Yıl 2024,
Cilt: 3 Sayı: 2, 191 - 206, 18.10.2024
Mukaddes Pala
,
Şenay Görücü Yılmaz
,
Elif Seren Tanriverdi
,
Ayten Gunduz
Leman Acun Delen
,
Dilara Altay Ozturk
Mesut Öterkuş
Proje Numarası
Project No:2021/7
Kaynakça
- Referans1 de Groot, R.J.B., S.C.; Baric, R.; Enjuanes, L.; Gorbalenya, A.E.; Holmes, K.V.; Perlman, S.; Poon, L.; Rottier, P.J.M.; Talbot, P.J.; Woo, P.C.Y.; Ziebuhr, J.; King, A.M.Q.; Adams, M.J.; Carstens, E.B.; Lefkowitz, E.J, Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses. 2011: p. 806 - 828 e17.
- Referans2 Troyano-Hernáez, P., R. Reinosa, and Á. Holguín, Evolution of SARS-CoV-2 envelope, membrane, nucleocapsid, and spike structural proteins from the beginning of the pandemic to September 2020: a global and regional approach by epidemiological week. Viruses, 2021. 13(2): p. 243.
- Referans3 Jackson, C.B., et al., Mechanisms of SARS-CoV-2 entry into cells. Nature reviews Molecular cell biology, 2022. 23(1): p. 3-20.
- Referans4 Zhang, J., et al., Structure of SARS-CoV-2 spike protein. Current Opinion in Virology, 2021. 50: p. 173-182.
- Referans5 Pal, M., et al., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus, 2020. 12(3).
- Referans6 Sharma, A., et al., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. International journal of antimicrobial agents, 2020. 56(2): p. 106054.
- Referans7 Babyn, P.S., et al., Severe acute respiratory syndrome (SARS): chest radiographic features in children. Pediatric radiology, 2004. 34(1): p. 47-58.
- Referans8 Saxton, R.A. and D.M. Sabatini, mTOR signaling in growth, metabolism, and disease. Cell, 2017. 168(6): p. 960-976.
- Referans9 Mazewski, C., et al., Type I interferon (IFN)-regulated activation of canonical and non-canonical signaling pathways. Frontiers in immunology, 2020. 11: p. 606456.
- Referans10 Fattahi, S., et al., PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy. Immunologic Research, 2022: p. 1-7.
- Referans11 Li, T., Diagnosis and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2. 0) working group of 2019 novel coronavirus, Peking union medical college hospital. Emerging microbes & infections, 2020. 9(1): p. 582-585.
- Referans12 Cui N, Z.X., Xu L, Preliminary CT findings of coronavirus disease 2019 (COVID-19). Clin Imaging, 2020. 65:124-132.
- Referans13 Tok YT, K.M., Erdem H, Sarıbal D, Salman Yılmaz S, Nohut OK, Karaali R, Balkan İİ, Mete B, Tabak ÖF, Aygün G, Midilli K, Detection of SARS-CoV-2 RNA in Upper Respiratory Swap Samples by Pooling Method. Balkan Med J, 2022. 39(1):48-54.
- Referans14 Livak, K.J. and T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods, 2001. 25(4): p. 402-408.
- Referans15 Hosmer Jr, D.W., S. Lemeshow, and R.X. Sturdivant, Applied logistic regression. Vol. 398. 2013: John Wiley & Sons.
- Referans16 Metz, C.E. Basic principles of ROC analysis. in Seminars in nuclear medicine. 1978. Elsevier.
- Referans17 JIANG, Y., et al, Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions. MedComm, 2022. 3.3: e154.
- Referans18 Yang, M., et al., The Translational Regulation in mTOR Pathway. Biomolecules, 2022. 12(6): p. 802.
- Referans19 Tang, Y., D.J. Kwiatkowski, and E.P. Henske, mTORC1 hyperactivation in lymphangioleiomyomatosis leads to ACE2 upregulation in type II pneumocytes: implications for COVID-19. European Respiratory Journal, 2021. 57(2).
- Referans20 Schreiber, K.H., et al., A novel rapamycin analog is highly selective for mTORC1 in vivo. Nature communications, 2019. 10(1): p. 1-12.
- Referans21 Andrade, M.A. and P. Bork, HEAT repeats in the Huntington's disease protein. Nature Genetics, 1995. 11(2): p. 115-116.
- Referans22 Yoshimura, S.H. and T. Hirano, HEAT repeats–versatile arrays of amphiphilic helices working in crowded environments? Journal of Cell Science, 2016. 129(21): p. 3963-3970.
- Referans23 Mashayekhi-Sardoo, H. and H. Hosseinjani, A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19. Journal of Basic and Clinical Physiology and Pharmacology, 2022. 33(1): p. 17-25.
