生物标签的探索:中药药性研究的新模式

中药药性研究在中药研究领域中处于核心与基础的地位。近年来,随着组学技术与生物信息学在该领域中的应用,一个新的概念——"生物标签"应运而生。生物标签是指可以表征药物作用(活性与毒性)及机制的内源性靶点,包括代谢物靶点、蛋白质靶点及基因靶点等。近年来,以生物标签为切入点的中药药性研究体系已逐步建立和完善。在此,本文对近年来的相关文献进行收集整理,分析总结生物标签在中药药性研究中的运用情况。生物标签可以用于表征中药的活性与毒性,为中药的安全使用及其应用范围的扩展提供了重要的参考依据。

Study on the Correlation between the Expression of Angiogenic Factor VEGF and Microsatellite Instability in Gastric Adenocarcinoma

Objective: To investigate the correlation between the microsatellite instability (MSI) and the expression of vascular endothelial growth factor (VEGF) in gastric adenocarcinoma. Methods: PCR SSCP method was used to detect MSI of thirty cases with gastric adenocarcinoma at five loci in each patient. Expression of VEGF was examined by the method of immunohistochemistry. Results: The positive of MSI was in 13 patients out of 30 patients (43.4%) in our study. Positive VEGF Immunostaining was detected in 18 patients (60.0%). VEGF was decreased in microsatellite instability high (MSI H) gastric adenocarcinoma. Conclusion: MSI H and microsatellite stable (MSS) gastric adenocarcinoma may follow a different pathway of angiogenesis. The low frequency of VEGF expression among MSI H cancer may partially explain why these cancers are less aggressive.

Proteome-based biomarkers in pancreatic cancer

Pancreatic cancer,as a highly malignant cancer and the fourth cause of cancer-related death in world,is characterized by dismal prognosis,due to rapid disease progression,highly invasive tumour phenotype,and resistance to chemotherapy.Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved.A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis.Furthermore,biomarkers for targeting,directing and assessing therapeutic intervention,as well as for detection of residual or recurrent cancer are also needed.Thus,the identification of adequate biomarkers in pancreatic cancer is of extreme importance.Recently,accompanying the development of proteomic technology and devices,more and more potential biomarkers have appeared and are being reported.In this review,we provide an overview of the role of proteome-based biomarkers in pancreatic cancer,including tissue,serum,juice,urine and cell lines.We also discuss the possible mechanism and prospects in the future.That information hopefully might be helpful for further research in the field.

Functional genomic approach to the study of biodiversitywithin Trichoderma

Trichoderma is a fungal genus of great and demonstrable biotechnological value, but its genome is poorly surveyed compared with other model microorganisms. Due to their ubiquity and rapid substrate colonization, Trichoderma species have been widely used as biocontrol organisms for agriculture, and their enzyme systems are widely used in industry. Therefore, there is a clear interest to explore beyond the phenotype to exploit the underlying genetic systems using functional genomics tools. The great diversity of species within the Trichoderma genus, the absence of optimized systems for its exploration, and the great variety of genes expressed under a wide range of ambient conditions are the main challenges to consider when starting a comprehensive functional genomics study. An initial project started by three Spanish groups has been extended into the project TRICHOEST, funded by the EU (FP5, QLRT-2001-02032) to target the transcriptome analysis of selected Trichoderma strains with biocontrol potential, in conditions related to antagonism, nutrient stress and plant interactions. Once specific conditions were defined, cDNA libraries were produced and used for EST sequencing. Nine strains from seven Trichoderma species have been considered in this study and an important amount of gene sequence data has been generated, analyzed and used to compare the gene expression in different strains. In parallel to sequencing, genomic expression studies were carried out by means of macro-arrays to identify genes expressed in specific conditions. In silico analysis of DNA sequencing data together with macro-array expression results have lead to a selection based on the potential use of the gene sequences. The selected clone sequences were completed and cloned in appropriate vectors to initiate functional analysis by means of expression studies in homologous and heterologous systems.

