57 resultados para Bcl-X1


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1.鲤鱼和草鱼的血液细胞包含红血球、淋巴球、单核球、嗜中性球、嗜酸性球及纺锤细胞。没有见到嗜碱性球。2.鲤鱼及草鱼的红血球数及血红蛋白量,在正常条件下,与水中溶氧量及成熟系数成十分显著的负相关。成熟雌鲤的红血球数(y)与溶氧量(x1)及成熟系数(x2)的迥归公式为:y=122+2.9x1-1.2x2。3.性腺发育程度及生殖活动强烈地影响鱼类血液有形成分。在生殖季节雄鱼的红血球数及血红蛋白量比雌鱼高,红血球沉降率则相反。白血球则在生殖季节及性腺退化吸收时比较活跃,而在非生殖季节两性之间无明显差异。4.发育成

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Hexabromocyclododecane (HBCD) is widely used as a brominated flame retardant, and has been detected in the aquatic environment, wild animals, and humans. However, details of the environmental health risk of HBCD are not well known. In this study, zebrafish embryos were used to assess the developmental toxicity of the chemical. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of HBCD (0, 0.05, 0.1, 0.5, and 1.0 mg L-1) until 96 h. Exposure to 0.1, 0.5, and 1.0 mg L-1 HBCD significantly increased the malformation rate and reduced survival in the 0.5 and 1.0 mg L-1 HBCD exposure groups. Acridine orange (AO) staining showed that HBCD exposure resulted in cell apoptosis. Reactive oxygen species (ROS) was significantly induced at exposures of 0.1, 0.5, and 1.0 mg L-1 HBCD. To test the apoptotic pathway, several genes related to cell apoptosis, such as p53, Puma, Apaf-1, caspase-9, and caspase-3, were examined using real-time PCR. The expression patterns of these genes were up-regulated to some extent. Two anti-apoptotic genes, Mdm2 (antagonist of p53) and Bcl-2 (inhibitor of Bax), were down-regulated, and the activity of capspase-9 and caspase-3 was significantly increased. The overall results demonstrate that waterborne HBCD is able to produce oxidative stress and induce apoptosis through the involvement of caspases in zebrafish embryos. The results also indicate that zebrafish embryos can serve as a reliable model for the developmental toxicity of HBCD. (C) 2009 Elsevier B.V. All rights reserved.

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The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc.

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The current-voltage (I-V) characteristics of a doped weakly coupled GaAs/AlAs superlattice (SL) with narrow barriers are measured under hydrostatic pressure from 1 bar to 13.5 kbar at both 77 and 300 K. The experimental results show that, contrary to the results in SL with wide barriers, the plateau in the I-V curve at 77 K does not shrink with increasing pressure, and becomes wider after 10.5 kbar. It is explained by the fact that the E-Gamma 1-E-Gamma 1 resonance peak is higher than the E-Gamma 1-E-X1 resonance peak. At 300 K, however, because of the more important contribution of the nonresonant component to the current, the plateau shrinks with increasing pressure. (C) 1999 American Institute of Physics. [S0021-8979(99)02008-3].

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研究了77K温度下掺杂弱耦合GaAs/AlAs窄垒超晶格在流体静压力下的垂直输运,发现其输运性质与宽垒超晶格有很大不同。当在压力下AlAs垒层中的X基态子能级降至E_(Γ1)子能级和E_(Γ2)子能级中间或更低能量位置时,未观察到Γ-Γ共振隧穿到Γ-X共振隧穿的转 变,I-V曲线上的平台并未随压力增大而收缩,反而稍有变宽。同时,平台电流随压力增大而增加,直到与E_(Γ1)-E(Γ1)共振峰电流相当。认为,由于垒层很薄,Γ电子隧穿通过垒层的几率很高,E_(Γ1)-E_(Γ1)共振峰显著高于E_(Γ1)-E_(X1)共振峰,因此,高场畴区内的输运机制在压力下仍由Γ-Γ级联共振隧穿控制。但由于X子级能随压力升高而降低,导致隧穿通过Γ-X垒的几率增加,非共振背景电流增大。由于电流连续性条件的要求,高场区的电场强度增强,导致在高压力下平台宽度随压力稍微变宽。

