Polybrominated diphenyl ethers (PBDEs), a group of flame retardants comprising 209 congeners, have become widespread environmental pollutants. High levels of PBDEs have been detected in human ...tissues, particularly in North America, and body burden is especially high in infants and toddlers because of exposure through breast milk and house dust. Increasing evidence, provided by animal studies, suggests that PBDEs are developmental neurotoxicants, although the underlying mechanisms are still unknown. Various PBDEs have been reported to cause oxidative stress and to induce apoptotic cell death in several cell types. In the present study, we investigated the comparative neurotoxicity in mouse cerebellar granule neurons of five brominated diphenyl ether (BDE) congeners, chosen among the most commonly found at the highest levels in human tissues. All BDE congener tested (BDE-47, BDE-99, BDE-100, BDE-153, and BDE-209) decreased cell viability and induced apoptotic cell death, which was prevented by antioxidants. They also caused oxidative stress, as indicated by an increase in reactive oxygen species and in lipid peroxidation. For all end points measured, the potency ranking of the congeners was BDE-100 > BDE-47 > BDE-99 > BDE-153 >> BDE-209. Measurement of BDE congener levels in neurons after exposure to different concentrations showed a significant accumulation in cells, which followed the same relative ranking. The findings suggest that all BDE congeners tested exhibit the same general mode of action (induction of oxidative stress–mediated apoptosis) and that the ability of each isomer to elicit such effects is dependent upon their accumulation in neurons, particularly in the microsomal fraction and the mitochondria.
In this paper, yolk-shell hollow nanospheres of amorphous calcium phosphate (ACP) are prepared, and its loading capacity is investigated by comparing with that of solid-shell hollow structure ACP and ...cage-shell hollow structure ACP. Results show that the products are yolk @ cage-shell of ACP with large shell’s pores size (15-40 nm) and large cavity volume. Adsorption results show that the loading capacity of yolk @ cage-shell hollow spherical ACP is very high, which is more than twice that of hollow ACP and 1.5 times of cage-like ACP. The main reasons are that the big shell’s pore size contributes the large molecular doxorubicin hydrochloride (DOX · HCl) to enter the inner of hollow spheres easier, and the yolk-shell structure provides larger interior space and more adsorption sites for loading drugs.
The antifungal agent voriconazole (VRC) exhibits extreme inter-individual and intra-individual variation in terms of its clinical efficacy and toxicity. Inflammation, as reflected by C-reactive ...protein (CRP) concentrations, significantly affects the metabolic ratio and trough concentrations of voriconazole.
(
) is an important component of the human intestinal microbiota. Clinical data have shown that
abundance is comparatively higher in patients not presenting with adverse drug reactions, and inflammatory cytokine (IL-1β) levels are negatively correlated with
abundance.
natural product capsular polysaccharide A (PSA) prevents various inflammatory disorders. We tested the hypothesis that PSA ameliorates abnormal voriconazole metabolism by inhibiting inflammation. Germ-free animals were administered PSA intragastrically for 5 days after lipopolysaccharide (LPS) stimulation. Their blood and liver tissues were collected to measure VRC concentrations. PSA administration dramatically improved the resolution phase of LPS-induced hepatic VRC metabolism and inflammatory factor secretion. It reversed inflammatory lesions and alleviated hepatic pro-inflammatory factor secretion. Both
and
data demonstrate that PSA reversed LPS-induced IL-1β secretion, downregulated the TLR4/NF-κB signaling pathway and upregulated CYP2C19 and P-gp. To the best of our knowledge, this study is the first to show that PSA from the probiotic
ameliorates abnormal voriconazole metabolism by inhibiting TLR4-mediated NF-κB transcription and regulating drug metabolizing enzyme and transporter expression. Thus, PSA could serve as a clinical adjunct therapy.
To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.
Sprague-Dawley rats with normal glucose levels were ...randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose PBG; using the oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting.
DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.
DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.
The Al-doped ZnO rod-like whiskers were synthesized by a simple hydrothermal method. The resistivity of Al-doped ZnO whisker (AZO
w) samples significantly decreased with the increase of Al
3+ ...concentration, and showed a minimum when Al
3+ doping concentration was 2.0%. If Al
3+ concentration continued to increase, namely more than 2.0%, the resistivity of Al-doped ZnO samples would increase. So, in this study the optimum Al doping concentration was 2.0%, and the lowest electric resistivity (3.959
×
10
4
Ω
cm) was obtained.
•Ni(OH)2 were prepared on nickel foam through a low-temperature hydrothermal route.•The Ni(OH)2 nanowires grown directly on the nickel foam without nickel salts added.•The as-prepared electrode ...exhibited a linear range of 0.1–6mM as glucose sensor.•The sensitivity of Ni(OH)2 nanowires modified Ni foam is 1598µA·mM−1·cm−2.
Ni(OH)2 nanowires were successfully fabricated on nickel foam via one step low-temperature hydrothermal route without nickel salts added. The results revealed that the prepared Ni(OH)2 nanowires with average diameter of about 200nm are arranged on porous sponge-shape nickel foam. The Ni(OH)2 nanowires modified Nickel foam electrode can be used as non-enzymatic glucose sensor with a high sensitivity of 1598µA·mM−1·cm−2, a linear range covering from 0.1mM to 6mM and a short response time within 3s at an applied bias of 0.55Vvs. Ag/AgCl. Furthermore, The Ni(OH)2 nanowires modified nickel foam electrode exhibited a good ability of selectivity and stability.
•The proportion of Ni3+/Ni2+ of the electrode treated by H2O2 solution were increased.•The Kcat of Ni3+-rich surface electrode is much bigger than the untreated electrode.•The NH4NiPO4·H2O/Ni foam ...exhibited a low enough detection limit of 0.009 µM.•Ni3+-rich surface electrode showed a ultra high sensitivity (11,361 µA·mM−1·cm−2).
We propose a new, simple and effective strategy to enhance the electro-catalytic activity by regulating the valence states of the electro-catalyst. The proportion of Ni3+/Ni2+ on the ammonium nickel phosphate/nickel foam electrode surface was increased after H2O2 solution treatment. The kinetic analysis results showed catalytic rate constants (Kcat) of Ni3+-rich surface electrode (4.028 × 106 cm3·mol−1·s−1) is bigger than the original electrode (4.928 × 105 cm3·mol−1·s−1), suggesting higher electro-catalytic activity of Ni3+-rich surface electrode. Ni3+-rich surface electrode shows an ultra high sensitivity (11,361 µA·mM−1·cm−2) in the range of 0.001–1 mM, which is much higher than the original electrode in the same linear range. And the sensitivity of 3579.9 µA·mM−1·cm−2 of Ni3+-rich surface electrode in the range of 2–4 mM is also enhanced compared with the original electrode.
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