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排序方式: 共有294条查询结果,搜索用时 218 毫秒
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目的 5-脂氧合酶活化蛋白(FLAP)抑制剂MK886对人食管癌细胞系(KYSE-150和TE-3)增殖和凋亡的影响及作用机制。方法用2.5、5、10、20、40和80μmol/L的MK886干预体外培养的KYSE-150和TE-3细胞;xCELLigence RTCA系统实时测定细胞增殖抑制率,同时确定半数抑制浓度(IC50)。流式细胞测量术检测食管癌细胞的细胞周期。Western blot检测细胞凋亡和自噬相关蛋白的表达。结果人食管癌细胞系(KYSE-150和TE-3)的增殖抑制率随着MK886浓度增加而增强(P<0.05),KYSE-150组的IC50浓度为29.11μmol/L,TE-3组的IC50浓度为27.47μmol/L。当MK886浓度增加至25μmol/L时,食管癌细胞G0/G1期滞后增加明显(P<0.001),MK886处理浓度增加到50μmol/L时,食管癌细胞G2/M期增加明显(P<0.001和P<0.05)... 相似文献
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Frank Zongo Christophe Ribuot Ahcène Boumendjel Innocent Guissou 《Fundamental & clinical pharmacology》2014,28(3):323-330
Waltheria indica is used in traditional pharmacopeia in Burkina Faso for the treatment of asthma and conditions of inflammation. To evaluate its pharmacological properties and isolate the active compounds, a study through a bioguided phytochemical approach was conducted. This search was guided by a two‐level investigation. First, we evaluated the impact of various fractions on the activity of enzymes involved in smooth muscle contraction (PDE4A1α) and inflammatory processes (PLA2, 5‐LOX). Second, we investigated the inhibitory effect of fractions on isolated rat trachea. The initial hydroalcoholic extract from roots of W. indica (HA), n‐hexane fraction (F1), dichloromethane fraction (F2), ethyl acetate fraction (F3), residuary fraction (F4) reduced enzyme activity of PDE4A1α (inhibition of 22–42% at 50 μg/mL), 5‐LOX (60–80% at 10 μg/mL), and PLA2 (42–94% at 100 μg/mL). On isolated rat trachea, only HA, F3, and fractions obtained from F3 by chromatography on silica gel column, using dichloromethane/methanol, dose dependently inhibited contraction induced by acetylcholine. IC50 was 1051 μg/mL for HA and comprised between 181 and 477 μg/mL for F3 and its fractions. The most active fractions were purified and led to the identification of (‐)‐epicatechin. (‐)‐epicatechin from W. indica dose dependently inhibited PLA2 (IC50 = 154.7 μm ) and 5‐LOX (IC50 = 15.8 μm ). In conclusion, both inhibition of PDE4A1α, 5‐LOX, and PLA2 activities and rat trachea relaxation by W. indica validate its use in traditional management of asthma and other conditions of inflammation. These effects should be, at least in part, attributed to the presence of (‐)‐epicatechin in roots of W. indica. 相似文献
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《Allergology international》2020,69(1):28-34
Eosinophils are multifaceted immune cells with diverse functions that enhance allergic inflammation. Cysteinyl leukotrienes (cys-LTs), mainly synthesized in eosinophils, are a class of inflammatory lipid mediators produced via multiple enzymatic reactions from arachidonic acid. Multiple clinical studies have reported dysregulated fatty acid metabolism in severe asthma and aspirin-exacerbated respiratory diseases. Therefore, understanding the mechanism responsible for this metabolic abnormality has attracted a lot of attention. In eosinophils, various stimuli (including cytokines, chemokines, and pathogen-derived factors) prime and/or induce leukotriene generation and secretion. Cell–cell interactions with component cells (endothelial cells, epithelial cells, fibroblasts) also enhance this machinery to augment allergic responses. Nasal polyp-derived eosinophils from patients with eosinophilic rhinosinusitis present a characteristic fatty acid metabolism with selectively higher production of leukotriene D4. Interestingly, type 2 cytokines and microbiome components might be responsible for this metabolic change with altered enzyme expression. Here, we review the regulation of fatty acid metabolism, especially cys-LT metabolism, in human eosinophils toward allergic inflammatory status. 相似文献
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黄芩素对肝癌HepG2细胞增殖和凋亡的影响及miR-34a在其机制中的作用 总被引:1,自引:0,他引:1
目的:观察12-脂氧合酶抑制剂黄芩素(Baicalein)对人肝癌细胞株HepG2增殖和凋亡的影响,并初步研究miR-34a在黄芩素影响HepG2细胞机制中的作用.方法:黄芩素(浓度分别为25、50和100 μmol/L)作用HepG2细胞24 h和48 h后,分别用Hoechst33342染色后荧光显微镜观察HepG... 相似文献
