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61.
Federico?Pozzo Michele?Dal BoEmail author Nadia?Peragine Riccardo?Bomben Antonella?Zucchetto Francesca?Maria?Rossi Massimo?Degan Davide?Rossi Annalisa?Chiarenza Alberto?Grossi Francesco?Di Raimondo Francesco?Zaja Gabriele?Pozzato Paola?Secchiero Gianluca?Gaidano Giovanni?Del Poeta Giorgio?Zauli Robin?Foà Anna?Guarini Valter?Gattei 《Journal of hematology & oncology》2013,6(1):83
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Cesare Ponzone Davide Berlanda Fabio Donzelli Valter Acquati Rosalba Ciulla Alberto Negrini Marco Rovati Douglas Evangelista Emilio Fata Daniele Ciceri Federico Perterlongo Walter Cabri 《Molecular biotechnology》2014,56(7):653-659
Natural colchicinoids and their semisynthetic derivatives are important active ingredients for pharmaceutical applications. Thiocolchicoside (3-demethoxy-3-glucosyloxythiocolchicine) is used in several countries as standard therapy for the treatment of diseases of the muscle–skeletal system, due to its potent antiinflammatory and myorelaxant properties. Manufacturing of thiocolchicoside requires a key step, the regioselective demethylation and glucosylation of chemically derivative thiocolchicine. High selectivity and efficiency of this transformation cannot be achieved in a satisfactory way with a chemical approach. In particular, the chemical demethylation, a part from requiring toxic and aggressive reagents, generates a complex mixture of products with no industrial usefulness. We report herein an efficient, direct and green biotransformation of thiocolchicine into thiocolchicoside, performed by a specific strain of Bacillus megaterium. The same process, with minor modifications, can be used to convert the by-product 3-O-demethyl-thiocolchicine into thiocolchicoside. In addition, we describe the B. megaterium strain selection process and the best conditions for this effective double biotransformation. The final product has a pharmaceutical quality, and the process has been industrialised. 相似文献
64.
Andrade-Neto VV de Matos-Guedes HL Gomes DC do Canto-Cavalheiro MM Rossi-Bergmann B Torres-Santos EC 《Memórias do Instituto Oswaldo Cruz》2012,107(3):416-419
Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)?? = 2 μM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC?? = 8 μM) and La10 (IC?? = 10 μM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance. 相似文献
65.
Abstract Stroke is one of the most debilitating diseases, and it is unfortunate that only a small percentage of patients can be treated with thrombolytic agents. Consequently, there is an urgent need of finding an alternative procedure for reoxygenating the so-called penumbra at the earliest time as possible for reducing morbidity and disability. A preliminary, preclinical study has been carried out by using rat hippocampal and cortical brain slices subjected to oxygen-glucose deprivation. Oxygen-ozone gaseous mixture appeared to be effective in reverting damage of brain tissues, supporting the evaluation of this approach in well-designed clinical trials in stroke patients. 相似文献
66.
Machado DF Silva VH Esteves CS Gargano R Macedo LG Mundim KC de Oliveira HC 《Journal of molecular modeling》2012,18(9):4343-4348
The main goal of this paper is to present the rovibrational energies and spectroscopic constants of the Cl(2) molecular system in the relativistic states [Formula: see text], A':(1)2( u ), A:(1)1( u ), [Formula: see text] and [Formula: see text]. More precisely, we have evaluated the Cl(2) ω ( e ), ω ( e ) x ( e ), ω ( e ) y ( e ), α ( e ), γ ( e ) and B ( e ) rovibrational spectroscopic constants using two different procedures. The first was obtained by combining the rovibrational energies, calculated through solving Schr?dinger's nuclear equation and the diatomic rovibrational energy equation. The second was obtained by using the Dunham method. The calculated properties are in good agreement with available experimental data. 相似文献
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Sirtuins in aging and age-related disease 总被引:20,自引:0,他引:20
Sirtuins have been the focus of intense scrutiny since the discovery of Sir2 as a yeast longevity factor. Functioning as either deacetylases or ADP ribosylases, Sirtuins are regulated by the cofactor NAD and thus may serve as sensors of the metabolic state of the cell and organism. Here we examine the roles of Sirtuins in diverse eukaryotic species, with special emphasis on their links to aging and age-related diseases including cancer, diabetes, and neurodegenerative disorders. 相似文献
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Recent studies in diverse organisms implicate proto-oncogenic pathways, including insulin-like growth factor-I (IGF-I), Ras and AKT/protein kinase B in the ageing process. Although IGF-I is thought to contribute to cancer by promoting growth and preventing apoptosis, evidence from model organisms suggests that proto-oncogene homologues might contribute to the DNA mutations and chromosomal damage that are observed in tumour cells by increasing DNA damage, in both dividing and non-dividing cells, and involving error-prone systems in DNA repair. This raises the possibility that cancer can be reduced by chronic downregulation of pro-ageing pathways. 相似文献