Synthesis and cytotoxic evaluation of novel 7-O-modified genistein derivatives

Two series of genistein (=5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) derivatives with heterocycles were prepared, in which genistein and heterocyclic moieties were separated by C(2) and C(3) spacers. Among the 24 compounds we prepared, 22, i.e., 3a-3k and 4a-4k, were reported for the first time, while the preparation of 2a and 2b was reported in our recent paper. The cytotoxic activities of these compounds were evaluated against human chronic myeloid leukemia cells (K562) and a human nasopharyngeal epidermoid tumor cell line (KB). Compounds 4a, 4d, 4e, 4h, and 4i showed remarkable anticancer activities in vitro that are comparable with 5-fluorouracil, an canonical anticancer drug. Structure-effect relationships were also discussed based on the experimental data obtained.     

Epigenetic hypothesis tests for methylation and acetylation in a triple microarray system.

To fully elucidate the functional relationship between DNA methylation and histone hypoacetylation in gene silencing, we have developed an integrated "triple" microarray system that allows us to begin to decipher the influence of epigenetic hierarchies on the regulation of gene expression in cancer cells. Our hypothesis is that in the promoter region of a silenced gene, reversal of two epigenetic factors (i.e., DNA demethylation and/or histone hyperacetylation) is highly correlated with gene reexpression after treatment of the human epithelial ovarian cancer cell line CP70 with the drug combination 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and trichostatin A (TSA), an inhibitor of histone deacetylases. To estimate the posterior probabilities for genes with altered expression, DNA methylation and histone acetylation status measured with a triple-microarray system, we have employed an established empirical Bayes model. Two methods have been proposed to test our hypothesis that DNA demethylation and histone hyperacetylation are highly correlated among those up-regulated genes. One method follows a weighted least squares regression, while the other is derived from a chi-square statistic. The data derived by these approaches, which have been further verified through bootstrap analyses, support the proposed epigenetic correlation (p-values are less than 0.001). Further simulations suggest that even if the constant variance and normality assumptions do not hold, the power of those two tests is robust.     

粘着斑激酶在bFGF引起细胞迁移中的动态变化及意义

本文旨在观察不同浓度碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)引起体外培养的ECV-304细胞迁移时粘着斑激酶(focal adhesion kinase,FAK)的动态变化及FAK与细胞迁移的关系。建立体外培养的ECV-304细胞划痕损伤模型,观察经不同剂量(0、5、10、15 ng/ml)bFGF作用12-24 h内细胞迁移距离(电脑图像测定)和FAK蛋白含量(Western blot)、活性(免疫沉淀加Western blot)和mRNA(RT-PCR)的动态变化。用免疫细胞化学(ABC法)染色研究整合素α3表达。结果发现,低浓度(5 ng/ml)bFGF促进细胞迁移,FAK蛋白含量增加42.07±2.02％、活性增加71.37±1.85％,与对照组比,差异显著(P<0.05),并与迁移距离呈正相关(P<0.05)。高浓度(15 ng/ml)bFGF抑制细胞迁移,FAK的变化相反。FAK mRNA的变化比蛋白变化早出现6 h。与对照细比,各实验组整合素α3表达无明显差异。由此可见,不同剂量bFGF对ECV-304细胞迁移的双相调节作用与FAK含量、活性与mRNA表达呈正相关,FAK在bFGF引起的细胞迁移的信号转导途径中起着重要作用。     

tmRNA的结构与功能

tmRNA是一类具有类似tRNA分子和mRNA分子双重功能的小分子RNA,它在一种特殊的翻译模式——反式翻译模式过程中发挥重要作用。最近又发现它与基因的表达调控及细胞周期的调控等生命过程密切相关。因此,关于tmRNA的研究已经引起了研究者的高度重视,它将是RNA组学研究的一个重要内容。文章主要论述了近年来关于tmRNA结构和功能方面的一些研究进展。Abstract: tmRNA is a dual small RNA similar to a tRNA and a mRNA which plays an important role in an unusual mode of translation——trans translation. Recently, it was found that tmRNA had something to do with regulating gene expression and cell cycle. So the researchers have paid much attention on such area. Furthermore, it is an important part in RNomics era. This article reviews the progress about the structure and function of tmRNA in recent years.     

