A Potent,Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K_d of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.     

大剂量睾丸照射对大鼠神经内分泌功能的影响

本研究应用 Wistar 雄性大鼠,接受10Gy X 射线睾丸局部照射,分别于照射后1、23、63及97天处死,观察下丘脑内源性阿片肽、垂体和睾丸内分泌功能的变化,试图阐明电离辐射神经内分泌效应及其作用机理。实验结果表明,照射后1天,下丘脑β-内啡肽(B-EP)含量明显增加,而血清黄体生成素(LH)、卵泡刺激素(FSH)和睾丸酮(TS)及睾丸环磷酸腺苷(cAMP)含量有不同程度的降低;照射后23天,β-EP 下降,并低于对照组,而 LH、FSH、TS 及 cAMP 明显高于对照组;照射后63天,β-EP 仍维持照射后23天的水平,亮氨酸脑啡肽(L-Enk)明显降低,LH 和 FSH 仍持续增高,而 TS 和 cAMP 明显低于对照组;照射后97天,LH 和 FSH 回降,但仍明显高于对照组,TS 和cAMP 仍持续降低,睾丸组织发生严重损伤。     

一种新颖的基于内分泌激素调控的智能控制器

神经内分泌系统对体内各种激素的调控，具备较好的自适应性和稳定性等特点。基于神经内分泌系统的激素分泌阋节原理和下丘脑-垂体-肾上腺素调节回路模型，设计了一种新颖的智能控制器，并给出了其控制参数的调整方法。该智能控制器具有两级控制体系结构，一级控制器能够根据实时控制偏差，依据激素分泌规律动态调整二级控制器的控制参数，从而提高了其稳定性和适应性。仿真结果表明：与传统PID控制器相比，该智能控制器的控制性能具有优越件。     

美托洛尔对舒张性心力衰竭兔神经内分泌系统的影响

目的研究美托洛尔对舒张性心力衰竭兔神经内分泌系统的影响。方法雄性新西兰兔30只随机分为3组：手术组在右侧肾动脉上1cm处行腹主动脉缩窄术;手术治疗组从术后第1天起应用美托洛尔治疗;假手术组作为对照组。术后观察心衰的临床表现,定期复查超声心动图,并监测全身和心肌局部AngⅡ、ET-1、NE和NT—proBNP变化。结果手术治疗组的心衰发生率明显低于手术组,心室结构和功能达到显著改善,血清AngⅡ（25．57vs38．16,P〈0．01）、ET-1（21．14vs35．96,P〈0．01）和血清与心肌NE（97．90vs128．51,P〈0．01;11．77vs17．28,P〈0．05）、NT—proBNP（221．92vs305．76,P〈0．01;24．33vs30．53,P〈0．05）显著降低。结论美托洛尔可有效抑制DHF兔的全身和心肌局部神经内分泌系统激活.     

胸腺神经内分泌肿瘤手术治疗及预后因素

目的　探讨胸腺神经内分泌肿瘤（neuroendocrine tumors of the thymus，NETT）的临床特点、手术为主的综合治疗经验及相关预后因素。方法　2004年12月至2013年12月在北京协和医院诊治并经手术病理证实为NETT的患者26例，其中男性18例，女性8例，回顾性分析其临床表现、影像学资料、手术为主的综合治疗方案、围术期并发症及随访情况。结果　26例患者就诊时中位年龄为46岁（13~75岁），中位病程为3.5个月（1~84个月）。起病隐匿，临床症状不特异，7例合并库欣综合征，1例合并多发性内分泌腺瘤病1型。胸部增强CT可见胸腺区占位。所有患者均接受开胸手术切除治疗，22例肿瘤大体完整切除。无围术期死亡病例，出现并发症3例。16例患者术后行辅助治疗。术后病理类型为高分化的神经内分泌癌20例（典型类癌8例，不典型类癌12例），低分化的神经内分泌癌6例（小细胞神经内分泌癌5例，大细胞神经内分泌癌1例）。Masaoka-Koga分期为Ⅰ期4例，Ⅱ期3例，Ⅲ期12例，Ⅳ期7例。长期随访结果示中位生存期为51.0个月，3年、5年生存率为71.0%和44.6%。多因素分析结果示肿瘤分化程度（P=0.039）及分期（P=0.012）是影响预后的因素。结论　NETT是一种罕见的侵袭性极强的恶性病变，临床表现不特异，早期诊断及治疗存在很大难度，早期行增强CT有助于发现病变及评估手术可行性。肿瘤分化程度及分期可能是影响预后的主要因素。     

Exocytosis,endocytosis and recycling of secretory vesicles in neuroendocrine cells,and its regulation by cortical actin

The cortical actin network is a mesh of filaments distributed beneath the plasmalemma that dynamically reacts in response to stimuli. This dynamic network of cortical filaments, together with motor myosin partners, adjusts the plasmalemma tension, organizes membrane protein microdomains, remodels the cell surface and drives vesicle motion in order to fine-tune exocytosis, endocytosis and recycling of secretory vesicles. In this review, we discuss how these mechanisms work in secretory cells.     

