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10.3389/fimmu.2020.590459 http://scihub22266oqcxt.onion/10.3389/fimmu.2020.590459 33362771!7756074!33362771     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33362771&cmd=llinks): Failed to open stream: HTTP request failed! 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A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection |pdf=|usr=}}{{33362771}} gab.com Text A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection JO: Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=33362771 #FOAvip BACKGROUND: SARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response. RESULTS: This study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub-network "Cluster 1" with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that "Cluster 1" is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as "host response signature network". Functional enrichment analysis with NDEx revealed that the "host response signature network" is predominantly associated with critical pathways, including "cytokines and inflammatory response", "non-genomic action of Vitamin D", "the human immune response to tuberculosis", and "lung fibrosis". Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-alpha induced Jak-STAT signaling pathway. CONCLUSION: This comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-alpha to control severe COVID-19. Twit Text FOAVip A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection ????Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=33362771 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33362771 #FOAvip English Wikipedia <ref>{{Cite pmid|33362771}}</ref> A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection #MMPMID33362771 Ahmed F Front Immunol 2020[]; 11 (ä): 590459 PMID33362771show ga BACKGROUND: SARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response. RESULTS: This study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub-network "Cluster 1" with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that "Cluster 1" is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as "host response signature network". Functional enrichment analysis with NDEx revealed that the "host response signature network" is predominantly associated with critical pathways, including "cytokines and inflammatory response", "non-genomic action of Vitamin D", "the human immune response to tuberculosis", and "lung fibrosis". Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-alpha induced Jak-STAT signaling pathway. CONCLUSION: This comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-alpha to control severe COVID-19. |*COVID-19 Drug Treatment[MESH] |Antiviral Agents/therapeutic use[MESH] |Cytokine Release Syndrome/*prevention & control[MESH] |Cytokines/blood[MESH] |Gene Expression Profiling[MESH] |Humans[MESH] |Pulmonary Fibrosis/pathology/prevention & control[MESH] |SARS-CoV-2/*drug effects[MESH] |Systems Biology/*methods[MESH] |Transcriptome/genetics[MESH]A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in(epmc).pdf DeepDyve Pubget Overpricing