雌激素受体β与乳腺癌

雌激素受体β(ERβ)与雌激素受体α(ERα)的结构相似,是一类配体调节的转录因子,属于核受体超家族,分布于乳腺等多种组织中,具有重要的生理病理学意义。本文简要综述雌激素受体β的基因结构、剪接变体、转录调节机制及其在乳腺癌发生发展、治疗预后和抗雌激素耐受中的意义。     

miR-424对雌激素受体α表达的抑制作用

目的:筛选能够抑制在乳腺癌发生中起关键作用的雌激素受体α(ERα)表达的microRNA(miRNA)分子,并在ERα阳性的乳腺癌细胞株中初步检测其生物学功能。方法:在ERα阳性的乳腺癌细胞ZR75-1中转染多种miRNA的表达载体,Western印迹检测ERα的表达水平,找到可以抑制ERα表达的miRNA分子;将该miRNA的表达载体转染ZR75-1后,在雌激素E2的作用下,检测该miRNA分子对细胞生长的影响。结果:经过筛选,得到能够抑制ERα表达的miRNA分子miR-424;生长曲线结果显示,miR-424能够在不依赖于E2的情况下阻抑ZR75-1的生长。结论:该研究为进一步研究miR-424在ERα信号通路中的生物学功能及研究乳腺癌的发生发展机制奠定了基础。     

PES1与雌激素受体存在相互作用

雌激素(E2)和雌激素受体(ER)在E2诱发的肿瘤中起着极其重要的作用.ER共调节因子通过与ER相互作用调节其生物学功能.PES1主要表达于E2的重要靶器官如乳腺、卵巢等组织中,并在乳腺癌细胞中高表达.用PCR技术构建HA标签的PES1全长以及1～322aa、312 ～588aa和414～588aa三个不同功能区片段的重组质粒.将不同的重组质粒与FLAG-ERα和或FLAGC-ERβ共转染293T细胞后进行免疫共沉淀,以验证PES1与ER是否有相互作用以及相互作用的区域.用含雌激素受体作用元件的荧光素酶报告基因( ERE-LUC)检测PES1对ERα和ERβ转录激活活性的影响.结果表明,PES1与ERα和ERβ均相互作用,且PES1的1～ 322aa区域与ERα和ERβ相结合.PES1能特异地、E2非依赖性抑制ERβ的转录激活活性.实验结果显示,PES1是一个新的ER共调节因子,需要进一步研究其在ERβ信号通路及其在E2诱发的肿瘤的作用.     

雌激素和孕激素受体在粉刺性乳痈的表达及意义

目的:探讨粉刺性乳痈患者雌激素受体(ER)、孕激素受体(PR)的表达及临床意义。方法:选择我院2017年1月～2018年12月收治的80例粉刺性乳痈患者,采用免疫组化法检测其乳腺病变组织ER、PR的表达,酶联免疫吸附法(ELISA)检测血清白介素-1β(interleukin-1β, IL-1β)、IL-6及肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平,分析乳腺病变组织ER、PR的表达与血清IL-1β、IL-6、TNF-α水平的相关性。结果:与普通乳腺炎组、乳腺导管扩张组比较,肉芽肿组、脓肿组血清IL-1β、IL-6、TNF-α水平明显升高,与肉芽肿组比较,脓肿组血清IL-1β、IL-6、TNF-α水平亦明显升高(P0.05)。普通乳腺炎组、乳腺导管扩张组血清IL-1β、IL-6、TNF-α水平比较差异无统计学意义(P0.05)。普通乳腺炎组、乳腺导管扩张组、肉芽肿组、脓肿组ER、PR的表达水平依次降低(P0.05)。普通乳腺炎组、乳腺导管扩张组ER、PR的表达与血清IL-1β、IL-6水平均呈显著负相关,而与血清TNF-α水平无显著相关性(P0.05);肉芽肿组、脓肿组ER、PR表达与血清IL-1β、IL-6、TNF-α水平均呈显著负相关(P0.05)。结论:粉刺性乳痈患者ER、PR呈低表达或失表达,且与炎症因子及病情严重程度具有良好相关性。     

