细胞色素P450调节肝脏药物代谢的途径

大量研究认为细胞色素P450与药物性肝损伤的病理生理过程密切相关,对其在肝损伤的作用已成为当前研究的一个热点.主要介绍细胞色素P450与药物性肝损伤的相关研究进展.     

KSHV MicroRNAs Mediate Cellular Transformation and Tumorigenesis by Redundantly Targeting Cell Growth and Survival Pathways

Kaposi''s sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi''s sarcoma, primary effusion lymphoma and multicentric Castleman''s disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.     

牦牛MC1R基因的克隆测序及其分析研究

以麦洼牦牛、斯布牦牛、天祝牦牛和九龙牦牛为研究对象,对黑色素皮质素受体1(Melanocortin receptor I,MCIR)基因编码区进行了克隆测序及分析.结果表明,牦牛的MC1R基因编码区全长954 bp,编码317个氨基酸:4个牦牛品种间及与普通牛间在MC1R基因的编码区内共有13个碱基差异,无碱基的插入和缺失现象,编码蛋白共有9个氨基酸差异.MC1R蛋白为亲水性蛋白,无信号肽,有糖基化位点和7个跨膜区.系统进化分析显示,麦洼牦牛与斯布牦牛的MC1R基因相似性最近.本研究结果时今后开展MC1R基因与牦牛毛色性状的相关性分析以及牦牛的毛色遗传机理、基因定位、基因表达调控等研究具有重要的意义.     

Cloning, expression, and identification of genes involved in the conversion of DL-2-amino-Delta2-thiazoline-4-carboxylic acid to L-cysteine via S-carbamyl-L-cysteine pathway in Pseudomonas sp. TS1138

Two novel genes (tsB, tsC) involved in the conversion of DL-2-amino-Delta2-thiazoline-4-carboxylic acid (DL-ATC) to L-cysteine through S-carbamyl-L-cysteine (L-SCC) pathway were cloned from the genomic DNA library of Pseudomonas sp. TS1138. The recombinant proteins of these two genes were expressed in Escherichia coli BL21, and their enzymatic activity assays were performed in vitro. It was found that the tsB gene encoded an L-ATC hydrolase, which catalyzed the conversion of L-ATC to L-SCC, while the tsC gene encoded an L-SCC amidohydrolase, which showed the catalytic ability to convert L-SCC to L-cysteine. These results suggest that tsB and tsC play important roles in the L-SCC pathway and L-cysteine biosynthesis in Pseudomonas sp. TS1138, and that they have potential applications in the industrial production of L-cysteine.     

Design, synthesis, and anti-tumor activity of (2-O-alkyloxime-3-phenyl)-propionyl-1-O-acetylbritannilactone esters

The extracts of Inula britannica have anti-inflammatory, anti-bacterial, anti-hepatitic, and anti-tumor activities. Various sesquiterpene lactones with cytotoxic properties including 1-O-acetylbritannilactone (1) have been isolated from this Chinese medicinal plant. Eight derivatives of 1-O-acetylbritannilactone, (2-O-alkyloxime-3-phenyl)-propionyl-1-O-acetylbritannilactone esters were designed and synthesized. Four of these compounds were tested to show inhibitory activity on the growth of human leukemia HL-60 and cancer Bel-7402 cell lines.     

抗菌肽作用机制的研究进展

抗菌肽是一类来源于多种生物、能有效杀灭病原体的小分子多肽,具有活性谱广、作用强且迅速、不易产生耐药等众多优点.作为新一代抗感染候选药物,抗菌肽的作用机制还未完全清楚,但目前有两种观点已得到公认,即胞膜渗透作用破坏胞膜结构完整性和作用于胞内不同靶点干扰细菌生长及代谢平衡.本文主要就抗菌肽理化性质、二级结构、作用机制以及后两者间的关系做一总结,以便更好的理解抗菌肽的构效关系,为合理设计抗菌肽提供理论基础.     

