基于网络药理学方法分析黄精芡实汤治疗糖尿病前期的分子机制。运用系统药理学方法查找并从中药系统药理学数据库和分析平台(TCMSP,http://Lsp.nwu.edu.cn/tcmsp.php)筛选黄精芡实汤方剂中各药材的活性成分及靶点,查找糖尿病前期相关基...基于网络药理学方法分析黄精芡实汤治疗糖尿病前期的分子机制。运用系统药理学方法查找并从中药系统药理学数据库和分析平台(TCMSP,http://Lsp.nwu.edu.cn/tcmsp.php)筛选黄精芡实汤方剂中各药材的活性成分及靶点,查找糖尿病前期相关基因,确定黄精芡实汤治疗糖尿病前期的靶点。利用Cytoscape构建"药物成分-靶标"网络,筛选关键化合物。利用STRING建立蛋白质相互作用(protein-protein interaction,PPI)网络,并通过Cytoscape-CytoNCA拓扑分析筛选核心靶点。通过R-clusterProfiler对靶基因进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,以预测其可能的信号通路,探究其分子机制。筛选得到黄精芡实汤79种活性成分及与糖尿病相关的靶点785个,GO和KEGG富集分析发现其功能主要与羧酸循环、肽结合、酰胺结合、水解酶活性、激酶活性调节等反应有关,富集在AGE-RAGE信号通路、TNF信号通路、AMPK信号通路、IL-17信号通路、胰岛素信号通路等。Western blot检测结果显示,黄精芡实汤含药血清能够显著降低胰岛素抵抗模型细胞AKT1、AGE、RAGE蛋白表达量。黄精芡实汤治疗糖尿病前期具有多途径、多靶点、多层次的特征,主要机制包括以zhonghualiaoine、黄芩素、山柰酚、木犀草素为代表的多成分,以通过作用于AKT1靶点,阻滞AGE-RAGE信号通路发挥诱导胰岛素抵抗的作用,以改善糖尿病前期状态作用,也为后续黄精芡实汤治疗糖尿病前期的机制研究及临床应用提供依据。展开更多
Maize landraces White Dent and Golden Queen played a very important role in the pre-hybrid era of maize production in China. However, dozens of accessions with the same names of White Dent and Golden Queen are preserv...Maize landraces White Dent and Golden Queen played a very important role in the pre-hybrid era of maize production in China. However, dozens of accessions with the same names of White Dent and Golden Queen are preserved in China National Genebank （CNG）. The present study investigated the genetic diversity of these two important groups of maize landraces, as well as the relationships within and among them. Thirty-four landrace accessions with the name of White Dent and 10 with Golden Queen preserved in CNG were fingerprinted with 52 simple sequence repeats with tailed primer M13. Summary statistics including average number of alleles per locus, gene diversity/expected heterozygosity, and observed heterozygosity were carried out using PowerMarker ver. 3.25 software. The test of Hardy-Weinberg equilibrium （HWE） and linkage disequilibrium （LD） of all the 44 maize landrace accessions were also performed by PowerMarker. We observed a significant differentiation in terms of the average number of alleles between White Dent and Golden Queen （6.44 alleles per locus in White Dent, 4.48 in Golden Queen）, while both groups of maize landraces had a relatively high but similar gene diversity （0.61 of White Dent, 0.63 of Golden Queen）. The fixation index （FST） was only 0.0044, while the percentage of loci deviated from Hardy-Weinberg equilibrium within these two groups of White Dent and Golden Queen was 32.69 and 3.92%, respectively. The rather high genetic diversity and average number of alleles per locus confirmed that both groups of landraces had a rather broad germplasm base. The extremely low fixation index showed that there was little genetic variation between White Dent and Golden Queen and the molecular variation within these two groups was remarkably high, indicating no genetic drift between White Dent and Golden Queen and suggesting different improvement approaches to these two important groups of landraces. Hardy-Weinberg equilibrium test revealed that the group of White Dent was deviated from 展开更多
基于转录组测序技术对黄精芡实汤治疗的糖尿病前期模型小鼠进行测序,探究治疗糖尿病前期可能的机制。首先对BKS-DB小鼠正常组、糖尿病前期模型组(模型组)和黄精芡实汤治疗组(治疗组)进行转录组测序,获取小鼠骨骼肌标本中的差异表达基因...基于转录组测序技术对黄精芡实汤治疗的糖尿病前期模型小鼠进行测序,探究治疗糖尿病前期可能的机制。首先对BKS-DB小鼠正常组、糖尿病前期模型组(模型组)和黄精芡实汤治疗组(治疗组)进行转录组测序,获取小鼠骨骼肌标本中的差异表达基因,并对各组进行血清生化指标检测,筛选得到黄精芡实汤干预糖尿病前期的核心基因。运用基因本体论(Gene Ontology,GO)数据库和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库对差异表达基因进行GO和KEGG信号通路富集分析,最后进行RT-qPCR验证。结果发现模型小鼠经黄精芡实汤治疗后,空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(HOMA-IR)、血清总胆固醇(serum total cholesterol,TC)、甘油三脂(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平明显降低。差异基因筛选结果中,模型组与正常组相比共有1666个差异表达基因。治疗组与模型组相比共有971个差异表达基因。其中与胰岛素抵抗功能调节密切相关的IL-6、NR3C2基因在模型组和正常组之间显著上调,VEGFA基因在模型组和正常组之间显著下调,而在治疗组和模型组之间IL-6、NR3C2和VEGFA基因表达结果相反。GO功能富集分析发现,生物学过程注释中以细胞合成、周期和代谢过程为主,在细胞组分注释中以细胞内过程控制为主,在分子功能注释中以绑定分子功能为主。KEGG通路富集分析发现,涉及PTK6通路、CD28依赖的PI3K/AKT通路、p53途径等。因此,黄精芡实汤对糖尿病前期状态有改善作用,机制可能与IL-6、NR3C2和VEGFA调节的细胞周期、凋亡、PI3K/AKT通路、p53途径等生物学途径有关。展开更多
