Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis

Background. Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affect mucosal homeostasis and triggers inappropriate immune response. The purpose of the study was to identify significant biomarkers with potential therapeutic targets and the underlying mechanisms. Methods. The gene expression profiles of GSE48958, GSE73661, and GSE59071 are from the GEO database. Differentially expressed genes (DEGs) were screened by the GEO2R tool. Next, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, protein-protein interaction (PPI) was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Results. There were a total of 128 common DEGs genes, including 86 upregulated genes enriched in extracellular space, regulation of inflammatory response, chemokine-mediated signaling pathway, response to lipopolysaccharide, and cell proliferation, while 42 downregulated genes enriched in the integral component of the membrane, the integral component of the plasma membrane, apical plasma membrane, symporter activity, and chloride channel activity. The KEGG pathway analysis results demonstrated that DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. 18 central modules of the PPI networks were selected with Cytotype MCODE. Furthermore, 18 genes were found to significantly enrich in the extracellular space, inflammatory response, chemokine-mediated signaling pathway, TNF signaling pathway, regulation of cell proliferation, and immune response via reanalysis of DAVID. Conclusion. The study identified DEGs, key target genes, functional pathways, and pathway analysis of UC, which may provide potential molecular targets and diagnostic biomarkers for UC.

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Exploration of the Mechanism and Active Targets of Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia Based on Network Pharmacology

10.21203/rs.3.rs-147873/v1 ◽

2021 ◽

Author(s):

Haiyu Zhang ◽

Xuedong An ◽

De Jin ◽

Jiaxing Tian ◽

Wenke Liu ◽

...

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

Pathway Analysis ◽

Kegg Pathway ◽

Therapeutic Targets ◽

Mapk Signaling ◽

Network Pharmacology ◽

Bile Acid Metabolism ◽

Ppi Networks ◽

Kegg Pathway Analysis

Abstract BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.

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Integrated Transcriptional Profiling Analysis and Immune-Related Risk Model Construction for Intracranial Aneurysm Rupture

Frontiers in Neuroscience ◽

10.3389/fnins.2021.613329 ◽

2021 ◽

Vol 15 ◽

Author(s):

Dezhi Shan ◽

Xing Guo ◽

Guozheng Yang ◽

Zheng He ◽

Rongrong Zhao ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Signaling Pathway ◽

Immune Cell ◽

Risk Model ◽

Enrichment Analysis ◽

Cell Infiltration ◽

Enzyme Linked Immunosorbent Assay ◽

Immune Cell Infiltration ◽

Related Risk

Intracranial aneurysms (IAs) may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms are poorly understood. The aims of this study were to analyze the transcriptional profiles to explore the functions and regulatory networks of differentially expressed genes (DEGs) in IA rupture by bioinformatics methods and to identify the underlying mechanisms. In this study, 1,471 DEGs were obtained, of which 619 were upregulated and 852 were downregulated. Gene enrichment analysis showed that the DEGs were mainly enriched in the inflammatory response, immune response, neutrophil chemotaxis, and macrophage differentiation. Related pathways include the regulation of actin cytoskeleton, leukocyte transendothelial migration, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and chemokine signaling pathway. The enrichment analysis of 20 hub genes, subnetworks, and significant enrichment modules of weighted gene coexpression network analysis showed that the inflammatory response and immune response had a causal relationship with the rupture of unruptured IAs (UIAs). Next, the CIBERSORT method was used to analyze immune cell infiltration into ruptured IAs (RIAs) and UIAs. Macrophage infiltration into RIAs increased significantly compared with that into UIAs. The result of principal component analysis revealed that there was a difference between RIAs and UIAs in immune cell infiltration. A 4-gene immune-related risk model for IA rupture (IRMIR), containing CXCR4, CXCL3, CX3CL1, and CXCL16, was established using the glmnet package in R software. The receiver operating characteristic value revealed that the model represented an excellent clinical situation for potential application. Enzyme-linked immunosorbent assay was performed and showed that the concentrations of CXCR4 and CXCL3 in serum from RIA patients were significantly higher than those in serum from UIA patients. Finally, a competing endogenous RNA network was constructed to provide a potential explanation for the mechanism of immune cell infiltration into IAs. Our findings highlighted the importance of immune cell infiltration into RIAs, providing a direction for further research.