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本研究在潮棕壤上进行长期施肥试验(开始于1990年),涵盖了中国颇具代表性的8种施肥模式:不施肥(CK)、单施循环猪圈肥(M)、单施氮肥(N)、氮肥+循环猪圈肥(N+M)、氮肥+磷肥(NP)、氮肥+磷肥+循环猪圈肥(NP+M)、氮肥+磷肥+钾肥(NPK)、氮肥+磷肥+钾肥+循环猪圈肥(NPK+M)。 对1990年本底和2004年耕层(0~20cm)土壤样品以及1995年、2001年和2007年耕层(0~20cm)土壤样品进行无机磷分级测定。纵观这18年施肥处理,结果表明:有效或缓效态无机磷(Ca2-P、Ca8-P、Al-P和Fe-P)在无磷肥直接投入的情况下皆有不同幅度的下降,导致土壤无机磷收支赤字,在有磷肥直接投入的情况下,这些形态的无机磷不但能满足当季作物需求还有盈余,丰富了土壤P库;而O-P和Ca10-P这两种形态的无机磷的生物有效性很低,但可由盈余的有效态无机磷缓慢转化而来,长期试验结果表明,盈余有效态无机磷会逐渐转变成无效态,肥效降低;所有的施加循环猪圈肥的处理相对于单施化肥的处理能减缓无机磷素的下降,促进磷素缓慢积累,甚至能逐步建立起小规模的P库,可见循环猪圈肥不但能发挥前期供磷作用,也有较好的后期供磷作用。 各形态无机磷与速效P(Olsen-P)之间存在很好的相关性,对土壤中各形态无机磷与速效进行通径分析及逐步回归分析,在全部引入各因子的情况下得出回归方程:Y=15.127+2.158x1+0.152x2+0.265x3+0.168x4-0.128x5-0.247x6 (R2=0.9997,F=571.78,Pr=0.032;Y、x1、x2、x3、x4、x5和x6分别代表Olsen-P、Ca2-P、Ca8-P、Al-P、Fe-P、O-P和Ca10-P的含量),这进一步明确了各因子间的关系。无机磷分级与速效含量测定相结合,可以为评价土壤供磷力提供更科学的理论依据。 循环猪圈肥(M)对土壤无机磷形态的影响与矿质磷肥截然不同,对几种有机物料(大豆秸秆粉、玉米秸秆粉、新鲜猪粪和腐熟猪粪)进行无机磷分级测定,研究发现:秸秆粉中各形态无机磷的含量甚微,而新鲜猪粪中含量较高,各种有机物料中Ca2-P、Ca8-P和Al-P的含量明显高于其它组分,新鲜猪粪与秸秆粉混合堆腐,其Ca2-P和Ca8-P含量有所下降,腐熟猪粪中有效态的无机磷组分主要来自新鲜猪粪。循环猪圈肥(M)在施入土壤初期,会提供大量的Ca2-P和Ca8-P,这两部分主要来自新鲜猪粪,并且随着土壤微生物的活动,循环猪圈肥(M)将再次缓慢释放出Ca2-P和Ca8-P,发挥后效作用;循环猪圈肥(M)在施入土壤初期还能提供相当数量的Al-P、Fe-P和O-P,但是,与Ca2-P和Ca8-P不同的是,这三种形态无机磷后期释放较少。 为进一步明确土壤无机磷形态变化除了受施肥影响之外有无其它干扰,对三种茬口(一季玉米茬、大豆茬、连作玉米茬)的无机磷分级与速效P进行相关性分析,发现,一季玉米茬、大豆茬口中二者都表现出良好的相关性,而连作玉米茬口中二者相关性弱于前两者,可以说明不同的茬口对于无机磷组分含量影响是不同的。大豆根茬分解释放出的有效态无机磷素成为翌年植物生长一个重要的速效P库。这为合理地评价土壤供磷力、指导磷肥管理提供了科学的理论依据。 本研究选择8种典型的施肥模式来模拟我国农田土壤供磷力的发展。在早期单施有机肥的条件下,循环猪圈肥(M)能释放部分磷素以供作物生长所需,随着施肥年限的增加,其在土壤中残效累积,能建立起小规模的无机P库,在农业发展中对于提高土壤供磷力极为重要;氮肥的施用,加速了作物对磷素的吸收,使得磷素输出加剧,磷素利用率提高,充分利用土壤磷素,间接地提高土壤供磷力,但是土壤P库仍是入不敷出;氮肥配施循环猪圈肥(N+M),尽管有循环猪圈肥的投入,还是很难满足作物对磷素的需求,土壤供磷力相对低下;磷肥开始施用以后,大大改善了土壤的供磷状况,每年土壤中残存的各无机磷组分有部分盈余,土壤P库逐步扩大,土壤供磷水平大大提高;钾肥的引入,农田土壤供磷水平开始出现转折,因为钾肥能促进磷素的吸收,使得磷素被大量带出农田系统,作物体内磷素含量数据也证明了这一点。

