Heart failure(HF) is the terminal stage of various cardiovascular diseases, characterized by high morbidity and mortality, and it represents one of the major disease burdens for families and society. In recent years, as research on the molecular mechanisms of HF has deepened, a competing endogenous RNA(ceRNA) network mediated by long non-coding RNAs(lncRNAs) and circular RNAs(circRNAs) has been gradually constructed. Extensive research results have confirmed that the ceRNA network is widely involved in pathological processes such as inflammation, oxidative stress, myocardial hypertrophy, apoptosis, remodeling of extracellular matrix components and structure, and ferroptosis in HF. It reveals the complex pathological mechanisms of HF at the epigenetic level. Traditional Chinese medicine(TCM) plays a unique role in improving symptoms and prognosis of HF and intervenes in the ceRNA network in HF through multi-level and multi-target mechanisms. It improves key pathological processes such as myocardial fibrosis and inflammation, making progress in treating HF at the molecular level. This article summarized recent Chinese and international research on the regulatory mechanisms of ceRNA networks in HF, elaborated on the mechanisms of action of ceRNA networks in different pathological stages of HF, and summarized how effective components and compounds of TCM intervene in the ceRNA network to improve HF, so as to refine the molecular mechanisms of HF and provide directions for more precise molecular targeted therapeutic strategies.
Humans ; Heart Failure/metabolism* ; Medicine, Chinese Traditional ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Circular/genetics* ; RNA, Long Noncoding/metabolism* ; Gene Regulatory Networks/drug effects* ; RNA/metabolism* ; RNA, Competitive Endogenous

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

In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.
Drugs, Chinese Herbal ; therapeutic use ; Dysmenorrhea ; drug therapy ; genetics ; metabolism ; Female ; Gene Regulatory Networks ; drug effects ; Humans ; Leiomyoma ; drug therapy ; genetics ; metabolism ; Pelvic Inflammatory Disease ; drug therapy ; genetics ; metabolism

Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi-channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM.
Drug Interactions ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gene Regulatory Networks ; drug effects ; Humans ; Medicine, Chinese Traditional

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