scholarly journals Transcriptomic Analysis of Spleen Revealed Mechanism of Dexamethasone-Induced Immune Suppression in Chicks

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 513 ◽  
Author(s):  
Yujie Guo ◽  
Aru Su ◽  
Huihui Tian ◽  
Minxi Zhai ◽  
Wenting Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Immune Suppression ◽  
Molecular Genetic ◽  
Daily Injection ◽  
Receptor Interaction ◽  
P Value ◽  
Specific Mechanism ◽  
Base Pairs ◽  
Protein Protein Interaction ◽  
Iga Production

Stress-induced immunosuppression is a common problem in the poultry industry, but the specific mechanism of its effect on the immune function of chicken has not been clarified. In this study, 7-day-old Gushi cocks were selected as subjects, and a stress-induced immunosuppression model was successfully established via daily injection of 2.0 mg/kg (body weight) dexamethasone. We characterized the spleen transcriptome in the control (B_S) and model (D_S) groups, and 515 significant differentially expressed genes (SDEGs) (Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced (FPKM) > 1, adjusted p-value (padj) < 0.05 and Fold change (|FC|) ≥ 2) were identified. The cytokine-cytokine receptor interaction signaling pathway was identified as being highly activated during stress-induced immunosuppression, including the following SDEGs—CXCL13L2, CSF3R, CSF2RB, CCR9, CCR10, IL1R1, IL8L1, IL8L2, GHR, KIT, OSMR, TNFRSF13B, TNFSF13B, and TGFBR2L. At the same time, immune-related SDEGs including CCR9, CCR10, DMB1, TNFRSF13B, TNFRSF13C and TNFSF13B were significantly enriched in the intestinal immune network for the IgA production signaling pathway. The SDEG protein-protein interaction module analysis showed that CXCR5, CCR8L, CCR9, CCR10, IL8L2, IL8L1, TNFSF13B, TNFRSF13B and TNFRSF13C may play an important role in stress-induced immunosuppression. These findings provide a background for further research on stress-induced immunosuppression. Thus, we can better understand the molecular genetic mechanism of chicken stress-induced immunosuppression.

scholarly journals A Network Pharmacology-based Analysis of the Molecular Mechanism of Tanreqing in the Treatment of the Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Liuliu Yang ◽  
Minyong Wen ◽  
Wenjiang Zheng ◽  
Xiaohong Liu ◽  
yong wang
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Chemical Constituents ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Clinical Treatment ◽  
Laboratory Research ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Protein Protein Interaction

Abstract Background: This paper discusses the molecular mechanism of Tanreqing (TRQ) in the treatment of the coronavirus disease 2019 (COVID-19) using the network pharmacology approach. Our study provides new ideas on the laboratory research and clinical treatment of the disease. Method: Information on the chemical constituents of TRQ and the genes targeted by the disease was collected. The common gene targets of the drug and the disease were input into the Search Tool for the Retrieval of Interacting Genes/Proteins（STRING）database to understand the interaction among target proteins. The protein–protein interaction (PPI) network and a network of the chemical constituents of TRQ and their targets were constructed using Cytoscape. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R program and other relevant software packages. Results: Twenty-eight active chemical constituents and 365 gene targets were identified for TRQ. Out of these genes, 113 were also found to be involved in the pathogenesis of the disease. Enrichment analysis revealed the therapeutic role that TRQ could have played in the treatment of COVID-19, via the regulation of important pathways such as the renin–angiotension system, neuroactive ligand–receptor interaction, phospholipase D (PLD) signaling pathway, calcium signaling pathway, and the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Conclusions: This study attempts to predict the molecular mechanism of TRQ in the treatment of COVID-19, and suggests TRQ intervention through multiple targets and pathways in processes including inflammatory response, immune regulation, and apoptosis during the treatment of the disease. This study indicates the potential rational application of TRQ in the clinical treatment of COVID-19.

scholarly journals Identification of Core Biomarkers Associated with Outcome in Glioma: Evidence from Bioinformatics Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Rong-Xin Geng ◽  
Ning Li ◽  
Yang Xu ◽  
Jun-hui Liu ◽  
Fan-en Yuan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Receptor Interaction ◽  
Normal Brain ◽  
Gabaergic Synapse ◽  
Protein Protein Interaction ◽  
P53 Signaling ◽  
Kaplan Meier ◽  
Search Tool ◽  
Upregulated Genes

