A new method for post Genome-Wide Association Study (GWAS) analysis of colorectal cancer in Taiwan

Recently, single nucleotide polymorphisms (SNPs) located in specific loci or genes have been identified associated with susceptibility to colorectal cancer (CRC) in Genome-Wide Association Studies (GWAS). However, in different ethnicities and regions, the genetic variations and the environmental factors can widely vary. Therefore, here we propose a post-GWAS analysis method to investigate the CRC susceptibility SNPs in Taiwan by conducting a replication analysis and bioinformatics analysis. One hundred and forty-four significant SNPs from published GWAS results were collected by a literature survey, and two hundred and eighteen CRC samples and 385 normal samples were collected for post-GWAS analysis. Finally, twenty-six significant SNPs were identified and reported as associated with susceptibility to colorectal cancer, other cancers, obesity, and celiac disease in a previous GWAS study. Functional analysis results of 26 SNPs indicate that most biological processes identified are involved in regulating immune responses and apoptosis. In addition, an efficient prediction model was constructed by applying Jackknife feature selection and ANOVA testing. As compared to another risk prediction model of CRC for European Caucasians population, which performs 0.616 of AUC by using 54 SNPs, the proposed model shows good performance in predicting CRC risk within the Taiwanese population, i.e., 0.724 AUC by using 16 SNPs. We believe that the proposed risk prediction model is highly promising for predicting CRC risk within the Taiwanese population. In addition, the functional analysis results could be helpful to explore the potential associated regulatory mechanisms that may be involved in CRC development.     

FamPipe: An Automatic Analysis Pipeline for Analyzing Sequencing Data in Families for Disease Studies

In disease studies, family-based designs have become an attractive approach to analyzing next-generation sequencing (NGS) data for the identification of rare mutations enriched in families. Substantial research effort has been devoted to developing pipelines for automating sequence alignment, variant calling, and annotation. However, fewer pipelines have been designed specifically for disease studies. Most of the current analysis pipelines for family-based disease studies using NGS data focus on a specific function, such as identifying variants with Mendelian inheritance or identifying shared chromosomal regions among affected family members. Consequently, some other useful family-based analysis tools, such as imputation, linkage, and association tools, have yet to be integrated and automated. We developed FamPipe, a comprehensive analysis pipeline, which includes several family-specific analysis modules, including the identification of shared chromosomal regions among affected family members, prioritizing variants assuming a disease model, imputation of untyped variants, and linkage and association tests. We used simulation studies to compare properties of some modules implemented in FamPipe, and based on the results, we provided suggestions for the selection of modules to achieve an optimal analysis strategy. The pipeline is under the GNU GPL License and can be downloaded for free at http://fampipe.sourceforge.net.

This is a PLOS Computational Biology Software article.

     

c-src在大鼠卵巢中的表达及其在原始卵泡生长启动中的作用初探

目的：研究原癌基因c-src在大鼠卵巢的表达,及其在原始卵泡启动过程中的作用。方法：取2日龄SD雌性大鼠卵巢,在Waymouth培养体系中培养0．4、8d后,首先采用RT-PCR方法证实大鼠卵巢中有c-src的表达,再体外合成其RNA小干扰片段（small interference RNA,siRNA）转染培养中的卵巢组织进行RNA干扰,用HE染色及RT-PCR筛选最佳干扰片断并用慢病毒包装后检测干扰效果。结果：随着培养天数的增加,原始卵泡在卵泡总数中所占比例逐渐减少;c—src mRNA在原始卵泡中有表达,经筛选用最佳干扰片断siRNA1慢病毒包装进行RNA干扰,发现干扰后,与空白组、空白载体组相比,最佳干扰组c—src mRNA含量明显下降,原始卵泡在卵泡总数中所占比例相对更多,原始卵泡发育受到抑制。结论：c-src在原始卵泡中有表达,并在一定程度上促进了原始卵泡的发育。     

Synthesis and evaluation of ursolic acid derivatives as potent cytotoxic agents

Structural modification was performed at the C-3 and C-28 positions of ursolic acid (UA). Ten UA derivatives with distinct electrical property were synthesized. They could be divided into two groups according to their charge under physiological conditions: (1) Group I negatively charged and (2) Group II positively charged. The anti-proliferative capability of the derivatives was evaluated against HepG2, AGS, HT-29 and PC-3 cells by the MTT assay. Flow cytometry and Annexin V/PI dual staining assay were carried out to explore the antitumor mechanism. The results showed the cytotoxic capacity of the compounds was: Group I相似文献   

产木聚糖酶厌氧真菌菌株筛选及产酶培养条件研究*

从12株分离自反刍动物瘤胃及粪样的厌氧真菌中筛选到一株木聚糖酶高产菌,编号为A4,初步鉴定为Neocallimastix属菌。以稻草秸、玉米秸、花生秸、滤纸片段为发酵底物,经39℃厌氧培养,A4菌产生的木聚糖酶活分别为14.31U/mL、11.39U/mL、6.99U/mL和13.38U/mL。对A4菌产生木聚糖酶的条件进行优化,结果发现,培养基中无细胞瘤胃液浓度对A4菌产生的木聚糖酶活无显著影响;但酵母膏浓度从1.0g/L降至0.5g/L后,A4菌产生的木聚糖酶活显著下降(P<0.05)。     

