75 research outputs found

    RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state

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    RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer

    Cytotoxicity and ion release of alloy nanoparticles

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    It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel–Titanium or Cobalt–Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5–250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel–Iron, and Nickel–Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 μM. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media

    Exploration of stable sonoelectrocatalysis for the electrochemical reduction of oxygen

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    A series of modified electrodes were prepared both via solvent evaporation and electrochemical cycling of azobenzene and derivatives and various quinones and assessed for their suitability as oxygen reduction electro-catalysts and sonoelectrocatalysts. Glassy carbon electrodes were modified via solvent evaporation with 1,2-dihydroxyanthraquinone and 1,2-diazonium-9,10-anthraquinone while edge plane and basal plane pyrolytic graphite electrodes were modified by the same procedure with 9,10-phenanthraquinone. The stability of the attached moiety was accessed in each case under ultrasound. For comparison the same electrode substrates were modified with 9,10-phenanthraquinone by electrochemical cycling and also exposed to ultrasound. The observed results suggest the use of the glassy carbon electrodes modified with azobenzene and derivatives via solvent evaporation as the optimal carbon based sonoelectrocatalysts for oxygen reduction in term of stability under insonation and high catalytic rate. © 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim

    The search for stable and efficient sonoelectrocatalysts for oxygen reduction and hydrogen peroxide formation: azobenzene and derivatives

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    We report the electrochemical reduction of oxygen using glassy carbon electrodes modified with azobenzene, hydroazobenzene. or fast black K salt (2.5-dimethoxy-4-[(4-nitrophenyl)azo] benzenediazonium tetrachlorozincate). The performance of the electrodes under ultrasound was explored. At the highest intensity (87 W cm-2) with one hour continuous insonation, voltammetric signals for azobenzene decreased by 7%, hydroazobenzene by 9% and fast black K by 18%. The catalytic rate constants of the immobilised species towards oxygen reduction were assessed via cyclic, rotating disc and sono-voltammetry. The rate constants were found to be 6.1 × 103 M-1 s-1 for azobenzene, 7.4 × 103 M -1 s-1 for hydroazobenzene and 10.4 × 103 M-1 s-1 for fast black K. These values suggest the use of these modified electrodes as practical hydrogen peroxide generators

    Electrochemical Determination of Manganese Solubility in Mercury via Amalgamation and Stripping in the Room Temperature Ionic Liquid n-Hexyltriethylammonium Bis(trifluoromethanesulfonyl)imide, [N-6,N-2,N-2,N-2][NTf2]

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    The solubility of manganese in mercury was determined electrochemically via amalgamation and stripping in the room temperature ionic liquid n-hexyltriethylammonium bis(trifluoromethanesulfonyl)imide, [N 6,2,2,2][NTf2]. A hemispherical mercury electrode was made by electrodepositing mercury onto a planar platinum microelectrode. Cyclic voltammetry of Mn2+ in [N6,2,2,2][NTf2] at the mercury microhemisphere electrode was investigated at temperatures of 298, 303 and 313 K. The solubility of Mn in Hg was determined on the basis of the charge under the reduction peak (Mn2+ → Mn0) and the corresponding reoxidation. © 2008 WILEY-VCH Verlag

    Electrochemical determination of oxalate at pyrolytic graphite electrodes

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    The electrocatalytic oxidation of oxalate at several carbon based electrodes including basal plane (BPPG) and edge plane (EPPG) pyrolytic graphite and glassy carbon (GC) electrode, was studied. The electrodes were examined for the sensing of oxalate ions in aqueous solutions and all three electrodes showed a response to oxalate additions. The peak of oxalate oxidation at BPPG electrode appeared at lower potential, +1.13 V vs. SCE, than at EPPG (+1.20 V vs. SCE) and GC electrode (+1.44 V vs. SCE). Oxalate oxidation at BPPG electrode was studied in more details for response characteristics (potential and current), effects of pH, temporal characteristics of response potential and current. The results indicated that oxalate oxidation proceeds as two-electron process at the BPPG electrode with a transfer coefficient β and a diffusion coefficient D evaluated to be 0.45 and 1.03 (±0.04) × 10 -5 cm2 s-1 respectively. The BPPG electrode was found to be suitable for oxalate determination in aqueous media showing linear response to oxalate concentration with a sensitivity of 0.039 AM-1 and a limit of detection of 0.7 μM. © 2007 Wiley-VCH Verlag GmbH and Co. KGaA

    Sonoelectroanalysis - application to lead determination

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    Ultrasound and benefits of its application in electrochemistry and electroanalysis have been explained and demonstrated. Lead determination by stripping analysis coupled with insonation was used to illustrate advantages of employing ultrasound in electroanalysis. Quantitative analysis of lead under insonation was shown to be possible in different media, including organic and biological samples where electroanalytical techniques often fail to give satisfactory results due to passivation of electrodes in these complex matrices.</p
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