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Investigation of Potential Genetic Biomarkers and Molecular Mechanism of Ulcerative Colitis Utilizing Bioinformatics Analysis

10.21203/rs.2.13329/v1 ◽

2019 ◽

Author(s):

Jiaqi Zhang ◽

Xue Wang ◽

Lin Xu ◽

Zedan Zhang ◽

Fengyun Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gene Therapy ◽

Inflammatory Response ◽

Signaling Pathway ◽

Functional Enrichment ◽

Hub Genes ◽

Amyloid A ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway ◽

Potential Biomarkers

Abstract Objectives: To reveal the molecular mechanisms of ulcerative colitis (UC) and provide potential biomarkers for UC gene therapy. Methods: We downloaded the GSE87473 microarray dataset from the Gene Expression Omnibus (GEO) and identified the differentially expressed genes (DEGs) between UC samples and normal samples. Then ,a module partition analysis was performed based on a weighted gene co-expression network analysis (WGCNA),followed by pathway and functional enrichment analyses. Furthermore, we investigated the hub genes . At last, data validation was performed to ensure the reliability of the hub genes. Results: Between UC group and normal group, 988 DEGs were investigated . The DEGs were clustered into 5 modules using WGCNA. These DEGs were mainly enriched in functions such as the immune response, the inflammatory response and chemotaxis, and they were mainly enriched in KEGG pathways such as the cytokine-cytokine receptor interaction , chemokine signaling pathway, and complement and coagulation cascades. The hub genes, including dual oxidase maturation factor 2(DUOXA2), serum amyloid A (SAA) 1 and SAA2, TNFAIP3-interacting protein 3(TNIP3), C-X-C motif chemokine (CXCL1), solute carrier family 6 member 14(SLC6A14) and complement decay-accelerating factor (CD antigen CD55),were revealed as potential tissue biomarkers for UC diagnosis or treatment. Conclusions: This study provides supportive evidence that DUOXA2, A-SAA, TNIP3, CXCL1, SLC6A14 and CD55 might be used as potential biomarkers for tissue biopsy of UC, especially SLC6A14 and CD55, which may be new targets for UC gene therapy. Moreover, the DUOX2/DUOXA2, NF-κB /TNIP3 and CXCL1/CXCR2 pathways might play an important role in the progression of UC through the chemokine signaling pathway and inflammatory response.

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CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

Veterinariya, Zootekhniya i Biotekhnologiya ◽

10.36871/vet.zoo.bio.202009007 ◽

2020 ◽

Vol 1 (9) ◽

pp. 64-71

Author(s):

E. A. Klimov ◽

◽

E. K. Novitskaya ◽

S. N. Koval’chuk ◽

◽

...

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Dendritic Cells ◽

Inflammatory Response ◽

Signaling Pathway ◽

Adhesion Molecule ◽

Immune Evasion ◽

Intercellular Adhesion Molecule ◽

Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

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Glia Maturation Factor-Gamma Negatively Modulates TLR4 Signaling In Macrophages Induced by Lipopolysaccharide (LPS).

Blood ◽

10.1182/blood.v116.21.1482.1482 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1482-1482

Author(s):

