Wei-Chun Chou

Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan

BackgroundBisphenol A (BPA) is a sealant and flux of plastic materials and has been determined to be an endocrine-disrupting chemical. Prenatal exposure to BPA can lead to substantial adverse effects on fetal growth and development. This study was conducted to assess BPA concentration in pregnant women and umbilical cord blood, and to investigate whether maternal BPA exposure affected fetal outcomes including lower birth weight (LBW), smaller size for gestational age (SGA), and high leptin (HLP) and low adiponectin (LAD) secretion.MethodsWe measured the BPA levels of maternal blood (n = 97) and umbilical cord blood (n = 97) with a high-performance liquid chromatography/UV detector. The protein secretion of leptin and adiponectin were separately determined using enzyme-linked immunosorbent assay. A logistic regression was performed to estimate the effects of maternal exposure to BPA on LBW, SGA, and adverse action of adipokines in newborns.ResultsThe geometric means of BPA concentration in maternal blood and fetal cord blood were 2.5 ng/ml and 0.5 ng/ml, respectively. Elevated risks of LBW (OR 2.42, 95% confidence interval (CI) 1.72-3.36), SGA (OR 2.01, 95% CI 1.39-3.01), and adverse action of leptin (OR 1.67, 95% CI 1.12-2.25) and adiponectin (OR 1.25, 95% CI 1.52-3.97) were observed in male neonates in the highest quartile of maternal BPA exposure.ConclusionsElevated prenatal BPA exposure increased the risk of LBW, SGA, and adverse actions of adipokines in neonates, especially in male infants. These results provide further evidence that maternal exposure is correlated with adverse birth outcomes.

Modeling the impact of climate variability on diarrhea-associated diseases in Taiwan (1996-2007)

Diarrhea is an important public health problem in Taiwan. Climatic changes and an increase in extreme weather events (extreme heat, drought or rainfalls) have been strongly linked to the incidence of diarrhea-associated disease. This study investigated and quantified the relationship between climate variations and diarrhea-associated morbidity in subtropical Taiwan. Specifically, this study analyzed the local climatic variables and the number of diarrhea-associated infection cases from 1996 to 2007. This study applied a climate variation-guided Poisson regression model to predict the dynamics of diarrhea-associated morbidity. The proposed model allows for climate factors (relative humidity, maximum temperature and the numbers of extreme rainfall), autoregression, long-term trends and seasonality, and a lag-time effect. Results indicated that the maximum temperature and extreme rainfall days were strongly related to diarrhea-associated morbidity. The impact of maximum temperature on diarrhea-associated morbidity appeared primarily among children (0-14years) and older adults (40-64years), and had less of an effect on adults (15-39years). Otherwise, relative humidity and extreme rainfall days significantly contributed to the diarrhea-associated morbidity in adult. This suggested that children and older adults were the most susceptible to diarrhea-associated morbidity caused by climatic variation. Because climatic variation contributed to diarrhea morbidity in Taiwan, it is necessary to develop an early warning system based on the climatic variation information for disease control management.

Assessing the potential exposure risk and control for airborne titanium dioxide and carbon black nanoparticles in the workplace

PurposeThis study assessed the potential exposure risks for workers in the workplace exposed to airborne titanium dioxide nanoparticles (TiO2-NPs) and carbon black nanoparticles (CB-NPs). The risk management control strategies were also developed for the NP engineering workplace.MethodsThe method used in this study was based on the integrated multiple-path particle dosimetry model to estimate the cumulative dose of nanoparticles (NPs) in the human lung. The study then analyzed toxicological effects such as pulmonary cytotoxicity and inflammation and evaluated the health risk associated with exposure to NPs in the workplace. Risk control measures such as the use of ventilating systems and N95 respirator protection are also discussed.Results and discussionThis study found that: (1) the cumulative dose of CB-NPs was greater than that of TiO2-NPs in human lungs; (2) there is a potential health risk to workers exposed to TiO2-NPs and CB-NPs in the absence of control measures in the workplace, with higher health risks associated with CB-NPs than TiO2-NPs; and (3) the use of a ventilating system and an N95 respirator offers greater protection in the workplace and significantly reduces the health risks associated with NP exposure.ConclusionThe present risk management control strategy suggests that the most effective way to reduce airborne NPs is to incorporate the use of a ventilating system combined with N95 respirator protection. This will enable the concentrations of TiO2-NPs and CB-NPs to be reduced to acceptable exposure levels.

Assessing the potential risks to zebrafish posed by environmentally relevant copper and silver nanoparticles.

The manufacture of large quantities of engineered nanomaterials (NMs) may lead to unintended contamination of aquatic ecosystems. Biologically based monitoring techniques need to be developed to detect these emerging NMs. The purpose of this study was to develop a risk-based probability model to predict the potential hazards of nanoecotoxicity toward aquatic organisms posed by waterborne copper and silver nanoparticles (Cu/Ag NPs). Published experimental evidence based on Cu/Ag NP-zebrafish (Danio rerio) systems was adopted as the study data. A Hill model was used to reconstruct a concentration-mortality response profile. A cumulative Weibull predictive model was employed to estimate exposure thresholds. The derived probabilistic model can predict the potential risk of environmentally relevant Cu/Ag NPs for major Taiwanese rivers with predicted environmental concentrations of 0.06 (95% confidence interval (CI): 0.01-0.92) mgL(-1) for Cu NPs and 0.04 (0.01-0.11) mgL(-1) for Ag NPs. The results indicated that estimated thresholds were 0.10-0.48mgL(-1) (95% CI) for Cu NPs and 2.69-2.73mgL(-1) for Ag NPs. The probabilities of a risk quotient (RQ) of >1 ranged 17%-81% for zebrafish exposed to Cu NPs. This study found that Ag NP exposure scenarios posed no significant risks to zebrafish (RQ≪0.1).

