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Soraya M Kazuma Marcela F Cavalcante Andréia ER Telles Andrea Queiroz Maranh?o Dulcineia SP Abdalla 《MABS-AUSTIN》2013,5(5):763-775
The in vivo modified forms of low-density lipoprotein (LDL) are important for the formation of foam cells and as mediators of the immuno-inflammatory process involved in the progression of atherosclerosis. Electronegative LDL, LDL(-), is a LDL subfraction with pro-inflammatory properties that is present in human blood. To investigate possible atheroprotective effects, an anti-LDL(-) single-chain variable fragment (scFv) was expressed in the methylotrophic yeast Pichia pastoris and its activity was evaluated in vitro against macrophages and in experimental atherosclerosis in Ldlr-/- mice. The recombinant 2C7 scFv was produced in a yield of 9.5 mg of protein/L. The specificity and affinity of purified 2C7 scFv against LDL(-) was confirmed by ELISA. To assess the activity of 2C7 scFv on foam cell formation, RAW 264.7 macrophages were exposed to LDL(-) in the presence or absence of 2C7 scFv. The 2C7 scFv inhibited the uptake of LDL(-) by macrophages in a dose-dependent manner, and internalization of LDL(-) by these cells was found to be mediated by the CD36 and CD14 receptor. In addition, compared with untreated cells, lipid accumulation in macrophages was decreased, and the expression of Cd36, Tlr-4 and Cox-2 was downregulated in macrophages treated with 2C7 scFv. Importantly, compared with untreated mice, the treatment of Ldlr-/- mice with 2C7 scFv decreased the atherosclerotic lesion area at the aortic sinus. In conclusion, our data show that 2C7 scFv inhibits foam cell formation and atherosclerotic plaque development by modulating the expression of genes relevant to atherogenesis. These results encourage further use of this antibody fragment in the development of new therapeutic strategies that neutralize the pro-atherogenic effects of LDL(-). 相似文献
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Sery Gonedelé Bi Didier P Sokouri Kouakou Tiékoura Oulo Alla N?Nan Marcel Lolo Félix Gnangbé Assanvo SP N?Guetta 《Bioinformation》2014,10(11):671-678
Cête d׳Ivoire continues to have the highest HIV-1 prevalence rate in West Africa, although the infection number is in constant
decline. The external envelope protein of the viruses is a likely site of selection, and responsible for receptor binding and entry into
host cells, and therefore constitutes an ideal region with which to investigate the evolutionary processes acting on HIV-1. In this
study, we analyse 189 envelope glycoprotein V3 loop region sequences of viruse isolates from 1995 to 2009, from HIV-1 untreated
patients living in Cête d׳Ivoire, to decipher the temporal relationship between disease diversity, divergence and selection. Our
analyses show that the nonsynonymous and synonymous ratio (dN/dS) was lower than 1 for viral populations analysed within 15
years, which showed the sequences did not undergo adequate immune pressure. The phylogenetic tree of the sequences analysed
demonstrated distinctly long internal branches and short external branches, suggesting that only a small number of viruses
infected the new host cell at each transmission. In addition to identifying sites under purifying selection, we also identified neutral
sites that can cause false positive inference of selection. These sites presented form a resource for future studies of selection
pressures acting on HIV-1 enν gene in Cête d׳Ivoire and other West African countries. 相似文献
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Human clinical and psychophysical observations suggest that the taste
system is able to compensate for losses in peripheral nerve input, since
patients do not commonly report decrements in whole mouth taste following
chorda tympani nerve damage or anesthesia. Indeed, neurophysiological data
from the rat nucleus of the solitary tract (NST) suggests that a release of
inhibition (disinhibition) may occur centrally following chorda tympani
nerve anesthesia. Our purpose was to study this possibility further. We
recorded from 59 multi- and single- unit taste-responsive sites in the rat
NST before, during and after recovery from chorda tympani nerve anesthesia.
During anesthesia, average anterior tongue responses were eliminated but no
compensatory increases in palatal or posterior tongue responses were
observed. However, six individual sites displayed increased taste
responsiveness during anesthesia. The average increase was 32.9%.
Therefore, disinhibition of taste responses was observed, but infrequently
and to a small degree in the NST At a subset of sites, chorda
tympani-mediated responses decreased while greater superficial
petrosal-mediated responses remained the same during anesthesia. Since this
effect was accompanied by a decrease in spontaneous activity, we propose
that taste compensation may result in part by a change in signal-to-noise
ratio at a subset of sites.
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