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Leukotrienes, generated from arachidonic acid via the lipoxygenase pathway, play an important role in the pathophysiology of asthma. Therefore, leukotriene inhibitors, such as Zileuton, are used in the treatment of asthma. However, thromboxanes, generated from arachidonic acid via the cyclooxygenase pathway, play an important role in platelet aggregation and thrombosis. Therefore, we studied whether Zileuton, by shifting arachidonic acid to the cyclooxygenase pathway, enhances thromboxane production and, hence, platelet aggregation. Blood samples were collected from 10 asthmatic patients before and 2 weeks after standard Zileuton treatment. Spontaneous platelet aggregation was measured in platelet-rich plasma. Platelet-rich plasma was also used to determine thromboxane B(2), a stable metabolite of thromboxane A(2), as the indirect measure of thromboxane A(2) because thromboxane A(2) is too unstable for assay. Baseline thromboxane B(2) and platelet aggregation values in the 10 asthmatic patients were normal. Treatment with Zileuton for 2 weeks significantly increased thromboxane B(2) levels from baseline levels of 267 +/- 54 microg/l to 389 +/- 62 microg/l after 2 weeks of treatment (P < 0.0002). Spontaneous platelet aggregation also increased significantly from baseline values of 4.2 +/- 2.4% to 6.8 +/- 2.8% after 2 weeks of treatment (P < 0.0001). These results establish that Zileuton, an effective drug for asthma, adversely affects in vitro platelet function. The findings suggest that this drug, and perhaps related agents also, may pose a thrombotic risk; clinical attention will be needed to address this possibility. 相似文献
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B. Duncan X. Lascelles Stephanie King Simon Roe Denis J. Marcellin‐Little Samuel Jones 《Journal of orthopaedic research》2009,27(9):1204-1208
Understanding the neurobiology of pain in naturally occurring models of osteoarthritis (OA) may improve the understanding of human OA pain. Both COX and LOX have been associated with joint pain. This study evaluated COX‐1, COX‐2, and 5‐LOX expression and activity in a naturally occurring canine model of secondary OA. Hip joint capsule with synovial tissue (HJC) and femoral head subchondral bone (FH) was collected from normal dogs and dogs undergoing total hip replacement for coxofemoral joint OA. Tissues were analyzed for COX‐1, COX‐2, and LOX protein, and PGE2 and LTB4. Significantly more COX‐2 protein was present in OA HJC than normal joints (p = 0.0009). There was no significant difference in COX‐1 or LOX protein, although LOX protein was increased (p = 0.069). PGE2 concentration in normal and OA HJC was similar (p = 1.0). LTB4 concentration in OA HJC was significantly greater than normal HJC (p = 0.028). Significantly more COX‐1 (p = 0.0098), COX‐2 (p = 0.0028), and LOX (p = 0.0095) protein was present in OA FH tissue compared to normal FH tissue. There were no differences in PGE2 or LTB4 concentration in normal and OA FH tissue (p = 0.77 and p = 0.11). Together, these data suggest both COX‐2 and 5‐LOX are appropriate targets for the management of pain associated with naturally occurring OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 相似文献
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Platelet lipoxygenase defect (Wien-Penzing defect) in two patients with myocardial infarction 总被引:1,自引:0,他引:1
In 2 male patients (35 and 38 years) presenting with myocardial infarction an abnormal conversion of exogenous 14C-arachidonic acid by the patients' platelets, incubated in vitro, was observed. Neither patient's platelets showed evidence of a lipoxygenase pathway. Platelet thromboxane formation from exogenous and endogenous substrate was high, while the platelet aggregation responses were normal. A myeloproliferative syndrome was excluded by bone marrow puncture. Similar defects have only been described so far in patients with myeloproliferative syndrome. This defect may be causative for the onset of clinical thrombotic events. It is speculative whether in vivo therapy with r-IFN alpha 1c might be able to eradicate the pathological platelet clone. 相似文献
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