291 research outputs found

    Al-Pt MOCVD coatings for the protection of Ti6242 alloy against oxidation at elevated temperature

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    Results on isothermal oxidation at 873K for 90 h of Al-Pt coatings on Ti6242 coupons are reported. These coatings were obtained by low temperature, low pressure metalorganic chemical vapor deposition using Me3(MeCp)Pt(VI) and dimethylethylamine alane. Three coating architectures were investigated, namely pure Al, Pt and Al sequential sublayers, and co-deposited Al and Pt. Oxidation kinetics revealed a strong transient oxidation regime followed by a diffusion driven parabolic one. Such coatings allow to decrease oxidation kinetics more than one order of magnitude compared with those of the bare Ti6242. Scanning electron microscopy, second ion mass spectrometry, X-ray diffraction and transmission electron microscopy revealed that these coatings present a rough surface morphology. They are dense, they develop scales composed of γ-Al2O3 and δ-Al2O3 and they prevent titanium diffusion from the alloy to the surface. It is concluded that coatings produced by this process show promise for use as effective protection against oxidation of Ti6242 alloys and consequently they may raise the maximum operating temperature tolerated by corresponding parts in helicopter turboengines

    New highlights of resveratrol: a review of properties against ocular diseases

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    Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV’s potential adjuvant activity.Agence Nationale de la Recherche, France | Ref. ANR-11-LABX-002

    Effets des polyphénols de vin rouge sur la prolifération cellulaire et sur le métabolisme du resvératrol

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    Il est connu qu une consommation modérée de vin rouge protégerait contre de nombreuses pathologies, du fait notamment de ses polyphénols. Nous avons étudié en particulier l effet de ces polyphénols sur le cancer colorectal, l un des cancers les plus fréquents dans les pays industrialisés. Certains polyphénols purifiés de vin rouge, comme le resvératrol et la quercétine, montrent des effets antiprolifératifs contre les cellules de cancer colorectal.Notre première approche a consisté à utiliser des extraits polyphénoliques de vins rouges de Bourgogne. Nous avons alors étudié d une part, leurs effets in vitro sur la prolifération cellulaire de lignées tumorales colorectales humaines SW480 et les interactions entre ces polyphénols et le transport et le métabolisme du resvératrol ; et d autre part, les effets in vivo chez la souris CF-1 d une consommation régulière de ces polyphénols dans l alimentation sur la survenue de lésions pré-néoplasiques chimio-induites par l azoxyméthane au niveau du colon.Notre deuxième approche s est orientée vers les modifications de la structure chimique du resvératrol. Par l ajout de groupements méthoxyles et hydroxyles, et par l isomérisation de sa structure (cis ou trans), nous avons cherché à dégager des relations structures-fonctions du resvératrol et à créer des dérivés plus bioactifs.Nous montrons que les polyphénols du vin rouge inhibent la prolifération de cellules cancéreuses coliques, en bloquant le cycle cellulaire. Certains polyphénols du vin tel que la quercétine sont capables d augmenter la capacité des cellules SW480 à accumuler le resvératrol. [Nous montrons que] chez les souris, la prise régulière de polyphénols de vin rouge dans l alimentation diminue le nombre global de lésions pré-néoplasiques, et surtout les lésions de grande taille dont dérivent les polypes intestinaux. Les modifications chimiques de la structure du resvératrol montrent que les analogues méthoxylés du cis-resvératrol sont de puissants antiprolifératifs par blocage de la mitose, alors que le mécanisme d action des dérivés du trans-resvératrol bloque le cycle cellulaire au niveau de la phase S.Ce travail supporte l idée que le recours aux polyphénols du vin dans la prévention des adénocarcinomes coliques est possible et que ce champs de recherche est une voie prometteuse. Concernant des visées thérapeutiques, la recherche d analogues du resvératrol présentant une biodisponibilité accrue est une piste à poursuivreIt is known that moderate consumption of red wine may protect against many diseases, in particular because of its polyphenols. We studied in particular the effect of these polyphenols on colorectal cancer, one of the most common cancers in industrialized countries. Some purified polyphenols from red wine, like resveratrol and quercetin, showed antiproliferative effects against colorectal cancer cells.Our first approach was to use polyphenolic extracts from Burgundy red wine. We then studied their in vitro effects on human colorectal tumor cell lines SW480 s proliferation and the interactions between the polyphenols and the transport and metabolism of resveratrol; and secondly, the effects on CF-1 mice of regular consumption of these polyphenols in the diet on the occurrence of chemically induced pre-neoplastic lesions by azoxymethane in the colon.Our second approach was directed towards changes in the chemical structure of resveratrol. By the addition of hydroxyl and methoxyl groups, and the isomerization of its structure (cis or trans), we wanted to identify structure-function relationships of resveratrol and create more bioactive derivatives.We show that the red wine polyphenols inhibit proliferation of colon cancer cells by blocking the cell cycle. Some wine polyphenols such as quercetin are able to increase the ability of SW480 cells to accumulate resveratrol. [We show that] in mice, the regular intake of red wine polyphenols in the diet reduces the overall number of pre-neoplastic lesions, especially large lesions which may become intestinal polyps. The chemical changes in the structure of resveratrol show that the methoxylated analogues of cis-resveratrol are potent antiproliferatives by blocking mitosis, while the mechanism of action of derivatives of trans-resveratrol blocks the cell cycle at the S phase.This work supports the idea that the use of wine polyphenols in the prevention of colon adenocarcinomas is possible and that this field of research is a promising way. Concerning therapeutic purposes, the search for analogues of resveratrol with improved bioavailability is a way to pursueDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