广州市帽峰山森林公园森林景观多样性分析

城市森林对改善和美化城市景观起着重要作用.文中在景观分类的基础上,应用景观生态学原理,选取多样性指数、优势度、分离度和斑块密度指数四个指标,从景观的类型多样性、格局多样性和斑块多样性三个方面,对广州市帽峰山森林公园森林景观进行多样性分析.结果表明,经济果林、竹林破碎化程度较高;阔叶混交林类型保持完好,分离度也最小,黎葫林分离度最大;景观类型比例分布最不均衡,组成帽峰山森林公园的各景观类型所占比例差异小于广州地区.     

表达双功能融合蛋白（sCAR-EGF）腺病毒载体的构建及其活性检测

为了提高腺病毒载体用于基因治疗的靶向性,采用PCR和体外连接的方法构建了柯萨奇病毒-腺病毒受体(Coxsackievirus-AdenovirusReceptor)胞外段sCAR和表皮生长因子(Epidermalgrowthfactor)EGF融合基因,然后将此融合基因插入穿梭质粒pDC315。利用Ad-MAX腺病毒系统,将重组质粒pDC315-sCAR-EGF与腺病毒骨架质粒pBHGloxΔE13cre共同转染AD-293细胞,成功包装出一种复制缺陷型腺病毒Ad5-CMV-sCAR-EGF。经PCR鉴定该病毒含有sCAR-EGF融合基因片段,Westernblotting证实该病毒能表达sCAR-EGF融合蛋白。体外试验证实该病毒感染细胞所产生的融合蛋白能够引导携带报告基因的腺病毒Ad5-CMV-luc高水平感染肿瘤细胞,为高水平表达EGFR的肿瘤的靶向性基因治疗提供了新的手段。     

Synthesis and cytotoxic evaluation of a series of resveratrol derivatives

A total of 17 resveratrol (=(E)-5-[2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol) derivatives were synthesized from resveratrol (RES) through a facile approach. Among them, 13 compounds, 2 and 6-17, were reported for the first time, while 1 and 3-5 had already been reported several years ago. The cytotoxic activities of these compounds were evaluated against human nasopharyngeal epidermoid tumor cell line KB, and compounds 1 and 8-11 showed strong anticancer activities in vitro, comparable with that of 5-fluorouracil, an anticancer drug. On the basis of the experimental data obtained, structure-activity relationships are discussed.     

Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28

Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. CML28, a recently discovered cancer-testis (CT) antigen from chronic myelogenous leukemia, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A*0201 is one of the most common histocompatibility molecule in Chinese, we aim at identifying CML28 peptides presented by HLA-A*0201. A panel of CML28-derived antigenic peptides was predicted using a computer-based program. Four peptides with highest predicted score were synthesized and tested for their binding affinities to HLA-A*0201 molecule. Then these peptides were assessed for their immunogenicity to elicit specific immune responses mediated by CTLs both in vitro, from PBMCs sourced from four healthy HLA-A*0201⁺ donors, and in vivo, in HLA-A*0201 transgenic mice. One of the tested peptides, CML28_(173–181), induced peptide-specific CTLs in vitro as well as in vivo, which could specifically secrete IFN-γ and lyse major histocompatibility complex (MHC)-matched tumor cell lines endogenously expressing CML28 antigen and CML28_(173–181) pulsed Jurkat-A2/Kb cells, respectively. These results demonstrate that CML28_(173–181) is a naturally processed and presented CTL epitope with HLA-A*0201 motif and has a promising immunogenicity both in vitro and in vivo. As CML28 is expressed in a large variety of histological tumors besides chronic myelogenous leukemia, we propose that the newly identified epitope, CML28_(173–181), would be of potential use in peptide-based, cancer-specific immunotherapy against a broad spectrum of tumors.     

广西洞穴贝尔蛛属一新种记述(蜘蛛目,幽灵蛛科)

记述产自广西乐业县的幽灵蛛科贝尔蛛属1新种,命名为同乐贝尔蛛Belisana tongle sp.nov..模式标本保存在河北大学生命科学学院.