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排序方式: 共有157条查询结果,搜索用时 15 毫秒
91.
Vallés SL Borrás C Gambini J Furriol J Ortega A Sastre J Pallardó FV Viña J 《Aging cell》2008,7(1):112-118
Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-β estradiol (0.2 n m ) or with nutritionally relevant concentrations of genistein (0.5 µ m ), and 48 h later treated with 5 µ m of amyloid beta (Aβ) for 24 h. We found that Aβ increased oxidative stress, measured as peroxide levels or oxidized glutathione/reduced glutathione ratio, which in turn, caused phosphorylation of p38 MAP kinase. Amyloid beta subsequently induced neuronal death. Inhibiting the MAP kinase pathway prevented cell death, confirming the role of p38 in the toxic effect of Aβ. All these effects were prevented when cells were pretreated for 48 h with oestradiol or genistein. Therefore, oestrogenic compounds rescue neurons from Aβ-induced cell death by preventing oxidative stress, which in turn inhibits the activation of p38, protecting neurons from cell death. Because hormone replacement therapy with oestradiol could cause serious setbacks, the potential therapeutic effect of phyto-oestrogens for the prevention of Aβ-associated neurodegenerative disorders should be more carefully studied in clinical research. 相似文献
92.
Sophisticated molecular biological research has revealed many virulence attributes in at least four pathogenic fungi, but the future study of fungal virulence requires investigators to distinguish between molecules that directly interact with the host, molecules that regulate these, and molecules that are always required for fungal growth and survival, independent of the host. 相似文献
93.
Smid M Galbiati S Vassallo A Gambini D Ferrari A Viora E Pagliano M Restagno G Ferrari M Cremonesi L 《Human genetics》2003,112(5-6):617-618
Short- and long-term persistence of fetal DNA in maternal plasma has been investigated. Short-term persistence at very low concentration was detected in 47 out of 105 women within two days after delivery. Twelve out of 13 samples re-tested within three days scored negative. No long-term persistence was detected in 172 women who had previous sons or abortions. Molecular microchimerism due to circulating fetal DNA persisting from previous pregnancies should not hamper non-invasive plasma-based prenatal testing. 相似文献
94.
A mechanical model for the determination of maximum speed in terrestrial tetrapods, designed for application to extinct species, is proposed. Only external bone measures and average body mass estimations are used as input data, and the hypothesis is made that leg bones are strong enough to endure the stress of running at maximum speed at a certain universal safety factor. The model is applied to a broad sample of living mammalian species to test its predictive power, and it is found to provide very good estimates of maximum running speed. 相似文献
95.
Luca Gambini Luca Rizzi Alessandro Pedretti Orazio Taglialatela-Scafati Mario Carucci Andrea Pancotti Corinna Galli Martin Read Emanuele Giurisato Sergio Romeo Ilaria Russo 《PloS one》2015,10(11)
Malaria is an infectious disease caused by Plasmodium parasites. It results in an annual death-toll of ~ 600,000. Resistance to all medications currently in use exists, and novel antimalarial drugs are urgently needed. Plasmepsin V (PmV) is an essential Plasmodium protease and a highly promising antimalarial target, which still lacks molecular characterization and drug-like inhibitors. PmV, cleaving the PExEl motif, is the key enzyme for PExEl-secretion, an indispensable parasitic process for virulence and infection. Here, we describe the accessibility of PmV catalytic pockets to inhibitors and propose a novel strategy for PmV inhibition. We also provide molecular and structural data suitable for future drug development. Using high-throughput platforms, we identified a novel scaffold that interferes with PmV in-vitro at picomolar ranges (~ 1,000-fold more active than available compounds). Via systematic replacement of P and P'' regions, we assayed the physico-chemical requirements for PmV inhibition, achieving an unprecedented IC50 of ~20 pM. The hydroxyethylamine moiety, the hydrogen acceptor group in P2'', the lipophilic groups upstream to P3, the arginine and other possible substitutions in position P3 proved to be critically important elements in achieving potent inhibition. In-silico analyses provided essential QSAR information and model validation. Our inhibitors act ‘on-target’, confirmed by cellular interference of PmV function and biochemical interaction with inhibitors. Our inhibitors are poorly performing against parasite growth, possibly due to poor stability of their peptidic component and trans-membrane permeability. The lowest IC50 for parasite growth inhibition was ~ 15μM. Analysis of inhibitor internalization revealed important pharmacokinetic features for PExEl-based molecules. Our work disclosed novel pursuable drug design strategies for highly efficient PmV inhibition highlighting novel molecular elements necessary for picomolar activity against PmV. All the presented data are discussed in respect to human aspartic proteases and previously reported inhibitors, highlighting differences and proposing new strategies for drug development. 相似文献
96.
