The measurement of bisphenol A and its analogues, perfluorinated compounds in twenty species of freshwater and marine fishes, a time-trend comparison and human health based assessment.

Our previous study in 2011 reported the detection of BPA and PFAAs in 20 species of marine and freshwater fishes. With an emerging evidence to suggest the metabolic-disrupting effects of BPA/PFAAs in animals, the present study was aimed to provide a time-trend analysis to determine the current concentrations of PFAAs and BPA in 20 commercially available Hong Kong species of fishes. Since the manufacture and use of BPA is being prohibited in most nations, the introduction of BPA alternatives has recently been incorporated in the markets. Therefore, the concentrations of BPB, BPF and BPS were determined. In the present study, all freshwater and seawater fish samples showed quantified concentrations [>Limit of Quantification (LOQ<0.5ng/g)] of BPA. BPF was detected in some marine (yellow seafin, bigeye, goldspotted rabbitfish, snubnose pompano, tongue sole, Bleeker's grouper and orange-spotted grouper) and freshwater fishes (mud carp, crucian carp, tilapia, catfish, mandarin fish, grass carp, grey mullet and spotted snakehead). Two of the compounds, BPS and BPB could only be identified in the marine fishes (snubnose pompano, yellow seafin). In PFAA analysis, PFOA, PFDA, PFOS, PFUdA and PFDoA were found in most of the marine and freshwater fishes. PFOS and PFOA were shown to be the two predominant PFAAs in fishes. On the basis of the measured concentrations of bisphenols, BPs (BPA, BPB, BPF, BPS) and PFAAs, the average daily intake for BPs (20.5-31.5ng/kgb.w./day) and PFAAs (1.17-1.83ng/kgb.w./day) were calculated and found to be lower than values of tolerable daily intake (TDI) established in Europe. However, as compared with our previous study in 2011, the present study revealed an approximate 10-fold increase in the concentrations of BPA in the fish samples. Although the hazard ratio of consuming fishes for BPA and PFAA exposure is expected to remain low, possible additive metabolic-disrupting effect of BPA and its analogues as well PFAAs should be taken into consideration for human health risk assessment.

iSlide: a 'big picture' interactive teledermatopathology e-learning system.

BACKGROUND: Dermatopathology training is often limited by facilities and a dearth of specialists. Advancements in information and communication technologies have made possible the adoption of innovative learning techniques, especially in places where specialists are lacking. OBJECTIVES: To implement and evaluate the performance of the iSlide system, which is an interactive dermatopathology training platform (http://scope.tmu.edu.tw/islide2/). METHODS: Fifty-two cases representing a variety of dermatopathology conditions and complications were used to set up the iSlide system, and virtual slides of these cases were produced. Medical students from the Dermatology Department of Taipei Medical University were taught to use the system. Performance of the system was evaluated and validated using questionnaires, the first comprising 20 questions and the second a shorter, six-question telephone-based survey on 15 of the 96 interns. Twenty cases prepared by the iSlide system were also presented at an international dermatopathology conference and evaluated by conference participants. RESULTS: Ninety-six students and 72 experts participated in the study. Ninety-two per cent of the students and 98% of the experts found the iSlide system to be a useful tool for learning dermatopathology. Of these, 82% of the students and 63% of the experts felt that iSlide was easy to use. CONCLUSIONS: iSlide is useful for dermatopathology. As only 82% of the student evaluators and 63% of the expert evaluators found the system easy to use, further work has to be done to improve the iSlide interface to make the system more user friendly.

Chemical and biological characterization of air particulate matter 2.5, collected from five cities in China.

Fifteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 samples collected in five different cities (Hong Kong (HK), Guangzhou (GZ), Xiamen (XM), Xi'an (XA) and Beijing (BJ)) in China in the winter 2012-13 [corrected] were analyzed by gas chromatography-mass spectrometry. The biological effects of organic extracts were assayed using the human bronchial epithelial cells BEAS-2B. All sixteen priority PAHs can be found in the PM2.5 samples of XA and BJ, but not in HK, GZ and XM, demonstrating the differential spatial source and distribution of PAHs. Our results showed that the total PAHs ranged from 3.35 to 80.45 ng/m(3) air, leading by BJ, followed by XA, XM, GZ and HK. In the cell culture study, transcript levels of pro-inflammatory cytokine interleukin-6 (IL-6), CYP1A1 and CYP1B1 were found to be induced in the treatment. The cells exposed to extracts from XA and BJ demonstrated significant migratory activities, indicating a sign of increase of tumorigenicity.

