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51.
天然产物中透明质酸酶抑制剂的研究 总被引:4,自引:0,他引:4
透明质酸酶抑制剂是对透明质酸酶的激活有抑制作用的物质。透明质酸酶是透明质酸的特异性裂解酶,而透明质酸在人体许多发育和调控过程中起重要作用,抑制透明质酸酶的活性可使透明质酸不被分解,维持正常的生理功能,笔者对天然产物中透明质酸酶抑制的研究开发进行了概述,并探讨了透明质酸酶抑制在医药及保健食品工业中的应用潜力。 相似文献
52.
53.
《Chronobiology international》2013,30(5):352-360
We report a comparison of fibrinolytic variables between 10 Caucasians on a predominantly European diet and 10 Greenland Eskimos on a traditional Inuit diet containing a substantial amount of fish and sea animals. We studied the diurnal variation in tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) antigens and activities during a 24-h period. Blood samples were taken every 4 h. The variations of the sinusoidal curves were evaluated by the Friedman χ2 test. t-PA and PAI-1 antigen in plasma fluctuated significantly during the 24 h (Eskimos p < 0.000007 and p < 0.0007; Caucasians p < 0.00003 and p < 0.02), with a peak in the early morning and a nadir in the afternoon. This also held true for PA1 activity (Eskimos p < 0.0008; Caucasians p < O.Ol), whereas t-PA activity showed an inverse but still significant pattern (Eskimos p < 0.006; Caucasians p < 0.0008). Amplitudes, areas underneath, and overall medians of the sinusoidal curves did not deviate between the two groups with respect to t-PA and PAL In contrast to the significant variation of t-PA and PAI, the plasma concentrations of fibrin degradation products (D-Dimer), a measure of effective fibrinolysis, remained constant during the 24 h, and the absolute differences between groups did not reach statistical significance. These findings suggest that circadian variation of fibrinolytic activators and inhibitors is a basic biologic phenomenon, which is not affected by life-style, dietary habits, or ethnic differences. Furthermore, the lack of diurnal variation in D-Dimer raises the question of whether there is a causal relationship between low morning activities of t-PA and the frequent onset of myocardial infarction at that time of day, as suggested by several authors. 相似文献
54.
Structural features and molecular evolution of Bowman-Birk protease inhibitors and their potential application 总被引:3,自引:0,他引:3
The Bowman-Birk inhibitors (BBIs) are well-studied serine protease inhibitors that are abundant in dicotyledonous and monocotyledonous plants. BBIs from dicots usually have a molecular weight of 8k and are double-headed with two reactive sites, whereas those from monocots can be divided into two classes, one approximately 8 kDa in size with one reactive site (another reactive site was lost) and the other approximately 16 kDa in size with two reactive sites. The reactive site is located at unique exposed surfaces formed by a disulfide-linked β-sheet loop that is highly conserved, rigid and mostly composed of nine residues. The structural features and molecular evolution of inhibitors are described, focusing on the conserved disulfide bridges. The sunflower trypsin inhibitor-1 (SFTI-1), with 14 amino acid residues, is a recently discovered bicyclic inhibitor, and is the most small and potent naturally occurring Bowman-Birk inhibitor.Recently, BBIs have become a hot topic because of their potential applications. BBIs are now used for defense against pathogens and insects in transgenic plants, which has advantages over using toxic and polluting insecticides. BBIs could also be applied in the prevention of cancer, Dengue fever, and inflammatory and allergic disorders, because of their inhibitory activity with respect to the serine proteases that play apivotal role in the development and pathogenesis of these diseases. The canonical nine-residue loop of BBIs/STH-1 provides an ideal template for drug design of specific inhibitors to target their respective proteases. 相似文献
55.
