Stargazin调节使君子酸受体亚基转运和突触靶向——疼痛治疗的新靶点

背景 使君子酸(α-amino-3 -hydroxy-5 -methy-4-isoxazole propionate,AMPA)受体是中介中枢神经系统兴奋性突触传递的主要受体,参与疼痛信号传递.Stargazin蛋白是一种AMPA受体调节蛋白,在AMPA受体中介的疼痛信号传递中扮演重要角色.目的 对Stargazin蛋白调节AMPA受体亚基在胞浆胞膜中的转运作用及与疼痛的关系作用进行回顾与总结.内容 Stargazin蛋白可调节AMPA受体不同亚基在胞浆胞膜转运,并通过与突触后膜致密蛋白-95 (postsynaptic density-95,PSD-95)的相互作用,促进AMPA受体亚基突触靶向；Stargazin还通过C末端自身磷酸化修饰改变与PSD-95蛋白相互作用的强度,控制AMPA受体的突触靶向.Stargazin通过调节AMPA受体的转运,间接调控AMPA受体中介的疼痛信号传递.趋向 下调Stargazin的表达或干扰其与兴奋性突触后PSD-95蛋白的相互作用,可间接抑制AMPA受体的功能,是未来疼痛治疗研究的新靶点.     

Neuroligin1与突触活动的相互作用

背景 Neuroligin1是突触细胞黏附分子(synaptic cell adhesion molecules,SynCAM)的一种,与Neurexin1β及突触后膜致密蛋白95(postsynaptic density protein 95,PSD-95)相结合形成跨突触复合物,这一跨突触信号可以中介使君子酸(a-amino-3-hydroxy-5-methyl4-isoxazole-propionate,AMPA)受体亚基突触靶向和突触前囊泡释放,在学习、记忆和疼痛中均具有重要作用.目的 对Neuroligin1与突触活动的相互作用进行回顾与总结.内容 Neuroligin1可通过调节AMPA受体、N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体的突触靶向来参与到突触活动中;相应的,突触活动也能诱导Neuroligin1的裂解和磷酸化,使突触活动趋于平衡.趋向 通过下调Neuroligin1的表达或干扰其与PSD-95蛋白或Neurexin1β的相互作用,可间接抑制AMPA受体的功能,是未来疼痛治疗的研究方向.     

突触后密度家族蛋白与疼痛研究进展

PSD是最早在电镜下发现的位于突触后膜的"致密物蛋白质".这种"致密物"是由一系列细胞骨架蛋白结合了多种与突触信号传递相关的分子(包括受体和各种激酶等)构成的特殊结构.其中一些成员,包括NMDA受体、CaMKII、PSD-93及PSD-95,与疼痛的发生、维持及治疗密切相关,并且彼此之间有着"微妙"的相互调节作用.     

钙黏蛋白在突触发育和突触可塑性调节中的作用

背景 钙黏蛋白（cadherin）是一类存在于细胞表面的跨膜糖蛋白,最初被认为是一种钙离子依赖性的细胞黏附分子,主要参与调节细胞黏附、促进细胞增殖、维持细胞极性等过程.近几年对cadherin调节突触发育和突触可塑性的研究取得了较大进展. 目的 围绕cadherin在突触发育和突触可塑性过程中的作用及其相关分子机制简要作一综述,旨在为神经系统疾病的治疗提供理论依据. 内容 Cadherin的概述,cadherin在突触发育和突触可塑性调节中的作用以及相关分子机制,cadherin与神经疾病. 趋向 随着cadherin在调节突触发育和突触可塑性过程中的研究不断深入,cadherin将成为治疗神经疾病的一个新型的靶点.     

Homer1a的研究进展

Homer1a是一种短型Homer蛋白,为突触后密度(postsynapie density,PSD)蛋白家族成员,即早基因(immediately early gene,IEG)表达产物,神经活动可诱导其快速而短暂的增加表达.组成型表达的长Homer与Shank蛋白一起将代谢型和离子型谷氨酸受体及其他受体连接成复合体,各受体的结构和功能通过长Homer发生联系,Homerla拮抗长Homer的这种功能.因此,活性诱导的Homerla表达增加具有重要的生理意义,在信号转导、受体在细胞的定位和突触形成、功能及可塑性方面起重要作用.其中Homerla对疼痛信号传递过程的影响及其对疼痛的治疗作用日益受到重视.     