Partitioning behavior of perfluorinated compounds between sediment and biota in the Pearl River Delta of South China.

Surface sediment and biota were collected from 12 sampling sites - seven along the Pearl River Delta and five along the Hong Kong coastline. Perfluorinated compound (PFC) concentrations were detected using a high-performance-liquid-chromatogram-tandem-mass-spectrometry system. Analytical results indicated that the total PFC concentrations were in the range of 0.15-3.11 ng/g dry weight in sediments, while the total PFC concentrations in oyster and mussel samples were between 0.46-1.96 and 0.66-3.43 ng/g wet weight, respectively. The major types of PFCs detected in the sediment samples were perfluorooctanesulfonic acid (PFOS) and perfluorobutanoic acid (PFBA), with concentrations ranging from low limits of quantification to 0.86±0.12 ng/g dry weight and 1.50±0.26 ng/g dry weight, respectively. In bivalve samples, PFOS was the dominant contaminant with concentrations ranging from 0.25±0.09 to 0.83±0.12 ng/g wet weight in oysters and 0.41±0.14 to 1.47±0.25 ng/g wet weight in mussels. An increase in PFC concentration was found to be correlated with increased human population density in the study areas.

Role of non-receptor protein tyrosine kinases in spermatid transport during spermatogenesis.

Non-receptor protein tyrosine kinases are cytoplasmic kinases that activate proteins by phosphorylating tyrosine residues, which in turn affect multiple functions in eukaryotic cells. Herein, we focus on the role of non-receptor protein tyrosine kinases, most notably, FAK, c-Yes and c-Src, in the transport of spermatids across the seminiferous epithelium during spermatogenesis. Since spermatids, which are formed from spermatocytes via meiosis, are immotile haploid cells, they must be transported by Sertoli cells across the seminiferous epithelium during the epithelial cycle of spermatogenesis. Without the timely transport of spermatids across the epithelium, the release of sperms at spermiation fails to occur, leading to infertility. Thus, the molecular event pertinent to spermatid transport is crucial to spermatogenesis. We provide a critical discussion based on recent findings in this review. We also provide a hypothetical model on spermatid transport, and the role of non-receptor protein tyrosine kinases in this event. We also highlight areas of research that deserve attention by investigators in the field.

Early embryogenesis in zebrafish is affected by bisphenol A exposure.

Exposure of a developing embryo or fetus to endocrine disrupting chemicals (EDCs) has been hypothesized to increase the propensity of an individual to develop a disease or dysfunction in his/her later life. Although it is important to understand the effects of EDCs on early development in animals, sufficient information about these effects is not available thus far. This is probably because of the technical difficulties in tracing the continuous developmental changes at different stages of mammalian embryos. The zebrafish, an excellent model currently used in developmental biology, provides new insights to the field of toxicological studies. We used the standard whole-mount in situ hybridization screening protocol to determine the early developmental defects in zebrafish embryos exposed to the ubiquitous pollutant, bisphenol A (BPA). Three stages (60-75% epiboly, 8-10 somite, and prim-5) were selected for in situ screening of different molecular markers, whereas BPA exposure altered early dorsoventral (DV) patterning, segmentation, and brain development in zebrafish embryos within 24 hours of exposure.

Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals.

INTRODUCTION: Exposure to endocrine disrupting chemicals (EDCs) has recently been linked to declining fertility in men in both developed and developing countries. Since many EDCs possess intrinsic estrogenic or androgenic activities, thus, the gonad is one of the major targets of EDCs. AREAS COVERED: For the past 2 decades, studies found in the literature regarding the disruptive effects of these EDCs on reproductive function in human males and also rodents were mostly focused on oxidative stress-induced germ cell apoptosis, disruption of steroidogenesis, abnormal sperm production and disruption of spermatogenesis in particular cell adhesion function and the blood-testis-barrier (BTB) function. Herein, we highlight recent findings in the field illustrating testis-specific proteins are also targets of EDCs. EXPERT OPINION: This information should be helpful in developing better therapeutic approach to manage ECD-induced reproductive toxicity. This information is also helpful to identify potential targets for male contraceptive development.