Understanding genetic diversity and population structure of landraces is important in utilization of these germplasm in breeding programs. In the present study, a total of 143 core maize landraces from the South Maize...Understanding genetic diversity and population structure of landraces is important in utilization of these germplasm in breeding programs. In the present study, a total of 143 core maize landraces from the South Maize Region （SR） of China, which can represent the general profile of the genetic diversity in the landraces germplasm of SR, were genotyped by 54 DNA microsatellite markers. Totally, 517 alleles （ranging from 4 to 22） were detected among these landraces, with an average of 9.57 alleles per locus. The total gene diversity of these core landraces was 0.61, suggesting a rather higher level of genetic diversity. Analysis of population structure based on Bayesian method obtained the samilar result as the phylogeny neighbor-joining （N J） method. The results indicated that the whole set of 143 core landraces could be clustered into two distinct groups. All landraces from Guangdong, Hainan, and 15 landraces from Jiangxi were clustered into group 1, while those from the other regions of SR formed the group 2. The results from the analysis of genetic diversity showed that both of groups possessed a similar gene diversity, but group 1 possessed relatively lower mean alleles per locus （6.63） and distinct alleles （91） than group 2 （7.94 and 110, respectively）. The relatively high richness of total alleles and distinct alleles preserved in the core landraces from SR suggested that all these germplasm could be useful resources in germplasm enhancement and maize breeding in China.展开更多
文摘基于网络药理学方法分析黄精芡实汤治疗糖尿病前期的分子机制。运用系统药理学方法查找并从中药系统药理学数据库和分析平台(TCMSP,http://Lsp.nwu.edu.cn/tcmsp.php)筛选黄精芡实汤方剂中各药材的活性成分及靶点,查找糖尿病前期相关基因,确定黄精芡实汤治疗糖尿病前期的靶点。利用Cytoscape构建"药物成分-靶标"网络,筛选关键化合物。利用STRING建立蛋白质相互作用(protein-protein interaction,PPI)网络,并通过Cytoscape-CytoNCA拓扑分析筛选核心靶点。通过R-clusterProfiler对靶基因进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,以预测其可能的信号通路,探究其分子机制。筛选得到黄精芡实汤79种活性成分及与糖尿病相关的靶点785个,GO和KEGG富集分析发现其功能主要与羧酸循环、肽结合、酰胺结合、水解酶活性、激酶活性调节等反应有关,富集在AGE-RAGE信号通路、TNF信号通路、AMPK信号通路、IL-17信号通路、胰岛素信号通路等。Western blot检测结果显示,黄精芡实汤含药血清能够显著降低胰岛素抵抗模型细胞AKT1、AGE、RAGE蛋白表达量。黄精芡实汤治疗糖尿病前期具有多途径、多靶点、多层次的特征,主要机制包括以zhonghualiaoine、黄芩素、山柰酚、木犀草素为代表的多成分,以通过作用于AKT1靶点,阻滞AGE-RAGE信号通路发挥诱导胰岛素抵抗的作用,以改善糖尿病前期状态作用,也为后续黄精芡实汤治疗糖尿病前期的机制研究及临床应用提供依据。
基金supported by the Special Program for Crop Germplasm Resources of the Ministry of Agriculture [(NB07-2130135-(25-30)-05]Natural Science Foundation of Beijing (6071003)+1 种基金Innovation Platform Program for Basic Research of Agricultural Breeding in Beijing (YZPT02-06)Scientific and Technological Key Project in Chongqing for Elite Variety Innovation of Rice and Maize (CSTC 2007AB1045)
文摘Maize landraces White Dent and Golden Queen played a very important role in the pre-hybrid era of maize production in China. However, dozens of accessions with the same names of White Dent and Golden Queen are preserved in China National Genebank （CNG）. The present study investigated the genetic diversity of these two important groups of maize landraces, as well as the relationships within and among them. Thirty-four landrace accessions with the name of White Dent and 10 with Golden Queen preserved in CNG were fingerprinted with 52 simple sequence repeats with tailed primer M13. Summary statistics including average number of alleles per locus, gene diversity/expected heterozygosity, and observed heterozygosity were carried out using PowerMarker ver. 