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Bisphenol A (BPA) is a plasticizer used in the manufacture of polycarbonate and epoxy resins. It was found that higher urinary BPA levels are more likely to be associated with coronary artery disease (CVD). In recent years, the increasing incidence of CVD among young people is observed, which may be related with inflammation rather than the traditional triple-H risk factors. BPA is an endocrine-disrupting chemical, and can induce oxidative stress and chronic inflammation since its estrogenic effect. Inflammatory responses could come from the stimulation of IκB kinases (IKKs) by estrogen receptors (ERs). Therefore, this study investigated the association of BPA exposure with the gene expression of pro-inflammatory response (ERs and IKKs), an inflammation biomarker of CVD (C-reactive protein, CRP), and physiologic index potency of CVD development symptoms in young adults. This study divided BPA exposure levels into high and low groups based on the median plasma BPA level (4.34 ng/mL), and found that the high BPA group obviously had higher BMI, blood pressure, plasma CRP levels, and gene expression of ERβ and IKKβ. BMI and gene expression of IKKβ were also positively correlated with plasma CRP secretion. Furthermore, the study subjects with potential CVD development symptoms had the increased levels of BPA (OR 2.10, 95% CI 0.83-5.39), CRP (OR 2.61, 95% CI 1.03-10.6) and IKKβ (OR 4.29, 95% CI 1.51-15.6). These results indicated that exposure to BPA is potentially associated with expression of pro-inflammatory genes related to CRP secretion, which may promote the risk of CVD development symptoms in young adults. This study highlighted the possible connection between BPA exposure and CVD development but the mechanism between them needs to be further explored.

The Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2) was an outbreak in December, 2019 and rapidly spread to the world. All variants of SARS-CoV-2, including the globally and currently dominant Delta variant (Delta-SARS-CoV-2), caused severe disease and mortality. Among all variants, Delta-SARS-CoV-2 had the highest transmissibility, growth rate, and secondary attack rate than other variants except for the new variant of Omicron that still exists with many unknown effects. In Taiwan, the pandemic Delta-SARS-CoV-2 began in Pingtung from 14 June 2021 and ceased at 11 July 2021. Seventeen patients were infected by Delta-SARS-CoV-2 and 1 person died during the Pingtung outbreak. The Public Health Bureau of Pingtung County Government stopped the Delta-SARS-CoV-2 outbreak within 1 month through measures such as epidemic investigation, rapid gene sequencing, rapidly expanding isolation, expanded screening of the Delta-SARS-CoV-2 antigen for people who lived in regional villages, and indirect intervention, including rapid vaccination, short lockdown period, and travel restrictions. Indirect environmental factors, such as low levels of air pollution, tropic weather in the summer season, and rural areas might have accelerated the ability to control the Delta-SARS-CoV-2 spread. This successful experience might be recommended as a successful formula for the unvaccinated or insufficiently vaccinated regions.

Single-walled carbon nanotubes (SWCNTs) are widely utilized for industrial, biomedical, and environmental purposes. The toxicity of Carboxylated SWCNTs (SWCNTs−COOH) in in vivo models, particularly Caenorhabditis elegans (C. elegans), and in vitro human cells is still unclear. In this study, C. elegans was used to study the effects of SWCNTs−COOH on lethality, lifespan, growth, reproduction, locomotion, reactive oxygen species (ROS) generation, and the antioxidant system. Our data show that exposure to ≥1 μg·L−1 SWCNTs−COOH could induce toxicity in nematodes that affects lifespan, growth, reproduction, and locomotion behavior. Moreover, the exposure of nematodes to SWCNTs−COOH induced ROS generation and the alteration of antioxidant gene expression. SWCNTs−COOH induced nanotoxic effects at low dose of 0.100 or 1.00 μg·L−1, particularly for the expression of antioxidants (SOD-3, CTL-2 and CYP-35A2). Similar nanotoxic effects were found in human cells. A low dose of SWCNTs−COOH induced ROS generation and increased the expression of catalase, MnSOD, CuZnSOD, and SOD-2 mRNA but decreased the expression of GPX-2 and GPX-3 mRNA in human monocytes. These findings reveal that background-level SWCNTs−COOH exerts obvious adverse effects, and C. elegans is a sensitive in vivo model that can be used for the biological evaluation of the toxicity of nanomaterials.

Type II diabetes (T2D) arises through insulin resistance and a progressive decrease in insulin secretion, which may be partly related to pancreatic beta-cell function decline, obesity, and eventual hyperglycemia [1]. The first line for managing hyperglycemia in patients with T2D includes lifestyle modifications and metformin monotherapy. However, many patients still showed poor glycemic control due to progressive deterioration during the course of T2D [2, 3]. On streptozotocin-induced T2D rats, tempeh fermentation has been shown to be a potentially beneficial dietary supplement for abnormal carbohydrate metabolism [4]. This study was a prospective open-label clinical trial. The data were collected from Kaohsiung Veterans General Hospital Pingtung Branch, Taiwan from August 2018 to July 2019. 35 eligible T2D participants with a mean age of 57.91 ± 10.17 years were enrolled. After taking 2 g tempeh capsules daily for a period of 3 months, the levels of HbA1C and triglyceride were noticeably decreased in the participants. A regression analysis revealed that cholesterol concentration had a significant positive correlation with the concentrations of LDL, but triglyceride concentration had a significant negative correlation with the concentrations of HDL in the pre- and the post-tempeh treatment.

Breastfeeding is recommended over formula feeding, but human breast milk (HBM) composition varies and can be affected by food additives. Whether flame-retardant polybrominated diphenyl ethers (PBDEs) found in HBM interact with lipid components of HBM to impede infant neurodevelopment is a critical public health issue. Using lipidomic analysis, we examined the association of PBDEs in HBM and HBM lipid components with infant neurodevelopment. HBM samples (n = 100) were collected at the beginning stage of breastfeeding and analyzed for 30 PBDE congeners as well as a group of lipid components by using high-resolution gas chromatography, mass spectrometry, and liquid chromatography time-of-flight mass spectrometry. Infants were examined at 8 to 12 months of age by using the Bayley-III to assess neurodevelopment. A total of seven PBDEs, 35 lipids, and 27 fatty acids in HBM showed significant associations with Bayley-III scores. Multivariate analysis confirmed that these candidate PBDEs and lipid components were significant predictors of infant neurodevelopment. Eicosapentaenoic acid and docosapentaenoic acid in HBM showed no association with infant neurodevelopment in the general Taiwanese population. While certain PBDEs may play a role, our findings indicate that the lipid components of HBM are directly important for infant neurodevelopment.

Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. We identified that 9,12-octadecadiynoic acid has a significantly positive correlation with infant adaptive behavioral development, which is a crucial neurodevelopment to manage risk from environmental stress. To further clarify the biological function of 9,12-octadecadiynoic acid in regulating neurodevelopment, Caenorhabditis elegans (C. elegans) was used as a model to investigate the effect of 9,12-octadecadiynoic acid on neurobehavioral development. Supplementation with 9,12-octadecadiynoic acid from the L1 to L4 stage in larvae affected locomotive behaviors and foraging ability that were not socially interactive, implying that 9,12-octadecadiynoic acid is involved in regulating the serotonergic neuronal ability. We found that supplementary 0.1 μM 9,12-octadecadiynoic acid accelerated the locomotive ability and foraging ability via increasing the expression of serotonin transporter mod-1. Antioxidant defense genes, sod-1, sod-3 and cyp-35A2 are involved in 9,12-octadecadiynoic acid-induced motor neuronal activity. Nevertheless, supplementary 9,12-octadecadiynoic acid at concentrations above 1 μM significantly attenuated locomotive behaviors, foraging ability, serotonin synthesis, serotonin-related gene expressions and stress-related gene expression, resulting in the decreased longevity of worms in the experiment. In conclusion, our study demonstrates the biological function of 9,12-octadecadiynoic acid in governing adaptive behavioral development.