    Resveratrol-Induced Xenophagy Promotes Intracellular Bacteria Clearance in Intestinal Epithelial Cells and Macrophages

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    Autophagy is a lysosomal degradation process that contributes to host immunity by eliminating invasive pathogens and the modulating inflammatory response. Several infectious and immune disorders are associated with autophagy defects, suggesting that stimulation of autophagy in these diseases should be beneficial. Here, we show that resveratrol is able to boost xenophagy, a selective form of autophagy that target invasive bacteria. We demonstrated that resveratrol promotes in vitro autophagy-dependent clearance of intracellular bacteria in intestinal epithelial cells and macrophages. These results were validated in vivo using infection in a transgenic GFP-LC3 zebrafish model. We also compared the ability of resveratrol derivatives, designed to improve the bioavailability of the parent molecule, to stimulate autophagy and to induce intracellular bacteria clearance. Together, our data demonstrate the ability of resveratrol to stimulate xenophagy, and thereby enhance the clearance of two invasive bacteria involved life-threatening diseases, Salmonella Typhimurium and Crohn's disease-associated Adherent-Invasive Escherichia coli. These findings encourage the further development of pro-autophagic nutrients to strengthen intestinal homeostasis in basal and infectious states

    Life cycle assessment of lithium-ion batteries and vanadium redox flow batteries-based renewable energy storage systems

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    Renewable energy has become an important alternative to fossil energy, as it is associated with lower greenhouse gas emissions. However, the intermittent characteristic of renewables urges for energy storage systems, which play an important role in matching the supply and demand of renewable-based electricity. The life cycle of these storage systems results in environmental burdens, which are investigated in this study, focusing on lithium-ion and vanadium flow batteries for renewable energy (solar and wind) storage for grid applications. The impacts are assessed through a life cycle assessment covering the batteries supply phase, their use and end-of-life, with experimental data from test set-ups. The battery composition is investigated in detail as a factor for the final impacts, by comparing two types of cathodes for the lithium-ion battery and the use of recycled electrolyte for the vanadium flow battery. Results indicate that the vanadium-based storage system results in overall lower impacts when manufactured with 100% fresh raw materials, but the impacts are significantly lowered if 50% recycled electrolyte is used, with up to 45.2% lower acidification and 11.1% lower global warming potential. The new lithium-ion battery cathode chemistry results in overall higher impacts, with 41.7% more particulate matter and 52.2% more acidification

    New 8-nitroquinolinone derivative displaying submicromolar in vitro activities against both Trypanosoma brucei and cruzi

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    International audienceAn antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 μM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = −0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds

    Low Rates of Both Lipid-Lowering Therapy Use and Achievement of Low-Density Lipoprotein Cholesterol Targets in Individuals at High-Risk for Cardiovascular Disease across Europe

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    Aims To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Methods and Results Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients’ 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE 5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE 10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels ( 2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as 1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72%and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin 40 mg/day or rosuvastatin 20 mg/day). Among veryhigh- risk patients, this figure was 8.4%. Conclusions There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in EuropeWriting support was provided by Oxford PharmaGenesis Ltd, Oxford, UK, and was funded by AstraZenec
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