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| 1 | Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology显示文摘BACKGROUND The coronavirus disease 2019(COVID-19),a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide,was described to be frequently accompanied by extrapulmonary manifestations,including liver dysfunction.Liver dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 patients.AIM To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.METHODS The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed.Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways.The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis,fibrosis,non-alcoholic fatty liver disease(NAFLD),and hepatitis A/B/C.Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.RESULTS Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,DNAJB1,IGF2,EGFR,and HDGF.Concordantly,the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling(liver cirrhosis,Fibrosis,NAFLD,and hepatitis A/B/C).Moreover,we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function,including cytochrome P450 family members,ACAD11,CIDEB,GNMT,and GPAM.Consequently,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity.In correspondence with the RNA-seq data analysis,we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction.CONCLUSION Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling,mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction. | Sarah Musa Hammoudeh Arabella Musa Hammoudeh Poorna Manasa Bhamidimarri Bassam Mahboub Rabih Halwani Qutayba Hamid Mohamed Rahmani Rifat Hamoudi | 2021 | World Journal of Gastroenterology2021，27，21： | 2 |
| 2 | Remode- ling in Asthma 显示文摘 | Ce line Bergeronl Wisam A1 - Ramli Qutayba Hamid | 2009 | Proc Am Thorac Soc2009，6，： | 1 |
| 3 | Role of Transforming Growth Factor-[Beta] in Airway Remodeling in Asthma显示文摘 | Halwani Rabih Al-Muhsen Saleh Al-Jahdali Hamdan Hamid Qutayba | 2011 | American Journal of Respiratory Cell and Molecular Biology2011，，2： | 1 |
| 4 | TheCCR3 Receptor Is Involved in Eosinophil Differentiation and Is Up-Regtdated by Th2 Cytokines in CD34 + Progenitor Cells显示文摘 | Bouchaib Iamkhioued Soussi Gounni Abdelilah Qutayba Hamid | 2002 | Immunol2002，169，： | 1 |
| 5 | T helper type 2 eytokine reee- tors and associated transcription factors GATA-3, C-MAF and signal transducer and activator of transcription factor-6 in induced sputum of atopic asthmatic patients 显示文摘 | Rame T Qutayba H Lisa C | 2003 | Chest2003，123，6： | 1 |
| 6 | Respiratory pathophysiologic responses in flammation of small airways in asthma显示文摘 | qutayba Hamid Yunling Song Thomasc | 1997 | Jallergy Clin Immunol1997，100，： | 1 |
| 7 | Pathogenesis of Small Airways in Asthma 显示文摘 | Qutayba Hamid | 2012 | Respiration2012，84，1： | 1 |
| 8 | IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines显示文摘 | Sophie Molet Qutayba Hamid Francis Davoine b Esra Nutku Rame Taha a Nathalie Pagé Ron Olivenstein Jack Elias Jamila Chakir | 2001 | The Journal of Allergy and Clinical Immunology2001，，3： | 1 |
| 9 | Remodeling in Asthma显示文摘 | Ce line Bergeronl Wisam Al-Ramli Qutayba Hamid | 2009 | Proc Am Thorac Soc2009，6，： | 1 |
| 10 | Inflammation of small airways in asthma显示文摘 | Qutayba Hamid Yunling Song Thomas C. Kotsimbos Eleanor Minshall Tony R. Bai Richard G. Hegele James C. Hogg | 1997 | The Journal of Allergy and Clinical Immunology1997，，1： | 1 |
| 11 | T H 17-associated cytokines (IL-17A and IL-17F) in severe asthma显示文摘 | Wisam Al-Ramli David Préfontaine Fazila Chouiali James G. Martin Ron Olivenstein Catherine Lemière Qutayba Hamid | 2009 | The Journal of Allergy and Clinical Immunology2009，，5： | 1 |
| 12 | IL-17 is increased in asthmatic asthmatic airways and induced human bronchial fibroblasts to produce cytokines显示文摘 | Sophie M Qutayba H francis D | 2001 | J Allergy Clin Immunol2001，108，3： | 1 |
| 13 | Remodeling in asthma显示文摘 | Saleh Al-Muhsen Jill R. Johnson Qutayba Hamid | 2011 | The Journal of Allergy and Clinical Immunology2011，，3： | 1 |
| 14 | T helper type 2 cytokine receptors and associated transcription factors GATA-3,c-MAF,and signal transducer and activator of transcription factor-6 in induced sputum of a topic asthmatic patients显示文摘 | Rame T Qutayba H Lisa C | 2003 | Chest2003，123，6： | 1 |
| 15 | Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4 + T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-γ显示文摘 | Stephen R. Durham Sun Ying Veronica A. Varney Mikila R. Jacobson Robert M. Sudderick Ian S. Mackay A.Barry Kay Qutayba A. Hamid | 1996 | The Journal of Allergy and Clinical Immunology1996，，6： | 1 |
| 16 | Airway remodelling in asthma: From benchside to clinical practice 显示文摘 | CELINE B MERI K T QUTAYBA H | 2010 | Can Respir J2010，17，4： | 1 |
| 17 | Pathogenesis of Small Airways in Asthma显示文摘 | Qutayba Hamid | 2012 | Res- piration2012，84，： | 1 |
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