We collected the data on the Sendeng-4 chemical composition corresponding targets through the literature and from Drug Bank, SuperT arget, TTD(Therapeutic Targets Database) and other databases and the relevant signali...We collected the data on the Sendeng-4 chemical composition corresponding targets through the literature and from Drug Bank, SuperT arget, TTD(Therapeutic Targets Database) and other databases and the relevant signaling pathways from the KEGG(Kyoto Encyclopedia of Genes and Genomes) database and established models of the chemical composition-target network and chemical composition-target- disease network using Cytoscape software, the analysis indicated that the chemical composition had at least nine different types of targets that acted together to exert effects on the diseases, suggesting a "multi-component, multi-target" feature of the traditional Mongolian medicine. We also employed the rat model of rheumatoid arthritis induced by Collgen Type II to validate the key targets of the chemical components of Sendeng-4, and three of the key targets were validated through laboratory experiments, further confirming the anti-inflammatory effects of Sendeng-4. In all, this study predicted the active ingredients and targets of Sendeng-4, and explored its mechanism of action, which provided new strategies and methods for further research and development of Sendeng-4 and other traditional Mongolian medicines as well.展开更多
Blood-based mieroRNA (miRNA) signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behi...Blood-based mieroRNA (miRNA) signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, "preserved" miRNAs, i.e., miRNAs that are not dysregulated in any disease, and their biological impact have been explored to a very limited extent. We set out to systematically determine their role in regulatory networks by defining groups of highly-dysregulated miRNAs that contribute to a disease signature as opposed to preserved housekeeping miRNAs. We further determined preferential targets and pathways of both dysregulated and preserved miRNAs by computing multi-layer networks, which were compared between housekeeping and dysregulated miRNAs. Of 848 miRNAs examined across 1049 blood samples, 8 potential housekeepers showed very limited expression variations, while 20 miRNAs showed highly-dysregulated expression throughout the investigated blood samples. Our approach provides important insights into miRNAs and their role in regulatory networks. The methodology can be applied to systematically investigate the differences in target genes and pathways of arbitrary miRNA sets.展开更多
基金supported by the National Natural Science Foundation of China(No.81160550)Inner Mongolia Natural Science Foundation(No.2013JQ03)2010 Science and Technology Project of social development in Inner Mongolia
文摘We collected the data on the Sendeng-4 chemical composition corresponding targets through the literature and from Drug Bank, SuperT arget, TTD(Therapeutic Targets Database) and other databases and the relevant signaling pathways from the KEGG(Kyoto Encyclopedia of Genes and Genomes) database and established models of the chemical composition-target network and chemical composition-target- disease network using Cytoscape software, the analysis indicated that the chemical composition had at least nine different types of targets that acted together to exert effects on the diseases, suggesting a "multi-component, multi-target" feature of the traditional Mongolian medicine. We also employed the rat model of rheumatoid arthritis induced by Collgen Type II to validate the key targets of the chemical components of Sendeng-4, and three of the key targets were validated through laboratory experiments, further confirming the anti-inflammatory effects of Sendeng-4. In all, this study predicted the active ingredients and targets of Sendeng-4, and explored its mechanism of action, which provided new strategies and methods for further research and development of Sendeng-4 and other traditional Mongolian medicines as well.
基金funded by the European Union (FP7 Best Ageing,6031)Saarland University,Medical Faculty.Authors acknowledge the contribution of Comprehensive Biomarker Center (CBC),Heidelberg,in funding the study
文摘Blood-based mieroRNA (miRNA) signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, "preserved" miRNAs, i.e., miRNAs that are not dysregulated in any disease, and their biological impact have been explored to a very limited extent. We set out to systematically determine their role in regulatory networks by defining groups of highly-dysregulated miRNAs that contribute to a disease signature as opposed to preserved housekeeping miRNAs. We further determined preferential targets and pathways of both dysregulated and preserved miRNAs by computing multi-layer networks, which were compared between housekeeping and dysregulated miRNAs. Of 848 miRNAs examined across 1049 blood samples, 8 potential housekeepers showed very limited expression variations, while 20 miRNAs showed highly-dysregulated expression throughout the investigated blood samples. Our approach provides important insights into miRNAs and their role in regulatory networks. The methodology can be applied to systematically investigate the differences in target genes and pathways of arbitrary miRNA sets.