scholarly journals Identification of COVID-19 and Dengue Host Factor Interaction Networks Based on Integrative Bioinformatics Analyses

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjiang Zheng ◽  
Hui Wu ◽  
Chengxin Liu ◽  
Qian Yan ◽  
Ting Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Options ◽  
Enrichment Analysis ◽  
Host Factor ◽  
Interaction Networks ◽  
Biological Functions ◽  
Bioinformatics Analyses ◽  
Health Crisis ◽  
Tissue Specific ◽  
Factor Interaction

BackgroundThe outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection.MethodsTo further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents.ResultsWe explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone.ConclusionsThis study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.

scholarly journals Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjiang Zheng ◽  
Ting Wang ◽  
Peng Wu ◽  
Qian Yan ◽  
Chengxin Liu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Bioinformatics Analysis ◽  
Interaction Analysis ◽  
Clinical Sample ◽  
Enrichment Analysis ◽  
Host Factor ◽  
Interaction Networks ◽  
Host Factors ◽  
Pathway Enrichment Analysis ◽  
Factor Interaction

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction.Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions.Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.

scholarly journals Cystic Fibrosis: Systems Biology Analysis from Homozygous p.Phe508del Variant Patients’ Samples Reveals Perturbations in Tissue-Specific Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Joice de Faria Poloni ◽  
Thaiane Rispoli ◽  
Maria Lucia Rossetti ◽  
Cristiano Trindade ◽  
José Eduardo Vargas
Keyword(s):  
Cystic Fibrosis ◽  
Enrichment Analysis ◽  
Autosomal Recessive Disorder ◽  
Bronchial Epithelium ◽  
Interaction Networks ◽  
Homozygous State ◽  
Functional Interaction ◽  
Tissue Specific ◽  
Ppi Networks ◽  
Cf Transmembrane Conductance Regulator

Cystic fibrosis (CF) is an autosomal recessive disorder, caused by diverse genetic variants for the CF transmembrane conductance regulator (CFTR) protein. Among these, p.Phe508del is the most prevalent variant. The effects of this variant on the physiology of each tissue remains unknown. This study is aimed at predicting cell signaling pathways present in different tissues of fibrocystic patients, homozygous for p.Phe508del. The study involved analysis of two microarray datasets, E-GEOD-15568 and E-MTAB-360 corresponding to the rectal and bronchial epithelium, respectively, obtained from the ArrayExpress repository. Particularly, differentially expressed genes (DEGs) were predicted, protein-protein interaction (PPI) networks were designed, and centrality and functional interaction networks were analyzed. The study reported that p.Phe508del-mutated CFTR-allele in homozygous state influenced the whole gene expression in each tissue differently. Interestingly, gene ontology (GO) term enrichment analysis revealed that only “neutrophil activation” was shared between both tissues; however, nonshared DEGs were grouped into the same GO term. For further verification, functional interaction networks were generated, wherein no shared nodes were reported between these tissues. These results suggested that the p.Phe508del-mutated CFTR-allele in homozygous state promoted tissue-specific pathways in fibrocystic patients. The generated data might further assist in prediction diagnosis to define biomarkers or devising therapeutic strategies.

scholarly journals Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1284 ◽  
Author(s):  
Maryam Abedi ◽  
Yousof Gheisari
Keyword(s):  
Gene Expression ◽  
Diabetic Nephropathy ◽  
Signaling Pathways ◽  
Protein Interaction ◽  
Enrichment Analysis ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Pathway Enrichment Analysis ◽  
Complex Disorders ◽  
Pathway Enrichment

In spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critical signaling pathways related to diabetic nephropathy. GSE1009 dataset was downloaded from Gene Expression Omnibus database and the gene expression profile of glomeruli from diabetic nephropathy patients and those from healthy individuals were compared. The protein-protein interaction network for differentially expressed genes was constructed and enriched. In addition, topology of the network was analyzed to identify the genes with high centrality parameters and then pathway enrichment analysis was performed. We found 49 genes to be variably expressed between the two groups. The network of these genes had few interactions so it was enriched and a network with 137 nodes was constructed. Based on different parameters, 34 nodes were considered to have high centrality in this network. Pathway enrichment analysis with these central genes identified 62 inter-connected signaling pathways related to diabetic nephropathy. Interestingly, the central nodes were more informative for pathway enrichment analysis compared to all network nodes and also 49 differentially expressed genes. In conclusion, we here show that central nodes in protein interaction networks tend to be present in pathways that co-occur in a biological state. Also, this study suggests a computational method for inferring underlying mechanisms of complex disorders from raw high-throughput data.

scholarly journals Integrated bioinformatics analysis of potential pathway biomarkers using abnormal proteins in clubfoot

