پیوندهای مفید
آمار
| تعداد نشریات | 31 |
| تعداد شماره‌ها | 485 |
| تعداد مقالات | 4,742 |
| تعداد مشاهده مقاله | 7,380,612 |
| تعداد دریافت فایل اصل مقاله | 5,511,054 |
Assessment of Alterations in the Expression of P53 and Cyclin-D Genes in COVID-19 Patients Before and After Remdesivir Treatment | ||
| Journal of Genetic Resources | ||
| دوره 11، شماره 1، اردیبهشت 2025، صفحه 21-30 اصل مقاله (487.18 K) | ||
| نوع مقاله: Research Article | ||
| شناسه دیجیتال (DOI): 10.22080/jgr.2025.28440.1421 | ||
| نویسندگان | ||
| Somayeh Arabzadeh* 1؛ Sohameh Mohebbi2؛ Zahra Faal2؛ Neda Jalali2؛ Kayvan Saeedfar3 | ||
| 1Department of Biology, Faculty of Basic science, Ale Taha institute of higher education, Tehran, Iran | ||
| 2Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran. | ||
| 3Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran | ||
| تاریخ دریافت: 19 مرداد 1403، تاریخ بازنگری: 27 بهمن 1403، تاریخ پذیرش: 30 شهریور 1403 | ||
| چکیده | ||
| Coronavirus disease-19 (COVID-19), caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. The disease primarily spreads through respiratory droplets and manifests with a wide range of symptoms, from mild respiratory illness to severe pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. The virus manipulates the host cell cycle to create a favorable environment for its replication and propagation. One of the key regulators of the cell cycle is cyclin-D, a protein essential for the G1 to S phase transition in the cell cycle, and P53, a critical tumor suppressor and regulator of cell cycle arrest and apoptosis. Therapeutic strategies, including antiviral drugs like Remdesivir, have shown varying efficacy in managing symptoms and reducing mortality. This study obtained blood samples from 30 COVID-19 patients before and after Remdesivir treatment and 20 healthy individuals. RNA was isolated, and cDNA was subsequently synthesized. The expression levels of the p53 and cyclin-D genes were then assessed using Real-time PCR. The results demonstrate that cyclin-D expression increased 9 times in COVID-19 patients compared to the control group (P<0.001), which remained unaffected by Remdesivir treatment. Conversely, p53 gene expression was reduced by 50% in the patient group compared to the control group (P<0.05). Treatment with Remdesivir increased P53 gene expression twofold compared to the control group (P<0.001). Furthermore, P53 gene expression positively correlated with CRP (C Reactive Protein) levels in both the control and patient groups (P<0.01). The study's findings indicate that certain symptoms of COVID-19 may be linked to the virus's impact on crucial cell cycle genes, such as cyclin-D and p53. Remdesivir, by reducing inflammation and inhibiting viral replication, can help restore normal expression levels of these genes. This may support the therapeutic benefits of using Remdesivir in treating COVID-19. | ||
| کلیدواژه‌ها | ||
| Cell cycle؛ COVID-19؛ Cyclin-D؛ P53؛ Remdesivir | ||
| مراجع | ||
|
Akinci, E., Cha, M., Lin, L., Yeo, G., Hamilton, M. C., Donahue, C. J., ... & Sherwood, R. I. (2020). Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics. bioRxiv. https://doi.org/10.1101/2020.08.27.270819
Azarfar, F., Abbasi, B., Jalali, A., Abbasian, M.H. (2023). Investigation of the relationship between monocyte chemoattractant protein 1 rs1024611 variant and severity of COVID-19. Cytokine, 171:156367. http://doi.org/10.1016/j.cyto.2023.156367.