Wulin Aerbajinai ◽

Kyung Chin ◽

Hyun Woo Lee ◽

Jianqiong Zhu ◽

Griffin P. Rodgers

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Signaling Pathways ◽

Signaling Pathway ◽

Luciferase Assay ◽

Enzyme Linked Immunosorbent Assay ◽

Glia Maturation Factor ◽

Tlr4 Signaling ◽

Maturation Factor ◽

Nf Kappab

Abstract Abstract 1482 Toll-like receptor 4 (TLR4) plays a critical role in innate immunity that recognize pathogenic molecules and trigger inflammatory response. However, excessive activation of TLR4 activation may contribute to pathogenesis of autoimmune and inflammatory diseases. Therefore, the negative regulation of TLR4-triggered inflammatory response attracts much attention in recent years. Activation of TLR4 signaling pathways by lipopolysaccharide (LPS) leads to the production of a broad array of cytokines and mediators that coordinate the immune response in macrophages. Glia maturation factor gamma (GMFG), a member of the ADF/cofilin family of proteins that regulate actin cytoskeleton reorganization, is preferentially expressed in inflammatory cells, but its function in macrophages immune response remains unclear. In this study, we investigated whether GMFG participates in the molecular events underlying the inflammatory reaction to LPS in macrophages by knockdown of GMFG using small-interfering RNA approach. We show here that knockdown of GMFG significantly enhanced LPS-induced production of proinflammatory cytokines and chemokines, including TNF-alpha, IL-1beta, IL-8, and MCP-1 in human peripheral blood monocytes-derived macrophage as determined by quantitative real time-PCR and confirmed by enzyme-linked immunosorbent assay. Silencing of GMFG expression potentiates LPS-induced activation of p38, ERK1/2 and NF-kappaB signaling pathways by Western blot analysis. Moreover, luciferase assay revealed that gene silencing of GMFG promoted LPS-induced NF-kappaB activity for ∼2.5- to 4-fold. Furthermore, we found that TLR4 protein expression level were higher in GMFG-silenced macrophage compared with that of the control siRNA-transfected macrophages after stimulated with LPS for 1 hour. These results suggest that GMFG negatively regulation of TLR4 signaling-induced inflammatory cytokines by modulation of TLR4 expression levels and its down-stream NF-kappaB and p38 MAPK signaling pathway. In summary, we report that GMFG, in macrophage, function as a novel negative regulator that participates in the regulation of TLR4-signaling pathway, implicating that macrophage-specific modulation of GMFG may be beneficial in the treatment of inflammation as well as autoimmune disease. Disclosures: No relevant conflicts of interest to declare.

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Mechanisms of Berberine for the Treatment of Atherosclerosis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3568756 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Xuejiao Xie ◽

Xingyu Ma ◽

Siyu Zeng ◽

Wansi Tang ◽

Liucheng Xiao ◽

...

Keyword(s):

Signaling Pathway ◽

Pathway Analysis ◽

Kegg Pathway ◽

Functional Enrichment ◽

Network Pharmacology ◽

Foam Cell Formation ◽

Ppi Network ◽

The Core ◽

Ppi Networks ◽

Kegg Pathway Analysis

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.

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Herb-Partitioned Moxibustion Regulates the TLR2/NF-κB Signaling Pathway in a Rat Model of Ulcerative Colitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/949065 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Xiaomei Wang ◽

Yanan Liu ◽

Hongsheng Dong ◽

Luyi Wu ◽

Xiaoming Feng ◽

...

Keyword(s):

Ulcerative Colitis ◽

Immune Response ◽

Signaling Pathway ◽

Colonic Mucosa ◽

Regulatory Mechanism ◽

Acupuncture Points ◽

Local Immune Response ◽

Protein Levels ◽

Multiple Signaling ◽

Tlr2 Signaling

The TLR2/NF-κB signaling pathway plays an important role in the pathomechanism of ulcerative colitis (UC); acupuncture and moxibustion can improve the damage in colonic tissues of UC, but the regulatory mechanism remains unknown. This study observed the effect of moxibustion on the TLR2/NF-κB signaling pathway at the Tianshu (ST25) and Qihai (CV6) acupuncture points in the UC rat. The result shows that TLR2, IRAK1, and IKK-b mRNA and protein levels in the colonic mucosa were significantly higher in the UC rats than in the control rats. Herb-partitioned moxibustion reduced the expression of TLR2, IRAK1, and IKK-b mRNA and proteins in the UC rats. Similarly, the expression of NF-κB was significantly increased and IFN-βand IL-10 were significantly decreased in the colonic mucosa of UC rats, but herb-partitioned moxibustion reduced the expression of IFN-βand upregulating the expression of IFN-βand IL-10 significantly. It indicates that herb-partitioned moxibustion can inhibit the expression of multiple signaling molecules of the TLR2 pathway effectively, and it may modulate the excessive local immune response by inhibiting TLR2 signaling, thereby promoting the repair of damaged colonic mucosa.