Several studies have stated the harmful effects of PM2.5 to population health, including disruption of neurological development. However, the mechanism behind the neurodevelopmental effects of ambient PM2.5 and postnatal PBDEs and OCPs exposure is still unknown. Our goal was to determine influence of breastmilk residues, polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs), to the infants’ neurodevelopment with respect to high and low PM2.5 exposure areas. The participants were recruited from high PM2.5 exposure areas (n = 32) and low PM2.5 exposure areas (n = 23) of southern Taiwan. The extracted 14 PBDEs and 20 OCPs compounds were analyzed using gas chromatography coupled with mass spectrometer. The infants, aging from 8-12 months, were examined by Bayley Scales of Infants and Toddlers Development, Third Edition (Bayley-III) for neurodevelopment. Results showed that high PM2.5 exposure caused reduced head circumference and had significant effects on the motor skill and social emotional development. For breastmilk PBDEs, a positive correlation between BDE-196 and social emotion, after multivariate analysis with adjustment of confounders, was observed while BDE-99, 196, 197, and 207 showed higher magnitudes in low PM2.5 areas than in high PM2.5 areas. For OCPs, only γ- hexachlorcyclohexanes (γ-HCH) presented the significant difference between high and low PM2.5 exposure areas. Most breastmilk OCPs residues, including 4,4’-dichlorodiphenyltrichloroethane (4,4’-DDT), γ-HCH, endrin, and heptachlor epoxide showed negative impact on the Bayley-III scores after multivariate analysis. In conclusion, infants’ neurodevelopment was significantly correlated with the location of PM2.5 exposure and breastmilk intake of certain PBDEs and OCPs. Breastmilk OCPs might obviously affect infants’ neurodevelopment more compared to breastmilk PBDEs based on our finding. Moreover, this study further employs awareness about viable effects of PM2.5 in infants’ neurodevelopment.

Cooking oil fumes (CF) coming from night market stalls exhaust contain substantial amounts of air pollutants such as carbonyl compounds that may contribute to outdoor air pollution and may have adverse health effects on the Taiwanese population. Carbonyl emission characteristics depend on several factors, which include but are not limited to, the cooking style and food material being used. The current study evaluated carbonyl compound emissions from two scenarios: a standard kitchen cooking classroom with a stack gas tunnel and night market food stalls. The different cooking styles and food types cooked using a liquefied petroleum gas (LPG) stove, such as grilled chicken with (GCS) and without sauce (GC), mixed barbecue with sauce (MBS), grilled vegetables with sauce (GVS), stir-fried oyster omelet (OM), fried Taiwanese chicken nuggets (FN) in the kitchen cooking classroom, and grilled chicken with (GCS) and without sauce (GC), stir-fried oyster omelet (OM), grilled vegetables with sauce (GVS), and fried steak (FS) in the night market were evaluated for carbonyl carbon emissions. OM from the kitchen classroom and GCS from the night market showed the highest mean total carbonyl compound concentrations (1850 ± 682 ppb and 1840 ppb). Formaldehyde was found to be the most predominant carbonyl compound, with contribution percentages ranging from 70.9–99.58% of the total carbonyl emission factors in CFs. Grilled vegetables with sauce had the highest emission factor magnitude of 274 µg kg–1 wt. Factors such as the addition of sauce and grilling were also observed to increase carbonyl compound emissions. Corresponding health risks of carbonyl compounds in CFs for the night market vendors were also assessed. All values for cancer risk (R) were above the standard R value for workplace exposure, and HQ values were all greater than 1, suggesting a high risk for adverse health effects. Although our reported values were relatively high due to our sampling conditions, our study was first to be conducted in Taiwan and holds an important contribution to the global existing data of carbonyl compound emissions.

Human exposure to airborne PM2.5 has been linked to an increased risk of respiratory and cardiovascular diseases, possibly via the activation of systemic inflammation. However, the associations between airborne PM2.5 and systemic inflammation in humans remain inconclusive. Traffic-related air pollutants (TRAPs) are the major source of PM2.5 in urban areas; the adverse health effect of PM2.5 from TRAPs is currently a critical issue of public concern. The present cross-sectional study examines the relationship between PM2.5 exposure and systemic inflammation in order to consider the health impacts of TRAP PM2.5 on urban traffic conductors. All study participants, viz., office-based police officers (the reference) and traffic conductors (the exposure), were requested to carry a personal sampler to determine individual PM2.5 exposure. An adenovirus-based NF-κB luciferase reporter assay was used to determine the proinflammatory activity in serum samples collected from the study participants. The blood proinflammatory activity was presented as tumor necrosis factor-α (TNFα) equivalence (TNFα-EQ), which was extrapolated from the sigmoidal semi-logarithmic dose-response curve of the NF-κB reporter assay by TNFα. The levels of both personal PM2.5 exposure and blood proinflammatory activity (TNFα-EQ) in the exposure group (traffic conductors) were significantly higher than in the reference group (office-based police officers) (p < 0.05). The present study reveals a positive and significant association between personal PM2.5 exposure levels and blood TNFα-EQ levels in a linear regression model of y = 0.511x – 3.062 (y = log TNFα-EQ and x = log PM2.5; R = 0.231 and p = 0.047); the results suggest that exposure to TRAP PM2.5 significantly contributes to increased systemic inflammation in humans. This research provides clear evidence that long-term occupational exposure to TRAPs causes adverse health impacts, i.e., inflammation, on traffic conductors.

Non-thermal plasma (NTP) has been widely applied in the food and agricultural industries. It is still unknown whether natural bioactive compounds in seeds are affected by NTP treatment. Our goal was to examine whether the bioactive compounds in djulis (Chenopodium formosanum Koidz.) seed are changed after NTP treatment. The betacyanin, anthocyanin, total phenolic content (TPCs), total flavonoids (TFs), 2,2-diphenyl-1-picrylhydrazyl radical scavenging effects (DPPH), gallic acid, and rutin were compared in NTP-treated seed and an untreated control. Levels of betacyanin, anthocyanin, and TPCs in the seed were found to be significantly increased after the nitrogen (N2)-NTP treatment compared with the control (p &lt, 0.001). Inversely, the air-NTP treatment significantly weakened the performance of these bioactive compounds in the seed as compared to the control. Levels of TFs in both the air- and N2-NTP treated seed were significantly lower than those in the control (p &lt, 0.001). After the NTP treatment, DPPH was still at high levels, similar to those in the control. The djulis seed extract had antioxidant and anti-inflammatory effects on THP-1 (human-monocyte-cell line) cells. N2-NTP generated nitrogen reactive species that activated the bioactive compounds in the seed. In contrast, air-NTP produced oxygen and nitrogen reactive species inhibited the expression of these bioactive compounds.

Carbon-based engineered nanomaterials, such as graphene oxide nanoparticles (GO NPs), are widely available for application, but their potentially adverse health effects on humans still require investigation. In this study, the environmental levels of GO NPs are addressed to examine whether GO leads to adverse effects on an in-vivo model of Caenorhabditis elegans (C. elegans). Nematodes with prolonged exposure (L1 larvae to young adult) to GO NPs at 0.00100, 0.0100, 0.100, and 1.00 mg L–1 were used to evaluate the potential toxic effects, including lethality (acute toxicity), reproductive (brood size) and neurological (locomotion including head thrash and body bend) responses, longevity (lifespan), and oxidative stress (gene expression of sod-1, sod-3, and clt-2). Prolonged exposure to GO NPs was not found to induce lethality at the selective levels. In the brood-size and head-thrash tests, the biological responses in nematodes were significantly reduced at 0.0100-1.00 ng L–1 GO NP exposure as compared with the untreated control. The nematodes exposure to GO NPs at 0.00100–1.00 ng L–1 exhibited significant delays in body bending behavior compared with the control. In the examination of the longevity of nematodes, it was found that the lifespan of all GO NP-exposed worms was significantly shortened as compared to the untreated worms. Gene expression of sod-1, sod-3, and ctl-2 presented significantly higher induction folds in the exposed worms compared with the controls. Consequently, prolonged exposure to the low-dose GO NPs might be associated with disruption of reproduction and locomotion, attenuation of longevity, and induction of oxidative stress in nematodes.

