combination of ZnO NPs and chicken egg ovalbumin (OVA) by oropharyngeal aspiration on day 0 and day 7 and then were sacrificed 5 days later. The subsequent time course of airway inflammation in the mice after ZnO NPs exposure was evaluated on days 1, 7, and 14. To further determine the role of zinc ions, ZnCl2 was also administered. The inflammatory cell count, cytokine levels in the bronchoalveolar lavage fluid (BALF), and lung histopathology were examined. We found significant neutrophilia after exposure to high-dose ZnO NPs on day 1 and significant eosinophilia in the BALF at 7 days. However, the expression levels of the T helper 2 (Th2) cytokines IL-4, IL-5, and IL-13 increased significantly after 24h of exposure to only ZnO NPs and then decreased gradually. These results suggested that ZnO NPs could cause eosinophilic airway inflammation in the absence of allergens.
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http://dx.doi.org/10.1016/j.jhazmat.2015.05.023DOI Listing
October 2015

Effects of particulate air pollution and ozone on lung function in non-asthmatic children.

Environ Res 2015 Feb 6;137:40-8. Epub 2014 Dec 6.

Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei 100, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei 100, Taiwan. Electronic address:

Introduction: Information on the long-term effects of different air pollutant levels on lung function is relatively lacking in Asia and still inconclusive in the world. Age differential effects of air pollution are not known.

Objectives: To assess the acute and subchronic effects of ambient air pollution on lung function and compared among children of different ages.

Methods: From April to May 2011, a nationwide study was conducted on schoolchildren aged 6-15 years in 44 schools of 24 districts in Taiwan. Spirograms were obtained from 1494 non-asthmatic children. Air pollution data were retrieved from air monitoring stations within one kilometre of the schools. Using three-level hierarchical linear models, individual lung function was fitted to air pollution, with adjustments for demographics, indoor exposures, outdoor activity, and districts.

Results: Lung function changes per inter-quartile increase of the past two-months average levels of particulate matter <2.5 μm (PM2.5) and ozone (12 μg/m(3), 32-44 and 6.7 ppb, 32-38, respectively) were -103 and -142 ml on FVC, -86 and -131 on FEV1, and -102 and -188 ml/s on MMEF, respectively. Lag-1-day ozone exposure was associated with decreased MMEF. In children aged 6-10, PM2.5 was associated with decreased FEV1/FVC and MMEF/FVC ratios.

Conclusions: In children aged 6-15 years, sub-chronic exposure to ambient PM2.5 and ozone leads to reduced lung capacity, whereas acute exposure to ozone decreases mid-expiratory flow. In children aged 6-10 years, additional airway obstructive patterns in lung function may be associated with PM2.5 exposure.
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http://dx.doi.org/10.1016/j.envres.2014.11.021DOI Listing
February 2015

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model.

Toxicol Appl Pharmacol 2014 Dec 22;281(2):211-20. Epub 2014 Oct 22.

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24h/day, 7days/week, for a total of 16weeks. The average concentrations (mean [SD]) of PM2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05]μg/m(3), respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P<0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P<0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation.
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http://dx.doi.org/10.1016/j.taap.2014.10.005DOI Listing
December 2014
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