Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Synergistic Anti-Tumor Effects of Combination of Photodynamic Therapy and Arsenic Compound in Cervical Cancer Cells: In Vivo and In Vitro Studies

The effects of As4O6 as adjuvant on photodynamic therapy (PDT) were studied. As4O6 is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As4O6 alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% (P<0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As4O6 for inhibition of cervical cancer cell growth

An Improved Prediction Model for Ovarian Cancer Using Urinary Biomarkers and a Novel Validation Strategy

This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples withOC(mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772&ndash;0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714&ndash;0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool

Thyroid Hormone-Disrupting Potentials of Major Benzophenones in Two Cell Lines (GH3 and FRTL-5) and Embryo-Larval Zebrafish

Benzophenones (BPs) have been widely used in personal care products (PCPs) such as UV protectants. Sex endocrine-disrupting effects have been documented for some BPs, but, significant knowledge gaps are present for their thyroid-disrupting effects. To investigate the thyroid-disrupting potential of BPs, a rat pituitary (GH3) and thyroid follicle (FRTL-5) cell line were employed on six BPs, i.e., benzophenone (BP), benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), and benzophenone-8 (BP-8). Subsequently, zebrafish (Danio rerio) embryo exposure was conducted for three potent BPs that were identified based on the transcriptional changes observed in the cells. In GH3 cells, all BPs except BP-4 down-regulated the <i>Tshβ</i>, <i>Trhr</i>, and <i>Trβ</i> genes. In addition, some BPs significantly up-regulated the <i>Nis</i> and <i>Tg</i> genes while down-regulating the <i>Tpo</i> gene in FRTL-5 cells. In zebrafish embryo assay conducted for BP-1, BP-3, and BP-8, significant decreases in whole-body T4 and T3 level were observed at 6 day postfertilization (dpf). The up-regulation of the <i>dio1</i> and <i>ugt1ab</i> genes in the fish suggests that decreased thyroid hormones are caused by changing metabolism of the hormones. Our results show that these frequently used BPs can alter thyroid hormone balances by influencing the central regulation and metabolism of the hormones

Gene expression profiles of TC-1 cells treated with 0.15 ug/ml Radachorin/PDT and/or 3 uM of As₄O₆ for 1 day.

<p>Gene expression profiles of TC-1 cells treated with 0.15 ug/ml Radachorin/PDT and/or 3 uM of As₄O₆ for 1 day.</p

Hierarchical cluster analysis.

<p>(A) All the data were median centred and clustered using a hierarchical clustering. A cluster image representing 63 of the genes is shown in matrix format, where rows represent individual genes and columns represent each assay. Each cell in the matrix represents the expression level of a gene in an individual assay. Red and green cells reflect high and low expression levels, respectively. (B) Ten genes (p53 and NEAT pathways) showing statistically significant differences in three groups are shown as a cluster image. (C) MAPK pathway as a cluster image. (D) Cytokine-cytokine receptor interaction pathway. (E) Focal adhesion pathway. (F) Cell adhesion pathway.</p

Cell growth inhibition effects of photodynamic therapy and As₄O₆.

<p>(A) TC-1 cells (3×10³) were cultured in 12-well plates in triplicate overnight and treated with different concentrations of Radachlorin and PDT (6.25 J/cm²) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038583#s4" target="_blank">Materials and Methods</a>. After PDT, the cells were cultured for a predetermined time. (B) Inhibition effects of cell growth of As₄O₆ on TC-1 cells. TC-1 cells were cultured and treated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038583#s4" target="_blank">Materials and Methods</a>. After As₄O₆ treatment, the cells were cultured for a predetermined time. Cell viability was determined based on the MTT assay. (C) <i>In vitro</i> cell growth inhibitory effects of As₄O₆ plus Radachlorin/PDT on TC-1 cells. TC-1 cells were cultured with 3 uM of As₄O₆ and different doses of Radachlorin/PDT for 1 day, as described above. Cell viability was determined based on the MTT assay. Each bar represents a mean [± SD (vertical line)] of three replicates per dose (<i>n</i> = 3). * and #: significantly different (<i>P</i><0.05) from the control and the PDT by the student’s t-test. (D) Morphological changes of TC-1 cells. TC-1 cells were treated with 0.15 ug/ml Radachlorin/PDT or/and 3 uM of As₄O₆ for 1 day. Cells were then viewed under microscope. Pictures were taken with phase contrast microscopy at X300. (a) non-treated; (b) 0.15 ug/ml Radachlorin/PDT alone; (c) 3 uM As₄O₆ alone; (d) 3 uM As₄O₆ plus 0.15 ug/ml Radachlorin/PDT.</p

Differences in Nutritional Intake, Total Body Fat, and BMI Score between Twins

The present study aimed to investigate the coincidence of obesity and nutritional intake in monozygotic twins compared to dizygotic twins. The data from the Korean Genome and Epidemiology Study (KoGES) from 2005 through 2014 were analyzed. Participants &ge; 20 years old were enrolled. The 1006 monozygotic twins and 238 dizygotic twins were analyzed for differences in self-reported nutritional intake, total body fat, and body mass index (BMI) using a linear regression model. The estimated values (EV) with 95% confidence intervals (95% CI) of the difference in dietary intake, total body fat, and BMI score were calculated. The monozygotic twin group and the dizygotic twin group showed similar differences in nutritional intake, DEXA fat, and BMI (all p &gt; 0.05). The differences in nutritional intake of total calories and carbohydrates were lower in the monozygotic twin group than in the dizygotic twin group (all p &lt; 0.05). The differences in total body fat were lower in monozygotic twins than in dizygotic twins (adjusted EV = 2427.86 g, 95% CI = 1777.19&ndash;3078.53 and adjusted EV = 1.90%, 95% CI = 1.33&ndash;2.46). Monozygotic twins had more similar dietary habits for total calories and carbohydrate intake. Other nutritional factors did not show differential similarity between monozygotic and dizygotic twins. Total body fat was more concordant in monozygotic twins