Glioma is the most common neoplasm of the central nervous system (CNS); the progression and outcomes of which are affected by a complicated network of genes and pathways. We chose a gene expression profile of GSE66354 from GEO database to search core biomarkers during the occurrence and development of glioma. A total of 149 samples, involving 136 glioma and 13 normal brain tissues, were enrolled in this article. 1980 differentially expressed genes (DEGs) including 697 upregulated genes and 1283 downregulated genes between glioma patients and healthy individuals were selected using GeoDiver and GEO2R tool. Then, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plug-in was employed to imagine protein-protein interaction (PPI) of these DEGs. The upregulated genes were enriched in cell cycle, ECM-receptor interaction, and p53 signaling pathway, while the downregulated genes were enriched in retrograde endocannabinoid signaling, glutamatergic synapse, morphine addiction, GABAergic synapse, and calcium signaling pathway. Subsequently, 4 typical modules were discovered by the PPI network utilizing MCODE software. Besides, 15 hub genes were chosen according to the degree of connectivity, including TP53, CDK1, CCNB1, and CCNB2, the Kaplan-Meier analysis of which was further identified. In conclusion, this bioinformatics analysis indicated that DEGs and core genes, such as TP53, might influence the development of glioma, especially in tumor proliferation, which were expected to be promising biomarkers for diagnosis and treatment of glioma.

scholarly journals Bioinformatics Analysis of the Regulatory lncRNA-miRNA-mRNA Network in Patients with Neuropathic Pain

2020 ◽  
Author(s):  
Huai-Gen Zhang ◽  
Li Liu ◽  
Zhi-Ping Song ◽  
Da-Ying Zhang
Keyword(s):  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Biological Information ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Potential Therapeutic Application

Abstract Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Methods: Here, we explore the key molecules involved in the development of NP condition via identification of lncRNA-miRNA-mRNA expression pattern of patients with NP. We identified differentially expressed miRNAs, lncRNA and mRNA through a comprehensive analysis strategy. Subsequently, we used bioinformatics approach to perform pathway enrichment analysis on DEGs and protein-protein interaction analysis. Combined with the three datasets, the lncRNA-miRNA-mRNA network was constructed. It will then be used as targets for drug prediction. Results: The results showed that a total of 8,251 DEGs (4,193 upregulated and 4,058 downregulated) were identified from the three microarray datasets, 959 DEmiRs (455 upregulated and 504 downregulated), 2,848 DElncs (1,324 upregulated and 1,524 downregulated). GO analysis showed that DEGs are mainly enriched in blood circulation, regulation of membrane potential and regulation of ion transmembrane transport. KEGG results showed that DEGs are enriched in neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and MAPK signaling pathway. When the correlation is set to above 0.8, a total of 31 lncRNAs, 36 miRNAs and 24 mRNAs were screened in the lncRNA-miRNA-mRNAs network. The results of drug prediction indicated the targeted drugs mainly include INDOMETHACIN, GLUTAMIC ACID and PIRACETAM. Conclusion: The lncRNA-miRNA-mRNA network has been carried out a comprehensive biological information analysis and predicted the potential therapeutic application of drugs in patients with NP. The corresponding data has a certain reference for studying the pathological mechanism of NP.

scholarly journals The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson’s Disease Based on a Network Pharmacology Approach

2020 ◽  
Vol 11 ◽  
Author(s):  
Wanqing Du ◽  
Xiao Liang ◽  
Shanze Wang ◽  
Philip Lee ◽  
Yunling Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Paeonia Lactiflora ◽  
Protein Protein Interaction ◽  
Main Gene

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Paeonia lactiflora Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of P. lactiflora in treating PD utilizing a network pharmacology approach.Methods: The protein targets of P. lactiflora ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software.Results: Six active ingredients of P. lactiflora (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels.Conclusion:P. lactiflora may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of P. lactiflora in the treatment of PD and may contribute to novel drug development for PD.

scholarly journals Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Signaling Pathway ◽  
Aneurysm Rupture ◽  
Cytokine Receptor ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Regulatory Pathways ◽  
Ruptured Intracranial Aneurysm ◽  
Neurotrophin Signaling

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

scholarly journals Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruining Liu ◽  
Gang Li ◽  
Haoli Ma ◽  
Xianlong Zhou ◽  
Pengcheng Wang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Signaling Pathway ◽  
Wistar Rats ◽  
Cholesterol Metabolism ◽  
Expression Profiles ◽  
Receptor Interaction ◽  
Pathophysiological Mechanism ◽  
Rna Seq ◽  
Diaphragmatic Dysfunction ◽  
Controlled Mechanical Ventilation

