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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 | In vivo generation of dendritic cells by intramuscular codelivery of FLT3 ligand and GM-CSF plasmids 显示文摘 | Peretz Y Zhou ZF Halwani F | 2002 | Mol Ther2002，6，3： | 2 |
| 3 | Role of transforming growth factor-βin airway remodeling in asthma显示文摘 | HALWANI R AL-MUHSEN S AL-JAHDALI H | 2011 | Am J Respir Cell Mol Biol2011，44，： | 1 |
| 4 | Prognostic significance of p53,bcl-2,and Bax expression in early breast cancer显示文摘 | Linjawi A Kontogiannea M Halwani F | 2004 | J American College of Sur2004，198，1： | 1 |
| 5 | Transvaginal strangulated small intestinal hernia after abdominal sacrocolpopexy:case report and literature review显示文摘 | Halwani Y Nicolau-Toulouse V Oakes J | 2013 | Hernia2013，17，2： | 1 |
| 6 | T helper 17 cells in airway diseases: from laboratory bench to bedside 显示文摘 | Halwani R A1-Muhsen S Hamid Q | 2013 | Chest2013，143，2： | 1 |
| 7 | Prognosticsignificance of p53y bcl-2, and Bax expression in early breastcancer显示文摘 | Linjawi A Kontogiannea M Halwani F | 2004 | J Am Coll Surg2004，198，1： | 1 |
| 8 | Airway remodeling in asthma 显示文摘 | Halwani R A1-Muhsen S Hamid Q | 2010 | Curt Opin Pharmacol2010，10，3： | 1 |
| 9 | T helper 17 cells in airway diseases:from laboratory bench to bedside显示文摘 | Halwani R Al-Muhsen S Hamid Q | 2013 | Chest2013，143，2： | 1 |
| 10 | Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency显示文摘 | Sancho-Shimizu Vanessa de Diego Rebeca Pérez Lorenzo Lazaro Halwani Rabih Alangari Abdullah Israelsson Elisabeth Fabrega Sylvie Cardon Annabelle Maluenda Jerome Tatematsu Megumi Mahvelati Farhad Herman Melina Ciancanelli Michael Guo Yiqi AlS | 2011 | Journal of Clinical Investigation2011，，12： | 1 |
| 11 | Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL- 15 induces distinct CD8 memory subsets in SIV-infected macaques 显示文摘 | Halwani R Boyer JD Yassine-Diab B | 2008 | J Immunol2008，180，12： | 1 |
| 12 | Role of transforming growth factor-beta in airway remodeling in asthma显示文摘 | Halwani R Al-Muhsen S Al-Jahdali H | 2011 | Am J Respir Cell Mol Binl2011，44，2： | 1 |
| 13 | CC and CXC chemokines induce airway smooth muscle proliferation and survival 显示文摘 | Halwani R AL-Abri J Beland M | 2011 | J Immunol2011，186，41： | 1 |
| 14 | Role of transforming growth factor-beta in airway remodeling in asthma显示文摘 | Halwani R Al- Muhsen S Al- Jahdali H | 2011 | Am J Res Cell Mol Biol2011，44，2： | 1 |
| 15 | Role of transforming growth factor-J3 in airway remodeling in asthma 显示文摘 | Halwani R A1-Muhsen S A1-Jahdali H | 2011 | Am J Respir Cell Mol Biol2011，44，2： | 1 |
| 16 | Prognostic significance of p53,Bcl-2, and Bax expression in early breast cancer显示文摘 | Linjawi A Kontogiannea M Halwani F | 2004 | J Am Coll Surg2004，198，1： | 1 |
| 17 | Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer显示文摘 | Linjawi A Kontogiannea M Halwani F | 2004 | J Am Coll Surg2004，198，1： | 1 |
| 18 | Role of transfor-ming growth factor - beta in airway remodeling in asthma显示文摘 | Halwani R Al - Muhsen S Al - Jahdali H | 2011 | American Journal of Respiratory Cell and Molecular Biology2011，2，2： | 1 |
| 19 | In vivo generation of dendritic cells by intramuscular codelivery of FLT3 ligand and GM-CSF plasmids 显示文摘 | Peretz Y Zhou Z F Halwani F | 2002 | Mol Ther2002，6，3： | 1 |
| 20 | Glucocorti- coid receptor-beta up-regulation and steroid resistance induction by IL-17 and IL-23 cytokine stimulation in peripheral mononuclear cells 显示文摘 | Vazquez-Tello A Halwani R Hamid Q | 2013 | J Clin Immunol2013，33，2： | 1 |
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