It has been demonstrated that human exposure to polybrominated diphenyl ethers (PBDEs) might be associated with several adverse health effects. Dietary and microenvironmental sources are considered to be the main routes of PBDEs exposure. The study aimed to investigate PBDEs in residential indoor and outdoor air and further to assess the health risks in family members of different ages. Indoor and outdoor air samples from houses in residential areas were simultaneously collected for analysis of BDE-47, 99, 100, 153, 154, 183, 196, 197, 203, 206, 207, 208, and 209 by high-resolution gas chromatography/high-resolution mass spectrometry. PBDE concentrations were non-significantly higher indoors (81.1 pg/m3) than outdoors (42.7 pg/m3) (p = 0.513). For the outdoor air, the mean PBDE level was lower in air outside houses than in air from industrial and urban areas. Levels of Σ14PBDEs and BDE-209 in house indoor air were no higher in Taiwan than other countries. The daily intake of non-dietary PBDEs from house air and dust in Taiwan was highest in the toddlers (1–2 years old; 8.22 ng/kg b.w./day) and lowest in the male adults (≥ 20 years old; 0.562 ng/kg b.w./day) among family members. For Taiwanese, the risks of non-cancer (hazard quotient: HQ) and cancer (cancer risk: R) with neurobehavioral effects of exposure to non-dietary PBDEs in the home environment were assessed to be lower than the critical values of 1.00 and 1.00 × 10–6 for HQs and Rs, respectively. In conclusion, levels of indoor PBDEs and non-dietary daily intake were found to be low in home environments in Taiwan. This result suggests that PBDEs in the home environment are not harmful to family members from the newborn to the elderly if we only consider the neurobehavioral effects.

Endocrine disrupting compounds are a global concern, owing to their interference with the endocrine system of wildlife. In particular, natural estrogens at concentrations as low as ng/L level can interrupt the endocrine system of many organisms. A constructed wetland is an effective means of removing the residual levels of estrogen. This study investigates the estrogen degradation and sorption on colloids in a constructed wetland at hydraulic retention times (HRTs) of 27.5, 45.9, and 137.5 h. Three natural estrogens (i.e. estrone (E1), 17β-estradiol (E2), and estriol (E3)) are analyzed with liquid chromatography/tandem mass spectrometry. At HRT = 27.5 h, no degradation occurs; at HRT = 45.9 h, the degradation rates are 0–46.2%; and at HRT = 137.5 h, the degradation rates are 40–84.3%. Additionally, estrogen sorption coefficients (log KCOC values) range from 3.37 to 4.89. Average log KCOC values are 4.08 ± 0.33, 4.04 ± 0.34, and 4.11 ± 0.28 for E1, E2, and E3, respectively. At different HRTs, values of log KCOC increase with an increasing HRT. Analytical results indicate that constructed wetlands can remove residual natural estrogens. With an increasing HRT, the estrogen degradation rate increases as well as the estrogen sorption on colloids.

The goal of this report is to evaluate brominated persistent organic pollutants (POPs) in the indoor air and dust to further assess their health effects on thyroid hormones and neurodevelopment in infants, toddlers, and young children. This category of brominated POPs includes polybrmonated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDs), polybrominated biphenyls (PBBs), and polybrominated dibenzo-p-dioxins (PBDD/DFs). These organobromines are lipophilic compounds which resist physical and chemical degradation in the environment and biota, and so easily bioaccumulate in adipose tissue. Brominated POPs, particularly in brominated fire retardants (BFRs) such as PBDEs, HBCDs, and PBBs, are ubiquitous in indoor environments due to their inadvertent release from certain consumer products. Some of these organobromines have been recognized in some in-vitro and in-vivo studies to be neurotoxins and disrupt thyroid hormones, although the evidence from actual epidemiological studies is contradicted and inconsistent, especially for infants, toddlers, and young children, who are particularly vulnerable to these substances as they spend most of their time in the home. This report focuses on exposure to PBDEs, HBCDs, PBBs, and PBDD/DFs in the indoor dust and on the indoor aerosol, to explore their association with human health, particularly the disruption of thyroid hormones and neurodevelopment in early childhood.

CYP2A13, a human pulmonary specific cytochrome P450 enzyme, plays an important role in susceptibility to tobacco-specific nitrosamines (TSNAs)-induced lung cancer in humans. The pattern of CYP2A13 distribution in respiratory tract affects the susceptibility of the lung to carcinogens. CYP2A13 is expressed in the epithelium of trachea and bronchi; however its pattern of expression in human lung cancer remains largely unknown. This study aimed to determine the CYP2A13 expression in specimens from human non-small cell lung carcinomas (NSCLCs), i.e., adenocarcinoma and squamous carcinoma, by immunohistochemical (IHC) analysis and to identify the potential linkage between tumor CYP2A13 levels and some clinicopathological characteristics of NSCLC patients in Taiwan. The tumor CYP2A13 IHC staining signal was strong in 76% of the 112 study subjects. Study subjects (especially non-smoking or lung adenocarcinoma patients) with higher tumor CYP2A13 levels were younger. Multiple logistic regression analysis revealed that in younger subjects (age ≤ 66) and heavy smokers (pack-years ≥ 40), the odds ratio (OR) for positive tumor CYP2A13 staining was significantly higher than that for negative tumor CYP2A13 staining. Moreover, the association of EGFR gene mutations and positive tumor CYP2A13 staining was also revealed. In conclusion, these findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations.

In vivo studies indicate that prenatal or neonatal exposure of rodents to polybrominated diphenyl ethers (PBDEs) disrupts thyroid hormone balance, but few studies have reported an association of PBDEs and insulin-like growth factor 1 (IGF-1). The goal was to examine whether PBDEs exposure affects the levels of thyroid hormones and IGF-1 in cord blood. Study participants were healthy pregnant women recruited from the general population in central Taiwan between 2000 and 2001 and in southern Taiwan from 2007 to 2009. One-hundred-forty-nine breast milk samples ( n = 149), which were collected within one month after delivery, were analyzed using a high resolution gas chromatograph equipped with a high resolution mass spectrometer. The average and median levels of breast milk Σ 14 PBDEs were 5.34 and 3.38 ng/g lipid in 2000–2001 and 5.22 and 3.13 ng/g lipid in 2007–2009, respectively. In general, levels of PBDE congeners were very low in this study population and not significantly different between the years 2000–2001 and 2007–2009. Breast milk Σ 14 PBDEs were not significantly correlated with thyroid hormones and IGF-1 in cord blood. After examining multiple stepwise linear regression models with adjustment for maternal age, pre-pregnancy body mass index (BMI), parity, gestational age, and region (namely, central and southern Taiwan), we found that log of T4 in cord blood was significantly but slightly correlated with higher BDE-154 ( B = 0.113, p = 0.017) in breast milk. The log of FT4 concentration was significantly related to a decrease in the log of BDE-99 level ( B = −0.137, p = 0.043) and an increase in the log of BDE-154 level ( B = 0.158, p = 0.008). Meanwhile, the log of IGF-1 level was also significantly linked to an increase in the log of BDE-196 level ( B = 0.532, p = 0.028) and decrease in the log of BDE-85 level ( B = −0.235, p = 0.018). Few epidemiological studies report an association between PBDEs exposure and IGF-1. Based on our findings, further in vivo and epidemiological studies are encouraged and needed to explore associations between PBDEs exposure and levels of thyroid hormones and IGF-1.