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In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage,carbon ion irradiation resulted in an approximately 1.9–2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might,at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

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目的观察尼美舒利(nimesulide)对人乳腺癌细胞MCF-7辐射敏感性的影响,并探讨其可能机制。方法实验分为对照组、加药组、单纯照射组(radiation treatment,RT)及加药照射组,用噻唑蓝(MTT)法检测尼美舒利对MCF-7细胞生长抑制率的影响,并选择用药后72h测得的IC20-IC30(抑制浓度,inhibiting concentration,IC)对应的药物浓度作为辐射增敏工作浓度;克隆形成实验检测尼美舒利对MCF-7的放射增敏作用;通过流式细胞仪检测细胞周期分布的变化。Western印迹法检测与凋亡相关蛋白Bcl-2和Bax的表达水平;并用单细胞凝胶电泳技术检测DNA的损伤及修复。结果尼美舒利对MCF-7细胞的生长抑制作用呈时间依赖性和剂量依赖性,但对周期分布无明显变化。尼美舒利加药照射组与单纯照射组比较,克隆存活曲线的肩区变窄,bcl-2表达下调,但对Bax表达没有明显影响。尼美舒利本身不明显增加MCF-7的DNA损伤,但可明显延缓放射引起的SSB的修复。结论提示尼美舒利对人乳腺癌MCF-7细胞株具有辐射增敏作用,其放射增敏机制可能通过抑制DNA损伤修复并下调bcl-2来得以实现。

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先前的研究表明,肿瘤细胞中survivin的高表达与细胞对高传能线密度(LET)射线的辐射抗性相关。研究了survivin表达在高LET射线诱导的细胞凋亡中的作用,发现抑制survivin表达对高LETC离子辐射诱导的Bcl-2和Bax表达没有明显的影响。在高LET射线辐照中,survivin可能通过抑制caspase-3和-9活性的途径,抑制了细胞凋亡。

