靶向蛋白质泛素修饰及降解在前列腺癌治疗中的机遇与挑战

前列腺癌是中国发病率增长最快的男性肿瘤,抗雄激素治疗耐药是导致前列腺癌患者预后差的主要原因。因此,解决耐药性难题是前列腺癌转化研究的关键问题。哺乳动物细胞利用泛素-蛋白酶体系统实现蛋白质的靶向降解。因此,前列腺癌中关键的癌基因如雄激素受体（AR）的上游泛素化调控因子（如去泛素化酶）是潜在的治疗靶点。然而,这些酶具有较广的底物谱系,存在脱靶的可能性。近来,基于泛素-蛋白酶体系统开发的蛋白质降解靶向嵌合体（proteolysis-targeting chimeras,PROTAC）技术是最具前景和革命性的新型抗癌药物研发技术,能够利用特定E3泛素连接酶对靶蛋白进行降解而不影响其他底物。与传统小分子抑制剂相比,PROTAC分子在克服耐药性以及针对不可成药的靶点方面拥有巨大优势。目前,针对AR的PROTAC降解剂已在II期临床取得了成功,靶向蛋白质泛素化及降解途径的新技术将有望为前列腺癌的临床治疗带来新的突破。     

基于果蝇口腔感染的肠道训练免疫模型研究（英文）

目的 利用果蝇作为遗传工具从个体和分子层面研究果蝇的训练免疫效应,并为后续深入研究其分子机制提供依据。方法 首先构建无菌果蝇模型,在此基础上构建果蝇成虫及跨发育阶段训练免疫模型,用两种革兰氏阴性菌——胡萝卜软腐欧文氏菌（Erwinia carotovora carotovora 15）及铜绿假单胞菌（Pseudomonas aeruginosa）分别经口腔感染果蝇。在第一次感染完全消退后进行再次感染,然后通过比较果蝇在两个感染阶段的存活率和细菌量来衡量训练免疫的潜在效果。通过实时荧光定量PCR检测相应先天免疫相关基因的表达水平,研究革兰氏阴性菌对免疫缺陷（IMD）通路的诱导作用。结果 果蝇成虫及幼虫初次感染均可提高二次感染后的生存率、细菌清除效率及死亡时能承受的最高细菌负荷;二次感染的果蝇中,IMD通路中免疫反应基因的基础表达比未感染的高,这提供了获得感染抗性的分子基础;果蝇的免疫反应主要发生在中肠,二次免疫比初次免疫的效应更迅速且剧烈;二次免疫的果蝇中,肠道干细胞的数量显著多于初次感染。结论 果蝇肠道中强大的训练免疫可由同源或异源革兰氏阴性菌口腔感染引发,且免疫记忆可在整个发育阶段持...     

Antisense EGFR sequence reverses the growth properties of human liver carcinoma cell line BEL-7404 in vitro

A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore, JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene expression and reverse the malignant growth properties of human liver carcinoma cells in vitro.     

Four New C19-Diterpenoid Alkaloids from Aconitum nagarum Stapf

Four new aconitine-type C₁₉-diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A–D ( 1–4 ), together with eleven known compounds ( 5–15 ). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50%.     

Redescription of the Chengjiang arthropod Squamacula clypeata Hou and Bergström, from the Lower Cambrian, south-west China

The anatomy of the arthropod Squamacula clypeata Hou and Bergström, 1997 from the Lower Cambrian Chengjiang Lagersta¨tte is redescribed based on four newly excavated specimens. The new material was collected from localities recently discovered in the Kunming area, Yunnan Province, south-west China, and preserves remarkable details of the ventral morphology, revealed by preparation. Squamacula clypeata is dorsoventrally flattened and rounded in outline. The cephalon was covered by a wide, short shield, with a large doublure and a pair of uniramous antennae on the ventral side. The thorax consists of nine somites, each protected by a tergite and carrying at least one pair of biramous limbs. The pygidium is covered with a small rounded tergum. The endopod is segmented, equipped with short spines on the inner margin of the coxa and a claw-like structure distally, and the exopod flap-like, fringed with setae. The limbs in the pygidium are like those in the thorax in shape. Squamacula was most probably a nektobenthic predator. The spinose endopod could walk, grasp and grind. The large flap-like exopod was adapted for swimming and respiration. Its affinities lie with the Arachnomorpha, but the relationships with other known taxa remain ambiguous.     