Blood plasma concentrations of endocrine disrupting chemicals in Hong Kong populations.

In this study we report the human plasma concentrations of some common endocrine disrupting chemicals (EDCs) in the Hong Kong population. We have analyzed 153 plasma samples for the contaminants by methods involving labeled standards spiked into the samples. Quantification was performed using high performance liquid chromatography tandem mass spectrometry for bisphenol-A (BPA) and perfluorinated compounds (PFCs), and gas chromatography mass spectrometry methods for phthalates. We found BPA, several types of PFCs and phthalates in over 90% of the plasma samples. Perfluorooctane sulfonate (PFOS) was the dominant PFC, followed by perfluroroctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS). Eight out of ten phthalates were detected, with bis(2-ethylhexyl) phthalate (DEHP) as the most abundant, followed by bis(2-methoxyethyl) phthalate (DMEP) and dioctyl phthalate (DnOP). The levels of PFOS, PFOA, PFHxS and perfluorohexanoic acid (PFHxA) were significantly higher in the male plasma samples (p<0.05), while the mean plasma levels of DEHP and n-butyl benzyl phthalate (BBP) were significantly higher in the young age group (p<0.02). The presence of the selected EDCs in human blood plasma indicates common exposure routes among different population cohorts. Although the plasma levels of the EDCs were comparable to other countries, regular monitoring of human blood EDC contamination levels is necessary to provide a time-trend database for the estimation of exposure risk and to formulate appropriate public health policy.

PFOS-induced hepatic steatosis, the mechanistic actions on ß-oxidation and lipid transport.

BACKGROUND: Perfluorooctane sulfonate (PFOS) was produced by various industries and was widely used in diverse consumer products. Human sample analysis indicated PFOS contamination in body fluids. Animal studies revealed that PFOS tends to accumulate in livers and is able to induce hepatomegaly. However the underlying mechanism of PFOS-elicited hepatotoxicity has not yet been fully addressed. The objective of this study is to identify the cellular target of PFOS and to reveal the mechanisms of PFOS-induced toxicity. METHODS: In this study, mature 8-week old male CD-1 mice were administered 0, 1, 5 or 10 mg/kg/day PFOS for 3, 7, 14 or 21 days. Histological analysis of liver sections, and biochemical/molecular analysis of biomarkers for hepatic lipid metabolism were assessed. RESULTS: PFOS-induced steatosis was observed in a time- and dose-dependent manner. The gene expression levels of fatty acid translocase (FAT/CD36) and lipoprotein lipase (Lpl) were significantly increased by 10 and/or 5 mg/kg PFOS. Serum levels of very-low density lipoprotein were decreased by 14 days of PFOS exposure (p<0.05). The rate of mitochondrial ß-oxidation was also found to be significantly reduced, leading to the restriction of fatty acid oxidation for energy production. CONCLUSION: Taken together, the disturbance of lipid metabolism leads to the accumulation of excessive fatty acids and triglycerides in hepatocytes. GENERAL SIGNIFICANCE: Since PFOS-elicited pathological manifestation resembles one of the most common human liver diseases-nonalcoholic fatty liver disease, environmental exposure to PFOS may attribute to the disease progression.

Testicular signaling is the potential target of perfluorooctanesulfonate-mediated subfertility in male mice.