Beth A. Bouchard Matthew T. GisselMatthew F. Whelihan Kenneth G. MannSaulius Butenas 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Expression of tissue factor (TF) antigen and activity in platelets is controversial and dependent upon the laboratory and reagents used. Two forms of TF were described: an oxidized functional form and a reduced nonfunctional form that is converted to the active form through the formation of an allosteric disulfide. This study tests the hypothesis that the discrepancies regarding platelet TF expression are due to differential expression of the two forms.Methods
Specific reagents that recognize both oxidized and reduced TF were used in flow cytometry of unactivated and activated platelets and western blotting of whole platelet lysates. TF-dependent activity measurements were used to confirm the results.Results
Western blotting analyses of placental TF demonstrated that, in contrast to anti-TF#5, which is directed against the oxidized form of TF, a sheep anti-human TF polyclonal antibody recognizes both the reduced and oxidized forms. Flow cytometric analyses demonstrated that the sheep antibody did not react with the surface of unactivated platelets or platelets activated with thrombin receptor agonist peptide, PAR-1. This observation was confirmed using biotinylated active site-blocked factor (F)VIIa: no binding was observed. Likewise, neither form of TF was detected by western blotting of whole platelet lysates with sheep anti-hTF. Consistent with these observations, no FXa or FIXa generation by FVIIa was detected at the surface of these platelets. Similarly, no TF-related activity was observed in whole blood using thromboelastography.Conclusion and significance
Platelets from healthy donors do not express either oxidized (functional) or reduced (nonfunctional) forms of TF. 相似文献56.
Stephen J Peroutka 《Current opinion in biotechnology》1997,8(6):688-691
The long anticipated ‘genetic revolution’ in neuropsychiatry has yet to have an impact on the practice of clinical medicine. Excitement in the 1980s over major genetic breakthroughs in schizophrenia and manic depression, for example, has been replaced in the late 1990s by the sobering realization that most common neuropsychiatric disorders are multifactorial. Despite considerable effort and resources, no ‘causative’ genetic variation has been identified that plays a definitive major role in any common neuropsychiatric disorder. 相似文献
57.
In primate cells, assembly of a single HIV-1 capsid involves multimerization of thousands of Gag polypeptides, typically at the plasma membrane. Although studies support a model in which HIV-1 assembly proceeds through complexes containing Gag and the cellular adenosine triphosphatase ABCE1 (also termed HP68 or ribonuclease L inhibitor), whether these complexes constitute true assembly intermediates remains controversial. Here we demonstrate by pulse labeling in primate cells that a population of Gag associates with endogenous ABCE1 within minutes of translation. In the next approximately 2 h, Gag-ABCE1 complexes increase in size to approximately that of immature capsids. Dissociation of ABCE1 from Gag correlates closely with Gag processing during virion maturation and occurs much less efficiently when the HIV-1 protease is inactivated. Finally, quantitative double-label immunogold electron microscopy reveals that ABCE1 is recruited to sites of assembling wild-type Gag at the plasma membrane but not to sites of an assembly-defective Gag mutant at the plasma membrane. Together these findings demonstrate that a population of Gag present at plasma membrane sites of assembly associates with ABCE1 throughout capsid formation until the onset of virus maturation, which is then followed by virus release. Moreover, the data suggest a linkage between Gag-ABCE1 dissociation and subsequent events of virion production. 相似文献
58.
microRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR-338-3p, a target miRNA of BMP and activin membrane-bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR-338-3p increased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced HUVEC cells. Furthermore, overexpression of miR-338-3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox-LDL-induced HUVEC cells. Moreover, miR-338-3p overexpression increased TGF-β/Smad pathway activation in ox-LDL-induced HUVEC cells. A dual-luciferase reporter assay confirmed the direct interaction between miR-338-3p and the 3′-untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR-338-3p inhibition against ox-LDL-induced HUVEC cell injury. In conclusion, our study thus suggests that miR-338-3p promoted ox-LDL-induced HUVEC cell injury by targeting BAMBI and activating the TGF-β/Smad pathway, which may provide a novel and promising therapeutic target for AS. 相似文献
59.
Richard B. Silverman Graham R. Lawton Hantamalala Ralay Ranaivo Laura K. Chico Jiwon Seo D. Martin Watterson 《Bioorganic & medicinal chemistry》2009,17(21):7593-7605
Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood–brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications. 相似文献
60.
Bishop JG 《Molecular biology and evolution》2005,22(7):1531-1534
Polygalacturonase inhibitor proteins (PGIPs) protect plants against invasion by diverse microbial and invertebrate enemies that use polygalacturonase (PG) to breach the plant cell wall. Directed mutagenesis has identified specific natural mutations conferring novel defensive capability in green bean PGIP against a specific fungal PG. These same sites are identified as positively selected by phylogenetic codon-substitution models, demonstrating the utility of such models for connecting retrospective comparative analyses with contemporary, ecologically relevant variation. 相似文献