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991.
992.
Motexafin gadolinium (MGd) sensitizes malignant cells to ionizing radiation, although the underlying mechanisms for uptake and sensitization are both unclear. Here we show that MGd is endocytosed by the clathrin-dependent pathway with ensuing lysosomal membrane permeabilization, most likely via formation of reactive oxygen species involving redox-active metabolites, such as ascorbate. We propose that subsequent apoptosis is a synergistic effect of irradiation and high MGd concentrations in malignant cells due to their pronounced endocytic activity. The results provide novel insights into the mode of action of this promising anti-cancer drug, which is currently under clinical trials. 相似文献
993.
目的:用效应面法对蒙花苷的水解工艺进行优化,通过醛糖还原酶模型研究其水解物金合欢素醛糖还原酶的抑制活性。方法:建立水解物金合欢素体外生物酶模型,通过测定NADPH的荧光吸收,计算水解物金合欢素对醛糖还原酶的抑制率,从而得到水解物的醛糖还原酶抑制活性的IC50的平均值。在蒙花苷水解工艺中采用效应面法优化水解工艺,并对结果进行预测分析。结果:水解物金合欢素醛糖还原酶抑制活性,其IC50的平均值为2.74 mg·L-1。优选的水解工艺为水解时间7.4 h,硫酸甲醇0.54 mol·L-1,固液比3:1。结论:水解物金合欢素具有比蒙花苷较好的醛糖还原酶抑制活性。优选的蒙花苷水解工艺简便,预测性良好。 相似文献
994.
目的:研究广东地区汉族人群非综合征型唇腭裂(NSCL/P)的发生与其亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性的关联性。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对124例NSCL/P患者和273例健康人群的外周血液进行MTHFR基因C677T基因型检测,比较突变基因分布频率的差异强度。结果:病例组MTHFR基因突变纯合型(677TT)比例及携带T等位基因频率均高于对照组,差异有统计学意义(P0.05)。结论:广东地区汉族人群NSCL/P的发生与其MTHFR基因C677T多态性相关,等位基因C突变为T可能会增加患NSCL/P的风险。 相似文献
995.
目的 探讨颈动脉粥样硬化超声表现与血浆同型半胱氨酸(Hcy)及MTHFR C677T基因多态性之间的相关性。方法 143例颈动脉粥样硬化患者作为动脉硬化组,再进一步细分为内膜增厚亚组(75例)与斑块亚组(68例),选择91名无颈动脉内膜增厚及斑块形成者作为对照组。对所有研究对象均进行血浆Hcy及MTHFR C677T基因多态性检测。结果 MTHFR C677T基因CC、CT及TT型血浆Hcy水平依次逐渐升高,各组间差异有统计学意义(P<0.05)。血浆Hcy是颈动脉粥样硬化的独立危险因素(P<0.05),而MTHFR C677T基因多态性未进入回归方程。结论 血浆Hcy升高是颈动脉粥样硬化的独立危险因素;MTHFR C677T基因多态性在颈动脉粥样硬化与正常人群中分布不同,并与血浆Hcy水平相关,但不是颈动脉粥样硬化的独立危险因素。 相似文献
996.
目的探讨细胞色素P450 2C9酶(CYP2C9)及维生素K环氧化物还原酶(VKORC)高活性患者对心瓣膜置换术后华法林抗凝的影响及对策。方法 2010年2月至2013年5月郑州大学第一附属医院心外科对CYP2C9及VKORC高活性40例患者行心瓣膜置换术,其中男18例、女22例,年龄40~51(45.18±2.93)岁。行二尖瓣置换术(MVR)18例,二尖瓣置换+三尖瓣成形术(TVP)14例,双瓣膜置换术(DVR)8例。根据术前是否行CYP2C9和VKORC1基因多态性检测,分为两组,A组:20例,术前未行CYP2C9和VKORC1基因多态性检测;B组:20例,术前已行CYP2C9和VKORC1基因多态性检测。术后定期复查国际标准化比值(INR),调整华法林用量,统计达到预期值时用药时间及并发症。随访时间3~12个月,出院后,每月1次电话随访,记录每次复查INR值、并发症发生及恢复情况。结果 A组2例术后发生脑梗死,2例发生腘动脉血栓,1例发生肺栓塞,1例出现瓣环血栓形成;14例分别于第15~20 d达到预期INR值,无明显血栓并发症。术后3个月行CYP2C9和VKORC1基因多态性检测,其中17例为CYP2C9*1/*1(*2CC/*3AA)阳性,VKORC1-1639 GA阳性;3例为CYP2C9*1/*1(*2CC/*3AA)阳性,VKORC1-1639 GG阳性。B组患者术后第2 d给予华法林推荐量的同时给予阿司匹林(100 mg/d)及低分子肝素(0.4 ml/d),分别于第5~9 d达到华法林预期值,后停用阿司匹林及低分子肝素;随访6个月无明显血栓并发症,仅1例出现鼻腔出血并发症,经鼻孔填塞后好转。结论术前行CYP2C9和VKORC1基因多态性检测,对心瓣膜置换术后华法林抗凝治疗有重要的指导意义。 相似文献
997.
