细胞对机械刺激感知的生物力学机制

细胞作为机体的基本单位,始终处于一个受力环境中。微环境中的细胞不仅受化学信号的影响,还受基质刚度、外界力载荷及胞外基质(ECM)结构的调控,这些都能影响细胞分化、迁移、形态发生、增殖等方面的生物学反应。目前,部分学者致力于细胞生物力学的应用和机制方面的探索,但对于细胞力学感知机理的认知仍无法形成一个完整的定论。本文将就整合素、G蛋白耦联受体、张力活化通道(SAC)、细胞核等介导的细胞生物力学感知通路作一综述。     

ACE、CYP11B2基因多态性与慢性心力衰竭患者醛固酮脱逸的关系

目的:研究CYP11B2-344C/T(醛固酮合成酶)及ACEI/D(血管紧张素转化酶)基因多态性与慢性心力衰竭(CHF)患者实施ACEI治疗后出现醛固酮脱逸表现的关系。方法:回顾分析2008年10月至2012年10月我科收治的252例CHF患者,全部患者应用ACEI治疗3月,醛固酮在基线以上为醛固酮脱逸,依据此标准将患者分为研究组(脱逸组,n=86)与对照组(非脱逸组,n=166),依据PCR(聚合酶链反应)及RFLP(片段长度限制多态性)等方法分别检测两组CYP11B2及ACE基因型,比较两组基因型频率的分布。结果:252例患者中,共86例出现醛固酮脱逸,发生率为34.1%。全部受试患者CYP11B2基因型及ACE基因型频率与Weinberg-Hardy平衡均相符(P均0.05)。研究组ACE I/D三种基因型的组间分布与对照组相较,无统计学差异(P0.05);CYP11B2基因TT型的频率与对照组相较,呈明显统计学差异(P0.05),等位基因C/T频率的组间分布同对照组相较,亦呈明显差异(P0.05)。研究组ACEI/D的基因多态性及CYP11B2-344C/T的多态性中,基因型联合组间分布与对照组相较,无统计学差异(P0.05)。结论:ACE基因多态性与CHF患者ACEI治疗后出现醛固酮脱逸无关,CYP11B2基因T等位基因及TT基因型多态性可能是CHF患者ACEI治疗后发生醛固酮脱逸的高危因素。醛固酮脱逸时,ACE、CYP11B2基因不具有协同效果。     

革兰氏阴性菌的Cpx双组分调控系统

细菌主要通过单组分、双组分、三组分调控系统来适应外界环境变化以保证自身的正常生长和繁殖。Cpx系统是革兰氏阴性菌中普遍存在的双组分调控系统之一,作为双组分调控系统的重要一元,它由细胞膜组氨酸蛋白激酶CpxA、细胞质响应调节蛋白CpxR以及细胞周质空间辅助调节蛋白CpxP构成。本文着重介绍了Cpx系统各组分的结构特征,并结合前人的文献和我们近期的研究成果,综述了Cpx系统信号整合的最新研究进展,提出了尚待解决的问题及进一步的研究方向,为科研人员对Cpx双组分调控系统的研究提供一定的帮助。     

天然来源抗肿瘤化合物作用于MAPK通路的机制

天然来源抗肿瘤活性产物是抗肿瘤药物先导化合物的重要资源。促分裂原活化蛋白激酶(MAPK)通路是细胞内重要的信号转导系统,可以调节细胞的生长、凋亡、黏附、迁移等过程,继而影响肿瘤的发生、发展、侵袭、转移,是潜在的抗肿瘤药物作用靶点之一。本文将对天然来源化合物作用于MAPK信号通路的靶点分子及生物效应进行阐述,为肿瘤的化学预防及治疗提供启发。     