- Referans24 Moni, M.A., et al., Gene expression profiling of SARS-CoV-2 infections reveal distinct primary lung cell and systemic immune infection responses that identify pathways relevant in COVID-19 disease. Briefings in bioinformatics, 2021. 22(2): p. 1324-1337.
- Referans25 Carapito, R., et al., Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort. Science Translational Medicine, 2022. 14(628): p. eabj7521.
- Referans26 Bunyavanich, S., A. Do, and A. Vicencio, Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. Jama, 2020. 323(23): p. 2427-2429.
- Referans27 Jackson, H., et al., Characterisation of the blood RNA host response underpinning severity in COVID-19 patients. Scientific Reports, 2022. 12(1): p. 1-14.
- Referans28 Zambalde, É.P., et al., Increased mTOR signaling and impaired autophagic flux are hallmarks of SARS-CoV-2 infection. Current Issues in Molecular Biology, 2022. 45(1): p. 327-336.
- Referans29 Bolourian, A. and Z. Mojtahedi, Obesity, and COVID‐19: The mTOR pathway as a possible culprit. Obesity Reviews, 2020.
- Referans30 Gordon, D.E., et al., A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 2020. 583(7816): p. 459-468.
- Referans31 Gassen, N.C., et al., SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. Nature communications, 2021. 12(1): p. 3818.
- Referans32 Ancochea J, I.J., Group SC-R, Soriano JBJJ, Evidence of gender differences in the diagnosis and management of coronavirus disease 2019 patients: an analysis of electronic health records using natural language processing and machine learning. J Women's Health, 2021 30:393–404.
- Referans33 Ramírez-Soto MC, O.-C.G., Arroyo-Hernández H, Sex differences in COVID-19 fatality rate and risk of death: an analysis in 73 countries, 2020–2021. Infezioni Med, 2021 29:402–7.
mTOR signaling pathway genes effect in COVID-19 infection
Yıl 2024,
Cilt: 3 Sayı: 2, 191 - 206, 18.10.2024
Mukaddes Pala
,
Şenay Görücü Yılmaz
,
Elif Seren Tanriverdi
,
Ayten Gunduz
Leman Acun Delen
,
Dilara Altay Ozturk
Mesut Öterkuş
Öz
Coronavirus disease 2019 (Covid-19) is an infectious disease that causes severe acute respiratory illness caused by coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses host-specific metabolic pathways, including mTOR. The mTOR pathway is hyperactive in viral respiratory tract infections and contributes positively to viral replication. 100 samples were evaluated, 50 patients (Female=23, Male=27), and 50 controls (Female=29, Male=21). The patients were individuals who were COVID-19 positive. We detected expression changes of 5 genes in mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) (MLST8, mTOR, RPTOR, MAPKAP1 and RICTOR). Serum samples were obtained from all patients. The expression changes of mTORC1 and mTORC2 Complex genes were evaluated with Real-time PCR method. Receiver operating curve (ROC) analysis was performed to define the diagnostic power of these genes. Expression changes of five genes in the mTORC1 and mTORC2 complex were statistically significant (p =0.001) and upregulated in serum. The area under the ROC Curve values indicating the diagnostic power of genes were 0.948, 0.771, 0.851, 0.798, and 0.805, respectively. These genes may be candidate for treatment targets. The high discriminative power of these genes in patients from controls indicates their diagnostic potential in serum samples.
Etik Beyan
This study has been approved by the clinical research ethics committee of Malatya Turgut Ozal University (2021/27).
Destekleyen Kurum
Malatya Turgut Ozal University
Proje Numarası
Project No:2021/7
Kaynakça
- Referans1 de Groot, R.J.B., S.C.; Baric, R.; Enjuanes, L.; Gorbalenya, A.E.; Holmes, K.V.; Perlman, S.; Poon, L.; Rottier, P.J.M.; Talbot, P.J.; Woo, P.C.Y.; Ziebuhr, J.; King, A.M.Q.; Adams, M.J.; Carstens, E.B.; Lefkowitz, E.J, Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses. 2011: p. 806 - 828 e17.
- Referans2 Troyano-Hernáez, P., R. Reinosa, and Á. Holguín, Evolution of SARS-CoV-2 envelope, membrane, nucleocapsid, and spike structural proteins from the beginning of the pandemic to September 2020: a global and regional approach by epidemiological week. Viruses, 2021. 13(2): p. 243.
- Referans3 Jackson, C.B., et al., Mechanisms of SARS-CoV-2 entry into cells. Nature reviews Molecular cell biology, 2022. 23(1): p. 3-20.
- Referans4 Zhang, J., et al., Structure of SARS-CoV-2 spike protein. Current Opinion in Virology, 2021. 50: p. 173-182.
- Referans5 Pal, M., et al., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus, 2020. 12(3).
- Referans6 Sharma, A., et al., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. International journal of antimicrobial agents, 2020. 56(2): p. 106054.