Osvaldo Fridman Rafael Porcile Virginia Vanasco Mariano N. Junco Luis Gariglio Miguel A. Potenzoni 《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(7):574-584
The substitution of cytosine (C) by thymine (T) at nucleotide 677 of the methylenetetrahydrofolate reductase (MTHFR) gene, which converts an alanine to a valine residue, is a frequent polymorphism with reduced specific activity, associated with moderate increase in plasma homocysteine levels (tHcy) and risk of vascular diseases. Objectives. This study was designed to investigate an association of this polymorphism with tHcy and vascular risk factors. Methods. We used a cross-sectional study on subjects affiliated to three health centers from Buenos Aires city. The diagnosis of hypertension was ascertained by patients' clinical history. Only subjects under long-term antihypertensive treatment were included. Results. Samples from 138 physically active individuals (44 men and 94 women) randomly selected were included. The mean tHcy was significantly higher amongst hypertensives (HT) than normotensives (NT). The risk of hypertension was compared in subjects with CC genotype and the combined number of subjects with at least one T allele (CT/TT). There was no significant difference regarding the risk of hypertension between NT and HT groups in the overall sample. However, as obesity is considered a risk factor for hypertension development, when only HT (n?=?29) and NT (n?=?66) subjects with body mass index below 30 kg/m2 (BMI<30) were compared, subjects bearing CT/TT presented a significantly higher risk of hypertension than those bearing the CC genotype and significantly higher concentration of tHcy. Conclusions. Our results indicate an association of hyper-tHcy and MTHFR C677T mutation with hypertension. MTHFR C677T mutation may contribute to hypertension or affect the development of hypertension through hyperhomocysteinemia. 相似文献
998.
目的 建立单核苷酸多态性(SNP)的基因芯片检测法,并初步应用于结直肠癌患者MTHFR基因位点C677T的多态性检测,分析其位点突变与致病性的关系.方法 采用醛基修饰玻璃基片,阵列检测亚甲基四氢叶酸还原酶(MTHFR)C677T基因型,生物素标记显色.应用该芯片检测78例结直肠癌患者及40例健康对照组MTHFR基因C677T多态性,并分析MTHFR基因多态性与结直肠癌的相关性.结果 建立检测MTHFR基因SNP的基因芯片.采用基因芯片法检测病例组中MTHFR基因的C677T位点CC、CT、TT基因型分布频率分别为38.5%、53.8%、7.7%,健康对照组中C677T位点CC、CT、TT基因型分布频率分别为35.0%、62.5%、2.5%.结论 成功建立检测SNP的基因芯片法.MTHFR基因位点C677T的基因多态性与结肠癌易感性无明显关系. 相似文献
999.
Min-Kyung Choi Jong-Min Han Hyeong-Geug Kim Jin-Suk Lee Jong-Suk Lee Jing-Hua Wang Seung-Wan Son Hye-Jung Park Chang-Gue Son 《Journal of ethnopharmacology》2013
Ethnopharmacologic relevance
Artemisia capillaris, also called “InJin” in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine.Aims
The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury.Materials and methods
Liver injury was induced by oral administration of 30% alcohol (10 mL/kg, twice per day) plus pyrazole (PRZ, 30 mg/kg) with/without WAC (50, 100 mg/kg, orally once per day) or silymarin (50 mg/kg) for 10 days. The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level, respectively.Results
Alcohol–PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol–PRZ treatment, but notably attenuated by WAC administration. Moreover, the alcohol–PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Alcohol–PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in hepatic tissues. However they were significantly normalized by WAC administration (p<0.05 or 0.01). In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH).Conclusions
These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines. 相似文献1000.
Pedro L. Falé Catarina Ferreira Federica Maruzzella Maria Helena Florêncio Fátima N. Frazão Maria L.M. Serralheiro 《Journal of ethnopharmacology》2013