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排序方式: 共有474条查询结果,搜索用时 46 毫秒
91.
Raimundo Fernandes de Araújo Júnior Vinícius Barreto Garcia Renata Ferreira de Carvalho Leit?o Gerly Anne de Castro Brito Emilio de Castro Miguel Paulo Marcos Matta Guedes Aurigena Antunes de Araújo 《PloS one》2016,11(2)
Aim
To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury.Methods
Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.Results
CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1β and NF-κB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI), procollagen type III (PCIII), and NF-κB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group.Conclusions
CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs) through suppression of inflammatory cytokines. 相似文献92.
Tiago Rodrigues Rita C. Guedes Daniel J.V.A. dos Santos Marta Carrasco Jiri Gut Philip J. Rosenthal Rui Moreira Francisca Lopes 《Bioorganic & medicinal chemistry letters》2009,19(13):3476-3480
(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1. 相似文献
93.
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95.
Patrícia Bacalhau Luís Fernandes M. Rosário Martins Fátima Candeias Elisabete P. Carreiro Óscar López A. Teresa Caldeira Jane Totobenazara Rita C. Guedes Anthony J. Burke 《Bioorganic & medicinal chemistry》2019,27(2):354-363
From a screening study of various potential inhibitors for cholinesterases (ChEs), compound (rac)-1 (4-((3-hydroxy-2-oxo-3-phenylindolin-1-yl) methyl) piperidin-1-ium chloride) showed an IC50 of 18?μM for butyrylcholinesterase (BuChE). Herein we present a toxicological and pharmacological evaluation of (rac)-1 to determine its potential for use as an alternative ChE inhibitor for the treatment of Alzheimer’s disease. The strategy adopted included in vivo and ex vivo studies with mouse models, Molecular Modelling and Saturation Transfer Difference (STD) NMR studies.Preliminary molecular docking studies were conducted with both (R) and (S)-1 with acetylcholinesterase (AChE) and BuChE, prior to advancing to the mouse model, and indeed favorable interactions were observed, with (R)-1 showing the best binding with AChE and (S)-1 with BuChE. STD-NMR studies were used to successfully validate these results. Toxicological studies were also conducted using the Artemia salina model, with donepezil as reference. It was found that in the in vivo mouse studies that (rac)-1 presented a slightly better inhibition of AChE (0.096?µmol.min?1.mg?1) than donepezil (0.112?µmol.min?1.mg?1) and the same level of inhibition for BuChE as donepezil (0.014?µmol.min?1.mg?1). 相似文献
96.
Platyscytus decempunctatus Carvalho is a small mirid living throughout its life cicle plant Solanum cernuum Vell. (Solanaceae). The internal morphology of P. decempunctatus was studied and found that the female has a telotrophic ovary with three ovarioles in the right ovary and five in the left one. In the male reproductive trait there is a well developed tubular accessory gland. The phytophagous feeding habitat of P. decempunctatus was confirmed by the observations of chlorophyll pigments in the gut of all dissected specimens. The tubular salivary glands and the Malpighian tubules were also discussed. 相似文献
97.
The goal of this work was to study some characteristics of the egg phase of three species of citrus root weevils. The insects were collected from citrus plants in Itapetininga, SP, and brought to the Laboratório de Biologia de Insetos of ESALQ/USP, in Piracicaba, SP, where the species Naupactus cervinus (Boheman), Naupactus versatilis (Hustache) and Parapantomorus fluctuosus (Boheman) were kept. Duration and viability of the egg phase were evaluated, and the lower temperature threshold and thermal constant (K) were calculated for these species. The species of citrus root weevils showed different duration of egg phases. The egg phase ranged from 40.4 to 13.8 N. cervinus, from 38.7 to 20.0 days for N. versatilis, and from 35.0 to 13.8 days for P. fluctuosus, depending upon temperature. The temperature thresholds of this stage were 8.1, 8.3, and 9.9 masculineC at thermal constant was 385.7, 397.7 and 294.1 degree-days, for N. cervinus, N. versatilis and P. fluctuosus respectively. The duration of the egg phases of N. cervinus and N. versatilis were similar at the same temperatures and P. fluctuosus had a faster development than Naupactus spp. in all temperatures tested. 相似文献
98.