Perfluorooctanesulfonate (PFOS) was produced and used by various industries and in consumer products. Because of its persistence, it is ubiquitous in air, water, soil, wildlife, and humans. Although the adverse effects of PFOS on male fertility have been reported, the underlying mechanisms have not yet been elucidated. Here, for the first time, the effects of PFOS on testicular signaling, such as gonadotropin, growth hormone, insulin-like growth factor, and inhibins/activins were shown to be directly related to male subfertility. Sexually mature 8-wk-old CD1 male mice were administered by gavages in corn oil daily with 0, 1, 5, or 10 mg/kg PFOS for 7, 14, or 21 days. Serum concentrations of testosterone and epididymal sperm counts were significantly lower in the mice after 21 days of the exposure to the highest dose compared with the controls. The expression levels of testicular receptors for gonadotropin, growth hormone, and insulin-like growth factor 1 were considerably reduced on Day 21 in mice exposed daily to 10 or 5 mg/kg PFOS. The transcript levels of the subunits of the testicular factors (i.e., inhibins and activins), Inha, Inhba, and Inhbb, were significantly lower on Day 21 of daily exposure to 10, 5, or 1 mg/kg PFOS. The mRNA expression levels of steroidogenic enzymes (i.e., StAR, CYP11A1, CYP17A1, 3beta-HSD, and 17beta-HSD) were notably reduced. Therefore, PFOS-elicited subfertility in male mice is manifested as progressive deterioration of testicular signaling.

Effects of perinatal exposure to bisphenol A and di(2-ethylhexyl)-phthalate on gonadal development of male mice.

PURPOSE: In this study, we investigated the effects of maternal transfer of bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP) during gestational and weaning periods on gonadal development of male offspring. METHODS: Pregnant CD-1 mice were administered by gavages in corn oil with 0.1, 1, or 10 mg/kg/day of BPA and DEHP from gestational days (GD1-21) to the weaning period (postnatal days (PND) 1-21). RESULTS: Our data indicated that the exposure significantly reduced the male-to-female sex ratio and the sizes of the gonads of male pups as recorded at PND15. The testes of the perinatally exposed male pups were developed less and the expression levels of testicular anti-mullerian hormone, androgen receptor, cyclin A, and StAR were significantly lesser than the control male pups. The less developed testes were accompanied with significant reductions in the expression levels of Gnrh and Fsh at the hypothalamic-pituitary levels. The negative effects were found to be persistent in the sexually mature pups at PND42. CONCLUSION: Our data reveal that the maternal transfer of BPA and DEHP may impose negative influence on the development and functions of the reproductive system of male pups.

Histone deacetylase inhibitor-induced cellular apoptosis involves stanniocalcin-1 activation.

Our previous studies have demonstrated the involvement of HIF-1 and p53 in the regulation of stanniocalcin-1 (STC1) gene transcription in human cancer cells. In this study, we reported that the treatment of human colon adenoma HT29 cells with a histone deacetylase (HDAC) inhibitor (i.e. trichostatin A, TSA) induced both cellular apoptosis and STC1 expression. The activation of STC1 expression was also observed in other TSA-treated human cancer cells (i.e. SKOV3, CaCo-2, Jurkat and CNE-2 cells). STC1 mRNA was rapidly induced within 4 h in TSA-treated HT29 cells, and was found to be transcriptionally regulated and was independent of new protein synthesis as revealed by ActD and CHX treatment respectively. The induction was correlated with increased cellular levels of acetyl histone H3 and H4 and acetyl NFkappaB. Chromatin immunoprecipitation (ChIP) assay showed the increased binding of acetyl histone H3 and H4 to STC1 promoter in the TSA-treated cells. A cotreatment of HT29 cells with a NFkappaB inhibitor (parthenolide) significantly inhibited the TSA-induced cellular levels of acetyl NFkappaB p65 and abolished the stimulation of STC1 gene expression. ChIP assay also demonstrated that TSA treatment increased while TSA/parthenolide cotreatment decreased NFkappaB p65 binding to STC1 gene promoter. In the STC1-luciferase promoter construct (1 kb) study, the data implied that the promoter can be activated by TSA treatment. Interestingly, the promoter region contains 2 putative NFkappaB binding sites. Consistent with the STC1mRNA expression data, TSA/parthenolide cotreatment also significantly inhibited the TSA-induced STC1 promoter-driven luciferase activity. Importantly, TSA-induced apoptotic process was found to be significantly reduced by the silencing of STC1 expression. This is the first study to show that histone hyper-acetylation and the recruitment of activated NFkappaB stimulated STC1 gene expression. In addition, our results support the notion that STC1 is a pro-apoptotic factor.