雌激素受体β共调节因子的研究进展

雌激素受体(ER)包括α和β等2种,均为核受体。ERβ在乳腺癌预后和激素治疗耐受中有重要意义,其活性受与之相互作用的共调节因子的影响。这些共调节因子有的能与2种ER发生作用,有的只能特异地作用于其中一种。本文简要综述了与ERβ相互作用的共调节因子的相关研究进展。     

乳腺癌中雌激素受体α表达水平调节的分子机制

雌激素受体α(ERα)在乳腺癌的发生发展中扮演重要角色,因而ERα成为乳腺癌治疗的分子靶标。ERα的表达水平在乳腺癌患者中差异较大,即使同一患者,在乳腺癌的不同阶段也可能有很大的差别。乳腺癌内分泌治疗的疗效以及预后都与ERα表达水平密切相关。影响ERα表达水平的分子机制复杂,众多调节分子在染色质、转录、转录后、翻译和翻译后等水平参与ERα表达水平的调节。在染色质和转录水平,许多分子通过直接或间接地与ERα启动子的相互作用改变ERα的转录;在转录后/翻译水平,一些microRNA通过诱导ERαmRNA的降解和/或抑制其翻译降低ERα的水平;在翻译后水平,许多分子通过泛素-蛋白酶体途径调节ERα蛋白水平。文章从不同水平,对这些调节分子的调节机制进行简要综述。     

LRP16对乳腺癌MCF-7细胞增殖的影响

用Northern印迹方法检测雌二醇 (17β E2 )对LRP16mRNA表达的时间及剂量依赖性调控作用 .构建LRP16基因启动子序列调控的萤光素酶报告子 (pS0 ) ,并与雌激素受体α和 β(ERα和ERβ)表达载体共转染COS 7和MCF 7细胞后测定萤光素酶活性 .将LRP16基因的表达载体转染MCF 7细胞 ,测定过表达LRP16对细胞的生长特性的影响 .17β E2 使MCF 7细胞中LRP16mRNA表达水平增加 ,增加幅度未显示出 17β E2 培养时间和剂量的依赖性 .pS0 与ERα表达载体共转染细胞的相对萤光素酶活性较非共转染组 (对照组 )及pS0 ERβ表载体共转染组升高 5～ 10倍 .LRP16基因过表达促进MCF 7细胞的增殖 .研究表明 ,雌激素可能通过ERα上调乳腺癌MCF 7细胞LRP16基因的表达并促进细胞增殖     

性类固醇激素受体ER、AR和PR在牛蛙胃肠胰的定位

本文用免疫组织化学技术检测及光密度定量分析,研究4种性类固醇激素受体在牛蛙(Rana catesbeiana)胃肠胰内的定位及表达的强弱,探讨4种性类固醇激素在牛蛙胃肠胰中的功能。染色结果显示,4种性类固醇激素受体在牛蛙胃肠胰内都有分布,雌雄之间分布差异较小。雌激素受体α(ERα)主要分布在牛蛙胃腺、直肠固有层和胰腺中;雌激素受体β(ERβ)主要分布在食道上皮、直肠固有层和胰腺中;雄激素受体(AR)主要分布在食道上皮、直肠固有层和胰腺中;孕激素受体(PR)主要分布在空肠、食道上皮和胰腺中。光密度检测结果显示,雌激素受体α(ERα)在牛蛙胃和直肠中阳性反应最强,在胰腺中相对较弱。雌激素受体β(ERβ)在牛蛙直肠中阳性反应最强,胰腺和食道次之。雄激素受体(AR)在食道中阳性反应相对较强,其他部位都较弱。孕激素受体(PR)在空肠中的阳性反应较强,其他部位都较弱。雌激素受体α(ERα)在胃中以及雄激素受体(AR)在食道和直肠中的免疫阳性反应均是雌性牛蛙强于雄性牛蛙,雌激素受体β(ERβ)在胰腺中的免疫阳性反应是雄性牛蛙强于雌性牛蛙。4种性类固醇激素受体中,雌激素受体α(ERα)和雌激素受体β(ERβ)在牛蛙胃肠胰中的分布最多,雄激素受体(AR)、孕激素受体(PR)的分布相对较少。性类固醇激素受体主要分布在食道、胃、直肠和胰腺中,其中,分布最多的部位是胃和直肠。4种性类固醇激素受体在牛蛙胃肠胰内的分布表明,性类固醇激素对牛蛙消化功能特别是胃和直肠的功能具有多方面的调节作用。     