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放射治疗是肿瘤三大治疗手段之一(手术治疗、放疗、化疗),如何提高肿瘤细胞的放射敏感性一直是科研人员关注的研究方向。电离辐射导致细胞死亡的主要方式是细胞凋亡,然而肿瘤细胞内往往细胞凋亡信号通路异常,降低了治疗效果。其中细胞内高水平表达的细胞凋亡抑制蛋白(Inhibitor of Apoptosis Protein,IAP)抑制了caspase分子的活性,而caspase分子正是细胞凋亡的执行分子。因此科学家们通过各种手段尤其是RNA干涉的方法以抑制肿瘤细胞内细胞凋亡抑制蛋白的表达及蛋白活性来达到提高肿瘤治疗效果的目的。 Survivin是凋亡抑制蛋白家族的一员,该蛋白在大多数恶性肿瘤中高表达,而在正常组织中检测不到,因此具有组织特异性。Survivin参与肿瘤细胞分化并抑制肿瘤细胞凋亡,它的高表达被证明与很多恶性肿瘤对放射治疗中产生的辐射抗性相关。本文主要研究了不同LET射线辐照下人肝癌HepG2细胞 survivin的表达及其表达对重离子诱导的生物学效应的影响。首先,我们使用不同LET的碳离子束和X射线辐照HepG2细胞,采用标准克隆形成法确定其辐射敏感性,利用流式细胞技术(FCM)检测辐射后细胞周期分布,RT-PCR和western blotting检测survivin的表达。结果显示,人肝HepG2癌细胞经不同LET射线照射,survivin表达是不同的。与低LET的X射线相比,高LET碳离子诱导的细胞损伤和周期阻滞更明显,从而诱导了更强烈的survivin表达。 接着,根据Genbank提供的survivin序列,合成特异性survivin-siRNA寡核苷酸,转染HepG2细胞,抑制survivin的表达。我们发现siRNA转染后诱导了细胞G2/M期阻滞,增加了自发性和辐射诱导的细胞凋亡。在碳离子辐照后,siRNA细胞克隆存活率明显下降。这些结果显示survivin表达是细胞产生高LET辐射抗性的关键因素。最后,我们初步探讨了在细胞凋亡过程中,survivin基因的作用机制。发现抑制survivin表达,对离子束辐射诱导的Bcl-2和Bax表达没有明显的影响。Survivin表达直接抑制了caspase-3和-9的活性,从而抑制了细胞凋亡。以上的实验结果表明:不同LET射线辐照细胞后survivin出现差异表达,与X射线相比,高LET重离子诱导的HepG2细胞中survivin表达更明显,以survivin为靶基因的siRNA技术应用于HepG2细胞,可以极大提高该细胞对重离子辐射的敏感性。本论文研究为临床应用重离子束治疗癌症提供了非常有用的基础数据,同时也为重离子束放射治疗联合基因治疗提供了新的思路

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目的:研究肿瘤抑制子BRCA1在人乳腺癌细胞辐射抗性中的作用,并探讨其作用机制。材料和方法:利用实时细胞分析系统检测辐射对细胞存活的影响;流式细胞术检测辐射对细胞周期分布的影响;RT-PCR检测辐射导致的BRCA1、Bax和Bcl-2在 mRNA水平变化;Western blot方法检测辐射诱导的蛋白表达水平的变化; In-cell western定量检测辐射引起的蛋白表达水平的变化; AO/EB染色法检测辐射导致的细胞死亡情况。结果:第一,分别用1Gy和4Gy x射线和碳离子束辐照人乳腺癌细胞MCF-7,研究MCF-7对不同LET射线的辐射敏感性差异。结果显示,x射线组1Gy辐射导致细胞存活显著下降,4Gy辐射对细胞存活影响不明显;而碳离子束辐射对细胞生长无抑制作用。与x射线组比较,碳离子辐射诱导了更低的亚“G1”期细胞百分数和更显著的G2期阻滞现象。同时碳离子束辐射诱导BRCA1磷酸化水平和p21表达上调,Bax表达下调。以上结果表明MCF-7对辐射的耐受性与凋亡功能相关,而BRCA1 Ser-1524磷酸化作用可能参与细胞周期和凋亡的信号调控。第二,研究BRCA1在咖啡因诱导的辐射增敏效应中作用。当2mM咖啡因联合4Gy的x射线或碳离子束辐射处理MCF-7细胞后,观察到细胞存活显著下降,辐射诱导的G2期阻滞被废除,BRCA1和p21蛋白表达被抑制,而p53表达水平无明显变化。结果表明咖啡因诱导的MCF-7细胞的辐射增敏作用可能与G2期阻滞被废除相关,BRCA1可能参与该过程的信号调节。第三, 利用BRCA1功能正常的MCF-7细胞和BRCA1功能缺失的HCC1937细胞进一步研究BRCA1对细胞辐射敏感性的影响。辐射显著抑制了HCC1937细胞存活,但对MCF-7细胞存活无明显影响。与HCC1937细胞相比,辐射诱导MCF-7细胞发生显著的G2期阻滞。辐射诱导HCC1937细胞发生晚期凋亡,而MCF-7细胞则多发生早期凋亡,且MCF-7细胞凋亡数明显少于HCC1937细胞。RT-PCR检测结果显示,辐射增强了MCF-7细胞中BRCA1的mRNA 水平,抑制了Bax的mRNA 水平,对Bcl-2的影响不明显;而HCC1937细胞中Bax的mRNA表达水平则被增强。同时辐射诱导MCF-7细胞中BRCA1和p21蛋白表达增强,Bax表达下降,Bcl-2水平略有增高。而HCC1937细胞Bax表达水平增强,但p21和Bcl-2的表达水平则检测不到。这些结果表明,正常的BRCA1功能对Bcl-2的转录表达是必须的,BRCA1通过上调p21水平,下调Bax/Bcl-2影响细胞的辐射敏感性。结论: BRCA1在人乳腺癌细胞的辐射抗性发生中发挥重要作用,BRCA1通过上调p21水平诱导G2期阻滞,下调Bax/Bcl-2抑制凋亡信号,使得细胞对辐射诱导的凋亡产生抗性,最终导致细胞对辐射产生耐受性

