Activated nuclear factor-κB (NF-κB) plays an important role in the development of cardiovascular disease (CVD) through its regulated genes and microRNAs (miRNAs). However, the gene regulation profile remains unclear. In this study, primary mouse vascular endothelial cells (pMVECs) were employed to detect CVD-related NF-κB-regulated genes and miRNAs. Genechip assay identified 77 NF-κB-regulated genes, including 45 upregulated and 32 downregulated genes, in tumor necrosis factor α (TNFα)-treated pMVECs. Ten of these genes were also found to be regulated by NF-κB in TNFα-treated HeLa cells. Quantitative real-time PCR (qRT-PCR) assay confirmed the up-regulation of Egr1, Tnf, and Btg2 by NF-κB in the TNFα-treated pMVECs. The functional annotation revealed that many NF-κB-regulated genes identified in pMVECs were clustered into classical NF-κB-involved biological processes. Genechip assay also identified 26 NF-κB-regulated miRNAs, of which 21 were upregulated and 5 downregulated, in the TNFα-treated pMVECs. Further analysis showed that nine of the identified genes are regulated by seven of these miRNAs. Finally, among the identified NF-κB-regulated genes and miRNAs, 5 genes and 12 miRNAs were associated with CVD by miRWalk and genetic association database analysis. Taken together, these findings show an intricate gene regulation network raised by NF-κB in TNFα-treated pMVECs. The network provides new insights for understanding the molecular mechanism underlying the progression of CVD.
Animals ; Cardiovascular Diseases/genetics* ; Cells, Cultured ; Endothelial Cells/drug effects* ; Gene Regulatory Networks ; Mice ; MicroRNAs/physiology* ; NF-kappa B/physiology* ; Tumor Necrosis Factor-alpha/pharmacology*

The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.
Adult ; Androgens/pharmacology* ; Computer Simulation ; Epididymis/metabolism* ; Epithelial Cells/metabolism* ; Epithelium/metabolism* ; Gene Expression Profiling ; Gene Regulatory Networks/drug effects* ; Humans ; Male ; MicroRNAs/genetics* ; Primary Cell Culture ; Receptors, Androgen/metabolism* ; Sequence Analysis, RNA

OBJECTIVETo investigate the mechanisms of Panax notoginseng saponins (PNS) in treating coronary heart disease (CHD) by integrating gene interaction network and functional enrichment analysis.

METHODSText mining was used to get CHD and PNS associated genes. Gene-gene interaction networks of CHD and PNS were built by the GeneMANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identifified by network analysis.

RESULTSThe 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene-gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS.

CONCLUSIONSThe key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network.

Coronary Disease ; drug therapy ; genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; drug effects ; Humans ; Panax notoginseng ; chemistry ; Phytotherapy ; Saponins ; pharmacology ; therapeutic use

OBJECTIVETo explore the intersection and regulation mechanism of "efficacy-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method.

METHODThe gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database.

RESULTThere were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways.

CONCLUSIONIn the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways.

Aconitum ; chemistry ; toxicity ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Gene Regulatory Networks ; drug effects ; Humans ; Rhizome ; chemistry ; toxicity

OBJECTIVETo re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin.

METHODSMicroarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis.

RESULTSA total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway.

CONCLUSIONGenes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

Aging ; drug effects ; genetics ; Animals ; Cell Cycle ; drug effects ; genetics ; Curcumin ; pharmacology ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; drug effects ; genetics ; Gene Expression Regulation ; drug effects ; Gene Regulatory Networks ; drug effects ; Genes, Insect ; Protein Biosynthesis ; drug effects ; genetics ; Protein Interaction Maps ; drug effects ; genetics ; Receptors, Notch ; genetics ; metabolism ; Ribosomes ; drug effects ; metabolism ; Signal Transduction ; drug effects ; genetics ; Tumor Suppressor Protein p53 ; metabolism ; Wnt Signaling Pathway ; drug effects ; genetics

As regulating the function of the liver and spleen of the famous traditional formula, Sini San is widely used in the treatment of various diseases caused by liver depression and Qi stagnation, and its efficacy is significant clinically. Recently it is discovered that Sini San is effective in the treatment of nervous system diseases such as depression. Furthermore, there is a lot of literature about the effect of Sini San on the molecular mechanism of antidepressant. However, the anti-depression mechanism of Sini San is not very clear, in our present study, based on the auxiliary mechanism elucidation system for Chinese medicine and network pharmacology system to construct the chemical ingredients of the target interactions and disease-related protein of the interaction network. Results show that there are 263 chemical ingredients and 19 corresponding targets of depression in Sini San network. Sini San can anti-depressant effect through G-protein coupled receptor protein signaling pathway, cAMP system, neurological system process and neurotransmitter secretion, inflammatory response, neuroendocrine, metal ion transport and so on. These studies provided valuable clues for the mechanism and treatment of anti-depressant.
Animals ; Antidepressive Agents ; administration & dosage ; chemistry ; Databases, Factual ; Depression ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Signal Transduction

