脂联素经肝X受体α途径对RAW 264.7巨噬细胞ABCG1表达的影响

泡沫细胞形成是动脉粥样硬化发生的关键环节,胆固醇逆转运可以防止泡沫细胞形成,ATP结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)在胆固醇逆转运中起着很重要的作用,可将细胞内胆固醇转运至高密度脂蛋白(high density lipoprotein,HDL).肝X受体α(liver X receptorα,LXRα)可通过调节其靶基因ABCG1的表达来调控胆固醇逆转运.脂联素有很广泛的心血管保护作用,但对RAW 264.7巨噬细胞ABCG1表达的影响尚不清楚.为了研究脂联素对RAW 264.7巨噬细胞ABCG1表达的影响及其机制,采用实时荧光定量PCR、蛋白质印迹法检测ABCG1和LXRα的表达,使用液体闪烁计数仪检测胆固醇流出率,并利用siRNA干扰技术抑制LXRα的表达来研究LXRα在脂联素调节ABCG1中的作用.结果表明,脂联素浓度依赖性和时间依赖性地上调ABCG1和LXRα的mRNA和蛋白质的表达,促进巨噬细胞胆固醇流出.经LXRα siRNA处理后,脂联素上调ABCG1的作用消失,胆固醇流出率也相应减少.上述结果提示,脂联素经LXRα途径促进RAW 264.7巨噬细胞ABCG1表达和胆固醇流出,防止泡沫细胞形成,减轻动脉粥样硬化.     

研究: 脂联素经肝X受体α途径对RAW 264.7巨噬细胞ABCG1表达的影响

泡沫细胞形成是动脉粥样硬化发生的关键环节,胆固醇逆转运可以防止泡沫细胞形成,ATP结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)在胆固醇逆转运中起着很重要的作用,可将细胞内胆固醇转运至高密度脂蛋白(high density lipoprotein,HDL)．肝X受体α (liver X receptor α,LXRα)可通过调节其靶基因ABCG1的表达来调控胆固醇逆转运．脂联素有很广泛的心血管保护作用,但对RAW 264.7巨噬细胞ABCG1表达的影响尚不清楚．为了研究脂联素对RAW 264.7巨噬细胞ABCG1表达的影响及其机制,采用实时荧光定量PCR、蛋白质印迹法检测ABCG1和LXRα的表达,使用液体闪烁计数仪检测胆固醇流出率,并利用siRNA干扰技术抑制LXRα的表达来研究LXRα在脂联素调节ABCG1中的作用．结果表明,脂联素浓度依赖性和时间依赖性地上调ABCG1和LXRα的mRNA和蛋白质的表达,促进巨噬细胞胆固醇流出．经LXRα siRNA处理后,脂联素上调ABCG1的作用消失,胆固醇流出率也相应减少．上述结果提示,脂联素经LXRα途径促进RAW 264.7巨噬细胞ABCG1表达和胆固醇流出,防止泡沫细胞形成,减轻动脉粥样硬化．     

肝X受体——肝纤维化治疗新的分子靶点

肝X受体(liver X receptor, LXR)具有典型的核受体结构,包含LXRα(NR1H3)和LXRβ(NR1H2)两种同源亚型。作为一种多功能的转录因子,LXRα可诱导参与胆固醇逆转运、肝糖原代谢以及脂肪酸合成的基因表达,且能抑制一系列炎症反应。LXR特别是LXRα不仅在肝纤维化进程中异常低表达,而且在病毒性肝炎、酒精性和非酒精性脂肪肝等形成的肝纤维化疾病中均发挥了一定的作用,提示LXRα与肝纤维化有密切关系。因此,本文就LXR在肝纤维化中发挥的调节作用展开综述。     

肝X受体α在泡沫细胞胆固醇流出中的调控作用

以THP-1巨噬细胞源性泡沫细胞为研究对象,观察肝X受体α(LXRα)在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的调控作用.结果发现,22(R)-羟基胆固醇剂量依赖性增加THP-1巨噬细胞源性泡沫细胞胆固醇流出, 而DIDS剂量依赖性减少THP-1巨噬细胞源性泡沫细胞胆固醇流出.逆转录聚合酶链反应显示, 22(R)-羟基胆固醇可增加THP-1巨噬细胞源性泡沫细胞LXRα mRNA的表达, DIDS可抑制THP-1巨噬细胞源性泡沫细胞LXRα mRNA的表达.结果提示,LXRα在巨噬细胞源性泡沫细胞胆固醇流出中起着重要的调控作用,这为开发和寻找抗动脉粥样硬化药物提供了新的思路.     

