Research Article
BibTex RIS Cite

Year 2025, Volume: 15 Issue: 3, 504 - 516, 30.09.2025

Mustafa Öztatlıcı , Hülya Öztatlıcı , Derya Dilek Kançağı , Raife Dilek Turan , Gözde Yalçın , Bulut Yurtsever , Didem Çakirsoy , Selen Abanuz , Cihan Taştan , Samed Özer , Gamze Tumentemur , Murat Kasap , Gürler Akpınar , Büşra Şen Halıcıoğlu , Sevda Demir , Dilek Telci , Fikrettin Şahin , Mehmet İbrahim Tuğlu , Ercüment Ovalı

https://doi.org/10.33808/clinexphealthsci.1512385

Abstract

References

  • Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085-2094. https://doi.org/10.1007/s10067-020-05190-5.
  • Frisoni P, Neri M, D’Errico S, Alfieri L, Bonuccelli D, Cingolani M, Di Paolo M, Gaudio RM, Lestani M, Marti M, Martelloni M, Moreschi C, Santurro A, Scopetti M, Turriziani O, Zanon M, Scendoni R, Frati P, Fineschi V. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: From viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Sci Med Pathol. 2021;1-15. https://doi.org/10.1007/s12024-021-00414-9.
  • Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, Nakane T, Zivanov J, Neufeldt CJ, Cerikan B, Lu JM, Peukes J, Xiong X, Kräusslich HG, Scheres SHW, Bartenschlager R, Briggs JAG. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 2020;588(7838):498-502. https://doi.org/10.1038/s41586-020-2665-2.
  • Lean FZX, Lamers MM, Smith SP, Shipley R, Schipper D, Temperton N, Haagmans BL, Banyard AC, Bewley KR, Carroll MW, Brookes SM, Brown I, Nuñez A. Development of immunohistochemistry and in situ hybridization for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens. Sci Rep. 2020;10(1):1-9. https://doi.org/10.1038/s41598-020-78949-0.
  • Sia, S. F., Yan, L. M., Chin AWH, Fung K., Choy K. T., Wong AYL, Kaewpreedee P., Perera RAPM, Poon LLM, Nicholls JM, Peiris M., Yen H.‐L. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 2020;583(7818):834-838. https://doi.org/10.1038/s41586-020-2342-5.
  • Turan RD, Tastan C, Dilek Kancagi D, Yurtsever B, Sir Karakus G, Ozer S, Abanuz S, Cakirsoy D, Tumentemur G, Demir S, Seyis U, Kuzay R, Elek M, Kocaoglu ME, Ertop G, Arbak S, Acikel Elmas M, Hemsinlioglu C, Hatirnaz Ng O, Akyoney S, Sahin I, Kayhan CK, Tokat F, Akpinar G, Kasap M, Kocagoz AS, Ozbek U, Telci D, Sahin F, Yalcin K, Ratip S, Ince U, Ovali E. Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice. Sci Rep. 2021;11(1):15799. https://doi.org/10.1038/s41598-021-95086-4.
  • Sir Karakus G, Tastan C, Dilek Kancagi D, Yurtsever B, Tumentemur G, Demir S, Turan RD, Abanuz S, Cakirsoy D, Seyis U, Ozer S, Elibol O, Elek M, Ertop G, Arbak S, Acikel Elmas M, Hemsinlioglu C, Kocagoz AS, Hatirnaz Ng O, Akyoney S, Sahin I, Ozbek U, Telci D, Sahin F, Yalcin K, Ratip S, Ovali E. Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates. Sci Rep. 2021;11(1):5804. https://doi.org/10.1038/s41598-021-83930-6.
  • Williams, M.S. 1993. Single-radial-immunodiffusion as an in vitro potency assay for human inactivated viral vaccines. Vet Microbiol. 1993;37(3-4):253-62. https://doi.org/10.1016/0378-1135(93)90027-5.
  • Taştan C, Yurtsever B, Sir Karakuş G, Dilek Kançaği D, Demir S, Abanuz S, Seyis U, Yildirim M, Kuzay R, Elibol Ö, Arbak S, Açikel Elmas M, Birdoğan S, Sezerman OU, Kocagöz AS, YalÇin K, Ovali E. SARS-CoV-2 isolation and propagation from Turkish COVID-19 patients. Turk J Biol. 2020;44(3):192-202. https://doi.org/10.3906/biy-2004-113.
  • Eren SA, Tastan C, Karadeniz KB, Turan RD, Cakirsoy D, Kancagi DD, Yilmaz SU, Oztatlici M, Oztatlici H, Ozer S, Tumentemur G, Baykal AT, Ovali E. Lentiviral micro-dystrophin gene treatment into late-stage mdx mice for Duchene Muscular Dystrophy disease. Curr. Gene Ther. 2023;23:304–315.