Porous artificial bone substitutes, especially bone scaffolds coupled with osteobiologics, have been developed as an alternative to the traditional bone grafts. The bone scaffold should have a set of properties to provide mechanical support and simultaneously promote tissue regeneration. Among these properties, scaffold permeability is a determinant factor as it plays a major role in the ability for cells to penetrate the porous media and for nutrients to diffuse. Thus, the aim of this work is to characterize the permeability of the scaffold microstructure, using both computational and experimental methods. Computationally, permeability was estimated by homogenization methods applied to the problem of a fluid flow through a porous media. These homogenized permeability properties are compared with those obtained experimentally. For this purpose a simple experimental setup was used to test scaffolds built using Solid Free Form techniques. The obtained results show a linear correlation between the computational and the experimental permeability. Also, this study showed that permeability encompasses the influence of both porosity and pore size on mass transport, thus indicating its importance as a design parameter. This work indicates that the mathematical approach used to determine permeability may be useful as a scaffold design tool. 相似文献
99.
Pontual EV Napoleão TH Dias de Assis CR de Souza Bezerra R Xavier HS Navarro DM Coelho LC Paiva PM 《Archives of insect biochemistry and physiology》2012,79(3):135-152
Aedes aegypti control is crucial to reducing dengue fever. Aedes aegypti larvae have developed resistance to organophosporous insecticides and the use of natural larvicides may help manage larval resistance by increasing elements in insecticide rotation programs. Here, we report on larvicidal activity of Moringa oleifera flower extract against A. aegypti L(1), L(2), L(3), and L(4) as well as the effect of flower extract on gut trypsin and whole-larval acetylcholinesterase from L(4.) In addition, the heated flower extract was investigated for larvicidal activity against L(4) and effect on larval gut trypsin. Moringa oleifera flower extract contains a proteinaceous trypsin inhibitor (M. oleifera flower trypsin inhibitor, MoFTI), triterpene (β-amyrin), sterol (β-sitosterol) as well as flavonoids (kaempferol and quercetin). Larvicidal activity was detected against L(2), L(3), and L(4) (LC(50) of 1.72%, 1.67%, and 0.92%, respectively). Flower extract inhibited L(4) gut trypsin (MoFTI K(i) = 0.6 nM) and did not affect acetylcholinesterase activity. In vivo assay showed that gut trypsin activity from L(4) treated with M. oleifera flower extract decreased over time (0-1,440 min) and was strongly inhibited (98.6%) after 310 min incubation; acetylcholinesterase activity was not affected. Thermal treatment resulted in a loss of trypsin inhibitor and larvicidal activities, supporting the hypothesis that flower extract contains a proteinaceous trypsin inhibitor that may be responsible for the deleterious effects on larval mortality. 相似文献
100.
A programme has been established to characterize the long-term behaviour of cancellous bone. Fresh bovine cancellous specimens of dimensions 10 x 10 x 10 mm3 and 10 x 40 x 3.6 mm3 were manufactured and used within the testing programme. Results published in the literature indicate that the long-term behaviour of cancellous bone is well described by a power law, which is a very similar response of typical polymers. So far, dynamic mechanical tests (DMA) in three-point bending, under frequencies between 0.01 and 100 Hz at room temperature, confirmed the published results in a qualitative way. Nevertheless, the measured dimensionless damping, tan delta, was slightly higher than the values reported in the literature for the compact bone. The relaxation curves were obtained from dynamic tests and confirmed that bone relaxation modulus can be described by a power law function of time. Tests under constant compression strain rate were performed at four different strain rates: 0.15/s, 0.015/s, 0.0015/s and 0.00015/s and strain rate dependent behaviour was observed. An average elastic bending modulus of 300 MPa was obtained. 相似文献