Structural conservation and food habit-related liver expression of uncoupling protein 2 gene in five major Chinese carps

The full-length cDNA of grass carp (Ctenopharyngodon idellus) and silver carp (Hypophthalmichthys molitrix) uncoupling protein 2 (UCP2) was obtained from liver. The grass carp UCP2 cDNA was determined to be 1152 bp in length with an open reading frame that encodes 310 amino acids. Five introns (Intron 3, 4, 5, 6 and 7) in the translated region, and partial sequence of Intron 2 in the untranslated region of grass carp UCP2 gene were also obtained. Gene structure comparison between grass carp and mammalian (human and mouse) UCP2 gene shows that, the UCP2 gene structure of grass carp is much similar to that of human and mouse. Partial UCP2 cDNA sequences of bighead carp (Aristichthys nobilis) and mud carp (Cirrhinus molitorella), were further determined. Together with the common carp (Cyprinus carpio) UCP2 sequence from GenBank (AJ243486), multiple alignment result shows that the nucleotide and amino acid sequences of the UCP2 gene, were highly conserved among the five major Chinese carps that belong to four subfamilies. Using beta-actin as control, the ratio UCP2/beta-actin mRNA (%) was determined to be 149.4 +/- 15.6 (common carp), 127.4 +/- 22.1(mud carp), 96.7 +/- 12.7 (silver carp), 94.1 +/- 26.8 (bighead carp) and 63.7 +/- 16.2 (grass carp). The relative liver UCP2 expression of the five major Chinese carps, shows a close relationship with their food habit: benthos and detritus-eating fish (common carp and mud carp) > planktivorious fish (silver carp and bighead carp) > herbivorous fish (grass carp). We suggest that liver UCP2 might be important for Chinese carps to detoxify cyanotoxins and bacteria in debris and plankton food.     

Changes in landscape pattern of alpine wetlands on the Zoige Plateau in the past four decades

Based on RS, GIS and Apack software, the indices of landscape pattern such as landscape area index, landscape diversity index and landscape fragmentation index were chosen in order to describe changes in the spatial pattern of alpine wetland landscape on the Zoige Plateau during 1966–2000. Results showed that alpine wetland landscape was characteristic of marsh wetlands, which had the biggest patch number and the largest area. The alpine wetland landscape had higher spatial heterogeneity. The largest area appeared in Zoige County with the highest wetland ratio; comparatively, Aba County and Luqu County had much lower wetland ratio. The total area of alpine wetland landscape decreased rapidly during 1966–1986, but it began to increase after 1986. The wetland landscape area shrank by 59857.83 hm² during 1966–2000. The alpine wetland landscape showed the characteristics of concentrated distribution in the past four decades, with higher convergence and dominance indices. The centroid of wetland landscape moved 12.54 km in the northwest direction firstly, 11.33 km in the southeast direction, and then 1.1 km in the north direction.     

模拟氮沉降对长白山岳桦林下草本植物和土壤肥力的短期影响

选取长白山岳桦林中的岳桦-蟹甲草群落（Comm.Betula ermanii-Parasenecio forrestii）、岳桦-藜芦群落（Comm.Betula ermanii-Veratrum nigrum）和岳桦-小叶章群落（Comm.Betula ermanii-Deyeuxia purpurea）开展野外模拟氮沉降实验,采用野外原位模拟实验方法,设置对照（0 kg·hm^-2·a^-1）、低氮（30 kg·hm^-2·a^-1）、中氮（50 kg·hm^-2·a^-1）和高氮（100 kg·hm^-2·a^-1）4个氮处理水平,测定草本植物生长状况和土壤肥力,研究岳桦林下草本层植物和土壤肥力对氮沉降的短期响应。结果显示：（1）岳桦林下草本植物随氮沉降量的增加而加速生长,小叶章对氮沉降的响应较为敏感,藜芦次之,蟹甲草最弱;（2）氮添加造成林下土壤肥力发生变化,有机质含量下降,特别是岳桦-小叶章群落下的土壤有机质含量下降最明显;土壤总氮和速效氮含量增大,岳桦-蟹甲草群落下的土壤总氮和速效氮增加最多;土壤总磷和速效磷含量减小,岳桦-小叶章群落下的土壤总磷和速效磷含量的减少最多。本研究结果表明氮添加在短期内会促进长白山岳桦林下草本植物生长,尤其是小叶章的生长,加快土壤有机质的分解和磷的释放,逐步改变土壤肥力并反馈给植物,促使其进一步变化。