  • Birinci, H., Vatansever, H. S., Yüncü, M. Effect of kisspeptin-54 on ovarian levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in an experimental model of ovarian hyperstimulation syndrome (OHSS). Reprod Fertil Dev. 2021;33(16):799-809. https://doi.org/10.1071/RD21140.
  • Özbilgin, M. K., Demirören, S., Üçöz, M., Oztatlici, M. Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c. Andrologia. 2012;53(7):e14071. https://doi.org/10.1111/and.14071.
  • Liu, M. W., Su, M. X., Tang, D. Y., Hao, L., Xun, X. H., Huang, Y. Q. Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression. BMC Pulm Med. 2019;19(1):35. https://doi.org/10.1186/s12890-019-0799-5.
  • Abolaban, F. A., Djouider, F.M. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development. Open Life Sci. 2021;16(1), 558-570. https://doi.org/10.1515/biol-2021-0051.
  • Jansen J, Reimer KC, Nagai JS, Varghese FS, Overheul GJ, de Beer M, Roverts R, Daviran D, Fermin LAS, Willemsen B, Beukenboom M, Djudjaj S, von Stillfried S, van Eijk LE, Mastik M, Bulthuis M, Dunnen WD, van Goor H, Hillebrands JL, Triana SH, Alexandrov T, Timm MC, van den Berge BT, van den Broek M, Nlandu Q, Heijnert J, Bindels EMJ, Hoogenboezem RM, Mooren F, Kuppe C, Miesen P, Grünberg K, Ijzermans T, Steenbergen EJ, Czogalla J, Schreuder MF, Sommerdijk N, Akiva A, Boor P, Puelles VG, Floege J, Huber TB. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 2021;29(2):217-231. https://doi.org/10.1016/j.stem.2021.12.010
  • Milross, L., Majo, J., Cooper, N., Kaye, P. M., Bayraktar, O., Filby, A., Fisher, A. J. Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19. Lancet Respir Med. 2022;10(1):95-106. https://doi.org/10.1016/s2213-2600(21)00408-2.
  • Shang C, Zhuang X, Zhang H, Li Y, Zhu Y, Lu J, Ge C, Cong J, Li T, Li N, Tian M, Jin N, Li X. Inhibition of Autophagy Suppresses SARS-CoV-2 Replication and Ameliorates Pneumonia in hACE2 Transgenic Mice and Xenografted Human Lung Tissues. J Virol. 2021;95(24):e0153721. https://doi.org/10.1128/JVI.01537-21.
  • Halfmann PJ, Iida S, Iwatsuki-Horimoto K, Maemura T, Kiso M, Scheaffer SM, Darling TL, Joshi A, Loeber S, Singh G, Foster SL, Ying B, Case JB, Chong Z, Whitener B, Moliva J, Floyd K, Ujie M, Nakajima N, Ito M, Wright R, Uraki R, Warang P, Gagne M, Li R, Sakai-Tagawa Y, Liu Y, Larson D, Osorio JE, Hernandez-Ortiz JP, Henry AR, Ciuoderis K, Florek KR, Patel M, Odle A, Wong LR, Bateman AC, Wang Z, Edara VV, Chong Z, Franks J, Jeevan T, Fabrizio T, DeBeauchamp J, Kercher L, Seiler P, Gonzalez-Reiche AS, Sordillo EM, Chang LA, van Bakel H, Simon V; Consortium Mount Sinai Pathogen Surveillance (PSP) study group; Douek DC, Sullivan NJ, Thackray LB, Ueki H, Yamayoshi S, Imai M, Perlman S, Webby RJ, Seder RA, Suthar MS, García-Sastre A, Schotsaert M, Suzuki T, Boon ACM, Diamond MS, Kawaoka Y. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature. 2022 Mar;603(7902):687-692. https://doi.org/10.1038/s41586-022-04441-6.
  • Hartmann, C., Miggiolaro, A. F. R. D. S., Motta, J. D. S. J., Baena Carstens, L., Busatta Vaz De Paula, C., Fagundes Grobe, S., de Souza Nunes, L. H., Marques, G. L., Libby, P., Moura, L. Z., de Noronha, L., Pellegrino Baena, C. The Pathogenesis of COVID-19 myocardial injury: An immunohistochemical study of postmortem biopsies. Front Immunol. 2021;12:748417. https://doi.org/10.3389/fimmu.2021.748417.
  • Pessolani, T. G., de Legaria, M. M. F., Apellániz, M. E., Moreno, S. S., Cortés, M. D. M. L., Sánchez, S. G. Multi-organ pathological findings associated with COVID-19 in postmortem needle core biopsies in four patients and a review of the current literature. Rev Esp Patol. 2021;54(4), 275-280. https://doi.org/10.1016/j.patol.2020.09.003