In vivo studies have demonstrated that prenatal or neonatal exposure to polybrominated diphenyl ethers (PBDEs) causes developmental neurotoxicity. However, there is a lack of human data. Our hypothesis was that PBDEs would result in lower infant neurodevelopment scores. This is a post hoc analysis of previous studies. Fourteen PBDEs in 70 breast milk were analyzed using a high-resolution gas chromatograph/high-resolution mass spectrometer. Infant neurodevelopment at the age of 8-12 mo was determined using the Bayley Scales of Infants and Toddlers Development, third edition (Bayley-III). The median of Σ14 PBDEs (the sum of 14 PBDE congeners) was 2.92 ng/g lipid. The Σ14 PBDE concentrations were not correlated with Bayley-III scores on cognitive, language, motor, social-emotional, or adaptive behavior scales. A significantly inverse association between brominated diphenyl ether (BDE)-209 and the cognitive scale was found after multivariate stepwise linear regression analyses (B = -0.007, adjusted R = -0.224, p = 0.032). In contrast, the language scale was positively correlated with BDE-196 (B = 0.096, adjusted R = 0.315, p = 0.002). Our results are consistent with most in vivo studies, suggesting that prenatal or postnatal exposure to BDE-209 potentially delays the neurological development.

The study aimed to examine the impact of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on infant neurodevelopment. PBDEs levels in 36 cord blood samples were analyzed with a high-resolution-gas-chromatograph/high-resolution-mass-spectrometer and infant neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. The mean and median of Σ(11)PBDEs were 6.63 and 4.63 ng/g lipid, respectively. As compared to the lower PBDEs group (Σ(11)PBDEs 4.63 ng/g lipid), the higher PBDEs group (Σ(11)PBDEs 4.63 ng/g lipid) had a significantly higher actual odds ratio (OR = 1.13, p 0.05) of the cognition score as well as a lower odds ratio (OR = 0.904, p 0.01) of the adaptive behavior score, suggesting that prenatal PBDEs exposure may potentially affect infant neurodevelopment.

Long chain polyunsaturated fatty acids (LC-PUFA), ARA (arachidonic acid, 20:4 n − 6) and DHA (docosahexaenoic acid, 22:6 n − 3) have positive effects and environment pollutants, polychlorinated dibenzo- p -dioxins/dibenzofurans(PCDD/F) and polychlorinated biphenyls (PCB) have negative effects on neural development during early life. Placental dioxin/PCB serves as markers for cumulative exposure to fetus. Fatty acid composition of placenta depends on nutrient supply during pregnancy, serving as indicators for fetal ARA and DHA accretion. This study investigated correlation between placental PCDD/F and PCB toxic equivalent (TEQ) and LC-PUFA in 34 pregnant women from Taiwan. Placental PCDF TEQ were inversely correlated with placental ARA ( p = 0.020), C20:3 n − 6 ( p = 0.01), C22:4 n − 6 ( p = 0.04), C22:5 n − 6 ( p p = 0.03), but ARA and DHA did not vary with PCDD, dioxin-like and indicator PCB. After adjustment for age and body mass index, a one-unit PCDF TEQ increase was associated with 1.021%w/w and 0.312%w/w decreases in ARA ( β = −1.021, p = 0.03) and DHA ( β = −0.312, p = 0.03). Since ARA and DHA were unrelated to three classes of toxins, and a weak negative association was found with PCDF, these data provide no basis for discouraging marine fish consumption during pregnancy for Taiwan women on the basis of these organics. Pregnant women should consume fish for its unique package of nutrients while avoiding few species with high organic pollutant or mercury contamination.

Using one particulate zinc oxide (ZnO) and two soluble zinc compounds (Zn(NO(3))(2) and Zn(CH(3)COO)(2)), we aimed to clarify if zinc ions (Zn(2+)), like particulate ZnO, caused inflammatory responses in vascular endothelial cells. Treatments of human umbilical vein endothelial cells (HUVECs) with 368.6 μM of each zinc compound caused marked increases in IκBα phosphorylation and intercellular adhesion molecule-1 (ICAM-1) expression. Treatments with Zn(CH(3)COO)(2) (50-350 μM) induced a dose-dependent ICAM-1 expression. These results show that Zn(2+) alone is sufficient to induce similar levels of ICAM-1 expression as ZnO particles, suggesting that dissolved Zn(2+) may play the major role in inflammatory effect of ZnO particles on vascular endothelial cells.

This study investigated inflammatory effects of zinc oxide (ZnO) particles on vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human umbilical vein endothelial cells (HUVECs) were characterized by assaying cytotoxicity, cell proliferation, and glutathione levels. A marked drop in survival rate was observed when ZnO concentration was increased to 45 μg/ml. ZnO concentrations of ≤3 μg/ml resulted in increased cell proliferation, while those of ≤45 μg/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations ≤45 μg/ml were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein, an indicator of vascular endothelium inflammation, revealing that ZnO particles induced a dose-dependent increase in ICAM-1 expression and marked increases in NF-κB reporter activity. Overexpression of IκBα completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-κB plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-α, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-κB-dependent manner, and ZnO synergistically enhanced TNF-α-induced ICAM-1 expression. Both 50 and 100-nm ZnO particles agglomerated to similar size distributions. This study reveals an important role for ZnO in modulating inflammatory responses of vascular endothelial cells via NF-κB signaling, which could have important implications for treatments of vascular disease.

Dioxin exposure has been positively associated with human type II diabetes. Because lipophilic dioxins accumulate mainly in adipose tissue, this study aimed to determine if dioxins induce metabolic dysfunction in fat cells. Using 3T3-L1 cells as an in vitro model, we analyzed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model dioxin, on adipogenic differentiation, glucose uptake, and lipolysis. TCDD inhibited adipogenic differentiation, as determined by using oil droplet formation and adipogenic marker gene expression, including PPARgamma (peroxisome proliferator-activated receptor gamma), C/EBPalpha (CCAAT/enhancer-binding protein alpha), and Glut4 (glucose transporter type 4). Effects of TCDD on glucose uptake were evaluated using fully differentiated 3T3-L1 adipocytes, revealing that TCDD significantly attenuated insulin-induced glucose uptake dose dependently. Inhibition of aryl hydrocarbon receptor (AhR) by alpha-naphthoflavone (alpha-NF), an AhR inhibitor, did not prevent the inhibitory effect of TCDD on glucose uptake, suggesting that TCDD attenuates insulin-induced glucose uptake in an AhR-independent manner. Effects of TCDD on lipolysis were determined using glycerol release assay. We found that TCDD had no marked effect on isoproterenol-induced glycerol release in fully differentiated 3T3-L1 adipocytes. These results provide in vitro evidence of TCDD's effects on fat cell metabolism, suggesting dioxin exposure in development of insulin resistance and type II diabetes.