Assessing the cancer risk associated with arsenic-contaminated seafood.

Tens of millions of people worldwide ingest excessive amounts of arsenic (As) through drinking water and food. The dietary intake of seafood is the major As exposure route in humans and can cause As-related adverse health effects including cancers. The aim of this study was to quantify potential cancer risks of As exposure for children and adults through seafood consumption. By coupling the age-specific physiologically based pharmacokinetic (PBPK) model and a Weibull-based dose-response function, a more accurate estimate of urinary arsenic metabolites could be achieved to better characterize potential cancer risks. The simulation results show that the proportion of inorganic As, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in human urine are estimated to total 6.7, 26.9, and 66.4% for children, and 6.2, 27.4, and 66.4% for adults, respectively. The estimated median cumulative cancer incidence ratios were respectively 2.67x10(-6) and 3.83x10(-6) for children and adults, indicating a low cancer risk for local residents exposed to As through the consumption of seafood. However, it is necessary to incorporate other exposure routes into the model to make it more realistic. The methodology proposed here can not only be applied to calculate the concentrations of As metabolites in urine, but also to provide a direct estimation of adverse health effects caused by the calculated internal concentrations.

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

BackgroundEndometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.ResultsECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle.ConclusionsThe results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women.

Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from Taiwan.

Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001–2002 in Taiwan. We collected maternal urine samples during the 3rd trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and N7-methylguanosine (N7-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N7-MeG (beta  = 0.35, p<0.001) and oxidative 8-oxodG (beta  = 0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta  = -0.23, p = 0.041). Maternal N7-MeG was also associated with a decreased 1-min Apgar score (beta  = −0.25, p = 0.042). Mutual adjustment for iAs and N7-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta  = −0.28, p = 0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N7-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.

Assessing airborne PM-bound arsenic exposure risk in semiconductor manufacturing facilities.

The purpose of this study was to investigate the inhalation risks on the workers (operator and administrator) exposure to airborne particulate matter-bound arsenic (PMAs) in semiconductor manufacturing facilities. We reanalyzed published empirical data of the personal exposure levels and size distributions of airborne PMAs and linked a human respiratory tract model to calculate the concentrations deposited in target lung regions. We used a physiologically based pharmacokinetic model with a dose-response relationship based on an empirical three-parameter Hill equation model to simulate the exposure time-dependent arsenic dose profiles in human tissues and to estimate quantitatively the inhalation exposure risks. Results show that the threshold level of As(III) for lipid peroxidation response (LPO) on human lung epithelial cells was estimated to be 11.89 (95% CI: 8.09-15.69) microM, whereas 16.39 (95% CI: 12.56-20.22) microM for oxidative DNA damage on human dermal cells. Risk analysis shows that the LPO responses were estimated to be 3.79 (95% CI: 2.44-5.33) for operator and 0.03 (95% CI: 0.01-0.10) for administrator at a risk of 0.5. The 10% probability (risk=0.1) of human dermal cells affected by oxidative DNA damage responses is approximately 27.21% (95% CI: 12.71-67.02%) for operator and 0.03% (95% CI: 0.01-0.07%) for administrator. This study suggests that a potential link between inhalation exposure risk of operator to airborne PMAs in semiconductor manufacturing workplace.

Modeling human health risks of airborne endotoxin in homes during the winter and summer seasons

Endotoxin, a component of gram-negative bacterial cell walls, is a pro-inflammatory agent that induces local and systemic inflammatory responses in normal subjects which can contribute to the risk of developing asthma and chronic obstructive lung diseases. A probabilistic approach linking models of exposure, internal dosimetry, and health effects was carried out to quantitatively assess the potential inhalation risk of airborne endotoxin in homes during the winter and summer seasons. Combining empirical data and modeling results, we show that the half-maximum effect of the endotoxin dose (ED50) was estimated to be 707.9 (95% confidence interval (CI): 308.8-1287.0) endotoxin units (EU) for body temperature change, 481.8 (95% CI: 333.2-630.3) EU for elevation of neutrophils, and 1174.5 (95% CI: 816.0-1532.9) EU for elevation of the cytokine, interleukin-6. Our study also suggests that airborne endotoxin in homes may pose potential risks, and a higher risk for elevation of neutrophils and cytokine interleukin-6 appeared in winter season than in summer. Our study offers a risk-management framework for discussion of future studies of human respiratory exposure to airborne endotoxin.

A probabilistic approach to quantitatively assess the inhalation risk for airborne endotoxin in cotton textile workers

Endotoxin, a component of gram-negative bacterial cell walls, is a proinflammatory agent that induces local and systemic inflammatory responses in normal subjects which can contribute to the risk of developing asthma and chronic obstructive lung diseases. A probabilistic approach linking models of exposure, internal dosimetry, and health effects were carried out to quantitatively assess the potential inhalation risk of airborne endotoxin for workers in cotton textile plants. Combining empirical data and modeling results, we show that the half-maximum effects of the endotoxin dose (ED50) were estimated to be 3.3 x 10(5) (95% confidence interval (CI): 1.9-14.7 x 10(5)) endotoxin units (EU) for the blood C-reactive protein (CRP) concentration, 1.1 x 10(5) (95% CI: 0.6-1.7 x 10(5))EU for the blood polymorphonuclear neutrophil (PMN) count, and 1.5 x 10(5) (95% CI: 0.4-2.5 x 10(5))EU for the sputum PMN count. Our study offers a risk-management framework for discussing future establishment of limits for respiratory exposure to airborne endotoxin for workers in cotton textile plants.