  • De Maio, F., Cascio, E. L., Babini, G., Sali, M., Della Longa, S., Tilocca, B., Roncada, P., Arcovito, A., Sanguinetti, M., Scambia, G., Urbani, A. Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis. Microbes Infect. 2020;22(10):592-597. https://doi.org/10.1016/j.micinf.2020.08.006.
  • Shepley-McTaggart A, Sagum CA, Oliva I, Rybakovsky E, DiGuilio K, Liang J, Bedford MT, Cassel J, Sudol M, Mullin JM, Harty RN. SARS-CoV-2 Envelope (E) protein interacts with PDZ-domain-2 of host tight junction protein ZO1. PLoS One 2021;16(6):e0251955. https://doi.org/10.1371/journal.pone.0251955.
  • Stewart CA, Gay CM, Ramkumar K, Cargill KR, Cardnell RJ, Nilsson MB, Heeke S, Park EM, Kundu ST, Diao L, Wang Q, Shen L, Xi Y, Zhang B, Della Corte CM, Fan Y, Kundu K, Gao B, Avila K, Pickering CR, Johnson FM, Zhang J, Kadara H, Minna JD, Gibbons DL, Wang J, Heymach JV, Byers LA. Lung cancer models reveal SARS-CoV-2-induced EMT contributes to COVID-19 pathophysiology. bioRxiv. 2021;2020.05.28.122291. https://doi.org/10.1101/2020.05.28.122291. Update in: J Thorac Oncol. 2021 Nov;16(11):1821-1839.
  • Herrero, R., Sanchez, G., Lorente, J. A. New insights into the mechanisms of pulmonary edema in acute lung injury. Ann Transl Med. 2018;6(2):32. https://doi.org/10.21037/atm.2017.12.18.
  • Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, Sepe PA, Resasco T, Camporotondo R, Bruno R, Baldanti F, Paolucci S, Pelenghi S, Iotti GA, Mojoli F, Arbustini E. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911-915. https://doi.org/10.1002/ejhf.1828.
  • Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, Shen J, Zhou Y, Shi ZL, Zhou P, Peng K. SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther. 2020;5(1):235. https://doi.org/10.1038/s41392-020-00334-0.
  • Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, Bucci E, Piacentini M, Ippolito G, Melino,G. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020;27(5):1451-1454. https://doi.org/10.1038/s41418-020-0530-3.
  • Ho HT, Peischard S, Strutz-Seebohm N, Klingel K, Seebohm G. Myocardial damage by sars-cov-2: Emerging mechanisms and therapies. Viruses. 2021;13(9):1880. https://doi.org/10.3390/v13091880
  • Lindner D, Fitzek A, Bräuninger H. Association of cardiac infection with sars-cov-2 in confirmed covid-19 autopsy cases. JAMA Cardiol. 2020;5(11):1281-1285. https://doi.org/10.1001/jamacardio.2020.3551.
  • DeDiego, M. L., Nieto-Torres, J. L., Regla-Nava, J. A., Jimenez-Guardeño, J. M., Fernandez-Delgado, R., Fett, C., Castano-Rodriguez, C., Perlman, S., Enjuanes, L. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913-24. https://doi.org/10.1128/JVI.02576-13.
  • Delgado-Roche, L., Mesta, F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch Med Res. 2020;51(5):384-387. https://doi.org/10.1016/j.arcmed.2020.04.019.
  • Chernyak, B. V., Popova, E. N., Prikhodko, A. S., Grebenchikov, O. A., Zinovkina, L. A., Zinovkin, R. A. COVID-19 and Oxidative Stress. Biochemistry (Mosc). 2020;85(12):1543-1553. https://doi.org/10.1134/S0006297920120068.
  • Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0.
  • Carvacho I, Piesche M. RGD-binding integrins and TGF-β in SARS-CoV-2 infections - novel targets to treat COVID-19 patients? Clin Transl Immunology. 2021;10(3):e1240. https://doi.org/10.1002/cti2.1240.
  • Vaz de Paula CB, Nagashima S, Liberalesso V, Collete M, da Silva FPG, Oricil AGG, Barbosa GS, da Silva GVC, Wiedmer DB, da Silva Dezidério F, Noronha L. COVID-19: Immunohistochemical analysis of tgf-β signaling pathways in pulmonary fibrosis. Int J Mol Sci. 2021;23(1):168. https://doi.org/10.3390/ijms23010168.
  • Xu L, Tan B, Huang D, Yuan M, Li T, Wu M, Ye C. Remdesivir inhibits tubulointerstitial fibrosis in obstructed kidneys. Front Pharmacol. 2021;12:626510. https://doi.org/10.3389/fphar.2021.626510.

Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model

Year 2025, Volume: 15 Issue: 3, 504 - 516, 30.09.2025

Mustafa Öztatlıcı , Hülya Öztatlıcı , Derya Dilek Kançağı , Raife Dilek Turan , Gözde Yalçın , Bulut Yurtsever , Didem Çakirsoy , Selen Abanuz , Cihan Taştan , Samed Özer , Gamze Tumentemur , Murat Kasap , Gürler Akpınar , Büşra Şen Halıcıoğlu , Sevda Demir , Dilek Telci , Fikrettin Şahin , Mehmet İbrahim Tuğlu , Ercüment Ovalı

https://doi.org/10.33808/clinexphealthsci.1512385

Abstract

Objective: Coronavirus disease 2019 (COVID-19) is an infectious outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and virus-related deaths are increasing day by day. For this reason, vaccine studies and their urgent use are of great importance to prevent the pandemic. In this study, multi-organ damages caused by SARS-CoV-2 virus in human- angiotensin-converting enzyme type 2 (ACE2) transgenic mice and the protective effects of OZG-38.61.3 gamma irradiated SARS-CoV-2 vaccine against viral damage were investigated.
Methods: For this purpose, transgenic K18-hACE2 BALB/c mice were randomly allocated into 4 groups, negative control group (NC), positive control group (PC, SARS-CoV-2 infected), and 2 different doses of OZG-38.61.3 vaccine (Challenge 1, dose of 10 13 and Ch2, 10 14 viral particle after SARS-CoV-2 infection). After the administrations, lung, heart and kidney tissues were examined by histopathological, immunohistochemical and TUNEL analysis.
Results: Our results showed that the vaccine doses decreased the apoptosis, oxidative stress and inflammation parameters caused by virus in lung, heart, and kidney tissues. It was also found that the vaccine protected the expressions of tight junction proteins in the kidneys.
Conclusion: According to our findings, it is suggested that the OZG-38.61.3 can be an effective and protective vaccine that can be safely used against the SARS-CoV-2 virus.