Polybrominated diphenyl ethers (PBDEs) have documented effects on thyroid functions and rodent behavior in vivo. Epidemiological studies, however, have revealed only limited information about associations between PBDE exposure and menstruation characteristics. Our goal was to examine whether high breast milk PBDE levels in reproductive-age females lead to interference with menstruation characteristics. We analyzed 15 PBDE congeners in 46 breast milk samples. Fifteen PBDE congeners (BDE-15, 28, 47, 49, 99, 100, 153, 154, 183, 196, 197, 203, 207, 208, and 209) were analyzed using a gas chromatograph equipped with a high resolution mass spectrometer. The mean sum of PBDEs (ΣPBDEs) in breast milk was 3.42 ng/g lipid. Women's age at menarche was not correlated with breast milk PBDE levels. Increased BDE-208 and 209 levels were significantly associated with the prolonged length of average and the longest menstrual cycle independent of age, pre-pregnant BMI, and parity. Higher concentrations of ΣPBDEs and the higher brominated PBDEs from BDE-183 to 209, except 197, were significantly linked to women whose menstruation periods were still coming irregularly at the sampling time. Age-adjusted odds ratios (ORs) of BDE-153, 183, 207, 208, and ΣPBDEs were significantly higher in women with length of average menstrual cycle >32 days, compared to the control. Women whose menstruation periods still came irregularly when they were 18 years old had higher age-adjusted ORs of BDE-207, 208, 209, and ΣPBDEs than those whose periods came regularly at the same age. Although ΣPBDEs and certain higher brominated PBDEs appear to have potential to prolong length of average menstrual cycle and delay the age when menstruation periods begin coming regularly, these findings are not conclusive because our sample size is small and more scientific evidence is needed. Keywords: Polybrominated diphenyl ethers (PBDEs), Breast milk, Menstruation, Female reproduction, Breastfeeding

Environmental estrogenic chemicals interrupt endocrine systems and generate reproductive abnormalities in wildlife, especially natural and synthetic estrogenic steroid hormones such as 17beta-estradiol (E2), estrone (E1), estriol (E3), 17alpha-ethynylestradiol (EE2), and diethylstilbestrol (DES). Concentrated animal feedlot operations (CAFOs) are of particular concern since large amounts of naturally excreted estrogens are discharged into aquatic environments. This study investigated E2, E1, E3, EE2, and DES with high performance liquid chromatography/tandem mass (HPLC-MS/MS) analyses along Wulo Creek in southern Taiwan, near a concentrated livestock feedlot containing 1,030,000 broiler chickens, 934,000 laying hens, 85,000 pigs, and 1500 cattle. Sampling was performed from December 2008 to May 2009, in which 54 samples were collected. Experimental results indicate that concentrations of EE2 were lower than the limit of detection (LOD), and concentrations of DES were only detected twice. Concentrations ranged from 7.4 to 1267 ng/L for E1, from not detected (ND) to 313.6 ng/L for E2, and from ND to 210 ng/L for E3. E1 had the highest average mass fraction (72.2 + or - 3.6%), which was significantly higher than E3 (16.2 + or - 1.7%) and E2 (11.5 + or - 2.6%). Additionally, the mean E2 equivalent quotient (EEQ) ranged from 17.3 to 137.9 ng-E2/L. Despite having a markedly lower concentration than E1, E2 more significantly contributed (52.4 + or - 6.0%) EEQ than E1 (19.7 + or - 3.5%). Moreover, the concentrations of E2, E1, and E3 upstream were significantly higher than concentrations downstream, suggesting a high attenuation effect and fast degradation in the study water. Most concentrations in winter season were higher than those of spring season due to the low dilution effect and low microbial activity in the winter season. Based on the results of this study, we recommend further treatment of the wastewater discharge from the feedlot.

Only few studies have focused on organochlorine pesticides (OCPs) in breast milk and the related health risks for women in Taiwan. Our goal is to examine breast milk OCPs and their associations with female reproductive function (infertility, gynecological diseases, and menstruation characteristics) as well as their correlation with sociodemographic parameters (age, pre-pregnant body mass index (BMI), annual incomes, population, birth year, and parity) and dietary habit. The breast milk samples were collected in southern Taiwan (n = 68) from 2013 to 2016 and the OCP residues were analyzed using high resolution gas chromatography with low resolution mass spectrometry (HRGC/LRMS). The results show that the most abundant OCP residues in the breast milk was ΣDDT with the geometric mean ± standard deviation of 9.81 ± 7.52 ng−1 lipid−1 followed by ΣHCH (0.539 ± 0.557 ng−1·lipid−1). In the principal component analysis, cis-chlordane (cis-CHL) and γ-HCH were found to be related to participants who received medical treatment for infertility, and 4,4′-DDT was associated with those who received gynecological surgery. The logistic regression showed that the odds ratio (OR) of log γ-hexachlorocyclohexane (γ-HCH) was higher for mothers who had received medical treatment for infertility than for the normal group (OR = 25.6, p = 0.035) after adjustments for age, pre-pregnant BMI, annual income, population (i.e., native-born Taiwanese), birth year, and parity. Cow milk and beef consumption as well as menstruation characteristics such as average menstrual period (>5 days), shortest menstrual period (

The aim of the present study was to determine associations between the occurrence of PBDEs in breast milk of women and their demographic parameters. Participants were randomly recruited from the general population in southern Taiwan. Thirty two breast milk samples were collected and subsequently 30 congeners of PBDEs were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. The mean and median of SigmaPBDEs were 3.54 and 3.31 ng/g lipid, respectively. SigmaPBDE levels in breast milk were not significantly correlated with age and pre-pregnant BMI of Taiwanese mothers. We did find, however, that the higher hexaBDE level was significantly related to older age (29 years). Higher levels of SigmaPBDEs and higher brominated PBDEs, such as nonaBDEs and decaBDE, had slightly but not significantly negative correlations with lower pre-pregnant BMI (or =21 kg/m(2)). There were no significant differences in PBDE levels among parity and ethnic groups. SigmaPBDE levels in Taiwanese breast milk were lower than those reported from the United States or Canada. SigmaPBDE levels of the present study (2007-2008) are significantly lower than those found in our previous report (2000-2001). Although our results were limited by the sampling size, preliminary results suggest the exploratory relations to show positive associations of PBDE homologues (e.g. triBDEs and hexaBDEs) with maternal age. PBDEs pattern of breast milk may have changed after pentaBDEs were stopped to use in Taiwan.

We measured the concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the flue gas and the ambient atmosphere of a power plant fueled by heavy oil in northern Taiwan. The mean emission concentration and I-TEQ concentration of total PCDD/Fs were 0.292 ng/N m3 and 0.016 ng I-TEQ/N m3, respectively. All PCDD/F emission concentrations in the flue gas were supposed to meet the Environmental Protection Administration Executive Yuan, R.O.C. standard (1.0 ng I-TEQ/N m3 from 2008). Furthermore, the mean I-TEQ concentration in the ambient atmosphere was 0.011 pg I-TEQ/N m3, which was much lower than the environmental quality standards for dioxins in Japan (0.6 pg TEQ/N m3). Also, the PCDD/F emission factor was 0.188 ng I-TEQ/L fuel, which was comparable to the data issued in US EPA [EPA, Locating and estimating air emissions from sources of dioxins and furans, Office of Air Quality Planning and Standards, Research Triangle Park, NC, DCN No. 95-298130-54-01, 1997] (0.2 ng I-TEQ/L of fuel). Also, the result of the correlations of PCDD/Fs and operational parameters illustrated that the positively significant correlation (r = 0.502, p = 0.048) was found only between PCDD/Fs (I-TEQ) and the flue gas emission temperature (125–157 °C). However, PCDD-TEQ/PCDF-TEQ ratios were statistically significantly associated with the decreased flue gas flow (r = −0.659, p = 0.006), moisture (r = −0.612, p = 0.012) and flue gas temperature (r = −0.503, p = 0.047). For proper environmental management of dioxins, it is necessary to establish a complete emission inventory of PCDD/Fs, and, in particular, the government should pay more attention to power plants to address the information shortage.