海人藻酸受体功能调节机制在脊髓痛觉敏化中的作用

海人藻酸（kainate, KA）受体在中枢神经系统中广泛分布,通过调节外周和中枢感觉神经元之间的兴奋性信号参与疼痛处理。近年研究发现,多个与KA受体功能相关的蛋白在KA受体功能调节机制中发挥重要作用,从而参与伤害性疼痛信号的传递。文章通过综述KA受体特点、KA受体在疼痛通路中的表达与分布以及KA受体功能调节机制,包括...     

代谢型谷氨酸受体与吗啡耐受和依赖

谷氨酸通过离子型和代谢型谷氨酸受体(metabotropic Slutmate receptors,mGluRs)发挥作用,其中mGluRs是G蛋白耦联受体,分为3组共8个亚型,通过突触前和突触后作用参与离子通道活动调节、神经递质释放、突触传递和突触町塑性等生理病理过程.研究表明mGluRs与吗啡耐受和依赖密切有关.现就近年来各种类型的mGluRs参与吗啡耐受和依赖的研究进展作一综述.     

全麻药突触前作用机制的研究进展

影响突触传递是大多数麻醉药的作用机制,近来其突触前效应逐渐引起重视.本文阐述了麻醉药对神经递质释放和调节分子机制的最新研究进展,为分析全麻药对突触传递的效应及完整地揭示麻醉药影响的突触传递机制提供了良好的基础.     

血小板反应蛋白在突触形成中的作用及机制研究进展

目的对近年来血小板反应蛋白(thrombospondins,TSPs)在中枢神经系统(central nervous system,CNS)突触形成中的作用及机制进行综述。方法广泛查阅近年来与TSPs在CNS突触形成中有关的国内外文献,对TSPs结构特征、在CNS疾病中的作用及发生机制进行综述。结果 TSPs作为一种寡聚糖蛋白,在血管生成、炎症、成骨、细胞增殖和细胞凋亡等方面具有重要作用。在神经系统中,TSPs与电压依赖性钙通道、神经连接蛋白以及其他细胞外基质蛋白和细胞表面受体结合,参与和调节CNS中突触的形成、成熟以及功能等多个过程。结论 TSPs作为一种寡聚细胞外基质蛋白,在突触形成、CNS损伤后突触修复等方面发挥重要作用。     

抗胆碱酯酶药对突触传递功能与离子通道的影响

抗胆碱酯酶(AchE)药对突触传递功能及离子通道产生多部位、多环节的影响:通过干扰运动神经末梢钾、钙离子电流,增加或减少乙酰胆碱(Ach)的释放;作用于突触前Ach释放的反馈调节系统;抑制Ach的合成;缩短突触后离子通道开放时间;引起通道阻滞与脱敏感阻滞;阻抑Ach和受体的结合或自身与受体结合起兴奋作用。其结果是强化或抑制抗AchE药逆转非去极化阻滞的效应。     

2015年乳腺癌辅助化疗进展

【摘要】〓乳腺癌是危害我国女性健康的头号杀手,尽管近年来辅助化疗的研究进展突飞猛进,但临床中仍有不少问题未能明确,如辅助化疗的合适人群、化疗的开始时间、蒽环及紫杉类的地位和用法、强化维持治疗的作用、疗效及预后的生物标志物等。本文结合乳腺癌辅助化疗在临床上的常见问题和2015年各大乳腺癌会议阐述乳腺癌辅助化疗的最新进展。     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

西宁地区烧伤病人动脉血气分析观察

对高海拔地区的27例烧伤病人动脉血气变化进行了分析和观察。结果证明:无论是存活病人还是死亡病人伤后均存在有低氧血症问题。并且在死亡病人和烧伤合并吸入性损伤病人其低氧血症的发生早于单纯烧伤病人。提示:吸入性损伤病人应立即行气管切开术以保障氧气供给,单纯烧伤病人可常规吸氧以维持正常血 PaO_2,ARDS 均发生在合并吸入性损伤的病人,高频喷射通气技术对纠正低氧血症有一定效果。     

Controversies in Fistula in Ano

Managing a complex fistula in ano can be a daunting task for most surgeons; largely due to the two major dreaded complications—recurrence & fecal incontinence. It is important to understand the anatomy of the anal sphincters & the aetiopathological process of the disease to provide better patient care. There are quite a few controversies associated with fistula in ano & its management, which compound the difficulty in treating fistula in ano. This article attempts to clear some of those major controversies.     

