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91.
Maristela B. Portela Ivete P.R. Souza Celina M. Abreu Martinna Bertolini Carla Holandino Celuta S. Alviano André L.S. Santos Rosangela M.A. Soares 《Journal of oral pathology & medicine》2010,39(10):753-760
J Oral Pathol Med (2010) 39 : 753–760 Background: There are several kinds of oral soft tissue lesions that are common manifestations observed in human immunodeficiency virus (HIV)‐infected children; for example, linear gingival erythema (LGE) that is a distinctive fiery red band along the margin of the gingivae. The etiology and pathogenesis of LGE are questionable, but a candidal origin has been suggested. Proteases are key virulence attributes produced by a variety of pathogenic fungi, including Candida. The objective of the present study is to identify the protease production in Candida species including, C. albicans (n = 5), C. dubliniensis (n = 1) and C. tropicalis (n = 1), isolated directly from typical LGE lesions observed in six HIV‐positive children, and also to test the effect of a serine protease inhibitor on the interaction of Candida spp. and epithelial cells in vitro. Methods: The ability of Candida strains to release proteases in the culture supernatant fluids was visualized by gelatin‐SDS–PAGE. Gel strips containing 30‐fold concentrated supernatant (1.5 × 108 yeasts) were incubated at 37°C for 48 h in 50 mM sodium phosphate buffer, pH 5.5. The concentrated supernatants were also incubated with fibronectin, laminin, immunoglobulin G, bovine serum albumin and human serum albumin. The effect of serine protease inhibitor on the interaction of Candida spp. and epithelial cells (MA 104) was measured after pre‐treatment of fungi with the inhibitor (phenylmethylsulphonyl fluoride, PMSF). Results: All the extracellular proteases were completely inhibited by PMSF, identifying these activities as serine‐type proteases. Interestingly, a common 62‐kDa serine protease was observed in all Candida strains. The culture supernatants, rich in serine protease activities, cleaved several soluble proteinaceous substrates. Additionally, we demonstrated that pre‐treatment of C. albicans, C. dubliniensis and C. tropicalis with PMSF diminished the interaction with epithelial cells. Conclusions: Collectively, our results show that Candida spp. isolated from LGE lesions produced and secreted serine proteases and these enzymes may be involved in the initial colonization events. 相似文献
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Green JB Fricke B Chetty MC von Düring M Preston GF Stewart GW 《Blood cells, molecules & diseases》2004,32(3):411-422
The 32kD membrane protein stomatin was first studied because it is deficient from the red cell membrane in two forms of the class of haemolytic anaemias known as "hereditary stomatocytosis." The hallmark of these conditions is a plasma membrane leak to the monovalent cations Na+ and K+: the protein is missing only in the most severely leaky of these conditions. No mutation has ever been found in the stomatin gene in these conditions. Stomatin-like proteins have been identified in all three domains of biology, yet their function remains enigmatic. Although the murine knock-out is without phenotype, we have identified a family showing a splicing defect in the stomatin mRNA, in which affected children showed a catastrophic multisystem disease not inconsistent with the now-known wide tissue distribution of stomatin. We report here a study of strongly homologous stomatin-like genes in prokaryotes, which reveals a close connection with a never-studied gene erroneously known as "nfed." This gene codes for a hydrophobic protein with a probable serine protease motif. It is possible that these stomatin-like genes and those which are known as"nfed" form an operon, suggesting that the two protein products are aimed at a common function. The corollary is that stomatin could be a partner protein for a membrane-bound proteolytic process, in both prokaryotes and in eukaryotes generally: this idea is consistent with experimental evidence. 相似文献
97.
目的研究半胱氨酸蛋白酶Caspase-3抑制剂Ac-DEVD-CMK及Calpain抑制剂ALLN干预治疗对大鼠局灶性脑缺血/再灌注模型Calpain表达的影响。方法大鼠随机分为经左侧侧脑室注射Ac-DEVD-CMK(DEVD组)、ALLN(ALLN组)、二者联合(DEVD+ALLN组)或溶剂二甲基亚砜组(DMSO组),以及缺血对照组(MCAO组),诱导左侧MCA缺血2h,再灌注24或48h;再灌注24h进行TTC染色观察梗死灶的形成情况;分别通过原位杂交和免疫组化技术检测鼠脑中Calpain mRNA及活性蛋白的表达。结果DMSO组的各项指标与MCAO组差异无显著性;DEVD组或ALLN组缺血侧脑中Calpain mRNA及活性蛋白的表达均明显减少,二者合用作用最强。结论Caspase-3与Calpain均在缺血性脑损伤中起重要作用,针对它们进行治疗干预具有潜在的临床应用价值。 相似文献
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摘 要 目的: 寻找抗EV71病毒新化合物。方法: 采用分子模拟技术,以EV71病毒3C蛋白酶活性口袋为靶,设计二肽、三肽,四肽,五肽和六肽等多个系列寡肽化合物,合成对接评分较高的寡肽化合物并进行抗EV71病毒活性筛选。结果: 五肽对接评分高于其他系列寡肽,显示五肽化合物与EV71 病毒3C蛋白酶有更强的键合力。研究中合成了两个评分较高的五肽化合物25和化合物16,体外抗EV71病毒活性实验显示化合物25活性较强(EC50=1.36 μmol·L-1,CC50=211.94 μmol·L-1, SI=155.84),而化合物16则无明显活性。结论:五肽化合物25可作为抗EV71病毒新骨架开展进一步研究。 相似文献
99.
Yuan He Deng-ning Xia Qiu-xia Li Jin-song Tao Yong Gan Chi Wang 《Acta pharmacologica Sinica》2015,36(9):1151-1160
Aim:
Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV.Methods:
SQV nanocrystals were prepared using anti-solvent precipitation–high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC.Results:
The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.Conclusion:
The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir. 相似文献100.
Ivan Gentile Emanuela Zappulo Antonio Riccardo Buonomo Riccardo Scotto Guglielmo Borgia 《Expert opinion on drug safety》2015,14(10):1631-1646
Introduction: The introduction of direct-acting antiviral (DAA) agents has revolutionized the treatment of hepatitis C virus (HCV) chronic infection. Non-structural 3 protease inhibitors are currently the most numerous class of DAAs on the market.Areas covered: This review mainly focuses on the tolerability and safety profile of asunaprevir (ASV)-containing DAA regimens. ASV is a second-wave protease inhibitor currently in Phase III clinical development in most countries and already available in Japan.Expert opinion: ASV shows potent antiviral effect and clinical efficacy on HCV genotypes 1 and 4. The all-oral combination daclatasvir/ASV reached high eradication rates in HCV genotype 1b and 4 infection, and a lower efficacy in genotype 1a infection. ASV presents a low potential for drug–drug interaction and a good tolerability as part of multiple, including all-oral, regimens. ASV is associated with a transient and usually mild increase in aminotransferase levels in a low percentage of cases. Due to the impaired pharmacokinetic profile observed in advanced liver disease, ASV use in patients with moderate or severe hepatic impairment is not allowed. In conclusion, ASV represents a powerful weapon against HCV infection and has to be considered an optimal option as a component of genotype tailored interferon-free combinations. 相似文献