Arthur-Mensah, R. A.-M., & Kyei, A. A. K. (2021). Impact of the COVID-19 pandemic on the professional training of student nurses from universities in Ghana. Pentvars Business Journal, 13 (2), 10-21. https://doi.org/10.62868/pbj.v13i2.158
Blair, H. A. (2023). Remdesivir: A review in COVID-19. Drugs, 83(13), 1215-1237. https://doi.org/10.1007/s40265-023-01926-0
Brodin, P. (2021). Immune determinants of COVID-19 disease presentation and severity. Nature Medicine, 27(1), 28-33. https://doi.org/10.1038/s41591-020-01202-8
Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent symptoms in patients after acute COVID-19. JAMA, 324 (6), 603-605. https://doi.org/10.1001/jama.2020.12603
Chellapandian, N., Sekizhar, V., Pillai, A. B., Venkatesan, R., & Srinivasan, R. (2024). Salivary levels of cell cycle regulatory proteins p53, cyclin D1, CDK 4 and protein carbonylation in post COVID-19 cohort - An observational study. Gene Reports, 37, 102010. https://doi.org/https://doi.org/10.1016/j.genrep.2024.102010
Chen, J. (2016). The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine, 6 (3), a026104. https://doi.org/10.1101/cshperspect.a026104
Cirulli, E. T., Schiabor Barrett, K. M., Riffle, S., Bolze, A., Neveux, I., Dabe, S., ... Washington, N. L. (2020). Long-term COVID-19 symptoms in a large unselected population. medRxiv, https://doi.org/10.1101/2020.10.07.20208702
Farahani, M., Niknam, Z., Amirabad, L. M., Amiri-Dashatan, N., Koushki, M., Nemati, M., ... & Tayebi, L. (2022). Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomedicine and Pharmacotherapy, 145, 112420. https://doi.org/https://doi.org/10.1016/j.biopha.2021.112420
Gudkov, A. V., Gurova, K. V., & Komarova, E. A. (2011). Inflammation and p53: a tale of two stresses. Genes and Cancer, 2(4), 503-516. https://doi.org/10.1177/1947601911409747
Gupta, R. K., & Mlcochova, P. (2022). Cyclin D3 restricts SARS-CoV-2 envelope incorporation into virions and interferes with viral spread. The EMBO Journal, 41(22), e111653. https://doi.org/10.15252/embj.2022111653
Harrison, S. M., Dove, B. K., Rothwell, L., Kaiser, P., Tarpey, I., Brooks, G., & Hiscox, J. A. (2007). Characterisation of cyclin D1 down-regulation in coronavirus infected cells. FEBS Letters, 581(7), 1275-1286. https://doi.org/10.1016/j.febslet.2007.02.039
Jalali, A., & Khoramipour, M. (2022). SARS-CoV-2: Review of structure, genome, genetic variants, and vaccines. Journal of Genetic Resources, 8 (1), 16-34. https://doi.org/10.22080/jgr.2021.21980.1270
Khan, M. A.-A.-K., & Islam, A. B. M. M. K. (2021). SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways. Frontiers in Molecular Biosciences, 8, 598583. https://doi.org/10.3389/fmolb.2020.598583
Kokic, G., Hillen, H. S., Tegunov, D., Dienemann, C., Seitz, F., Schmitzova, J., ... & Cramer, P. (2021). Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nature Communications, 12(1), 279. https://doi.org/10.1038/s41467-020-20542-0
Lamers, M. M., & Haagmans, B. L. (2022). SARS-CoV-2 pathogenesis. Nature Reviews Microbiology, 20(5), 270-284. https://doi.org/10.1038/s41579-022-00713-0
Li, J., Lai, S., Gao, G. F., & Shi, W. (2021). The emergence, genomic diversity and global spread of SARS-CoV-2. Nature, 600 (7889), 408-418. https://doi.org/10.1038/s41586-021-04188-6
Ma-Lauer, Y., Carbajo-Lozoya, J., Hein, M. Y., Müller, M. A., Deng, W., Lei, J., ... & von Brunn, A. (2016). p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1. Proceedings of the National Academy of Sciences, 113(35), E5192-E5201. https://doi.org/doi:10.1073/pnas.1603435113
Malande, O. O. (2020). My COVID-19 experience: picking up the pieces. African Health Sciences, 20(4), 1510-1513. https://doi.org/10.4314/ahs.v20i4.4
Merches, K., Breunig, L., Fender, J., Brand, T., Bätz, V., Idel, S., ... & Lorenz, K. (2022). The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro. Archives of Toxicology, 96(8), 2341-2360. https://doi.org/10.1007/s00204-022-03306-1
Montalto, F. I., & De Amicis, F. (2020). Cyclin D1 in cancer: A molecular connection for cell cycle control, adhesion and invasion in tumor and stroma. Cells, 9 (12), 2648. https://doi.org/10.3390/cells9122648
Moreno, S., Alcázar, B., Dueñas, C., González Del Castillo, J., Olalla, J., & Antela, A. (2022). Use of antivirals in SARS-CoV-2 infection: A critical review of the role of remdesivir. Drug Design, Development and Therapy, 16, 827-841. https://doi.org/10.2147/DDDT.S356951
Muralidar, S., Ambi, S. V., Sekaran, S., & Krishnan, U. M. (2020). The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2. Biochimie, 179, 85-100. https://doi.org/10.1016/j.biochi.2020.09.018
Ozaki, T., & Nakagawara, A. (2011). Role of p53 in cell death and human cancers. Cancers, 3(1), 994-1013. https://doi.org/10.3390/cancers3010994
Peiris, J. S. M., Yuen, K. Y., Osterhaus, A. D. M. E., & Stöhr, K. (2003). The severe acute respiratory syndrome. The New England Journal of Medicine, 349(25), 2431-2441. https://doi.org/10.1056/NEJMra032498