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8422
Author(s):  
Guiquan Cai ◽  
Xuan Yang ◽  
Ting Chen ◽  
Fangchun Jin ◽  
Jing Ding ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Protein Interactions ◽  
Regulatory Networks ◽  
Molecular Transport ◽  
Enrichment Analysis ◽  
Congenital Talipes Equinovarus ◽  
Bioinformatics Analyses ◽  
Human Phenotype ◽  
Vascular Abnormalities ◽  
Talipes Equinovarus

Background As one of the most common major congenital distal skeletal abnormalities, congenital talipes equinovarus (clubfoot) affects approximately one in one thousandth newborns. Although several etiologies of clubfoot have been proposed and several genes have been identified as susceptible genes, previous studies did not further explore signaling pathways and potential upstream and downstream regulatory networks. Therefore, the aim of the present investigation is to explore abnormal pathways and their interactions in clubfoot using integrated bioinformatics analyses. Methods KEGG, gene ontology (GO), Reactome (REAC), WikiPathways (WP) or human phenotype ontology (HP) enrichment analysis were performed using WebGestalt, g:Profiler and NetworkAnalyst. Results A large number of signaling pathways were enriched e.g. signal transduction, disease, metabolism, gene expression (transcription), immune system, developmental biology, cell cycle, and ECM. Protein-protein interactions (PPIs) and gene regulatory networks (GRNs) analysis results indicated that extensive and complex interactions occur in these proteins, enrichment pathways, and TF-miRNA coregulatory networks. Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins. Conclusion The results of the present study supported previously proposed hypotheses, such as ECM, genetic, muscle, neurological, skeletal, and vascular abnormalities. More importantly, the enrichment results also indicated cellular or immune responses to external stimuli, and abnormal molecular transport or metabolism may be new potential etiological mechanisms of clubfoot.

scholarly journals Network Pharmacology-Based Investigation of the Mechanism of Action of Plantaginis Herba in Hyperuricemia Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Rong Tang ◽  
Xiaoqing Peng ◽  
Yan Wang ◽  
Xiaohong Zhou ◽  
Hong Liu
Keyword(s):  
Signaling Pathways ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Active Ingredients ◽  
Bioinformatics Analyses ◽  
Network Construction ◽  
Kegg Analysis ◽  
Underlying Mechanisms

This study used a network pharmacology approach to investigate the potential active ingredients of Plantaginis Herba and its underlying mechanisms in hyperuricemia treatment. The potential active ingredients of Plantaginis Herba were obtained from TCMSP and ETCM databases, and the potential targets of the active ingredients were predicted using the Swiss TargetPrediction database. The potential therapeutic targets of hyperuricemia were retrieved from the GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. Then, the integrative bioinformatics analyses of candidates were performed by GO analysis, KEGG analysis, and PPI network construction. There were 15 predicted active ingredients in Plantaginis Herba and 41 common targets that may be involved in the treatment of hyperuricemia. A total of 61 GO annotations and 35 signaling pathways were identified by enrichment analysis ( P < 0.01 ). The underlying mechanisms of Plantaginis Herba may be related to insulin resistance, PI3K/AKT, TNF, VEGF, AMPK, and glucagon signaling pathways. Thus, the present study provided potential and promising strategies of Plantaginis Herba for hyperuricemia treatment.

scholarly journals Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets

2020 ◽  
Author(s):  
Rong Li ◽  
Yu Li ◽  
Xiao Liang ◽  
Lu Yang ◽  
Min Su ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Treatment Options ◽  
Network Pharmacology ◽  
Biological Functions ◽  
Bioinformatics Analyses ◽  
Inflammatory Reactions ◽  
Functional Roles ◽  
Pharmacological Targets ◽  
Predisposing Genes ◽  
Underlying Mechanisms

Abstract Objectives Patients with colorectal cancer (CRC) may be susceptible to the coronavirus disease-2019 (COVID-19). However, anti-CRC/COVID-19 treatment options are currently unavailable. Since niacin is a vitamin with cytoprotective and anti-inflammatory functions, this study aimed to evaluate the possible functional roles and underlying mechanisms of action of niacin as an anti-COVID-19 and -CRC therapy. Interventions We used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of niacin in CRC/COVID-19. Measurements and main results We revealed the clinical characteristics of CRC patients and COVID-19 patients, including predisposing genes, survival rate and prognosis. Moreover, the results of molecular docking analysis indicated that niacin exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions and signaling pathways of niacin in CRC/COVID-19. The analysis indicated that niacin could help in treating CRC/COVID-19 through cytoprotection, enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of cellular microenvironment. Furthermore, five core pharmacological targets of niacin in CRC/COVID-19 were also identified, including BCL2L1, PTGS2, IL1B, IFNG and SERPINE1. Conclusions This study, for the first time, revealed the niacin-associated molecular functions and pharmacological targets for treating CRC/COVID-19, as COVID-19 remains a serious pandemic. But the findings were not validated in actual CRC patients infected with COVID-19, so further investigation is needed to confirm the potential use of niacin for treating CRC/COVID-19.