In the present study, we investigated the effect of arecoline, a major areca nut alkaloid, on the 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)-induced activation of cytochrome P4501A1 (CYP1A1) in a human hepatoma cell line Huh-7. We treated Huh-7 cells with 10 nM TCDD in the presence of different concentrations of arecoline (50–300 μM). Our results indicated that arecoline attenuated the TCDD-induced CYP1A1 enzyme activation with an inhibitory effect on cell proliferation. By using real-time RT-PCR, we demonstrated that arecoline inhibited the TCDD-induced activations of CYP1A1 and AhR repressor (AhRR) mRNA expression in a similar pattern. Our results revealed that arecoline inhibited AhR mRNA expression with no direct effect on CYP1A1 enzyme activity. Therefore, in our present study, the observed inhibitory effect of arecoline on CYP1A1 activation was not due to the up-regulation of AhRR or direct inhibitory effect on CYP1A1. Taken together, here we have demonstrated that arecoline attenuates the TCDD-induced CYP1A1 activation mainly via down-regulation of AhR expression in human hepatoma cells, suggesting the possible involvement of arecoline in the AhR-mediated metabolism of environmental toxicants in liver.

In utero exposure to polybrominated diphenyl ethers (PBDEs) reduces the number of ovarian follicles in rat females and causes permanent effects on rat males. Little data have been gathered on the associations between PBDEs exposure and birth outcome and female menstruation characteristics in both epidemiological and animal studies. The aim of this study was to examine how PBDEs in breast milk are associated with infant birth outcome and maternal menstruation characteristics. Study participants were healthy women recruited from central Taiwan between December 2000 and November 2001. Twelve congener levels of PBDEs (BDE-17, 28, 47, 66, 85, 99, 100, 138, 153, 154, 183, 209) in 20 breast milk samples were measured by gas chromatography with high resolution mass spectrometer. The mean level of PBDEs in breast milk was 3.93±1.74 ng/g lipid. The estimated PBDE daily intake for a breastfed infant was 20.6 ng/kg b.w./day after delivery. After maternal age, pre-pregnant BMI, and parity were adjusted, increased PBDEs in breast milk was related with decreased birth outcome, particularly for birth weight and length, chest circumference, and Quetelet's index of infants. No significant differences in PBDEs were found between the two groups of menstrual cycle length higher and lower than 30 days after we adjusted for maternal age, pre-pregnant BMI, and parity. In utero exposure to low doses of PBDEs may result in lower birth weight and short or birth length. Our findings are limited based on the low doses of PBDEs and the small sampling size. Keywords: Polybrominated diphenyl ethers, Breast milk, Breastfeeding, Infants, Reproductive effects, Menstruation, Birth outcome, Birth weight, Daily intake

The aim was to determine the body burden of dioxins and polychlorinated biphenyls (PCBs) and whether they are associated with variables influencing reproduction. Our subjects were healthy women (mean age of 29 [SD=4.5]) from central Taiwan. The congeners of dioxins and dioxin-like PCBs in placentas (n=119) were identified using gas chromatography/high resolution mass spectrometry. The median levels of polychlorinated dibenzo-p-dioxins/dibenzofurans and PCBs were 10.2 (geometric mean [GM]: 9.8, 95% confidence interval [95% CI]: 8.8-10.9) and 2.7 (GM: 2.7, 95% CI: 2.3-3.1) pg WHO-TEQ/g lipid, respectively. Total TEQ level in placentas was significantly correlated with mothers' arm circumference (r=0.22, p=0.043). Increased body fat percentage was associated with higher total TEQ level in placentas. After adjustment for maternal age, pre-pregnant body mass index (BMI), and parity, placental dioxin-TEQ level higher in women (age 19 years) with irregular menstrual cycle than in those (age

Our goal was to develop a fast-screening method for measuring dioxin levels in soils. The adenovirus (Ad)-dioxin-responsive (DR) bioassay system (AdEasy-6XDRE-TATA-Luc) combined with a fast-cleanup system was examined under conventional conditions (i.e., with incubation at 37°C) and three alternative conditions [incubation at 37°C with addition of phorbol-12-myristate-13-acetate (PMA), incubation at 33°C, and incubation at 33°C with addition of PMA]. The best conditions for carrying out the Ad-DR bioassay was 33°C and no addition of PMA. The background level of soil dioxins determined by the chemical assay [6.49 ng I-TEQ/kg dry weight (dw)] was well correlated (Pearson's r = 0.873, p < 0.001) with that by the Ad-DR bioassay [expressed in ng bioanalytical equivalents (BEQ) 81.1 ng BEQ/kg dw] (n = 17). When surveyed in contaminated soil samples (n = 114) from industrial areas by the Ad-DR bioassay, dioxin levels were 117, 102, 98.5, and 112 ng BEQ/kg dw, respectively, in northern, central, southern, and eastern Taiwan.

Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-alpha (TNF-alpha), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-alpha-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB). To elucidate the role of GSH in regulation of AP-1, NF-kappaB, and VCAM-1 expression, we employed l-buthionine (S,R)-sulfoximine (BSO), a specific gamma-glutamylcysteine synthetase (gamma-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-alpha-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-kappaB activations by TNF-alpha. Moreover, we found that depletion of GSH would also attenuate the TNF-alpha-induced VCAM-1 expression with a down-regulation of the TNF-alpha-induced NF-kappaB activation and without significant effect on AP-1. On the other hand, the TNF-alpha-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-kappaB activity, suggesting that activation of both AP-1 and NF-kappaB was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-alpha-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-kappaB activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines.

Postnatal exposure to dioxins in breastfed infants occurs mainly during breast-feeding. The exposure to a substantial amount of endocrine disruptors in the early days of life may cause long-term health effects. Test subjects were healthy and primiparous mothers with a mean age of 28 (S.D. = 3.8) in 2001. The PCDD/F congeners were analyzed in the breast milk using gas chromatograph/high resolution mass spectrometry. The mean level of PCDD/Fs was 7.4 pg-WHO-TEQ/g lipid, which is significantly lower than the level found in individuals from other countries. The total PCDD WHO-TEQ levels in breast milk had a significant positive association with maternal age and a slightly negative association with perinatal BMI (body mass index of the period before and after the delivery). The estimated daily intake of 10.5 pg-WHO-TEQ/kg/day from individual breast milk was predicted for a breastfed infant at 6 months of age with proper assumption of 8 kg body weight, 854 g milk per day of consumption, 95% of dioxin absorption rate, and linear decline of dioxin during lactation. Based on the lower WHO-TEQ levels in the breast milk, breast-feeding should still be encouraged and continued in Taiwan.

This study determined PCDD/F and PCB levels in human milk, examined factors associated with levels of contamination, and assessed the infant body burden from breast-feeding. The congeners of PCDD/Fs, dioxin-like PCBs, and indicator PCBs were analyzed by HRGC/HRMS for 36 human milk samples from healthy women, aged 20-35 years, from December 2000 to November 2001 in central Taiwan. Mean levels of WHO-TEQs in human milk were 10.5 (95% CI=8.8-12.2) and 14.5 (95% CI=12.5-16.5) pg-TEQ/g lipid for those29 andor =29 years old, respectively. PCB 138 concentration significantly predicted total WHO-TEQs with r2=0.84 (p0.001). Milk level of dioxin-TEQ was 9.63 pg-TEQ/g lipid (95% CI=7.0-13.2) in those with a yearly income $29,000 compared to 6.3 pg-TEQ/g lipid (95% CI=5.2-7.6) for those whose yearly income was $18,000 per year. Women who reported being Buddhist (64.3 ng/glipid) had significantly higher indicator PCB concentrations than did those who reported being Taoist (35.3 ng/g lipid). The monthly dioxin intake of exclusively breastfed infants decreased with increasing duration of lactation. The cumulative dose of exclusively breastfed infants (76.5 ng TEQ, 95% CI=69.7-83.3) was significantly greater compared to that of formula-fed infants (CI=16.4-17.0) at one year and to that of infants at birth (3.90 ng TEQ, 95% CI=3.6-4.2). Our findings suggest that breast-feeding should be strongly encouraged for infants in Taiwan.

