Effect of TBT exposure on Na⁺-K⁺-ATPase enzyme activity in the brain of common carp (<i>Cyprinus carpio</i>).

<p>Data are presented as the mean ± S.D., <i>n</i> = 6 for each data point. ACT- acetone, E1-75 ng/L, E2-0.75 μg/L, E3-7.5 μg/L. Significant differences compared with control values are indicated by * <i>p</i><0.05, ** <i>p</i><0.01.</p

Integrated biomarker response (IBR) of all parameters measured in the fish brain after chronic exposure to TBT.

<p>ACT- acetone, E1-75 ng/L, E2-0.75 μg/L, E3-7.5 μg/L.</p

Correlation coefficients among the biochemical parameters measured in the brain of common carp (<i>Cyprinus carpio</i>) after long-term exposure to TBT.

<p>Notes: TBT, tributyltin; MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase; AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide.</p><p>Correlation coefficients among the biochemical parameters measured in the brain of common carp (<i>Cyprinus carpio</i>) after long-term exposure to TBT.</p

Effects of TBT on neurological parameters in the brain of common carp (<i>Cyprinus carpio</i>).

<p>Notes: AChE, acetylcholinesterase, U/mg protein; MAO, monoamine oxidase, U/mg protein; NO, nitric oxide, mmol/mg protein. ACT- acetone, E1-75 ng/L, E2-0.75 μg/L, E3-7.5 μg/L. Data are means ± S.D., <i>n</i> = 6. Significant differences compared with control values are presented by:</p><p>* <i>p</i><0.05</p><p>** <i>p</i><0.01</p><p>Effects of TBT on neurological parameters in the brain of common carp (<i>Cyprinus carpio</i>).</p

Two-way ANOVA of variance for the effects of TBT concentrations (TBT) and exposure time (Time) on parameters measured in the brain of common carp (<i>Cyprinus carpio</i>) after long-term exposure to TBT.

<p>Notes: Data were expressed by significant value.</p><p>Two-way ANOVA of variance for the effects of TBT concentrations (TBT) and exposure time (Time) on parameters measured in the brain of common carp (<i>Cyprinus carpio</i>) after long-term exposure to TBT.</p

Effect of TBT on antioxidant parameters in the brain of common carp (<i>Cyprinus carpio</i>).

<p>Notes: MDA, malondialdehyde, nmol/mg protein; SOD, superoxide dismutase, U/mg protein; CAT, catalase, U/mg protein; GR, glutathione reductase, mU/mg protein; GPx, glutathione peroxidase, mU/mg protein. ACT- acetone, E1-75 ng/L, E2-0.75 μg/L, E3-7.5 μg/L. Data are means ± S.D., <i>n</i> = 6. Significant differences compared with control values are presented by:</p><p>* <i>p</i><0.05</p><p>** <i>p</i><0.01</p><p>Effect of TBT on antioxidant parameters in the brain of common carp (<i>Cyprinus carpio</i>).</p

Ordination diagram of PCA of TBT concentrations, exposure time and all parameters measured in the fish brains after chronic exposure to TBT.

<p>Ordination diagram of PCA of TBT concentrations, exposure time and all parameters measured in the fish brains after chronic exposure to TBT.</p

Serum levels of hormones in patients with insomnia and controls.

<p>Abbreviations: PI, primary insomnia; DCI, depression-comorbid insomnia; HPA, Hypothalamus-pituitary-adrenal; HPT, Hypothalamus-pituitary-thyroid; HPG, Hypothalamus-pituitary-gonads; CRH, corticotrophin-releasing hormone; ACTH, adenocorticotropic hormone; TRH, thyrotrophin-releasing hormone; TSH, thyroid stimulating hormone; TT3, total triiodothyronine; TT4, total thyroxine; GnRH, gonadotropin-releasing hormone.</p><p>Expression: normal distribution variables (Means [SD]); nonnormal distribution variables (P₅₀ [P₂₅, P₇₅]).</p>*<p><i>P</i><0.05, Denotes a significant difference compared to controls;</p>#<p><i>P</i><0.05, Compared to DCI group.</p

RNA-Sequencing Analysis of TCDD-Induced Responses in Zebrafish Liver Reveals High Relatedness to <i>In Vivo</i> Mammalian Models and Conserved Biological Pathways

<div><p>TCDD is one of the most persistent environmental toxicants in biological systems and its effect through aryl hydrocarbon receptor (AhR) has been well characterized. However, the information on TCDD-induced toxicity in other molecular pathways is rather limited. To fully understand molecular toxicity of TCDD in an in vivo animal model, adult zebrafish were exposed to TCDD at 10 nM for 96 h and the livers were sampled for RNA-sequencing based transcriptomic profiling. A total of 1,058 differently expressed genes were identified based on fold-change>2 and TPM (transcripts per million) >10. Among the top 20 up-regulated genes, 10 novel responsive genes were identified and verified by RT-qPCR analysis on independent samples. Transcriptomic analysis indicated several deregulated pathways associated with cell cycle, endocrine disruptors, signal transduction and immune systems. Comparative analyses of TCDD-induced transcriptomic changes between fish and mammalian models revealed that proteomic pathway is consistently up-regulated while calcium signaling pathway and several immune-related pathways are generally down-regulated. Finally, our study also suggested that zebrafish model showed greater similarity to <i>in vivo</i> mammalian models than <i>in vitro</i> models. Our study indicated that the zebrafish is a valuable in vivo model in toxicogenomic analyses for understanding molecular toxicity of environmental toxicants relevant to human health. The expression profiles associated with TCDD could be useful for monitoring environmental dioxin and dioxin-like contamination.</p></div

Significantly regulated pathways in zebrafish after TCDD treatment, by GSEA analysis with cutoff FDR<0.25.

<p>Note: NES, normalized enrichment scores; NOM p-value, nominal p-value for enrichment; FDR, false discovery rate.</p