Unraveling the action mechanism of Buyang Huanwu Tang (BYHWT) for Cerebral Ischemia by Systematic Pharmacological Methodology

2020 ◽  
Vol 23 ◽  
Author(s):  
Shi-tang Ma ◽  
Ning Zhang ◽  
Ge Hong ◽  
Cheng-tao Feng ◽  
Sheng-wei Hong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Virtual Screening ◽  
Signaling Pathways ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Material Base ◽  
Lead Discovery ◽  
Binding Effect ◽  
Bioactive Ingredients ◽  
Compound Target

Background: Buyang Huanwu Tang (BYHWT) and relevant Traditional Chinese medicine (TCM) has its unique advantages in the treatment of cerebral ischemia. However, its pharmacological mechanism have not been fully explained. Objective: Base on the multi-component, also the entire disease network targets, the present study set out to identify major bioactive ingredients, key disease targets, and pathways of BYHWT against cerebral ischemia disease by systematic pharmacological methodology. Methods: Both the bioactive compounds from the BYHWT and the positive drugs against cerebral ischemia were fully investigated. The binding targets of the positive drugs were then obtained. A virtual screening protocol was then used to highlight the compound-target interaction. And network was constructed to visual the compound-target binding effect after docking analysis. Moreover，the targets enrichment analysis for biological processes and pathways were revealed to further explore the function of bio-targets protein gene and its role in the signal pathway. Results: A total of 382 active ingredients of the BYHWT and 23 candidate disease targets were identified. Virtual screening results indicated that multiple bioactive compounds targeted multiple proteins. Each compounds act on one or more targets. The mechanisms were linked to 20 signaling pathways, and the key mechanism was related to serotonergic synapse, calcium signaling pathway and camp signaling pathways. Conclusion: The present study explored the bioactive ingredients and mechanisms of BYHWT against cerebral ischemia by systematic pharmacological methodology. the novel methodology would provide a reference for the lead discovery of precursors, disease mechanism and material base for TCM.

Vitamin C as an Anticancer Agent: Regulation of Signaling Pathways

2020 ◽  
Vol 20 (21) ◽  
pp. 1868-1875
Author(s):  
Ghazala Butt ◽  
Ammad A. Farooqi ◽  
Aima Adylova ◽  
Rukset Attar ◽  
Seher Yilmaz ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Published Data ◽  
New Era ◽  
Molecular Oncology ◽  
Anticancer Effects ◽  
Oncogenic Pathways

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

A Brief Review on Dual Target of PARP1 and STAT3 for Cancer Therapy: A Novel Perception

2020 ◽  
Vol 16 (2) ◽  
pp. 115-134
Author(s):  
Kaviarasan Lakshmanan ◽  
Gowramma Byran ◽  
Manal Mohammed
Keyword(s):  
Signaling Pathways ◽  
Single Molecule ◽  
Treatment Options ◽  
Poor Response ◽  
Cytotoxic Agents ◽  
Acquired Drug Resistance ◽  
Single Target ◽  
New Strategy ◽  
Cancer Multiple ◽  
Almost All

Background: Cancer is a disease characterized by the uncontrolled growth and spread of abnormal cells. Around the world, over 10 million cancer cases occur annually. Half of all men and one-third of all women will develop some form of cancer during their lifetime. It is one of the most feared diseases, primarily because half of those diagnosed with cancer die from it. There are several treatments available for cancer. Almost all traditional cytotoxic agents suffer from severe toxicities and other undesirable side effects. Objective: In recent years, the development of targeted medicines has made significant achievements. Unfortunately, though these agents can block key regulators of signaling pathways in cancer, multiple compensatory pathways always attenuate pharmacological effect of single-target drugs. In addition, poor response rates and acquired drug resistance also represent a significant barrier to widespread use of targeted medicines. More recently, a number of combinatorial therapies have expanded treatment options, which can directly block several key signaling pathways and create a synergistic effect. Conclusion: Therefore, in order to overcome these barriers, the present investigation aims to develop a new strategy for designing a single molecule with inhibition of two receptors (PARP1 and STAT3) simultaneously and producing enhanced anti-cancer activity with less and/or null toxicity.

Determination of Usnic Acid Responsive miRNAs in Breast Cancer Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Usnic Acid ◽  
Enrichment Analysis ◽  
Breast Cancer Cell Lines ◽  
Pathway Enrichment Analysis ◽  
Molecular Heterogeneity ◽  
Proliferative Effect ◽  
Mcf 7

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.

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