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101.
Ligia Guerrero Julián Castillo Mar Qui?ones Santiago Garcia-Vallvé Lluis Arola Gerard Pujadas Bego?a Muguerza 《PloS one》2012,7(11)
Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. 相似文献
102.
103.
Kenny EE Pe'er I Karban A Ozelius L Mitchell AA Ng SM Erazo M Ostrer H Abraham C Abreu MT Atzmon G Barzilai N Brant SR Bressman S Burns ER Chowers Y Clark LN Darvasi A Doheny D Duerr RH Eliakim R Giladi N Gregersen PK Hakonarson H Jones MR Marder K McGovern DP Mulle J Orr-Urtreger A Proctor DD Pulver A Rotter JI Silverberg MS Ullman T Warren ST Waterman M Zhang W Bergman A Mayer L Katz S Desnick RJ Cho JH Peter I 《PLoS genetics》2012,8(3):e1002559
Crohn''s disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10−6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10−8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10−9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10−8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10−8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10−9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim. 相似文献
104.
Bromelia pinguin L. is a plant broadly distributed in Central America and Caribbean islands. The fruits have been used in traditional medicine
as anthelmintic, probably owed to the presence of a mixture of cysteine endopeptidases, initially termed pinguinain. This
work deals with the purification and characterization of the four main components of that mixture, two of them showing acid
pI and the other two alkaline pI. Molecular masses (SDS-PAGE and MALDI-TOF), N-terminal sequence and the reactivity and kinetic
parameters versus synthetic substrates (p-nitrophenyl-N-α-CBZ-amino acid esters, PFLNA, Z-Arg-Arg-p-NA, and Z-Phe-Arg-p-NA) of the studied peptidases are given, as well as the N-terminal sequences of the enzymes and the homology degree with
other plant endopeptidases. 相似文献
105.
Alioua A Lu R Kumar Y Eghbali M Kundu P Toro L Stefani E 《The Journal of biological chemistry》2008,283(8):4808-4817
The large conductance, voltage- and Ca2+-activated potassium (MaxiK, BK) channel and caveolin-1 play important roles in regulating vascular contractility. Here, we hypothesized that the MaxiK alpha-subunit (Slo1) and caveolin-1 may interact with each other. Slo1 and caveolin-1 physiological association in native vascular tissue is strongly supported by (i) detergent-free purification of caveolin-1-rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii) double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1 proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was unaffected by the smooth muscle MaxiK beta1-subunit. Sequence analysis revealed two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent, 1007YNMLCFGIY1015, and another mirror image, 537YTEYLSSAF545, to the consensus sequence, varphiXXXXvarphiXXvarphi. Deletion of 1007YNMLCFGIY1015 caused approximately 80% loss of Slo1-caveolin-1 association while preserving channel normal folding and overall Slo1 and caveolin-1 intracellular distribution patterns. 537YTEYLSSAF545 deletion had an insignificant dissociative effect. Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional expression near 70% without affecting channel voltage sensitivity, and deletion of 1007YNMLCFGIY1015 motif obliterated channel surface expression. The results suggest 1007YNMLCFGIY1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association with Slo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin-1-rich membranes. Because the caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end to the membrane. 相似文献
106.
de Cássia Dias S Sakauchi D Abreu PA de Lima Netto S Iourtov D Raw I Kubrusly FS 《Biotechnology letters》2008,30(5):807-812
Aprotinin, the most studied serine proteinase inhibitor, was isolated from porcine lung for the first time. The purified porcine
aprotinin had an Mr value of ∼7 kDa. It cross-reacted with polyclonal serum anti-commercial aprotinin. About 1 μg porcine
aprotinin inhibited 6 μg trypsin whereas 1 μg commercial soybean inhibitor inhibited only 1 μg trypsin. The aprotinin gene
was also isolated from porcine lung: the deduced amino acid sequence showed 74% identity to bovine aprotinin. 相似文献
107.
