Chun-Yu Chuang

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.

Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine: influence of taxi driving, smoking and areca chewing

Nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons are common air pollutants generated from automobile exhaust and cigarette smoke. This study was to investigate urinary 8-hydroxydeoxyguanosine (8-OHdG) as an effective biomarker on DNA damage from traffic exhaust and/or smoking in exposed and non-exposed individuals. With subject consents, the levels of plasma NOx, urinary 1-hydroxypyrene (1-OHP) and 8-OHdG were determined for 95 male taxi drivers and 75 male community residents as the reference group. After adjusting for associate variables, there was a significant correlation between the levels of urinary 8-OHdG and 1-OHP but not NOx. The average level of urinary 8-OHdG was significantly higher in drivers than in community men (13.4+/-4.7 vs. 11.5+/-4.7 microg/g creatinine in mean+/-standard deviation). Compared with non-smoking community men, the multivariate logistic regression showed that the odds ratios (OR) of having elevated levels of urinary 8-OHdG (greater than the overall median value, 12.1 microg/g creatinine) were 6.6 (95% confidence interval (CI)=2.1-20.8) for smoking community men, 5.0 (95% CI=1.7-14.7) for non-smoking taxi drivers and 4.6 (95% CI=1.4-15.0) for smoking taxi drivers. Higher risk was also observed for areca quid chewers compared with non-chewers (OR=1.6; 95% CI=1.1-3.6). In conclusion, taxi driving and smoking may contribute independently to elevated DNA damage using urinary 8-OHdG levels as a sensitive biomarker. This effect is most potent on heavy smokers.

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.

Associating emergency room visits with first and prolonged extreme temperature event in Taiwan: A population-based cohort study

The present study evaluated emergency room visit (ERV) risks for all causes and cardiopulmonary diseases associated with temperature and long-lasting extreme temperatures from 2000 to 2009 in four major cities in Taiwan. The city-specific daily average temperatures at the high 95th, 97th, and 99th percentiles, and the low 10th, 5th, and 1st percentiles were defined as extreme heat and cold. A distributed lag non-linear model was used to estimate the cumulative relative risk (RR) of ERV for morbidities associated with temperatures (0 to 3-day lags), extreme heat and cold lasting for 2 to 9 days or longer, and with the annual first extreme heat or cold event after controlling for covariates. Low temperatures were associated with slightly higher ERV risks than high temperatures for circulatory diseases. After accounting for 4-day cumulative temperature effect, the ERV risks for all causes and respiratory diseases were found to be associated with extreme cold at the 5th percentile lasting for >8 days and 1st percentile lasting for >3 days. The annual first extreme cold event of 5th percentile or lower temperatures was also significantly associated with ERV, with RRs ranging from 1.09 to 1.12 for all causes and from 1.15 to 1.26 for respiratory diseases. The annual first extreme heat event of 99th percentile temperature was associated with higher ERV for all causes and circulatory diseases. Annual first extreme temperature event and intensified prolonged extreme cold events are associated with increased ERVs in Taiwan.

Silver nanoparticles affect on gene expression of inflammatory and neurodegenerative responses in mouse brain neural cells.

Silver nanoparticles (AgNPs) have antibacterial characteristics, and currently are applied in Ag-containing products. This study found neural cells can uptake 3-5 nm AgNPs, and investigated the potential effects of AgNPs on gene expression of inflammation and neurodegenerative disorder in murine brain ALT astrocytes, microglial BV-2 cells and neuron N2a cells. After AgNPs (5, 10, 12.5 μg/ml) exposure, these neural cells had obviously increased IL-1β secretion, and induced gene expression of C-X-C motif chemokine 13 (CXCL13), macrophage receptor with collagenous structure (MARCO) and glutathione synthetase (GSS) for inflammatory response and oxidative stress neutralization. Additionally, this study found amyloid-β (Aβ) plaques for pathological feature of Alzheimers disease (AD) deposited in neural cells after AgNPs treatment. After AgNPs exposure, the gene expression of amyloid precursor protein (APP) was induced, and otherwise, neprilysin (NEP) and low-density lipoprotein receptor (LDLR) were reduced in neural cells as well as protein level. These results suggested AgNPs could alter gene and protein expressions of Aβ deposition potentially to induce AD progress in neural cells. Its necessary to take notice of AgNPs distribution in the environment.

Quantification of Interleukin-6 in cell culture medium using surface plasmon resonance biosensors

Interleukin (IL)-6, a multifunctional cytokine, is widely used as an index for illnesses such as inflammatory and autoimmune disorders, coronary artery disease, neurological disease, and gestational problems. It is thus very important to be able to precisely quantify the level of IL-6 for disease diagnosis and any subsequent therapy. Surface plasmon resonance (SPR) biosensors are sensitive in detecting the interaction between biomolecules by sensing the changes in the refractive index on the sensor chip. This study investigated the SPR technique to determine the IL-6 secretion of human fibroblast MRC5-CVI cells induced by lipopolysaccharide (LPS). To reduce non-specific binding, a mixed self-assembled monolayer of mercaptoundecanoic acid (MUA) and mercaptohexanol (MCH) was attached to the sensor, and then used for IL-6 determination using a sandwich type immunoassay. In addition, two antibody immobilization methods were applied to the sensor surface-direct immobilization and indirect immobilization via protein G affinity. The results demonstrated that the direct immobilization method had a better antibody binding capacity on the sensor surface. The level of cellular IL-6 secretion detected by the SPR biosensor showed a consistent correlation with the commercial kit of IL-6 enzyme-linked immunosorbent assay.

Prenatal diagnosis of de novo proximal interstitial deletion of 14q associated with cebocephaly.

We report on the prenatal diagnosis of a case of cebocephaly, alobar holoprosencephaly, and microcephaly associated with a de novo proximal interstitial deletion of the long arm of chromosome 14: del(14)(q13q21.1) or (q13q21.2). This is the third case of holoprosencephaly in association with a deletion in this region. The present report concerns the association between prenatal craniofacial development, a holoprosencephaly locus, and the chromosomal segment 14q13.

Two-sided effect of Cordyceps sinensis on dendritic cells in different physiological stages

Cordyceps sinensis (CS), a Chinese tonifying herb, has been widely used for centuries in Asian countries as a medicine and a health supplement. Although ample evidence indicates that CS can modulate immune responses, the functional effect of CS on dendritic cells (DCs) is still unclear. This study examines how CS affects human monocyte‐derived DCs in two physiological states: naïve and LPS‐induced inflammatory. Our experimental results demonstrate that CS acts as an activator and maturation inducer of immature DCs by stimulating the expression of costimulatory molecules and proinflammatory cytokines by DCs, enhancing the DC‐induced, allogeneic T cell proliferation, and reducing the endocytic ability of DCs. In contrast, CS suppresses the LPS‐induced, inflammatory response by decreasing the LPS‐induced expression of costimulatory molecules and proinflammatory cytokines by DCs. CS also suppresses the LPS‐induced, DC‐elicited, allogeneic T cell proliferation and shifts the LPS‐activated, DC‐driven Th1 response toward a Th2 response. These results demonstrate that CS differentially regulates the DC activities according to the presence or absence of the inflammatory signs. Restated, with the lack of an ongoing inflammatory environment, CS primes DCs toward a Th1‐type immunity, whereas in a potential inflammatory reaction, CS balances the over‐reactivity of elicited Th1 immunity. This investigation illustrates the Yin‐Yang balancing effects of CS as a medicine and a health supplement.

Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway.

In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.

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.