雌激素受体参与疼痛调控的研究进展

雌激素受体属转录因子核受体超家族成员。雌激素受体的两个亚型ERα和ERβ都有类似于核受体超家族成员的调节结构,介导雌激素参与生理和病理过程中的多种效应。ERα和ERβ广泛分布于神经系统中疼痛调节相关的区域,大量动物实验及临床研究资料证实ERα和ERβ参与急、慢性疼痛的调控。本文拟对雌激素受体的特性及其在疼痛调控中的作用予以阐述。     

雌激素受体亚型及其配体调节基因转录机制的研究

本文综述雌激素受体亚型（ERα和ERβ）的结构,功能,组织分布,生理作用及雌激素受体配体调节基因转录的机制,目的是深入系统地了解植物雌激素和选择性雌激素受体调节剂的作用路径及其组织特异性的发生机制,最终为提高雌激素类药物的选择性,优化以临床为基础的药物设计提供一条较为系统的思路。结果表明,ERα和ERβ对不同雌激素类化合物产生不同应答,配体的结构不同,调节基因转录的路径不同和募集的辅调节蛋白的不同是雌激素受体两种亚型组织特异性激活或抑制的主要原因。     

Antibiotics in the treatment of wounds in the victims of the earthquake in the Armenian SSR

Purulent wounds in 88 victims of the Armenian earthquake with the syndrome of long-term squeezing were examined microbiologically and the experience with using antimicrobial drugs for their treatment was analyzed. In all the cases microbial associations were detected, coliform and nonfermenting gram-negative bacilli, enterococci, anaerobes and yeast-like fungi being isolated from 80, 20, 15 and 25 per cent of the patients respectively. 130 bacterial strains were studied in detail. 80 to 100 per cent of the bacterial isolates were resistant to the antibiotics routinely used in surgical practice, i.e. benzylpenicillin, tetracycline, levomycetin, kanamycin, cephalothin and cefazolin and highly sensitive to new antimicrobial drugs belonging to ureidopenicillins (mezlocillin), quinolones (ciprofloxacin) and cephalosporins of the 3rd generation (cefoperazone and ceftazidime). Retrospective estimation of the antibiotic therapy revealed its inadequacy in 55.7 per cent of the patients for the most part because of the isolates resistance. The 19 variants of the antibiotic use prescribed by the physicians mainly included penicillins, aminoglycosides and their combinations (in 67.2 per cent of the cases). The use of the highly efficient drugs of the groups of ureidopenicillins and quinolones was extremely rare which was likely due to lacking of information on the drugs.     

Histogenesis of the taste buds of the vallate papilla in the in the rat in the postnatal stages of development

The developing taste buds of vallate papillae were studied with electron microscope in rats during the first 7 days after birth. Two types of cells--light and dark--are identified in the taste buds of a one day old animal. The apical parts of dark cells are characterized by numerous dark granules. A distinguishing feature of light cells is the presence of synaptic contacts with afferent intragemmal nerves. On the 4th day of development on the top of the apical parts of the cell, a microvillar apparatus is seen to form, which does not yet communicate with the oral cavity. On the 7th day, basal cells appear in the taste buds. Some of these cells are seen mitotically dividing. The differentiated microvillar apparatus now communicates with oral cavity. The structure of the taste buds is getting similar to that in the adults. The structural and functional peculiarities of the developing taste buds are discussed in association with the period of ontogenesis under consideration.     