核受体FXR在肝星状细胞及肝纤维化中的作用

法尼醇X受体(farnesoid X receptor,FXR)是核受体超家族的重要成员,以作为胆汁酸受体被大家所熟知.除了调节胆汁酸的合成和转运,FXR在调控葡萄糖代谢、甘油三酯代谢、炎症、凝血等方面也发挥重要作用.肝纤维化是慢性肝脏疾病发展成肝硬化的共同途径,终末期肝纤维化将导致肝硬化、肝衰竭,甚至危及生命.肝星状...     

肝X受体的研究进展

肝X受体(liver X receptors, LXRs)作为一种氧化型固醇激活的核受体,调控胆固醇代谢过程中一些关键基因的表达,是机体的胆固醇代谢感受器.另外,LXRs还参与调节机体其他生理活动,包括脂肪形成、糖代谢、巨噬细胞的天然免疫和炎症反应等.因此,LXRs有望作为治疗动脉粥样硬化、高胆固醇血症、2型糖尿病等的药物靶点.     

肝X受体调控非泡沫细胞对动脉粥样硬化的作用

肝X受体(liver X receptor,LXR)是体内代谢的关键调节因子之一,该因子转录活性受氧化型胆固醇调控。多项研究表明,LXR及其靶基因调节体内的甾醇和脂肪酸稳态,与动脉粥样硬化(atherosclerosis,AS)的发生发展联系密切。LXR有望作为治疗AS的靶点,除了通过调控巨噬细胞源性的泡沫细胞发挥抑制炎症及促进胆固醇的逆向转运等作用外,还对血管细胞及造血细胞有重要的调节作用。本文就LXR调控非泡沫细胞抗AS的分子机制展开综述,期望为AS的防治提供新的靶点和途径。     

肠道菌群与胆汁酸代谢的互相作用

肠道菌群是胃肠道的多种共生细菌和其他微生物的统称,是一个复杂而动态的微生物生态系统,有数十万亿个微生物。胆汁酸是胆汁的主要成分,由肝脏中的胆固醇合成并释放到肠道中以帮助消化吸收膳食脂肪。肠道菌群在胆汁酸代谢中发挥着重要作用,它借助胆盐水解酶和类固醇脱氢酶等通过脱氢、脱羟基和脱硫等作用改变胆汁酸池的组成;随后通过影响胆汁酸受体(如法尼醇X受体)再反馈调节胆汁酸代谢。此外胆汁酸可通过破坏细菌细胞膜和损伤DNA等抑制细菌的生长而直接改变肠道菌群结构,也可通过其受体间接改变肠道菌群结构。越来越多的研究揭示了肝脏胆汁酸和肠道菌群在调节宿主健康和疾病中的相互作用。因此,了解肠道菌群和胆汁酸代谢之间的相互作用对维持宿主健康具有重要意义。本文就胆汁酸的基本代谢过程以及其与肠道菌群的相互作用作一综述。     

LXRs在脂质代谢中的作用

LXRs ,为liverX activatedreceptors的简称 ,是核受体超家族的成员 ,包括两种同源亚型LXRα(NR1H3)和LXRβ(NR1H2 )。LXRs被内源性配体氧化甾醇或人工合成配体激活后 ,先与RXRα(retinoidXreceptorα ,亦称NR2B1)形成异二聚体 ,再与其靶基因的LXR调控元件结合 ,通过转录调节调控胆固醇的代谢、储存、吸收和转运 ,从而维持甾醇和脂肪酸代谢平衡。此外 ,LXRs也参与糖代谢调节 ,活化的LXRs可通过抑制肝脏糖异生而改变II型糖尿病动物的血糖水平。因此 ,LXRs有望成为治疗动脉粥样硬化和II型糖尿病的新靶点     

胆汁酸受体FXR 的研究进展

法尼酯衍生物X受体(FXR)是一种胆汁酸受体,在胆汁酸代谢和胆固醇代谢中发挥重要作用,并有望成为降低胆固醇,治疗某些心血管病及肝脏疾病的治疗靶点。本文介绍了FXR的发现、FXR在调控胆汁酸和脂质代谢中的作用,以及FXR在心血管疾病治疗中的应用前景。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.