46 research outputs found

    What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

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    Stilbenes are naturally occurring phytoalexins that generally exist as their more stable E isomers. The most well known natural stilbene is resveratrol (Res), firstly isolated in 1939 from roots of Veratrum grandiflorum (white hellebore) (1) and since then found in various edible plants, notably in Vitis vinifera L. (Vitaceae) (2). The therapeutic potential of Res covers a wide range of diseases, and multiple beneficial effects on human health such as antioxidant, anti-inflammatory and anti-cancer activities have been suggested based on several in vitro and animal studies (3). In particular, Res has been reported to be an inhibitor of carcinogenesis at multiple stages via its ability to inhibit cyclooxygenase, and is an anticancer agent with a role in antiangiogenesis (4). Moreover, both in vitro and in vivo studies showed that Res induces cell cycle arrest and apoptosis in tumor cells (4). However, clinical studies in humans evidenced that Res is rapidly absorbed after oral intake, and that the low level observed in the blood stream is caused by a fast conversion into metabolites that are readily excreted from the body (5). Thus, considerable efforts have gone in the design and synthesis of Res analogues with enhanced metabolic stability. Considering that reduced Res (dihydro- resveratrol, D-Res) conjugates may account for as much as 50% of an oral Res dose (5), and that D-Res has a strong proliferative effect on hormone-sensitive cancer cell lines such as breast cancer cell line MCF7 (6), we recently devoted our synthetic efforts to the preparation of trans-restricted analogues of Res in which the E carbon-carbon double bond is embedded into an imidazole nucleus. To keep the trans geometry, the two aryl rings were linked to the heteroaromatic core in a 1,3 fashion. Based on this design, we successfully prepared a variety of 1,4-, 2,4- and 2,5-diaryl substituted imidazoles including Res analogues 1, 2 and 3, respectively, by procedures that involve transition metal-catalyzed Suzuki-Miyaura cross-coupling reactions and highly selective N-H or C-H direct arylation reactions as key synthetic steps. The anticancer activity of compounds 1–3 was evaluated against the 60 human cancer cell lines panel of the National Cancer Institute (NCI, USA). The obtained results, that will be showed and discussed along with the protocols developed for the preparation of imidazoles 1–3, confirmed that a structural optimization of Res may provide analogues with improved potency in inhibiting the growth of human cancer cell lines in vitro when compared to their natural lead. (1) Takaoka,M.J.Chem.Soc.Jpn.1939,60,1090-1100. (2) Langcake, P.; Pryce, R. J. Physiological. Plant Patology 1976, 9, 77-86. (3) Vang, O.; et al. PLoS ONE 2011, 6, e19881. doi:10.1371/journal.pone.0019881 (4) Kraft, T. E.; et al. Critical Reviews in Food Science and Nutrition 2009, 49, 782-799. (5) Walle, T. Ann. N.Y. Acad. Sci. 2011, 1215, 9-15. doi: 10.1111/j.1749-6632.2010.05842.x (6) Gakh,A.A.;etal.Bioorg.Med.Chem.Lett.2010,20,6149-6151

    Thermodynamic Simulation of YBa2Cu3O6+x Film Growth Using Aerosol MOCVD

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    Future high power applications of high Tc superconducting materials (like YBa2CU3O6+x demand thick films with excellent electrical properties. The use of thin film deposition techniques is only possible when high deposition rates can be reached. A novel aerosol MOCVD technique using a liquid source has recently been developed and is very promising for this purpose. The precursor materials used are the [MATH]-diketonates of yttrium, barium and copper, dissolved in diethylene glycol dimethyl ether ("diglyme") in various concentrations. A preliminary thermodynamic simulation of the process is a useful tool for a deeper understanding of the stability limits of the superconducting phase and the on-going reactions during deposition. The results of these simulations have been used to optimise the process conditions for YBa2Cu3O6+x growth with good superconducting properties. A comparison between the simulation and the experimental results will be given and the influence of the main process parameters (deposition temperature, oxygen partial pressure, precursor concentration, ... ) will be shown

    YBCO coated conductors by reactive thermal co-evaporation

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    Coated tape conductors of YBCO require a deposition process allowing to obtain a high volume growth rate in order to produce long lengths of tape in a reasonable amount of time. We present our tape coating system where 15 parallel loops of travelling tape of 1 cm width can be coated simultaneously by reactive thermal co-evaporation. For high critical current densities, in-plane alignment of the YBCO film is necessary. Inclined substrate deposition (ISD) is a technique that allows to deposit in-plane oriented buffer layers suitable for YBCO growth at high deposition rates.We present results obtained for YBCO films grown on MgO-ISD buffer layers deposited by e-gun evaporation onto metallic tape substrates

    Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel

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    The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacking so far. We analyzed a large series of pediatric patients with lymphoblastic lymphoma treated within a prospective randomized trial (the Euro-LB 02 study). Among 193 lymphomas, in which a detailed immunohistochemical analysis was carried out, there were several unusual and diagnostically challenging morphologic and immunophenotypical variants. These included 11 lymphomas with mixed phenotypes expressing markers of at least 2 hematopoietic lineages, 7 terminal deoxynucleotide transferase-negative lymphoblastic lymphomas, and 3 undifferentiated hematopoietic neoplasms that could not be assigned to any lineage with certainty. Our data indicate that World Health Organization guidelines for lineage determination and subtyping of precursor cell leukemia need to be adapted before they can be applied to immunohistochemical diagnosis of lymphoma. Using the experience from this cohort we suggest a resource-saving diagnostic staining panel for the immunohistochemical analysis of precursor cell neoplasms in formalin-fixed paraffin-embedded tissue
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