Pera, M., Fernandez, P. L., Pera, M., Palacín, A., Cardesa, A., Dasenbrock, C., ... & Mohr, U. (2001). Expression of cyclin D1 and p53 and its correlation with proliferative activity in the spectrum of esophageal carcinomas induced after duodenal content reflux and 2, 6-dimethylnitrosomorpholine administration in rats. Carcinogenesis, 22(2), 271-277. https://doi.org/10.1093/carcin/22.2.271
de Sousa Pinto, M., Fontoura, L. G. O., da Rosa Borges, I., de Oliveira, G. R., de Melo Bisneto, A. V., Carneiro, L. C., ... & de Moraes Filho, A. V. (2024). Determination of the genotoxic potential of remdesivir and its possible influences on the expression of genes related to the cell cycle and apoptosis. Caderno Pedagógico, 21(4), e3867-e3867. https://doi.org/10.54033/cadpedv21n4-132
Prado, C. A. D. S., Fonseca, D. L. M., Singh, Y., Filgueiras, I. S., Baiocchi, G. C., Plaça, D. R., ... & Cabral‐Marques, O. (2023). Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID‐19 severity. Journal of Medical Virology, 95(2), e28450. https://doi.org/10.1002/jmv.28450
Richard, S. A., Pollett, S. D., Fries, A. C., Berjohn, C. M., Maves, R. C., Lalani, T., ... & Letizia, A. G. (2023). Persistent COVID-19 symptoms at 6 months after onset and the role of vaccination before or after SARS-CoV-2 infection. JAMA Network Open, 6(1), e2251360. https://doi.org/10.1001/jamanetworkopen.2022.51360
Rocha, S., Martin, A. M., Meek, D. W., & Perkins, N. D. (2003). p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-κB subunit with histone deacetylase 1. Molecular and Cellular Biology, 23(13), 4713-4727. https://doi.org/10.1128/MCB.23.13.4713-4727.2003
Schmitz, M. L., & Kracht, M. (2016). Cyclin-dependent kinases as coregulators of inflammatory gene expression. Trends in Pharmacological Sciences, 37(2), 101-113. https://doi.org/10.1016/j.tips.2015.10.004
Şimşek Yavuz, S., & Ünal, S. (2020). Antiviral treatment of COVID-19. Turkish Journal of Medical Sciences, 50(9), 611-619. https://doi.org/10.3906/sag-2004-145
Suryawanshi, R. K., Koganti, R., Agelidis, A., Patil, C. D., & Shukla, D. (2021). Dysregulation of cell signaling by SARS-CoV-2. Trends in Microbiology, 29(3), 224-237. https://doi.org/10.1016/j.tim.2020.12.007
Sydorenko, A. H. (2023). Antiviral drugs in the treatment for COVID-19. Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії, 23 (2), 156–159. https://doi.org/10.31718/2077-1096.23.2.2.156
Välikangas, T., Junttila, S., Rytkönen, K. T., Kukkonen-Macchi, A., Suomi, T., & Elo, L. L. (2022). COVID-19-specific transcriptomic signature detectable in blood across multiple cohorts. Frontiers in Genetics, 13, 929887. https://doi.org/10.3389/fgene.2022.929887
Wang, C., Pan, R., Wan, X., Tan, Y., Xu, L., Ho, C. S., & Ho, R. C. (2020). Immediate psychological responses and associated factors during the initial stage of the 2019 coronavirus disease (COVID-19) epidemic among the general population in China. International Journal of Environmental Research and Public Health, 17(5), 1729. https://doi.org/10.3390/ijerph17051729
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023). Targeting p53 pathways: mechanisms, structures and advances in therapy. Signal Transduction and Targeted Therapy, 8(1), 92. https://doi.org/10.1038/s41392-023-01347-1
Wang, X., Liu, Y., Li, K., & Hao, Z. (2023). Roles of p53-mediated host-virus interaction in coronavirus infection. International Journal of Molecular Sciences, 24(7), 6371. https://doi.org/10.3390/ijms24076371
Yuan, X., Yao, Z., Wu, J., Zhou, Y., Shan, Y., Dong, B., ... & Cong, Y. (2007). G1 phase cell cycle arrest induced by SARS-CoV 3a protein via the cyclin D3/pRb pathway. American Journal of Respiratory Cell and Molecular Biology, 37(1), 9-19. https://doi.org/10.1165/rcmb.2005-0345RC
Zanza, C., Romenskaya, T., Manetti, A. C., Franceschi, F., La Russa, R., Bertozzi, G., ... & Longhitano, Y. (2022). Cytokine storm in COVID-19: immunopathogenesis and therapy. Medicina, 58(2), 144. https://doi.org/10.3390/medicina58020144
Zhang, P., Wang, W., & Li, M. (2021). Circ_0010283/miR-377-3p/Cyclin D1 axis is associated with proliferation, apoptosis, migration, and inflammation of oxidized low-density lipoprotein-stimulated vascular smooth muscle cells. Journal of Cardiovascular Pharmacology, 78(3), 437-447. https://doi.org/10.1097/FJC.0000000000001076
Zhang, S., & El-Deiry, W. S. (2024). Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), trail death receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure. Oncotarget, 15, 275-284. https://doi.org/10.18632/oncotarget.28582
Zhang, Y., Peng, X., Xue, M., Liu, J., Shang, G., Jiang, M., ... & Hu, Y. (2023). SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway. Biogerontology, 24(5), 813-827. https://doi.org/10.1007/s10522-023-10019-0 | ||
|
آمار تعداد مشاهده مقاله: 101 تعداد دریافت فایل اصل مقاله: 100 |
||