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

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.

SUBMITTER: Li R

PROVIDER: S-EPMC7717147 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Li Rong R Li Yu Y Liang Xiao X Yang Lu L Su Min M Lai Keng Po KP

Briefings in bioinformatics 20210301 2

<h4>Objectives</h4>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.<h4>Interventions</h4>We used a series of network pharmacology-based and computational ...[more]

PMID: 33169132

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Project description:BackgroundCurrently, there are no efficient therapies for Alzheimer's disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients' frontal cortex, current study aims to identify the potential mechanisms of quercetin's pharmacological targets.Materials and methodsThe pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.ResultsIn the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.ConclusionThe role of quercetin in AD appears to be multifaceted, and it can affect patients' frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.

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Project description:BackgroundTo analyze the key prognostic genes and potential traditional Chinese medicine targets in glioblastoma (GBM) by bioinformatics and network pharmacology.MethodsGBM datasets were obtained from the Gene Expression Omnibus (GEO) database to clarify the differentially-expressed genes (DEGs) in the carcinoma and paracancerous tissues. The molecular functions (MF) and signaling pathways of enriched DEGs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen hub genes to focus on genes with greater clinical significance. The transcription expression and prognosis of hub genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. The important compounds and target molecules were obtained via the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. We identified the active ingredients by setting the property values of pharmacokinetic attribute values. We constructed the network of "Chinese medicine ingredients-DEGs target" and screened out the target genes and active ingredients with high correlation scores. Finally, molecular docking verification was carried out using AutoDock Tools and PyMOL.ResultsWe obtained 271 DEGs, including 212 up-regulated genes and 59 down-regulated genes and screened ten hub genes. GO and KEGG analyses suggested that the hub genes were mainly involved in the following biological processes: the cell cycle, cell division, and cell adhesion, as well as extracellular matrix adhesion-related pathways, the p53 signaling pathways, and cadherin binding involved in cell-cell adhesion. We established the interaction network between the components and DEGs to screen out the traditional Chinese medicine active component (luteolin) and target genes (BIRC5 and CCNB1) for the treatment of GBM. The molecular docking results showed that the bindings of protein receptors, BIRC5 and CCNB1, with the compound ligand, luteolin, were stable and formed by hydrogen bonding interaction.ConclusionsIn this study, we determined that luteolin potentially inhibits glioblastoma proliferation and migration through key target genes, BIRC5 and CCNB1, via bioinformatics and network pharmacology analysis, and affects the prognosis of GBM patients, providing new ideas for clinical targeted therapy and new drug development.

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

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

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