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

HER2 and VEGF expression in breast cancer and their correlations

Objective:The aim of our study was to detect the correlation between the expressions of HER2 and VEGF in breast cancer, and their relations with some pathological factors. Methods:By immunohistochemistry technique, the expressions of HER2 and VEGF in the post-operation samples of 117 cases with breast cancer were assessed, and their relations with some pathological factors were analysed by statistical methods. Fifty samples of hyperplasia of mammary glands were observed as the control. Results: The positive expression rates of HER2 and VEGF in breast cancer were both significantly higher than those in hyperplasia of mammary gland (P<0.05). The expressions of HER2 and VEGF were both correlated to lymph node metastasis (P<0.05), but showed no relations with age, histological type, histological stage, tumor size (P>0.05). The positive expression rate of HER2 had a positive correlation with those of VEGF (P<0.05, r=0.373). Conclusion: The expressions of HER2 and VEGF have no correlations with age, histological type, histological stage, tumor size, but are closely related with lymphatic metastasis. The positive expression rates of HER2 shows a positive correlation with those of VEGF.

Characteristics of Antisense Non-coding RNA in the INK4 Locus and Its Roles in Disease

Abstract With the development of genome-wide sequencing technology, 195 types of functional long non-coding RNAs （lncRNAs） have so far been found, and their cellular roles are gradually being revealed. Now lncRNAs have become a hotspot in the life science. These small molecules exist in almost all higher eukaryotes, and have very important regulatory roles in these organisms. This review briefly summarizes recent progress in researches on antisense non-coding RNA in the INK4 locus.

Characterizing and annotating the genome using RNA-seq data

Bioinformatics methods for various RNA-seq data analyses are in fast evolution with the improvement of sequencing technologies. However, many challenges still exist in how to efficiently process the RNA-seq data to obtain accurate and comprehensive results. Here we reviewed the strategies for improving diverse transcriptomic studies and the annotation of genetic variants based on RNA-seq data. Mapping RNA-seq reads to the genome and transcriptome represent two distinct methods for quantifying the expression of genes/transcripts. Besides the known genes annotated in current databases, many novel genes/transcripts(especially those long noncoding RNAs) still can be identified on the reference genome using RNA-seq. Moreover, owing to the incompleteness of current reference genomes, some novel genes are missing from them. Genome-guided and de novo transcriptome reconstruction are two effective and complementary strategies for identifying those novel genes/transcripts on or beyond the reference genome. In addition, integrating the genes of distinct databases to conduct transcriptomics and genetics studies can improve the results of corresponding analyses.

A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation

Thousands of proteins undergo arginine methylation,a widespread post-translational modification catalyzed by several protein arginine methyltransferases(PRMTs).However,global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each PRMT.Here,we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and translation.We demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing proteins.Different PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation motifs.Importantly,RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation regions.Moreover,inhibition of PRMTs globally alternates alternative splicing(AS)and suppresses translation.In particular,ribosomal proteins are extensively modified with methylarginine,and mutations in their methylation sites suppress ribosome assembly,translation,and eventually cell growth.Collectively,our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation.

Assessing protein-DNA interactions: Pros and cons of classic and emerging techniques

Investigation of protein-DNA interactions provides important information for understanding gene function and regulation, but identification and validation of specific interactions remain major challenges in the post-genomics era. Therefore, effective and economical methods to assess protein-DNA interactions are highly sought-after by molec- ular biologists.

Genomes and evolutionary genomics of animals

Alongside recent advances and booming applications of DNA sequencing technologies, a great number of complete genome sequences for animal species are available to researchers. Hundreds of animals have been involved in whole genome se- quencing, and at least 87 non-human animal species＇ complete or draft genome sequences have been published since 1998. Based on these technological advances and the subsequent accumulation of large quantity of genomic data, evolutionary genomics has become one of the most rapidly advancing disciplines in biology. Scientists now can perform a number of comparative and evolu- tionary genomic studies for animals, to identify conserved genes or other functional elements among species, genomic elements that confer animals their own specific characteristics and new phenotypes for adaptation. This review deals with the current ge- nomic and evolutionary research on non-human animals, and displays a comprehensive landscape of genomes and the evolution- ary genomics of non-human animals. It is very helpful to a better understanding of the biology and evolution of the myriad forms within the animal kingdom [Current Zoology 59 （1）： 87-98, 2013].