Elucidate the mechanism of Eucommiae Cortex in treatment of hypertension, to provide the basis for further research and development of Eucommiae Cortex. Our study using the entity grammar systems inference rules to analyse the interactions of chemical constituents of Eucommiae Cortex and disease target proteins at the molecular level, and got a biological network of Eucommiae Cortex anti-hypertension which inciude 602 nodes and 2 354 edges. We got 3 treatment of hypertension pathways of Eucommiae Cortex by analyzing biological network, that is, by inhibition of vascular remodeling to improve the deterioration of hypertension, reduce activity of polymorphism genetic genes related to essential hypertension, inhibition of carbonic anhydrase 1 to maintain the osmotic pressure, Eucommiae Cortex play the role of anti-hypertension.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Essential Hypertension ; Eucommiaceae ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; Signal Transduction ; drug effects

Salvia miltiorrhiza is a traditional Chinese medicine (TCM) and is widely used as a clinically medication for its efficiency in treating cardiovascular disease. Due to TCM is a comprehensive system, the mechanism of S. miltiorrhiza treating cardiovascular disease through integrated multiple pathways are still unclear in some aspects. With the rapid progress of bioinformatics and systems biology, network pharmacology is considered as a promising approach toward reveal the underlying complex relationship between an herb and the disease. In order to discover the mechanism of S. miltiorrhiza treating cardiovascular disease systematically, we use the auxiliary mechanism elucidation system for Chinese medicine, built up a molecule interaction network on the active component targets of S. miltiorrhiza and the therapeutic targets of cardiovascular disease to offer an opportunity for deep understanding the mechanism of S. miltiorrhiza treating cardiovascular disease from the perspective of network pharmacology. The results showed that S. miltiorrhiza treating cardiovascular disease through ten pathways as follows: improve lipid metabolism, anti-inflammation, regulate blood pressure, negatively regulates blood coagulation factor and antithrombotic, regulate cell proliferation, anti-stress injury, promoting angiogenesis, inhibited apoptosis, adjust vascular systolic and diastolic, promoting wound repair. The results of this paper provide theoretical guidance for the development of new drugs to treat cardiovascular disease and the discovery of new drugs through component compatibility.
Animals ; Cardiovascular Diseases ; drug therapy ; genetics ; metabolism ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Salvia miltiorrhiza ; chemistry ; Signal Transduction

To build the Dendrobium nobile -T2DM network, and elucidate the molecular mechanism of D. nobile to type 2 diabetes (T2DM). Collect the chemical composition of D. nobile and the targets on T2DM by retrieving database and documents, build the network of D. nobile to T2DM using the entity grammar systems inference rules. The molecular mechanism of D. nobile to T2DM includes: (1) regulating lipid metabolism by lowering triglyceride; (2) reducing insulin resistance; (3) protecting islet cells; (4) promoting the glucose-dependent insulin tropic peptide (GIP) secretion; (5) inhibiting calcium channel. Under the guidance of network pharmacology, through entity grammar systems inference rules we elucidate the molecular mechanism of D. nobile to T2DM, and provide the basis for the further development of health care products based on D. nobile.
Animals ; Calcium Channels ; genetics ; metabolism ; Databases, Factual ; Dendrobium ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hypoglycemic Agents ; administration & dosage ; chemistry ; Insulin Resistance ; Islets of Langerhans ; metabolism ; Triglycerides ; metabolism

Rhubarb is a traditional Chinese medicine (TCM), wildly used in treating the disease of hyperlipidemia. However, its components are complicated, so that it is still difficult to clear the specific roles of its various components in blood lipids regulation in. So we decide to systematically study the anti- hyperlipidemia mechanism of rhubarb. We integrated multiple databases, based on entity grammar systems model, constructed molecular interaction network between the chemical constituents of rhubarb and hyperlipidemia. The network includes 231 nodes and 638 edges. Thus we infer the interactions of active targets and disease targets to clarify the anti-hyperlipidemia mechanism. And find that rhubarb can promote excretion of cholesterol; inhibit clotting factors and improve blood circulation; inhibit the release of inflammatory cytokines and maintain fat metabolism balance; inhibit cholesterol and triglyceride synthesis; and other ways to achieve lipid-lowering effect. Thus this study provides reference for novel drug development and component compatibility, and also gives a new way for the systematically study of acting mechanism of traditional Chinese medicine.
Animals ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Lipid Metabolism ; Rheum ; chemistry ; Signal Transduction ; drug effects