Background Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA. Methodology A meta-analysis of three public microarray datasets was performed to screen for differentially expressed genes (DEGs) in exposure to BPA. The candidate genes of neuronal development were identified from gene ontology analysis in a reconstructed neuronal sub-network, and their gene expressions were determined using real-time PCR in 20 umbilical cord blood samples dichotomized into high and low BPA level groups upon the median 16.8 nM. Principal Findings Among 36 neuronal transcripts sorted from DAVID ontology clusters of 457 DEGs using the analysis of Bioconductor limma package, we found two neuronal genes, sex determining region Y-box 2 (Sox2) and paired box 6 (Pax6), had preferentially down-regulated expression (Bonferroni correction p-value

Losses of polynuclear aromatic hydrocarbons (PAHs) in methylene chloride during evaporation with a stream of nitrogen was systematically studied. The starting sample concentration levels were 0.167 μg/mL and 0.00333 μg/mL for each PAH. These two sets of test solutions were both evaporated from 300 mL to final volumes of 50, 30, 5, 3, and 1 mL, with a constant stream of nitrogen and in a water bath kept at 40°C. Each sample was analyzed by GC-FID. Factors affecting the percentage of analyte recovery include boiling points of analytes, the final sample volume and the starting sample concentration. When the diluted solutions were reduced from 300 mL to 1 mL, the recoveries for PAHs were all higher than 90%. However, when the concentrated solutions were evaporated to 1 mL, recoveries of all analytes dropped below 85%, and naphthalene, the most volatile PAH, dropped to 77.5%. if evaporation was halted to a final volume of 3∼5 mL, the recovery for PAHs in both concentrated and diluted solutions were st...

Our previous studies indicated that zinc induced inflammatory response in both vascular endothelial cells and promonocytes. Here, we asked if other metals could cause the similar effect on vascular endothelial cells and tried to determine its underlying mechanism. Following screening of fifteen metals, zinc and nickel were identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8 induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein expression of myeloid differentiation primary response protein-88 (MyD88), a Toll-like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly attenuated the zinc/nickel-induced inflammatory response, suggesting the critical roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI-095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8 expression and NFκB activation. The same CLI-095 treatment significantly blocked the zinc-induced IL-8 expression, however with no significant effect on the ICAM-1 expression and a minor inhibitory effect on the NFκB activation. The finding demonstrated the differential role of TLR-4 in regulation of the zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in NFκB activation by nickel, but not by zinc. Moreover, inhibition of NFκB by adenovirus-mediated IκBα expression and Bay 11-7025, an inhibitor of cytokine-induced IκB-α phosphorylation, significantly attenuated the zinc/nickel-induced inflammatory responses, indicating the critical of NFκB in the process. The study demonstrates the crucial role of TLRs in the zinc/nickel-induced inflammatory response in vascular endothelial cells and herein deciphers a potential important difference in NFκB activation via TLRs. The study provides a molecular basis for linkage between zinc/nickel exposure and pathogenesis of the metal-related inflammatory vascular disease.

A gasoline powered engine operated on a dynamometer was used to investigate the PAH (Polycyclic Aromatic Hydrocarbons) emission. A 95‐leadfree gasoline (95‐LFG) and a premium leaded gasoline (PLG) were used as power‐fuels. The engine was simulated for the idling condition and for the cruising speeds at 40, 80 and 110 km/hr. The concentrations of 21 individual PAHs in the engine exhaust, gasolines, and the ambient air were determined. Engine exhaust samples were collected by a PAH sampling system, while the ambient air sample was collected by using a standard PS‐1 sampler. Twenty one individual PAHs were analyzed primarily by a gas chromatography/mass spectrometer (GC/MS). Naphthalene (Nap) has the highest concentration in the liquid phase of both 95‐LFG and PLG, in which it accounts for respectively 98.3% and 76.6% of the total PAH. In term of the mean fraction of the total PAHs entering the 95‐LFG and PLG engines, the ambient air contributed less than 0.108% and 0.012%, respectively. Gasoline is...

Atmospheric particle and PAH (Polycyclic Aromatic Hydrocarbons) mass size distributions in both a traffic intersection and a rural site were measured with two MOUDIs (Micro‐orifice Uniform Deposit Impactors) and a NRI (Noll Rotary Impactor) from June 1994 to June 1995 in southern Taiwan. In the ambient air of the traffic intersection, both the total PAHs and total particle mass were found to be with unimodal size distributions, while at the rural site, they were found to be with bimodal size distributions. Twelve PAHs were found to have a significant bimodal‐distribution: Nap, AcPy, Flu, PA, Ant, FL, CYC, BaA, BkF, DBA, BbC and BghiP. The remaining PAHs (Acp, Pyr, CHR, BbF, BeP, BaP, PER, IND, and COR) had a unimodal or unimodal‐like distribution. In the ambient air of the traffic intersection, the cumulative fraction of total PAHs in the particle size range below 1,2.5, 10 and 25 μm, in sequence, were 50.9%, 74.2%, 90.8% and 95.9%, respectively, while those values at the rural site, in sequence,...

Our previous studies found that zinc oxide (ZnO) particles induced expression of intercellular adhesion molecule-1 (ICAM-1) protein in vascular endothelial cells via NF-κB and that zinc ions dissolved from ZnO particles might play the major role in the process. This study aimed to determine if zinc ions could cause inflammatory responses in a human promonocytic leukemia cell line HL-CZ. Conditioned media from the zinc-treated HL-CZ cells induced ICAM-1 protein expression in human umbilical vein endothelial cells (HUVEC). Zinc treatment induced chemokine and inflammatory cytokine release from HL-CZ cells. Inhibition of NFκB activity by over-expression of IκBα in HL-CZ cells did not block the conditioned medium-induced ICAM-1 protein expression in HUVEC cells. Zinc treatment induced activation of multiple immune response-related transcription factors in HL-CZ cells. These results clearly show that zinc ions induce chemokine and inflammatory cytokine release from human promonocytes, accompanied with activation of multiple immune response-related transcription factors. Our in vitro evidence in the zinc-induced inflammatory responses of vascular cells provides a critical linkage between zinc exposure and pathogenesis of those inflammatory vascular diseases.

Our goal was to design a follow-up cohort study for infant exposure to PBDEs. Thirty-five breastfed infants having breast milk PBDE levels were recruited from our cohort at approximately one-year old. Eleven PBDEs (BDE-47, 99, 100, 153, 154, 196, 197, 206, 207, 208, and 209) in breast milk were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. Infant development was determined using the Bayley Scales of Infant and Toddler Development, Third Edition. The mean of ΣPBDEs in breast milk was 7.00 ng/g lipid. Higher ΣPBDEs in breast milk was significantly correlated with a lower score of the cognitive scale (r=−0.369, p=0.029). Increased ΣPBDEs was significantly linked to decreased the adaptive behavior scale (p=0.017). After adjusting for maternal age, pre-pregnant body mass index (BMI), baby ' s sex, gestational age, and infant 's current age for testing Bayley scales, an adjusted odds ratio (OR) (OR=0.966, p=0.035) of the cognitive score in infants with BDE-100 ≥75 percentile was significantly lower compared with the control group (BDE-100

