Speciation of Antimony in PET Bottles Produced in Japan and China by X-ray Absorption Fine Structure Spectroscopy

The oxidation state and coordination environment of antimony (Sb) incorporated into polyethylene terephthalate (PET) bottles were estimated based on X-ray absorption fine structure (XAFS) at Sb K-edge. Prior to XAFS analyses, Sb concentrations in 177 PET bottles collected in Japan and China were determined, showing that 30.5% and 100% of Japanese and Chinese PET bottles, respectively, contained more than 10 mg/kg of Sb. Most of the bottles used for aseptic cold filling and carbonated drinks contained a larger amount of Sb. Extended X-ray absorption fine structure (EXAFS) showed that the first neighboring atom of Sb in PET was estimated to be oxygen with a coordination number of about three. In addition, the contribution of Sb to Sb shell was discounted in the EXAFS, showing that Sb was not present as Sb2O3 in PET, although Sb was initially added as Sb2O3 in the production of PET. This information is consistent with the coordination environment estimated from the polycondensation reaction catalyzed by Sb, where Sb can be present as either Sb glycolate or Sb glycolate binding to the end group of the PET polymer. X-ray absorption near-edge structure (XANES) showed that Sb(III) initially added as Sb2O3 into PET was partially oxidized and the Sb(V) fractions reached approximately 50% in some samples. However, the oxidation state and coordination environment of Sb in PET had no relationship with the concentrations of Sb that leached into water from PET. Based on the present XAFS results and previous studies on the effects of temperature and others, it was concluded that the leaching behavior of Sb into water is primarily due to the degradation of PET itself, but is not related to the Sb species in the PET bottles

Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer’s Disease-like Pathogenesis by Inhibiting Aβ Aggregation and Regulating Gut Microbiota

Alzheimer’s disease (AD) is a neurodegenerative disease associated with amyloid-β (Aβ) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aβ aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose­(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood–brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aβ and decreasing Aβ aggregation, effectively inhibiting Aβ deposition in the hippocampus; (2) decreasing Aβ-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aβ-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD

Effect of puerarin on activities of hepatic lipid metabolism-related enzymes (U/g of liver).

<p>ACCα: acetyl-CoA carboxylase α; FAS: fatty acid synthase; AMPK: AMP-activated protein kinase; CAT: carnitine acyltransferase; ACO: acyl-CoA oxidase; HSL: hormone-sensitive lipase.</p><p>Values are means ± SEM of 10 mice. Means within the same column but not sharing the same superscript letter are significantly different (<i>P</i><0.05).</p><p>Effect of puerarin on activities of hepatic lipid metabolism-related enzymes (U/g of liver).</p

Additional file 1: of Dietary supplement of Smilax china L. ethanol extract alleviates the lipid accumulation by activating AMPK pathways in high-fat diet fed mice

Table S1. The content of major components in SCLE. Figure S1 Chromatograms of standard mixture (A) and SCLE (B). 1: Chlorogenic acid, 2: Astilbin, 3: Engeletin, 4: Resveratrol. Table S2 The content of active constituent in SCLE. Table S3 Composition of the diets (g/kg). Figure S2 Microscopic examination of oil-O red stained liver sections from mice (magnification 400×). (DOC 9302 kb

Effect of puerarin on mRNA expression of hepatic lipid metabolism-related enzymes.

<p>The housekeeping genes used <i>β-actin</i> and <i>GADPH</i>.</p><p><i>FAS: fatty acid synthase; AMPK: AMP-activated protein kinase; PPARγ2: peroxisomes proliferator-activated receptor γ2; CAT: carnitine acyltransferase; ACO: acyl-CoA oxidase; HSL: hormone-sensitive lipase</i>.</p><p>Values are means ± SEM of 10 mice. Means within the same column but not sharing the same superscript letter are significantly different (<i>P</i><0.05).</p><p>Effect of puerarin on mRNA expression of hepatic lipid metabolism-related enzymes.</p

Effects of puerarin on the hepatic protein expression levels of AMPK, p-AMPK, PPARγ2, HSL and p-HSL.

<p>A: Western blot analysis of AMPK, p-AMPK, PPARγ2, HSL and p-HSL from the mice liver. B: Expression of AMPK, p-AMPK, PPARγ2, HSL and p-HSL protein normalized to β-actin and expressed relatively to control. Values are means ± SEM of 10 mice. Means within the same column but not sharing the same superscript letter are significantly different (P<0.05). AMPK: AMP-activated protein kinase; p-AMPK: phosphorylation of AMP-activated protein kinase; PPARγ2: peroxisomes proliferator-activated receptor γ2; HSL: hormone-sensitive lipase; p-HSL: phosphorylation of hormone-sensitive lipase.</p

Effect of puerarin on serum biochemical parameters and hepatic and feces lipid levels in mice.

<p>TC: total cholesterols; TG: triglycerides; GLU: glucose; NEFA: non-esterified fatty acids.</p><p>Values are means ± SEM of 10 mice. Means within the same row but not sharing the same superscript letter are significantly different (<i>P</i><0.05).</p><p>Effect of puerarin on serum biochemical parameters and hepatic and feces lipid levels in mice.</p

Effects of puerarin on body weight, liver weight and IPAT weight and energy intake in mice.

<p>Values are means ± SEM of 10 mice. Means within the same column but not sharing the same superscript letter are significantly different (P<0.05).</p><p>Energy from sucrose, com starch, dextrin and casein were 4 kcal/g. Energy from corn oil and beef tallow were 9 kcal/g. Energy from cellulose was 0 kcal/g.</p><p>Effects of puerarin on body weight, liver weight and IPAT weight and energy intake in mice.</p

Gene-specific primers and probes used in quantitative real-time PCR.

<p>FAS: fatty acid synthase; AMPK: AMP-activated protein kinase; PPARγ2: peroxisomes proliferator-activated receptor γ2; CAT: carnitine acyltransferase; ACO: acyl-CoA oxidase; HSL: hormone-sensitive lipase; GADPH: glyceraldehyde 3-phosphate dehydrogenase.</p><p>Gene-specific primers and probes used in quantitative real-time PCR.</p

Molecular dynamics simulations provide insights into the origin of gleevec’s selectivity toward human tyrosine kinases

<p>Protein kinases are critical drug targets against cancer. Since the discovery of Gleevec, a specific inhibitor of Abl kinase, the capability of this drug to distinguish between Abl and other tyrosine kinases, such as Src, has been intensely investigated but the origin of Gleevec’s selectivity to Abl against Src is less studied. Here, we performed molecular dynamics (MD) simulations, dynamical cross-correlation matrices (DCCM), dynamical network analysis, and binding free energy calculations to explore Gleevec’s selectivity based on the crystal structures of Abl, Src, and their common ancestors (ANC-AS) and the two constructed mutation systems (AS→Abl and AS→Src). MD simulations revealed that the conformation of the phosphate-binding loop (P-loop) was altered significantly in the AS→Abl system. DCCM results unraveled that mutations increased anticorrelated motions in the AS→Abl system. Community network analysis suggested that the P-loop established special contacts in the AS→Abl system that are devoid in the AS→Src system. The binding free energy calculations unveiled that the affinity of Gleevec to AS→Abl increased to near the Abl level, whereas its affinity to AS→Src decreased to near the Src level. Analysis of individual residue contributions showed that the differences were located mainly at the P-loop. This study is valuable for understanding the sensitivity of Gleevec to human tyrosine kinases.</p> <p>Communicated by Ramaswamy H. Sarma</p