Abstract Background Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. Results The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. Conclusions This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD.

scholarly journals Transcriptome Analysis of the Cecal Tonsil of Jingxing Yellow Chickens Revealed the Mechanism of Differential Resistance to Salmonella

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 979 ◽  
Author(s):  
Fei Wang ◽  
Jin Zhang ◽  
Bo Zhu ◽  
Jie Wang ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Differential Resistance ◽  
Receptor Interaction ◽  
Salmonella Infection ◽  
Poultry Products ◽  
Food Borne ◽  
Cecal Tonsil ◽  
Iga Production

Salmonella is one of the most common food-borne pathogens. It can be transmitted between chickens, as well as to people by contaminated poultry products. In our study, we distinguished chickens with different resistances mainly based on bacterial loads. We compared the cecal tonsil transcriptomes between the susceptible and resistant chickens after Salmonella infection, aiming to identify the crucial genes participating in the antibacterial activity in the cecal tonsil. A total of 3214 differentially expressed genes (DEGs), including 2092 upregulated and 1122 downregulated genes, were identified between the two groups (fold change ≥ 2.0, padj < 0.05). Many DEGs were mainly involved in the regulation of two biological processes: crosstalk between the cecal tonsil epithelium and pathogenic bacteria, such as focal adhesion, extracellular-matrix–receptor interaction, and regulation of the actin cytoskeleton and host immune response including the cytokine–receptor interaction. In particular, the challenged resistant birds exhibited strong activation of the intestinal immune network for IgA production, which perhaps contributed to the resistance to Salmonella infection. These findings give insight into the mRNA profile of the cecal tonsil between the two groups after initial Salmonella stimulation, which may extend the known complexity of molecular mechanisms in chicken immune response to Salmonella.

scholarly journals Characterization of Receptor Interaction and Transcriptional Repression by the Corepressor SMRT

1997 ◽  
Vol 11 (13) ◽  
pp. 2025-2037 ◽  
Author(s):  
Hui Li ◽  
Christopher Leo ◽  
Daniel J. Schroen ◽  
J. Don Chen
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Transcriptional Repression ◽  
Thyroid Hormone Receptor ◽  
Receptor Interaction ◽  
Basal Transcription ◽  
Protein Protein Interaction ◽  
Stable Association ◽  
Interacting Surfaces ◽  
Transcriptional Corepressors

Abstract SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) are two related transcriptional corepressors that contain separable domains capable of interacting with unliganded nuclear receptors and repressing basal transcription. To decipher the mechanisms of receptor interaction and transcriptional repression by SMRT/N-CoR, we have characterized protein-protein interacting surfaces between SMRT and nuclear receptors and defined transcriptional repression domains of both SMRT and N-CoR. Deletional analysis reveals two individual nuclear receptor domains necessary for stable association with SMRT and a C-terminal helix essential for corepressor dissociation. Coordinately, two SMRT domains are found to interact independently with the receptors. Functional analysis reveals that SMRT contains two distinct repression domains, and the corresponding regions in N-CoR also repress basal transcription. Both repression domains in SMRT and N-CoR interact weakly with mSin3A, which in turn associates with a histone deacetylase HDAC1 in a mammalian two-hybrid assay. Far-Western analysis demonstrates a direct protein-protein interaction between two N-CoR repression domains with mSin3A. Finally we demonstrate that overexpression of full-length SMRT further represses basal transcription from natural promoters. Together, these results support a role of SMRT/N-CoR in corepression through the utilization of multiple mechanisms for receptor interactions and transcriptional repression.

scholarly journals Expression of NF-κB associated lncRNAs in schizophrenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amin Safa ◽  
Elham Badrlou ◽  
Shahram Arsang-Jang ◽  
Arezou Sayad ◽  
Mohammad Taheri ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Roc Curves ◽  
P Value ◽  
Psychiatric Condition ◽  
Non Coding Rnas ◽  
Diagnostic Power ◽  
Regulation Of Growth ◽  
Peripheral Markers

Abstract NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = − 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value < 0.0001; Posterior beta = 0.467, P value < 0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P < 0.0001), followed by H19 (AUC = 0.815, P < 0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.

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