Increased cyclin B1/CDC 2 kinase activity and phosphorylation of Bcl-2 associated with paclitaxel-induced apoptosis in human nasopharyngeal carcinoma cells

Paclitaxel is a potential cancer chemotherapeutic agent for ovary, breast, and head and neck cancers; its effects on nasopharyngeal carcinoma (NPC) have not been reported previously. This study investigated the cytotoxic mechanism of paclitaxel in two NPC cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with pacli-taxel showed convoluted nuclei, condensed chromatin and decreased cellular and nuclear volume, and also exhibited genomic DNA degradation into multiple oligonucleosomal fragments, suggesting that pacli-taxel induced apoptosis in these cells. The effects of paclitaxel on apoptosis-related proteins including Bcl-2, Bax and CDC 2 were also detected. Although the levels of Bcl-2 and Bax were not changed in NPC cells following treatment with 5 nM-1 μM of paclitaxel, phosphorylation of Bcl-2 was significantly observed in the cells treated with 1 μM of paclitaxel for 12 hours. In addition, cyclin B1-associated CDC 2 kinase was highly activated in the NPC cells exposed to paclitaxel even at low (5 nM) concentration, and this result is associated with the finding that low concentration of paclitaxel is able to induce apoptosis in NPC cells.     

中国异皮属线虫一新种（线虫纲：垫刃目：异皮科）

本文描述采自河北省滦县寄生于白茅Ｉｍｐｅｒａｔｅ ｃｙｌｉｎｄｒｉｃａ ｖａｒ．Ｍａｊｏｒ的异皮属线虫一新种,中华异皮线虫Ｈｅｔｅｒｏｄｅｒａ ｓｉｎｅｎｓｉｓ ｓｐ．ｎｏｖ．;新种孢囊为柠檬形,阴门膜孔为两侧单膜孔型,下桥发达有泡状突;二龄幼虫口针基部球前部略凹陷,口孔侧唇外缘融合王头晕第１环纹内,即无明显侧唇,其体侧区有３条侧线与体环纹呈不完全网格状交叉;雄虫侧区有３条侧线与体环纹呈完全网格状     

红细胞4．1蛋白与血型糖蛋白C／D结合位点研究进展

红细胞膜骨架与脂双层间存在着相互作用,其中带4.1蛋白与血型糖蛋白C/D间的相互作用对维持正常红细胞的形态和机械稳定性起着重要作用,研究表明,带4.1蛋白在血型糖蛋白C、D上的结合位点分别位于血型糖蛋白C的第82～98位氨基酸残基和血型糖蛋白D的第61～77位氨基酸残基．     

硒对培养人胚肝细胞Ⅲ型前胶原,羟脯氨酸合成的影响

原代培养人胚肝细胞经１．１５６×１０￣(－７）ｍｏｌ／Ｌ硒预处理４ｈ,加入２０ｍｍｏｌ／Ｌ四氟化碳作用２０ｈ,观察硒对其Ⅲ型前胶原（ＰＣⅢ）和羟脯氨酸（Ｈｙｐ）生成的影响。结果培养液中ＰＣⅢ水平、细胞内Ｈｙｐ含量及细胞内外丙二醛（ＭＤＡ）水平均降低,与未加硒对照组比较差别有显著性（Ｐ＜０．０１）。而硒谷腕甘肽过氧化物酶（Ｓｅ－ＧＳＨ－ＰＸ）活性则较对照组显著增高（Ｐ＜０．００１）,且ＰＣⅢ水平与Ｓｅ－ＧＳＨ－Ｐ＿Ｘ／ＭＤＡ比值呈负相关（ｒ＝－０．９１５６,Ｐ＜０．０１）。提示硒可提高Ｓｅ－ＧＳＨ－Ｐ＿Ｘ／ＭＤＡ比值,抑制脂质过氧化激发的肝细胞胶原合成。     

植物种质资源的超低温保存研究进展（综述）

植物种质资源的超低温保存研究进展（综述）殷晓辉,舒理慧（武汉大学生命科学学院,武汉４３００７２）ＡＤＶＡＮＣＥＳＩＮＣＲＹＯＰＲＥＳＥＲＶＡＴＩＯＮＲＥＳＥＡＲＣＨＯＮＰＬＡＮＴＧＥＲＭＰＬＡＳＭ￥ＹｉｎｇＸｉａｏｈｕｉ;ＳｈｕＬｉｈｕｉ（Ｓｃｈｏｏ...