乳酸菌肽聚糖部分免疫增强作用的研究

以小鼠为实验材料研究了肽聚糖部分免疫学活性,结果表明:小鼠腹腔注射肽聚糖后,相比对照组而言, Z8、Z17肽聚糖组巨噬细胞(MΦ)吞噬率、吞噬指数都明显提高,血清溶菌酶活性显著增强,统计学分析差异极显著(P＜0．01)。肽聚糖对鸡新城疫疫苗免疫增强效果的观察表明,与对照组相比,Z8、Z17肽聚糖组能明显提高新城疫抗体水平,并使抗体高峰水平维持时间延长。同时动物实验也表明,两个肽聚糖组间活性差异不显著,没有特异性。     

机体胆汁酸肠-肝轴的研究进展

机体肠道与肝脏间的交互作用形成肠-肝轴,后者的紊乱是肝脏疾病发生的重要原因,而良好的肠道稳态和肝脏的保护对维持机体内环境的稳定起着重要作用。胆汁酸(胆盐)作为肠-肝轴循环中的重要组成成分,不仅参与了机体营养物质的消化代谢,还作为一种信号分子和代谢调节因子,能够激活核受体和G蛋白偶联受体(GPCR)信号通路参与调节肝脏脂质、葡萄糖和能量平衡,维持机体代谢平衡。本文将结合近年来有关胆汁酸的研究进展,从胆汁酸的来源、在肠-肝轴中的循环以及胆汁酸在机体中的作用等方面进行综述,以加深对肠-肝轴重要性的理解。     

Bromochloromethane,a Methane Analogue,Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract

Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production.     

Regulatory role for l-arginine in the utilization of amino acids by pig small-intestinal bacteria

We recently reported that bacteria from the pig small intestine rapidly utilize and metabolize amino acids (AA). This study investigated the effect of L-arginine on the utilization of AA by pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the pig small intestine. Bacteria were incubated at 37°C for 3 h in anaerobic AA media containing 0-5 mmol/L of arginine to determine the effect of arginine on the bacterial utilization of AA. Amino acids in the medium plus cell extracts were analyzed by high-performance liquid chromatography. Results indicated concentration-dependent increases in the bacterial utilization of arginine and altered fluxes of arginine into ornithine and citrulline in the bacteria. Net glutamine utilization increased in pure bacterial strains with increased concentrations of arginine. With the addition of arginine, net utilization of threonine, glycine, phenylalanine and branched-chain AA increased (P<0.05) in Streptococcus sp. and Klebsiella sp., but decreased in E. coli. Net utilization of lysine, threonine, isoleucine, leucine, glycine and alanine by jejunal or ileal mixed bacteria decreased (P<0.05) with the addition of arginine. Complete utilization of asparagine, aspartate and serine were observed in pig small-intestinal bacteria after 3 h of incubation. Overall, the addition of arginine affected the metabolism of the arginine-family of AA and the serine- and aspartate-family of AA in small-intestinal bacteria and reduced the utilization of most AA in ileal mixed bacteria. These novel findings indicate that arginine exerts its beneficial effects on swine nutrition partially by regulating AA utilization and metabolism in the small-intestinal microbiota.     

血浆及外周血中性粒细胞内髓过氧化物酶水平在冠心病临床诊断中的意义

目的:研究冠心病患者外周循环血中性粒细胞中髓过氧化物酶指数(MPXI)和血浆中髓过氧化物酶(MPO)浓度的改变及两者间相关性,探讨两者在冠心病临床诊断中的意义。方法:随机选取冠心病患者55例,按病情严重程度分为急性冠脉综征(ACS)组35例[包括不稳定心绞痛(UAP)组21例和急性心肌梗死(AMI)组14例]和稳定心绞痛(SAP)组20例,同时随机选取健康体检人员60例为正常对照组;采用ADVIA2120全自动血细胞分析仪检测MPXI,取血浆用ELISA法检测血浆MPO浓度。结果:ACS组MPXI(6.31±4.24)显著高于SAP组(3.38±2.14)和对照组(2.78±2.12),差异有统计学意义(P<0.05);SAP组MPXI高于正常对照组,差异无统计学意义(P>0.05)。ACS组血浆中MPO(1204.07±838.61 pmol/L)显著高于SAP组(755.97±426.23 pmol/L)和对照组(290.45±99.87 pmol/L),差异有统计学意义(P<0.05);SAP组MPO显著高于正常对照组,差异有统计学意义(P<0.05)。SAP组MPXI与MPO无相关性(r=0.424,P>0.05),ACS组MPXI与MPO呈负相关(r=-0.536,P<0.05)。结论:MPXI和MPO在冠心病的诊断中有意义,MPXI与血浆中MPO在ACS组中呈负相关。