β-半乳糖苷酶在体内外成骨细胞中的表达

目的 研究β—半乳糖苷酶(β—gal)在成骨细胞中的表达状况，为阐明MorquioB综合征的发病机制提供依据。方法 裸鼠各器官和骨组织标本行X-gal染色检测。抽取羊和人骨髓行骨髓基质细胞(BMSCs)培养，分为4组：I：Adv-hBMP-2转染组；Ⅱ：Adv—β—gal转染组；Ⅲ：未转染组；Ⅳ：地塞米松诱导组。分别行X-gal染色和RT-PCR检测β—gal的表达。结果 裸鼠骺板两侧、骨膜内面及松质骨的成骨细胞和破骨细胞可见多量β—gal的表达。未转染BMSCs组有少量β—gal的表达，其他3组细胞的β—gal表达增高。结论成骨细胞和破骨细胞可表达多量β—gal，该两种细胞的β—gal缺乏可能是MorquioB综合征骨骼异常的直接原因。     

Smoking-Attributable mortality in Spain in 2016

IntroductionSmoking-attributable mortality (SAM) is a valuable indicator that can be used to characterize the course and health burden of the smoking epidemic. The aim of this paper was to estimate SAM in Spain in 2016 in the population aged 35 and over, using the best available evidence.MethodsA smoking prevalence-dependent analysis based on the estimation of population-attributable fractions was performed. Smoking prevalence (never, former, and current smokers) was calculated from a combination of the Spanish Health Survey (2016) and the European Health Survey (2014); the relative risk of death among current and former smokers was taken from the follow-up of various cohorts; and mortality rates were obtained from National Center for Statistics data. SAM estimates are presented globally, and by sex, age groups, and major disease categories: cancer, cardiometabolic diseases and respiratory diseases.ResultsIn 2016, 56,124 deaths were attributed to tobacco consumption, 84% in men (47,000), and 50% in the population aged over 74 (27,795). Overall, 50% of SAM was due to cancer (28,281), 65% of which was lung cancer. One in 4 attributable deaths (13,849) occurred before the age of 65.ConclusionsOne in 7 deaths in Spain in 2016 were attributable to smoking. This estimation of SAM clearly highlights the great impact of smoking on mortality in Spain, mainly due to lung cancer and chronic obstructive pulmonary disease.     

MicroRNAs in hepatic pathophysiology in diabetes

MicroRNAs(miRNAs or miRs) are small approximately 22 nucleotide RNA species that are believed to regulate diverse metabolic and physiological processes.In the recent past,several reports have surfaced that demonstrate the role of miRNAs in various biological processes and numerous disease states.For a disease as complex as diabetes,the emergence of miRNAs as key regulators leading to the disease phenotype has added a novel dimension to the area of diabetes research.On the other hand,the liver,a metabolic hub,contributes in a major way towards maintaining normal glucose levels in the body as it can both stimulate and inhibit hepatic glucose output.This equilibrium is frequently disturbed in diabetes and hence,the liver assumes special significance considering the correlation between altered hepatic physiology and diabetes.While the understanding of the mechanisms behind this altered hepatic behavior is not yet completely understood,recent reports on the status and role of miRNAs in the diabetic liver have further added to the complexities of the knowledge of hepatic pathophysiology in diabetes.Here,we bring together the various miRNAs that play a role in the altered hepatic behavior during diabetes.     

Fluid-phase transcytosis in the primate epididymis in vitro and in vivo

Ligated tubules from the corpus epididymidis of men and monkeys were incubated in medium containing horseradish peroxidase (HRP) as a marker for fluid-phase endocytosis. HRP was localized by light and electron microscopy after 0, 15, 30 and 60 min of incubation. Movement between the cells was prevented by tight junctions, but bypass of this barrier was apparently achieved by an intracellular vesicular mechanism leading to a time-dependent appearance of HRP in the lumen. Uptake of HRP into basal cells and capture by the lysosomal apparatus of principal cells were also observed. HRP-filled vesicles also appeared in the basal, mid and apical cytoplasm of epithelial cells in the caput 1 h after injection of the tracer into the epididymal circulation of the monkey, suggesting that this pathway also operates in vivo.