scholarly journals Based on Network Pharmacology to Explore the Active Ingredients and Molecular Targets of Zuojin Pill for the Treatment of Ulcerative Colitis

2021 ◽  
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Rna Polymerase Ii ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components

Abstract Background: Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active component and mechanism of ZJP is still arcane. Objective: This study aims to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC.Methods: Firstly, the components and putative targets of ZJP were collected based on the herbal medicine target database, and a network containing the interaction between the putative targets of ZJP and the potential therapeutic targets of UC was established. Then topological parameters were calculated to identify the key targets in the network and the key targets were imported into David database to perform path enrichment analysis.Results: 7 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, response to drug, cellular response to lipopolysaccharide, MAPK cascade, inflammatory response, immune response, transcription from RNA polymerase II promoter, apoptotic process, regulation of sequence-specific DNA binding transcription factor activity and lipopolysaccharide-mediated signaling pathway. Moreover, PI3K-Akt signaling pathway, MAPK signaling pathway and Toll-like receptor signaling pathway were predicted to participate in the treatment of UC, which directly regulated by 7 active components of ZJP. Quercetin and isorhamnetin have great development value in the treatment of UC. Moupinamide and palmidin A are of great value for exploration because of their safety and innovation.Conclusion: ZJP mainly were directly involved in UC through inflammation and immune regulation by PI3K-Akt signaling pathway and MAPK signaling pathway.

scholarly journals Based on Network Pharmacology to Explore the Potential Bioactive Compounds and Mechanisms of Zuojin Pill for the Treatment of Ulcerative Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components

Background. Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active components and mechanisms of ZJP are still arcane. This study aimed to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC. Methods. Firstly, the components and putative targets of ZJP were collected based on herbal medicine target databases, and a network containing the interaction between the targets of ZJP and the potential therapeutic targets of UC was established. Then, topological parameters were calculated to identify the key targets in the network and, in turn, to import them into the David database to perform path enrichment analysis. Results. 14 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, MAPK cascade, inflammatory response, immune response, and the apoptotic process of UC. Moreover, the PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway, and Prolactin signaling pathway were predicted to participate in ZJP treating UC. Among them, 14 active components of ZJP directly regulate these pathways. Conclusion. ZJP could alleviate UC through the predicted components and mechanisms. The 14 predicted active components of ZJP may mainly play a therapeutic role for UC through synergistic regulation of the PI3K-Akt signaling pathway and MAPK signaling pathway.

scholarly journals Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Bin Liu ◽  
Xin Zheng ◽  
Jiajun Li ◽  
Xiong Li ◽  
Ruimei Wu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components ◽  
Effective Components

Abstract Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches. Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets. Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways. Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Min Shao
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Pathway Network ◽  
Context Score ◽  
The Common ◽  
The Individual

We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC), TargetScan context score (TSCS), and probabilities of conserved targeting (PCT)). An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR) < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.

scholarly journals Elaborate the Mechanism of Ancient Classic Prescriptions (Erzhi Formula) in Reversing GIOP by Network Pharmacology Coupled with Zebrafish Verification

2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Zhihui Cai ◽  
Huajun Wang ◽  
Jun Jiang ◽  
Shichang Xiao ◽  
Jianpeng Xiao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Optical Density ◽  
Bone Mineralization ◽  
Enrichment Analysis ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Akt Signaling Pathway ◽  
Active Components ◽  
Zebrafish Model

Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of “components-targets-signal pathway” was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased ( P < 0.05 ). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF ( P < 0.05 ). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through “multicomponent/multitarget/multipathway” and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model.

scholarly journals LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Wei Zhang ◽  
Feng Liang ◽  
Qingfeng Li ◽  
Hong Sun ◽  
Fei Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Liver Malignancy ◽  
Mitogen Activated Protein

Abstract Background Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated. Methods MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells. Results MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway. Conclusion MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.

scholarly journals Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

2022 ◽  
Vol 12 ◽  
Author(s):  
Jinlong Zhao ◽  
Fangzheng Lin ◽  
Guihong Liang ◽  
Yanhong Han ◽  
Nanjun Xu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Active Components ◽  
Treatment Of Osteoporosis ◽  
Effective Components