Ligia Noronha 《EcoHealth》2004,1(2):SU16
This article briefly discusses the evolution of ecosystem approaches, and illustrates the use of ecosystem approaches to assess human health and well-being in a mining context. It discusses the various elements that help distinguish such approaches from other approaches. Well-being here is understood broadly in terms of its “constituents” and “determinants,” of which health is an important constituent. Ecological, health, and social assessments highlighted a number of impacts from mining activity in Goa, India. These generated a list of issues of concern that were validated by stakeholders—community, industry, and government—which served as a basis for the development of tools to track mining-induced changes in health and well-being. The article concludes by reflecting on some of the challenges posed by the use of ecosystem approaches to assessing human health and well-being. 相似文献
108.
Superoxide dismutase, catalase and peroxidase activities do not confer protection against oxidative damage in salt-stressed cowpea leaves 总被引:10,自引:0,他引:10
109.
Scoaris Dde O Colacite J Nakamura CV Ueda-Nakamura T de Abreu Filho BA Dias Filho BP 《Antonie van Leeuwenhoek》2008,93(1-2):111-122
Aeromonas isolates from tap water, mineral water, and artesian well water were investigated for their ability to produce different
potential virulence factors or markers such as hemolysins, cytotoxins, phospholipase, DNase, hydrophobicity and their ability
to adhere to epithelial cells and to abiotic surfaces. The susceptibility to antibiotics of Aeromonas isolates was also examined. Majority of the isolates displayed hemolytic activity against sheep erythrocytes, while only
7 of the 23 Aeromonas strains displayed DNase activity and 4 of the 23 Aeromonas strains tested were regarded as positive for phospholipase production. Most of the isolates showed cytotoxic activities in
culture filtrate dilutions at titer of 1/8 or lower. No general relation between the strain isolated and the ability to interact
with epithelial cells could be established. Using the bacterial adherence to hydrocarbons method, most of the strains were
classified as highly hydrophilic. All five Aeromonas jandaei strains isolates, 9 of the 12 Aeromonas sp strains and four of the five Aeromonas hydrophila were multidrug resistant. The most active antimicrobial was ciprofloxacin (susceptible in 100% of the isolates), and the
least active antibiotic was ampicillin (resistance in 92% of the isolates). The majority of the isolates tested were not killed
by chlorine at 1.2 mg/l. Whether the high tolerance to chlorine of Aeromonas isolates can be linked to greater virulence is not know. 相似文献
110.
Ana Escrig Raquel Marin Pedro Abreu Jose Luis Gonzalez-Mora Manuel Mas 《Biology of reproduction》2002,66(1):185-189
This study assessed whether the in vivo production of nitric oxide (NO) in the penis is impaired in experimental diabetes and whether this phenomenon can be explained by abnormal levels of NO synthase isoenzymes and/or plasma androgens. Adult male Sprague-Dawley rats were injected with streptozotocin (STZ) (40 mg/kg, i.p.) or vehicle. One half of the STZ-treated animals received daily insulin replacement. Twelve weeks later, the animals were tested for mating behavior and erectile reflexes. They were then anesthetized with urethane (1 g/kg), and the NO levels in their corpora cavernosa were monitored electrochemically with porphyrin microsensors before and after electrostimulation of the cavernous nerve. The intracavernous pressure (ICP) was measured simultaneously. The diabetic animals had substantial impairment in the mating and erectile reflexes tests, decreased basal and stimulated NO levels in the corpora, and a reduced ICP response to cavernous nerve stimulation. Insulin replacement fully reversed the effects of diabetes on the mating reflexes, the basal NO signals, and the ICP responses to electrical field stimulation and partially restored the stimulated NO release. Neither diabetes nor diabetes with insulin treatment had significant effects on serum testosterone levels or NOS isoform (nNOS, eNOS, and iNOS) protein content in penile homogenates, indicating that the changes found in erectile function were independent of such variables. These results also suggest that the diabetes-induced reduction in corporeal NO levels could be mainly due to the lack of some essential cofactors for NOS activity rather than to changes in the amount of enzyme proteins. 相似文献