神经内分泌因子对体外培养肝细胞ApoB100 mRNA丰度的影响

目的分析神经内分泌因子胰岛素、胰高血糖素和瘦蛋白对体外培养肝细胞ApoB100 mRNA丰度的影响,以阐明其在奶牛肝极低密度脂蛋白(VLDL)组装与转运中的调控作用。方法在体外培养的肝细胞培养液中分别添加胰岛素、胰高血糖素和廋蛋白,应用实时荧光定量PCR法检测神经内分泌因子对体外培养肝细胞中载脂蛋白B100(ApoB100)mRNA丰度的影响。结果随着细胞培养液中胰岛素和瘦蛋白浓度的增加,肝细胞中ApoB100 mRNA的水平逐渐降低;而随着培养液中胰高血糖素浓度的升高,ApoB100 mRNA水平呈先升高后降低的趋势。结论神经内分泌因子胰岛素、胰高血糖素和瘦蛋白通过影响ApoB100 mRNA的表达水平来调控肝细胞中VLDL的组装与转运。     

Evidence of neuroendocrine disruption in freshwater mussels exposed to municipal wastewaters

The purpose of this study was to test the hypothesis that exposure to municipal effluents can disrupt the neuroendocrine system in Elliptio complanata freshwater mussels. The capacity of ozonation to mitigate these effects was also examined. Mussels were exposed for 14 days to a continuous flow of increasing concentrations of the effluent before and after ozonation. Neuroendocrinal effects were examined by tracking changes in acetylcholinesterase, glutamate, gamma-aminobutyrate, serotonin, dopamine and their respective adenylcyclase activities in synapse membranes, monoamine oxidase and vitellogenin-like proteins. Oxidative stress and damage were examined by superoxide dismutase and lipid peroxidation, respectively, in the visceral tissues. The results revealed that the exposure of freshwater mussels increased the levels of vitellogenin-like proteins in both the primary-treated and ozonated effluents, dopamine and glutamate, and decreased the turnover of the neurostimulant acetylcholine. Moreover, these endpoints were significantly correlated with oxidative stress and damage. A canonical analysis of the responses revealed that dopamine and the neuroexcitatory neuromediators-acetylcholesterase and glutamate-were the endpoints more strongly related with oxidative stress and damage. Mussel morphology and estrogenic biomarkers (vitellogenin-like proteins, gonad lipid stores) were also significantly related, albeit to a lesser extent, to oxidative stress and damage. In general, ozone treatment was not sufficient to mitigate the observed neuroendocrinal effects in freshwater mussels. We conclude that the continuous exposure of freshwater mussels to municipal wastewater effluents leads to neuroendrocinal alterations and to oxidative stress.     

X线照射弓状核损伤雄性大鼠头部对神经内分泌的影响

已知初生期大鼠注射谷氨酸钠(MSG)可引起下丘脑弓状核严重损毁。本研究表明,雄性大鼠出生后2d及4d,腹腔注射MSG(4mg/g体重),成年后神经内分泌系统功能发生明显改变。用MSG处理雄性大鼠经10Gy X线头部照射后48h,与非照射MSG处理组比较,血清LH、FSH、TSH和GH水平以及血清和尿睾丸酮含量趋于降低;而血清PRL水平趋于增高,垂体和睾丸cAMP含量变化不明显。提示,MSG损毁弓状核雄性大鼠神经内分泌系统调节功能失常,经10 GyX线头部照射后48h,不能出现正常大鼠头部照射后下丘脑-垂体系统功能增强的效应。     

低水平辐射诱导免疫系统兴奋效应的研究现状

本文扼要地叙述了近年来有关低水平辐射刺激免疫功能的主要实验研究结果。指出了低水平辐射全身作用后免疫增强过程中细胞间的相互关系,强调辅助性Ｔ细胞激活的中心地位。提供了低水平辐射促进Ｔ细胞信息传递的主要环节的资料。对文献中流行的两种解释免疫兴奋效应的假说进行了分析评价,指出低水平辐射优先损伤抑制性Ｔ细胞或促进前体细胞凋亡的设想未能获得实验资料的支持。提出了低水平辐射改变神经内分泌调节功能在免疫兴奋效应