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Network analyses of circular RNAs expression profiles and their hub genes in pancreatic ductal adenocarcinoma

10.21203/rs.2.15313/v1 ◽

2019 ◽

Author(s):

Yanyan Tang ◽

Ping Zhang

Keyword(s):

Gene Expression ◽

Pancreatic Ductal Adenocarcinoma ◽

Signaling Pathway ◽

Pathway Analysis ◽

Kegg Pathway ◽

Expression Profiles ◽

Ductal Adenocarcinoma ◽

Ppi Network ◽

Hub Genes ◽

Kegg Pathway Analysis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumor in digestive system. CircRNAs involve in lots of biological processes through interacting with miRNAs and their targeted mRNA. We obtained the circRNA gene expression profiles from Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) between PDAC samples and paracancerous tissues. Bioinformatics analyses, including GO analysis, KEGG pathway analysis and PPI network analysis, were conducted for further investigation. We also constructed circRNA‑microRNA-mRNA co-expression network. A total 291 differentially expressed circRNAs were screened out. The GO enrichment analysis revealed that up-regulated DEGs were mainly involved metabolic process, biological regulation, and gene expression, and down-regulated DEGs were involved in cell communication, single-organism process, and signal transduction. The KEGG pathway analysis, the upregulated circRNAs were enriched cGMP-PKG signaling pathway, and HTLV-I infection, while the downregulated circRNAs were enriched in protein processing in endoplasmic reticulum, insulin signaling pathway, regulation of actin cytoskeleton, etc. Four genes were identified from PPI network as both hub genes and module genes, and their circRNA‑miRNA-mRNA regulatory network also be constructed. Our study indicated possible involvement of dysregulated circRNAs in the development of PDAC and promoted our understanding of the underlying molecular mechanisms.

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Study on the mechanism of Jiawei Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome based on network pharmacological analysis

Medical Research ◽

10.6913/mrhk.202109_3(3).0006 ◽

2021 ◽

Vol 3 (3) ◽

pp. 50-64

Author(s):

Binyan MO

Keyword(s):

Myelodysplastic Syndrome ◽

Signaling Pathway ◽

Pathway Analysis ◽

Biological Function ◽

Kegg Pathway ◽

Topological Analysis ◽

Kegg Pathway Analysis ◽

Cellular Sensitivity ◽

Linggui Zhugan Decoction ◽

Function Enrichment

the research method of network pharmacology is used to explore the material basis and mechanism of modified Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome. Methods: the main active components of 8 traditional Chinese medicines of Jiawei Linggui Zhugan Decoction were searched through tcmsp database, and the target was predicted. The relevant targets of myelodysplastic syndrome were searched through geo database, and the common action targets were obtained by intersection of traditional Chinese medicine targets and disease targets. The core targets were selected by topological analysis with Cytoscape software. Finally, go-bp biological function enrichment and KEGG pathway analysis were carried out based on R software. Results: according to the database analysis, there were 248 active compounds and 3695 targets in the modified Linggui Zhugan decoction, of which 34 were common targets with metabolic syndrome; Through the topological analysis of common targets, 9 core targets were selected. Go-bp biological function enrichment and KEGG pathway analysis found that it can play its therapeutic role through p53, AGE-RAGE, cellular sensitivity, NF KB and other signal pathways. Conclusion: modified Linggui Zhugan decoction may play a therapeutic role through p53 signaling pathway, AGE-RAGE signaling pathway, cellular sensitivity, NF kappa B signaling pathway and cell cycle, so as to provide a new scientific basis for its clinical and basic research.

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