Changes in the size of the nucleoli of the Purkinje cells in the canine cerebellum in the postresuscitation period

The changes in the size of Purkinje cell (PC) nucleolus in the lateral and medial cerebellum zones were studied in dogs with different degree of neurologic status recovery after clinical death of various etiology and duration. PC always possess one nucleolus in the control and experimental groups. In the case of complete neurologic status recovery of animals the area of PC nucleolus increases in both zones studied, irrespective of the cause of clinical death. In the case of neurologic disorders the increase in PC nucleolus area is clearly expressed only in the medial zone of the cerebellum, being insignificant in the lateral zone. It is suggested that adaptive characteristics of PC are distinct in the two compared zones, which leads to greater PC vulnerability in the lateral zone during deep hypoxia.     

Frequency of the stages in the cycle of the seminiferous epithelium in the rat

This study determined the optimum number of tubules to be counted per testis cross section, and the number of animals per treatment group, when changes in stage frequencies in the cycle of the seminiferous epithelium are criteria for assessing effects of treatment on spermatogenesis. A data base of 9,672 observed and staged tubules was collected from testicular cross sections of 15 Sprague-Dawley rats. A significant variation between animals was found for the frequencies of Stages I, II, IV, VI, VIII, and XIII. Computer simulation was used to randomly select different combinations of animal and tubule numbers from the observed data. Stage frequency means from each simulation experiment were compared statistically to observed mean frequencies. A model that used data from all 14 stages was analyzed. The following conclusions were made: a) a minimum of 200 tubule cross sections/testis is recommended for estimating stage frequencies; b) for a fixed number of tubules scored, the number of animals sampled is more important than the number of tubules per animal in reducing variance; c) to detect a difference of 2 standard deviations from the mean with a 2% error rate and examining 200 tubules/testis, at least 12 animals must be used per group when assessing all 14 stages; d) when individual stages are examined using 10 animals per group, only Stage VII has 80% or greater power of test (alpha = 0.05) to detect a frequency difference; e) pooling stages into 3-4 groups is recommended to improve the power of detecting a treatment difference.     

Self-organization in the determination of the size of the axial structures in the embryogenesis of the clawed toad

Experiments were performed using X. laevis embryos during gastrulation and neurulation (stages 10, 11 1/2, 12 1/2, 13 1/2, 15 and 18). Part of presumptive epidermis and lateral plate mesoderm was removed, and embryos raised until stage 25. The size of axial structures (notochord, somite mesoderm, central nervous system) was determined using serial histological sections and compared with that of control embryos. In experimental embryos, the size of axial structures was decreased. Until a specific stage of development, close correlation was found between the volume of embryonic compartment corresponding to a particular, structure and the volume of presumptive epidermis and lateral plate mesoderm. This stage is individual for each axial organ: middle gastrula (stage 11 1/2) for notochord, late gastrula (stage 12 1/2) for somite mesoderm, and late neurula (stage 18) for central nervous system. This data suggest that differentiation pattern of ecto-mesodermal rudiment is subject to regulation during gastrulation-neurulation, and subdivision of ectoderm and mesoderm into axial and non-axial tissues is a self-organizing process.     

Role of the mediodorsal nucleus of the thalamus in the function of generalization in the cat

In chronic experiments on cats contribution of the thalamic mediodorsal nucleus to the organization of the processes of generalization and abstraction was studied by means of alternation method. Electrolytic ablation of the nucleus retarded the learning and impeded the initial stages of formation of the generalization function. Mechanisms of thalamic dementia are discussed.