New Insights into the Sorption and Detoxification of Chromium(VI) by Tetraethylenepentamine Functionalized Nanosized Magnetic Polymer Adsorbents: Mechanism and pH Effect

In this study, sorption and detoxification mechanisms of chromium­(VI) by tetraethylenepentamine (TEPA)-functionalized nanosized magnetic polymer adsorbents, named as TEPA-NMPs, have been studied. Mechanisms of adsorption and solid state in situ redox of Cr­(VI) at different pH were proposed based on batch tests, thermodynamic and kinetic studies, and XPS, XRD, and FTIR analyses of the adsorbents before and after Cr­(VI) adsorption/desorption. The results showed that the adsorption of Cr­(VI) on TEPA-NMPs could be related to electrostatic attraction, and partially formation of Cr­(III) through solid state in situ reduction of Cr­(VI) via charge transport on the surface of the TEPA-NMPs, and further coordination interactions between Cr­(III) and amine groups (NH₂). The Fe₃O₄ magnetic core, C–O–C and C–OH groups in the adsorbents might play important roles during the redox process. TEPA-NMPs were testified to be potential adsorbents for detoxification of Cr­(VI) with high efficiency

Genistein Ameliorates Non-alcoholic Fatty Liver Disease by Targeting the Thromboxane A₂ Pathway

Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has yet received approval. Genistein, an isoflavonoid derived from soybean, ameliorates high-fat-diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid (AA) is a major ingredient of animal fats, and the AA cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein was against NAFLD by targeting the AA cascade. Using a mouse model, we showed that genistein supplementation improved high-fat-diet-induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities, and glucose tolerance. The thromboxane A₂ (TXA₂) pathway was aberrantly active in NAFLD, evidenced by an elevation of circulating TXA₂ and hepatic thromboxane A₂ receptor expression. Mechanistically, we found that genistein directly targeted cyclooxygenase-1 activity as well as its downstream TXA₂ biosynthesis, while the TXA₂ pathway might mediate NAFLD progression by impairing insulin sensitivity. Taken together, our study revealed a crucial pathophysiological role of the TXA₂ pathway in NAFLD and provided an explanation as to how genistein was against NAFLD progression

Genistein Ameliorates Non-alcoholic Fatty Liver Disease by Targeting the Thromboxane A₂ Pathway

Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has yet received approval. Genistein, an isoflavonoid derived from soybean, ameliorates high-fat-diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid (AA) is a major ingredient of animal fats, and the AA cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein was against NAFLD by targeting the AA cascade. Using a mouse model, we showed that genistein supplementation improved high-fat-diet-induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities, and glucose tolerance. The thromboxane A₂ (TXA₂) pathway was aberrantly active in NAFLD, evidenced by an elevation of circulating TXA₂ and hepatic thromboxane A₂ receptor expression. Mechanistically, we found that genistein directly targeted cyclooxygenase-1 activity as well as its downstream TXA₂ biosynthesis, while the TXA₂ pathway might mediate NAFLD progression by impairing insulin sensitivity. Taken together, our study revealed a crucial pathophysiological role of the TXA₂ pathway in NAFLD and provided an explanation as to how genistein was against NAFLD progression

The influence of site-directed mutation on <i>Siganus canaliculatus</i> Δ4 <i>Fad</i> promoter activity.

<p>The site-directed mutants were constructed on the basis of bioinformatics analysis. Each plasmid complex was transfected in triplicate in three independent experiments. Data are means ± SEM (n = 3), bars without share a common letter (a, b, c or d) indicated significant difference among them (ANOVA followed by Tukey's multiple comparison test; <i>P</i> < 0.05).</p

The structure and deletion analysis of 5’ flanking sequence of <i>Siganus canaliculatus</i> Δ4 <i>Fad</i>.

<p>Deletion constructs are represented on the left. Non-coding exons are shown by black boxes. The intron is indicated with a black line between the two exons. Sequence is numbered relative to the transcription start site (TSS), speculated to be the first base of the first 5’ non-coding exon. Promoter activity of constructs is represented with the values representing normalized activity (Firefly luciferase: Renilla luciferase) on the right. Asterisks indicate that the influence of eicosapentaenoic acid (EPA), compared with absolute ethyl alcohol (AEA) treatment, was significant (Student’s <i>t</i>—test; <i>P</i><0.05).</p

The core promoter region of <i>Siganus canaliculatus</i> Δ4 <i>Fad</i>.

<p>Numbers are relative to the supposed transcription start site (TSS). The TF binding sites predicted by corresponding software are shown above with shadow parts in the sequence. The underlined parts indicate the probe region of EMSA.</p

Q-PCR analysis of HNF4α and Δ4 <i>Fad</i> gene expression in rabbitfish primary hepatocytes transfected with HNF4α mRNA or not.

<p>Relative expression of target genes were quantified for each transcript and were normalized with <i>18S rRNA</i> by 2^{− ΔΔCt} method. The white column is the control groups and the black is experiment groups transfected with HNF4α mRNA. Results are means ± SEM (n = 6), the Asterisks indicate that compared with the control group, the influence of HNF4α mRNA treatment to HNF4α and Δ4 <i>Fad</i> gene expression is significant in experiment group (Student’s <i>t</i> -test; <i>P</i> < 0.05).</p

The electrophoretic mobility shift assay (EMSA) of <i>Siganus canaliculatus</i> Δ4 <i>Fad</i> core promoter with its liver proteins.

<p>The reaction was carried out in lane 1 (no proteins, 5’ biotin labeled probe), lane 2 (liver cytoplasmic proteins, 5’ biotin labeled free probe), lane 3 (liver cytoplasmic proteins, unlabeled competitor probe, 5’ biotin labeled free probe), lane 4 (liver nucleus proteins, 5’ biotin labeled probe), lane 5 (liver nucleus proteins, unlabeled competitor probe, 5’ biotin labeled probe). Band A is gel shift of DNA-protein complexes. Band B is the free probe.</p

COG Function Classification of nucleus proteins binding to the core promoter.

<p>The DNA-protein complex isolated from lane 4 was analyzed by LC-MS. The 83 proteins identified in liver nucleus protein sample were classified into different functions with COG (Cluster of Orthologous Group of proteins) method. The number above the column stands for the amount of proteins identified in COG Function Classification.</p

The TF binding sites predicted by software online and information for site-directed mutants.

<p>The TF binding sites predicted by software online and information for site-directed mutants.</p