Cytokinesis and cancer： Polo loves ROCK＇n＇ Rho（A）

Cytokinesis is the last step of the M (mitosis) phase, yet it is crucial for the faithful division of one cell into two. Cytokinesis failure is often associated with cancer. Cytokinesis can be morphologically divided into four steps: cleavage furrow initiation, cleavage furrow ingression, midbody formation and abscission. Molecular studies have revealed that RhoA as well as its regulators and effectors are important players to ensure a successful cytokinesis. At the same time, Polo-like kinase 1 (Plk1) is an important kinase that can target many substrates and carry out different functions during mitosis, including cytokinesis. Recent studies are beginning to unveil a closer tie between Plk1 and RhoA networks. More specifically, Plk1 phosphorylates the centralspindlin complex Cyk4 and MKLP1/CHO1, thus recruiting RhoA guanine nucleotide-exchange factor (GEF) Ect2 through its phosphopeptide-binding BRCT domains. Ect2 itself can be phosphorylated by Plk1 in vitro. Plk1 can also phosphorylate another GEF MyoGEF to regulate RhoA activity. Once activated, RhoA-GTP will activate downstream effectors, including ROCK1 and ROCK2. ROCK2 is among the proteins that associate with Plk1 Polo-binding domain (PBD) in a large proteomic screen, and Plk1 can phosphorylate ROCK2 in vitro. We review current understandings of the interplay between Plk1, RhoA proteins and other proteins (e.g., NudC, MKLP2, PRC1, CEP55) involved in cytokinesis, with particular emphasis of its clinical implications in cancer.     

Polymorphisms in PPARD, PPARG and APM1 associated with four types of Traditional Chinese Medicine constitutions

Based on the theory of constitution of Traditional Chinese Medicine (TCM), the human population is divided into nine constitutions including one balanced constitution (Normality) and eight unbalanced constitutions (Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution). Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms (SNPs) in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Pro12Ala in Yin-deficiency and PPARD rs2076167, APM1 rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotype13 (Hap13) of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hap14 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes of PPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.     

省藤属11种棕榈藤亲缘关系的AFLP分析

分别对棕榈科11种省藤属植物的基因组总DNA进行EcoRⅠ+TaqⅠ与EcoRⅠ+PstⅠ限制性双酶切,采用AFLP标记技术分析其亲缘关系.用12对引物对11种棕榈藤的30个代表植株进行选择性扩增,共得到扩增谱带998条,其中多态条带981条,多态性带达98.3%.用MEGA 4.0软件中p-distance计算结果显示,11种棕榈藤30份样本间的遗传距离在0.050～0.391之间,平均为0.297;当遗传距离为0.15时,11种棕榈藤可聚为4个组;第Ⅰ组包括直立省藤、滇南省藤、杖藤、小省藤、勐腊鞭藤、长鞭藤、褐鞘省藤共7个种,第Ⅱ组仅有云南省藤1个种,第Ⅲ组由宽刺藤和泽生藤2个种构成,第Ⅳ组仅含省藤一种,可能为新种.AFLP检测结果表明,以形态特征为依据所划分的鞭轴亚属(Rhachicirrus)植物单独聚为一类;而原始省藤亚属(Protocalamus)和省藤亚属(Calamus)两个亚属的物种在整个聚类图上互相交叉渗透,各亚属植物未能独立成组;省藤亚属植物种之间遗传分化程度较高.因此,省藤属植物之间的亲缘关系和分亚属的标准、依据还需更深入地研究.     

黑蕊虎耳草中岩白菜素没食子酸酯类及其对丙型肝炎丝氨酸蛋白酶的抑制作用

研究了黑蕊虎耳草(Saxifraga melanocentra)中岩白菜素衍生物的化学和生物活性,从其地上部分分离纯化得到一个新的岩白菜素没食子酸酯,主要通过1维和2维核磁共振波谱鉴定结构为11-氧-(4-氧甲基没食子酰)岩白菜素[11-O-(4-O-methylgalloyl) bergenin(1)] ,该化合物对丙型肝炎丝氨酸蛋白酶(HCVNS3serine protease)具有抑制活性,其IC50为0.32 mg/mL。     

Targeted gene disruption by use of a group 11 intron （targetron） vector in Clostridium acetobutylicum

Dear Editor： Clostridium acetobutylicum, a gram-positive, anaerobic, spore-forming bacterium, is capable of using a wide variety of carbon sources to produce acetone, butanol and ethanol. To improve solvent productivity of C. acetobutylicum, metabolic engineering is considered as a useful tool in developing strains with industrially desirable character-istics. However, to date, there are few useful methods for genetic manipulation of C. acetobutylicum, especially for gene disruption. To our knowledge, two types of vectors, including non-replicative and replicative integrative plasmids, have been developed for gene-inactivation in C. acetobutylicum. By using non-replicative integrative plasmids, buk and solR genes of C. acetobutylicum were inactivated [1,2]. However, due to their low frequencies of transformation and recombination, the non-replicative integrative plasmids are usually transformed at less than 1 integrative transformant per mg plasmid DNA. To obtain the integrative mutant, it may require higher transformation frequencies up to 10^5, but the typical transformation fre-quencies were reported at 10^3 [3].[第一段]