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提出了低价林早期诊断的新思路 ,即根据低价林的形成规律 ,在林分还未表现出低价林状况时就能诊断出其发展趋势 ,以便及时采取相应的经营管理措施 .以辽西油松林为例 ,从生态因子途径开展了低价林的早期诊断研究 ,建立了基于单因素实验和判别分析的生态因子途径早期诊断技术 .研究表明 ,土层厚度X1、有机质含量X2 、土壤全氮含量X3 、土壤含水率X4、土壤微生物总数量X5可选择作为油松低价林早期诊断的敏感指标 ;在综合诊断时引入了判别分析的数量分类方法 ,并根据判别分析的思路建立了油松林生长状况生态因子途径早期诊断方法 ,其步骤 :1)确定判别指标 ;2 )建立判别函数Y =1.5 96X1-0 .5 1X2 - 3.196X3 +1.6 2 2X4+1.898X5;3)通过判别函数和研究对象的各项判别指标值进行早期诊断 .低价林早期诊断的技术与方法尚有待进一步地研究、检验和完善 .

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利用遥感技术和多元回归方法,分析了东北平原杨树人工林的立地因子与TM(thematic mapper)影像的关系,建立杨树林生长与植被因子和土壤因子的关系,拟合立地因子——林木生长模型。结果表明:在吉林省农安县南部的防护林类型中,以可溶性总盐(X1)和pH值(X2)为影响林木高(H)生长的主导因子,回归方程为:H=8.431-119.699X1+1.617X2(P<0.01);在吉林省农安县北部防护林类型中,以有机质含量(X1)和0.01~0.25mm粒级含量(X2)为影响林木高(H)生长的主导因子,回归方程为:H=16.421+2.616X1-0.089X2(P<0.01)。回归关系达到了显著水平,根据立地因子,可以预测东北平原农田防护林中的双杨快杨(Populus×xiaozhuanica)和北京杨(Populus×beijingensis)的林木生长状况。

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为探求便捷有效的小面积城市森林三维绿量的测算方法,根据林木生长的分形原理,采用逐步回归方法获取了沈阳城市森林三维绿量的13个模拟方程,并对其影响因素进行分析.结果表明:13个模拟方程的决定系数(R2)在0.612~0.842,残差分析没有呈现明显图样,模型精度均在87%(α=0.05)和83%(α=0.01)以上,其中最便捷的模拟方程是ln■=7.468+0.926 lnx1[■为模拟三维绿量,x1为每公顷胸高断面积(SDB)].模拟方程的标准回归系数与16个树木特征间的相关关系显示,影响沈阳城市森林三维绿量的最主要因素是每公顷胸高断面积(SDB).

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The new topological indices A(x1)-A(x3) suggested in our laboratories were applied to the study of structure-property relationships between color reagents and their color reactions with yttrium. The topological indices of twenty asymmetrical phosphone bisazo derivatives of chromotropic acid were calculated. The work shows that QSPR can be used as a novel aid to predict the molar absorptivities of color reactions and in the long term to be helpful tool in-color reagent design. Multiple regression analysis and neural network were employed simultaneously in this study. The results demonstrated the feasibility and the effectiveness of the method.