- Referans7 Babyn, P.S., et al., Severe acute respiratory syndrome (SARS): chest radiographic features in children. Pediatric radiology, 2004. 34(1): p. 47-58.
- Referans8 Saxton, R.A. and D.M. Sabatini, mTOR signaling in growth, metabolism, and disease. Cell, 2017. 168(6): p. 960-976.
- Referans9 Mazewski, C., et al., Type I interferon (IFN)-regulated activation of canonical and non-canonical signaling pathways. Frontiers in immunology, 2020. 11: p. 606456.
- Referans10 Fattahi, S., et al., PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy. Immunologic Research, 2022: p. 1-7.
- Referans11 Li, T., Diagnosis and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2. 0) working group of 2019 novel coronavirus, Peking union medical college hospital. Emerging microbes & infections, 2020. 9(1): p. 582-585.
- Referans12 Cui N, Z.X., Xu L, Preliminary CT findings of coronavirus disease 2019 (COVID-19). Clin Imaging, 2020. 65:124-132.
- Referans13 Tok YT, K.M., Erdem H, Sarıbal D, Salman Yılmaz S, Nohut OK, Karaali R, Balkan İİ, Mete B, Tabak ÖF, Aygün G, Midilli K, Detection of SARS-CoV-2 RNA in Upper Respiratory Swap Samples by Pooling Method. Balkan Med J, 2022. 39(1):48-54.
- Referans14 Livak, K.J. and T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods, 2001. 25(4): p. 402-408.
- Referans15 Hosmer Jr, D.W., S. Lemeshow, and R.X. Sturdivant, Applied logistic regression. Vol. 398. 2013: John Wiley & Sons.
- Referans16 Metz, C.E. Basic principles of ROC analysis. in Seminars in nuclear medicine. 1978. Elsevier.
- Referans17 JIANG, Y., et al, Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions. MedComm, 2022. 3.3: e154.
- Referans18 Yang, M., et al., The Translational Regulation in mTOR Pathway. Biomolecules, 2022. 12(6): p. 802.
- Referans19 Tang, Y., D.J. Kwiatkowski, and E.P. Henske, mTORC1 hyperactivation in lymphangioleiomyomatosis leads to ACE2 upregulation in type II pneumocytes: implications for COVID-19. European Respiratory Journal, 2021. 57(2).
- Referans20 Schreiber, K.H., et al., A novel rapamycin analog is highly selective for mTORC1 in vivo. Nature communications, 2019. 10(1): p. 1-12.
- Referans21 Andrade, M.A. and P. Bork, HEAT repeats in the Huntington's disease protein. Nature Genetics, 1995. 11(2): p. 115-116.
- Referans22 Yoshimura, S.H. and T. Hirano, HEAT repeats–versatile arrays of amphiphilic helices working in crowded environments? Journal of Cell Science, 2016. 129(21): p. 3963-3970.
- Referans23 Mashayekhi-Sardoo, H. and H. Hosseinjani, A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19. Journal of Basic and Clinical Physiology and Pharmacology, 2022. 33(1): p. 17-25.
- Referans24 Moni, M.A., et al., Gene expression profiling of SARS-CoV-2 infections reveal distinct primary lung cell and systemic immune infection responses that identify pathways relevant in COVID-19 disease. Briefings in bioinformatics, 2021. 22(2): p. 1324-1337.
- Referans25 Carapito, R., et al., Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort. Science Translational Medicine, 2022. 14(628): p. eabj7521.
- Referans26 Bunyavanich, S., A. Do, and A. Vicencio, Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. Jama, 2020. 323(23): p. 2427-2429.
- Referans27 Jackson, H., et al., Characterisation of the blood RNA host response underpinning severity in COVID-19 patients. Scientific Reports, 2022. 12(1): p. 1-14.
- Referans28 Zambalde, É.P., et al., Increased mTOR signaling and impaired autophagic flux are hallmarks of SARS-CoV-2 infection. Current Issues in Molecular Biology, 2022. 45(1): p. 327-336.
- Referans29 Bolourian, A. and Z. Mojtahedi, Obesity, and COVID‐19: The mTOR pathway as a possible culprit. Obesity Reviews, 2020.
- Referans30 Gordon, D.E., et al., A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 2020. 583(7816): p. 459-468.
- Referans31 Gassen, N.C., et al., SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. Nature communications, 2021. 12(1): p. 3818.
- Referans32 Ancochea J, I.J., Group SC-R, Soriano JBJJ, Evidence of gender differences in the diagnosis and management of coronavirus disease 2019 patients: an analysis of electronic health records using natural language processing and machine learning. J Women's Health, 2021 30:393–404.
- Referans33 Ramírez-Soto MC, O.-C.G., Arroyo-Hernández H, Sex differences in COVID-19 fatality rate and risk of death: an analysis in 73 countries, 2020–2021. Infezioni Med, 2021 29:402–7.