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

Identification of microRNA-Regulated Pathways through a Integration of Mcrorna-mRNA Microarray and Bioinformatics Analysis in CD34+ Cells of Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3238-3238
Author(s):  
Xiao Li ◽  
Xu Feng ◽  
Chunkang Chang ◽  
Qi He ◽  
Wu Lingyun
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Calcium Signaling Pathway ◽  
Cd34 Cells ◽  
Mrna Microarray

Abstract Background MicroRNAs (miRNAs) are considered to play a key role in the pathogenesis of myelodysplastic syndromes (MDS). However, the effect of miRNA and targeted mRNA on signal transduction is not fully understood in MDS. Objective The objective of this study is to identify the miRNAs-regulated pathways. Methods Affymetrix GeneChip microRNA and PrimeView Array were used to analyze miRNAs and gene expression profile of CD34+ cells in 12 MDS patients and 6 healthy controls. Comprehensive bioinformatics analysis of the coordinate expression of miRNAs and mRNAs including Difference, Go, Pathway, Pathway-network, miRNA-Gene-Network and miRNA-Go-Network analysis was performed to identify the miRNAs-regulated networks. Results 1. 34 differentially expressed miRNAs (5 up- and 29 down-regulated miRNAs) and 1783 mRNAs (405 up- and 1378 down-regulated mRNAs) in CD34+ cells from MDS and Healthy controls were identified by miRNA and mRNA microarray, respectively (Fig.1). 2. 25 dysregulated miRNAs and 234 targeted mRNAs were identified by a combination of Pearson's correlation analysis and prediction by TargetScan; 394 target relationship of miRNAs was established (Fig.2). 3. Go analysis revealed that these miRNA-mRNAs pairs were involved in signal transduction, apoptotic process, DNA-dependent transcription regulation, protein phosphophoration, etc. Pathway analysis showed that MAPK, JAK/STAT and PI3K/Akt signaling pathways might be regulated by these miRNA-mRNAs pairs (Fig.3). 4. The pathway-network analysis revealed that MAPK signaling pathway, Jak-Stat signaling pathway and apoptosis signaling pathway (displayed by red cycle) located in the downstream of signal networks (Fig. 3E). Dysregulation of These pathways may be more meaningful for explaining the pathogenesis of MDS. 5. Through a combination of Pathway, miRNA-Gene-Network and miRNA-Go- Network analysis, 29 miRNA-mRNA-regulated pathways were identified such as miR-148a/TEK/PI3K-Akt signaling pathway, miR-195/BDNF/MAPK signaling pathway, miR-195/DLL1/Notch signaling pathway, miR-145/CCND2/ JAK-STAT signaling pathway, etc. (Table 1). Conclusion Alteration expression of several miRNAs and targeted mRNAs might have an important impact on cancer-related cellular pathways including MAPK, PI3K/Akt, JAK/STAT, etc. The role of these miRNAs-mediated pathways in pathogenesis of MDS merit further investigation. Fig. 1 Affymetrix mcroRNA and mRNA microarray in MDS Fig. 1. Affymetrix mcroRNA and mRNA microarray in MDS Fig. 2 Significant miRNA-mRNA pairs identified through a integration of mcroRNA-mRNA microarray Fig. 2. Significant miRNA-mRNA pairs identified through a integration of mcroRNA-mRNA microarray Table 1. Parts of dysregulated miRNAs, genes and targeted pathway in MDS MicroRNA Style Gene_synbol Pathway miR-148a Down TEK PI3K-Akt signaling pathway ITGA9 PI3K-Akt signaling pathway KIT PI3K-Akt signaling pathway HMGA2 Transcriptional misregulation in cancer miR-145 Down HHEX Transcriptional misregulation in cancer MEIS1 Transcriptional misregulation in cancer miR-200c Down EFNA1 PI3K-Akt signaling pathway KLF3 Transcriptional misregulation in cancer miR-195 Up BDNF MAPK signaling pathway CDC25B MAPK signaling pathway DLL1 Notch signaling pathway MRAS MAPK signaling pathway miR-17 Up CAMK2D Calcium signaling pathway miR-19a Up MAML1 Notch signaling pathway SLC8A1 Calcium signaling pathway THBS1 Proteoglycans in cancer TNF MAPK signaling pathway TNFRSF1B Adipocytokine signaling pathway ACSL1 Adipocytokine signaling pathway EDNRB Calcium signaling pathway miR-19b Up CALM1 Calcium signaling pathway TNF Proteoglycans in cancer Fig. 3 Go and pathway analysis Fig. 3. Go and pathway analysis Disclosures No relevant conflicts of interest to declare.