3.25 software. The test of Hardy-Weinberg equilibrium （HWE） and linkage disequilibrium （LD） of all the 44 maize landrace accessions were also performed by PowerMarker. We observed a significant differentiation in terms of the average number of alleles between White Dent and Golden Queen （6.44 alleles per locus in White Dent, 4.48 in Golden Queen）, while both groups of maize landraces had a relatively high but similar gene diversity （0.61 of White Dent, 0.63 of Golden Queen）. The fixation index （FST） was only 0.0044, while the percentage of loci deviated from Hardy-Weinberg equilibrium within these two groups of White Dent and Golden Queen was 32.69 and 3.92%, respectively. The rather high genetic diversity and average number of alleles per locus confirmed that both groups of landraces had a rather broad germplasm base. The extremely low fixation index showed that there was little genetic variation between White Dent and Golden Queen and the molecular variation within these two groups was remarkably high, indicating no genetic drift between White Dent and Golden Queen and suggesting different improvement approaches to these two important groups of landraces. Hardy-Weinberg equilibrium test revealed that the group of White Dent was deviated from
文摘基于转录组测序技术对黄精芡实汤治疗的糖尿病前期模型小鼠进行测序,探究治疗糖尿病前期可能的机制。首先对BKS-DB小鼠正常组、糖尿病前期模型组(模型组)和黄精芡实汤治疗组(治疗组)进行转录组测序,获取小鼠骨骼肌标本中的差异表达基因,并对各组进行血清生化指标检测,筛选得到黄精芡实汤干预糖尿病前期的核心基因。运用基因本体论(Gene Ontology,GO)数据库和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库对差异表达基因进行GO和KEGG信号通路富集分析,最后进行RT-qPCR验证。结果发现模型小鼠经黄精芡实汤治疗后,空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(HOMA-IR)、血清总胆固醇(serum total cholesterol,TC)、甘油三脂(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平明显降低。差异基因筛选结果中,模型组与正常组相比共有1666个差异表达基因。治疗组与模型组相比共有971个差异表达基因。其中与胰岛素抵抗功能调节密切相关的IL-6、NR3C2基因在模型组和正常组之间显著上调,VEGFA基因在模型组和正常组之间显著下调,而在治疗组和模型组之间IL-6、NR3C2和VEGFA基因表达结果相反。GO功能富集分析发现,生物学过程注释中以细胞合成、周期和代谢过程为主,在细胞组分注释中以细胞内过程控制为主,在分子功能注释中以绑定分子功能为主。KEGG通路富集分析发现,涉及PTK6通路、CD28依赖的PI3K/AKT通路、p53途径等。因此,黄精芡实汤对糖尿病前期状态有改善作用,机制可能与IL-6、NR3C2和VEGFA调节的细胞周期、凋亡、PI3K/AKT通路、p53途径等生物学途径有关。
基金supported by the Program for Germplasm Innovation and Utilization from the Minis-try of Agrculture of China (2006BAD13B03)Beijing Natural Science Foundation (6071003)Doctoral Foundation of Southwest University, China(SWUB2008037)
文摘Understanding genetic diversity and population structure of landraces is important in utilization of these germplasm in breeding programs. In the present study, a total of 143 core maize landraces from the South Maize Region （SR） of China, which can represent the general profile of the genetic diversity in the landraces germplasm of SR, were genotyped by 54 DNA microsatellite markers. Totally, 517 alleles （ranging from 4 to 22） were detected among these landraces, with an average of 9.57 alleles per locus. The total gene diversity of these core landraces was 0.61, suggesting a rather higher level of genetic diversity. Analysis of population structure based on Bayesian method obtained the samilar result as the phylogeny neighbor-joining （N J） method. The results indicated that the whole set of 143 core landraces could be clustered into two distinct groups. All landraces from Guangdong, Hainan, and 15 landraces from Jiangxi were clustered into group 1, while those from the other regions of SR formed the group 2. The results from the analysis of genetic diversity showed that both of groups possessed a similar gene diversity, but group 1 possessed relatively lower mean alleles per locus （6.63） and distinct alleles （91） than group 2 （7.94 and 110, respectively）. The relatively high richness of total alleles and distinct alleles preserved in the core landraces from SR suggested that all these germplasm could be useful resources in germplasm enhancement and maize breeding in China.