Polybrominated diphenyl ethers (PBDEs) causing thyroidal effects have been demonstrated in in vivo and in vitro studies. PBDEs with structural similarities to thyroid hormones have increased recently, but the health effects for thyroid hormones have not been well studied. The study aimed to determine PBDE levels in cord blood and further to explore associations between prenatal PBDE exposures and thyroid hormones in cord blood. Fifty-four cord blood samples were collected after delivery. Cord-blood levels of BDE-15, 28, 47, 99, 100, 153, 154, and 183 were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. Thyroid hormones were determined by an automated chemiluminescence analyzer. The mean, median, and standard deviation of ΣPBDEs were 4.72, 3.49, and 6.36 ng/g lipid, respectively. To adjust for confounding by maternal age, pre-pregnant BMI and gestational age, stepwise multiple linear regression was used after log(2) transformation of the exposure variables. A doubling of BDE-154 was associated with 0.043 ng/mL lower triiodothyronine (T3) values (adjusted r=-0.245, p=0.043). Likewise a doubling of BDE-153 was associated with 0.143 ng/mL lower free T3 (FT3) values and a doubling of BDE-183 with 0.084 ng/mL lower FT3 values (adjusted r=-0.487, p=0.023). In contrast, the T4 (thyroxine)/T3 ratio increased by 4.93 (adjusted r=0.277, p=0.017) when doubling BDE-100 exposure. No significant associations with BDE-47 or any other of the PBDEs was found. Our findings of an inverse relationship between BDE-153, BDE-154 or BDE-184 and thyroid hormones confirm the results of animal experiments but are in contrast to most epidemiological studies.

A recombinant Huh7-PPRE-Luc cell line for analyzing the peroxisome proliferator response element (PPRE)-driven luciferase activity was established. The cells exhibited a good dose–response induction in PPRE-driven luciferase activity by three subtypes of peroxisome proliferator-activated receptor (PPAR) agonists as well as by a retinoid X receptor agonist, 9-cis-retinoic acid. Among five environmental chemicals tested, benzyl butyl phthalate and bisphenol induced PPRE-driven luciferase activation in Huh7-PPRE-Luc cells and caused adipogenic differentiation of 3T3-L1 cells. This recombinant Huh7-PPRE-Luc cell line would be useful for screening potential environmental obesogens with PPAR activity.

To investigate the possible involvement of betel-quid chewing in adipocyte dysfunction, we determined the effects of arecoline, a major alkaloid in areca nuts, on adipogenic differentiation (adipogenesis), lipolysis, and glucose uptake by fat cells. Using mouse 3T3-L1 preadipocytes, we showed that arecoline inhibited adipogenesis as determined by oil droplet formation and adipogenic marker gene expression. The effects of arecoline on lipolysis of differentiated 3T3-L1 adipocytes were determined by the glycerol release assay, indicating that arecoline induced lipolysis in an adenylyl cyclase-dependent manner. The diabetogenic effects of arecoline on differentiated 3T3-L1 adipocytes were evaluated by the glucose uptake assay, revealing that > or = 300 microM arecoline significantly attenuated insulin-induced glucose uptake; however, no marked effect on basal glucose uptake was detected. Moreover, using 94 subjects that were randomly selected from a health check-up, we determined the association of betel-quid chewing with hyperlipidemia and its related risk factors. Hyperlipidemia frequency and serum triglyceride levels of betel-quid chewers were significantly higher than those of non-betel-quid chewers. In this study, we demonstrated that arecoline inhibits adipogenic differentiation, induces adenylyl cyclase-dependent lipolysis, and interferes with insulin-induced glucose uptake. Arecoline-induced fat cell dysfunction may lead to hyperlipidemia and hyperglycemia/insulin-resistance. These findings provide the first in vitro evidence of betel-quid chewing modulation of adipose cell metabolism that could contribute to the explanation of the association of this habit with metabolic syndrome disorders.

The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P0.01) and fish oil capsules (beta = 0.39, P0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P0.01) and processed fish products (beta = 0.59, P0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure.

The aim of the present study is to determine whether levels of polybrominated diphenyl ethers in breast milk in the general population are associated with demographic parameters, socioeconomic status, lifestyle factors, and occupational exposure. Forty-six participants are randomly selected from healthy women recruited between April 2007 and April 2008 from local hospitals in southern Taiwan. Thirty PBDE isomers in breast milk are analyzed using a gas chromatograph with a high resolution mass spectrometer. The mean+/-standard deviation of Sigma PBDEs in breast milk is 3.59+/-1.07 ng/g lipid. Our current value of Sigma PBDEs in breast milk is 0.7-fold lower compared to the past value in our previous study between 2000 and 2001. Higher levels of Sigma PBDEs might be significantly associated with older maternal age and maternal age of the present study is between 22 and 42 years old. Levels of Sigma PBDEs and certain PBDEs in breast milk are not correlated with maternal pre-pregnant BMI (Body mass index), parity, and lipid contents of breast milk. The Sigma PBDEs level in breast milk is lower in more educated women after controlling for age and pre-pregnancy BMI in our subjects. The main factors associated with Sigma PBDEs in breast milk are age and education level among the binary variables of demographic, socioeconomic, and lifestyle characteristics in this report. The exploratory relationships are found between PBDEs in breast milk and age, education level, or occupational exposure due to small sampling size.

The aim of this study was to examine levels of PBDEs in breast milk associated with seafood consumptions of Taiwanese mothers. Our participants were selected from healthy women recruited between December 2000 and November 2001 from a medical center in central Taiwan. The congeners of PBDEs in 20 milk samples were analyzed by a gas chromatograph with a high resolution mass detector. The mean level of BDE47 in breast milk from mothers with pre-pregnant BMI22.0kg/m2 had a significantly higher magnitude compared to those with pre-pregnant BMIor = 22.0kg/m2 (1.59 vs. 0.995ng/g lipid, p=0.041). We did not find significant correlations between PBDEs exposure levels and women's age, parity, blood pressure, annual household income, and education level. Women who ate more fish and meat did not show significantly higher PBDE levels than those who ate less, but a significant difference in PBDE levels was demonstrated between the higher (2.15ng/g lipid) and lower (3.98ng/g lipid) shellfish consuming subjects (p=0.002) after an adjustment for the confounders. The ratios of PCB153/BDE47, PCB153/BDE153, and PCB153/PBDEs were significantly correlated with frequent consumption of fish and shellfish. The PCB153/BDE153 ratio was not associated with the other dietary habits (i.e. meat). The ratios of PCB153/PBDEs may therefore be a new indicator for exposure as a result of seafood consumption.

Dioxin-responsive element-mediated chemical activated luciferase expression (DRE-CALUX) is one of alternative bioassays for the determination of dioxin levels. We have previously established a DRE-CALUX cell line, Huh7-DRE-Luc, by using stable transfection of Huh-7 cells with a reporter plasmid (4xDRE-TATA-Luc) carrying a DRE-driven firefly luciferase gene. It was also shown that arecoline, a major areca nut alkaloid, inhibited the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cytochrome P450 1A1 (CYP1A1) activation in Huh-7 cells. The TCDD-activated aryl hydrocarbon receptor (AhR) induces the DRE-CALUX activation and CYP1A1 gene expression via binding to DRE in promoter regions of these dioxin-responsive genes. In the present study, the effect of arecoline on the TCDD-induced activation of DRE-CALUX and CYP1A1 enzyme in Huh7-DRE-Luc and Huh-7 cells, respectively, was examined. It was found that arecoline inhibited TCDD-induced CYP1A1 activation and however enhanced TCDD-induced DRE-CALUX activation. This finding indicates the differential effect of arecoline on the endogenous dioxin-responsive CYP1A1 and on a stably transfected DRE-driven reporter in human hepatoma cells. The present study suggests that induction of DRE-CALUX alone does not necessarily parallel with endogenous CYP1A1 gene expression, and that the reporter assay may detect interactions that are not functional in endogenous gene.