scholarly journals Mechanism of Modified Danggui Sini Decoction for Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chaoqun Feng ◽  
Min Zhao ◽  
Leiming Jiang ◽  
Ziang Hu ◽  
Xiaohong Fan
Keyword(s):  
Molecular Docking ◽  
Inflammatory Response ◽  
Knee Osteoarthritis ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Kegg Pathway ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Akt Signaling Pathway

Objective. This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. Methods. The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of “drugs-active components-disease targets” was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. Results. Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. Conclusion. Modified Danggui Sini Decoction has the hierarchical network characteristics of “multicomponent, multitarget, multifunction, and multipathway” in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.

scholarly journals Identification and Functional Analysis of Serum Specific MiRNAs in Recurrent Aphthous Somatitis Patients With Excess-heat or Yin-deficiency

2020 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background:To identity key miRNAs as signatures for recurrent aphthous stomatitis(RAS)with Excess-heat or Yin-deficiency bymiRNA microarrays. Method: Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat oryin-deficiencysyndrome and healthy individuals. CoremicroRNAs (miRNAs) were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out andgene-pathway-networks werevisualized to better understand the relationship between differentgenes and pathways.Result:(1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients ofyin-deficiency syndrome. Among them, 9 miRNAs werescreened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four randommiRNAs(hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validatedby real-time PCR method. 14 miRNAs werescreened out in yin-deficiency syndrome group(7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2)A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group.These targets were enriched inGO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enrichedGO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane andenrichedKEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway.Conclusion:Hsa-miR-20b-5p in patients with RAS could act as the novel target for syndromeclassification of the disease. It is upregulated in RAS patients with excess-heat syndrome while downregulated in patients with yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of RAS with excess-heat syndrome or yin-deficiency syndrome, respectively.

scholarly journals Exploring the Mechanisms of Arsenic Trioxide (Pishuang) in Hepatocellular Carcinoma Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xinmiao Wang ◽  
Luchang Cao ◽  
Jingyuan Wu ◽  
Guanghui Zhu ◽  
Xiaoyu Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Arsenic Trioxide ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Topological Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Nf Kappa B

Objective. Arsenic trioxide (Pishuang, Pishi, arsenolite, As2O3, and CAS 1327-53-3), a naturally occurring and toxic mineral as a drug for more than 2000 years in China, has been found to have a valuable function in hepatocellular carcinoma (HCC) in recent years. However, its exact mechanism remains to be elucidated. Therefore, this study was intended to explore the potential anti-HCC mechanism of arsenic trioxide through network pharmacology. Methods. The potential targets of arsenic trioxide were collected from PubChem and TargetNet. HCC targets were obtained from the GeneCards database. Then, a protein-protein interaction (PPI) network of arsenic trioxide and HCC common targets was established using STRING. GO and KEGG pathway enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, an arsenic trioxide-target-pathway-HCC network was built by Cytoscape 3.2.1, and network topological analysis was carried out to screen the key candidate targets. Results. A total of 346 corresponding targets of arsenic trioxide and 521 HCC-related targets were collected. After target mapping, a total of 52 common targets were obtained. GO analysis showed that the biological process was mainly involved in the negative regulation of cellular senescence, response to tumor necrosis factor, and cellular response to hypoxia. Molecular functions included NF-kappa B binding, enzyme binding, p53 binding, and transcription factor binding. Cellular components mainly were replication fork, ESC/E(Z) complex, RNA polymerase II transcription factor complex, and organelle membrane. KEGG pathways were mainly enriched in the PI3K-Akt signaling pathway, VEGF signaling pathway, p53 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, NF-kappa B signaling pathway, FoxO signaling pathway, ErbB signaling pathway, and MAPK signaling pathway. In the arsenic trioxide-target-pathway-HCC network, targets such as AKT1, RAF1, RELA, TP53, and PTEN had a higher degree. Conclusions. Our study showed that key targets of arsenic trioxide were mainly involved in multiple biological processes and pathways. It provided a theoretical basis for the screening of drug targets.

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