Andreas Prlić Thomas A Down Eugene Kulesha Robert D Finn Andreas Kähäri Tim JP Hubbard 《BMC bioinformatics》2007,8(1):333
Background
The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence. 相似文献97.
Glycosylation sites and site-specific glycosylation in human Tamm- Horsfall glycoprotein 总被引:4,自引:1,他引:3
The N-glycosylation sites of human Tamm-Horsfall glycoprotein from one
healthy male donor have been characterized, based on an approach using
endoproteinase Glu-C (V-8 protease, Staphylococcus aureus ) digestion and a
combination of chromatographic techniques, automated Edman sequencing, and
fast atom bombardment mass spectrometry. Seven out of the eight potential
N-glycosylation sites, namely, Asn52, Asn56, Asn208, Asn251, Asn298,
Asn372, and Asn489, turned out to be glycosylated, and the potential
glycosylation site at Asn14, being close to the N-terminus, is not used.
The carbohydrate microheterogeneity on three of the glycosylation sites was
studied in more detail by high-pH anion-exchange chromatographic profiling
and 500 MHz1H-NMR spectroscopy. Glycosylation site Asn489 contains mainly
di- and tri-charged oligosaccharides which comprise, among others, the
GalNAc4 S (beta1-4)GlcNAc terminal sequence. Only glycosylation site Asn251
bears oligomannose-type carbohydrate chains ranging from Man5GlcNAc2to
Man8GlcNAc2, in addition to a small amount of complex- type structures.
Profiling of the carbohydrate moieties of Asn208 indicates a large
heterogeneity, similar to that established for native human Tamm-Horsfall
glycoprotein, namely, multiply charged complex-type carbohydrate
structures, terminated by sulfate groups, sialic acid residues, and/or the
Sda-determinant.
相似文献
98.
99.
O.B. Achy F. Paycha D.J. Gambini M. Duet A. Kouamé-Koutouan J.-P. Patrick I. Peretti 《Médecine Nucléaire》2013,37(10-11):545-554
From HO Anger's analogic gamma camera to digital camera, developed countries are at the time of hybrid cameras SPECT/CT and PET/CT. Sub-Saharan black Africa in the image of Côte d’Ivoire, a country with limited medical resources shows an important delay in the evolution of the health system in general and particularly in medical imaging equipment. The purpose of this paper was to approach the issues, challenges and sustainable strategy for the implementation of hybrid imaging SPECT/CT in a developing country where the rate of morbidity and mortality remains high due to infectious but also cancer diseases because of the inadequacy of the health technical platform. To address these challenges, Côte d’Ivoire like many countries in sub-Saharan Africa with limited medical resources must design, test and develop clinical strategies adapted to developing countries. Health authorities of this country must develop a policy for sustainable financing of medical imaging, including the training of the adequate health personnel according to a model of corporate leadership. In this perspective, Côte d’Ivoire must have a SPECT/CT instead of a simple gamma camera. This would allow to optimize its diagnostic health system in oncology, bone and joint disease and in many other medical disciplines. And especially since the SPECT/CT is a high-performance device that has largely demonstrated its diagnostic efficiency and that can be used as SPECT alone or as isolated CT. In addition, this country should take over digital imaging in the context of cooperation with some countries of Africa and Europe ahead in the field of modern medical imaging, seeking assistance from international organizations (IAEA, RAD-AID, WHO,…). Finally this country should implement methods of assessment, types of performance indicators to guide planning for future projects of its system. 相似文献
100.