Keywords

COVID-19 SARS-CoV-2 human ACE2 transgenic mouse Organ damage Vaccination

References

  • Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085-2094. https://doi.org/10.1007/s10067-020-05190-5.
  • Frisoni P, Neri M, D’Errico S, Alfieri L, Bonuccelli D, Cingolani M, Di Paolo M, Gaudio RM, Lestani M, Marti M, Martelloni M, Moreschi C, Santurro A, Scopetti M, Turriziani O, Zanon M, Scendoni R, Frati P, Fineschi V. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: From viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Sci Med Pathol. 2021;1-15. https://doi.org/10.1007/s12024-021-00414-9.
  • Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, Nakane T, Zivanov J, Neufeldt CJ, Cerikan B, Lu JM, Peukes J, Xiong X, Kräusslich HG, Scheres SHW, Bartenschlager R, Briggs JAG. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 2020;588(7838):498-502. https://doi.org/10.1038/s41586-020-2665-2.
  • Lean FZX, Lamers MM, Smith SP, Shipley R, Schipper D, Temperton N, Haagmans BL, Banyard AC, Bewley KR, Carroll MW, Brookes SM, Brown I, Nuñez A. Development of immunohistochemistry and in situ hybridization for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens. Sci Rep. 2020;10(1):1-9. https://doi.org/10.1038/s41598-020-78949-0.
  • Sia, S. F., Yan, L. M., Chin AWH, Fung K., Choy K. T., Wong AYL, Kaewpreedee P., Perera RAPM, Poon LLM, Nicholls JM, Peiris M., Yen H.‐L. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 2020;583(7818):834-838. https://doi.org/10.1038/s41586-020-2342-5.
  • Turan RD, Tastan C, Dilek Kancagi D, Yurtsever B, Sir Karakus G, Ozer S, Abanuz S, Cakirsoy D, Tumentemur G, Demir S, Seyis U, Kuzay R, Elek M, Kocaoglu ME, Ertop G, Arbak S, Acikel Elmas M, Hemsinlioglu C, Hatirnaz Ng O, Akyoney S, Sahin I, Kayhan CK, Tokat F, Akpinar G, Kasap M, Kocagoz AS, Ozbek U, Telci D, Sahin F, Yalcin K, Ratip S, Ince U, Ovali E. Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice. Sci Rep. 2021;11(1):15799. https://doi.org/10.1038/s41598-021-95086-4.
  • Sir Karakus G, Tastan C, Dilek Kancagi D, Yurtsever B, Tumentemur G, Demir S, Turan RD, Abanuz S, Cakirsoy D, Seyis U, Ozer S, Elibol O, Elek M, Ertop G, Arbak S, Acikel Elmas M, Hemsinlioglu C, Kocagoz AS, Hatirnaz Ng O, Akyoney S, Sahin I, Ozbek U, Telci D, Sahin F, Yalcin K, Ratip S, Ovali E. Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates. Sci Rep. 2021;11(1):5804. https://doi.org/10.1038/s41598-021-83930-6.
  • Williams, M.S. 1993. Single-radial-immunodiffusion as an in vitro potency assay for human inactivated viral vaccines. Vet Microbiol. 1993;37(3-4):253-62. https://doi.org/10.1016/0378-1135(93)90027-5.
  • Taştan C, Yurtsever B, Sir Karakuş G, Dilek Kançaği D, Demir S, Abanuz S, Seyis U, Yildirim M, Kuzay R, Elibol Ö, Arbak S, Açikel Elmas M, Birdoğan S, Sezerman OU, Kocagöz AS, YalÇin K, Ovali E. SARS-CoV-2 isolation and propagation from Turkish COVID-19 patients. Turk J Biol. 2020;44(3):192-202. https://doi.org/10.3906/biy-2004-113.
  • Eren SA, Tastan C, Karadeniz KB, Turan RD, Cakirsoy D, Kancagi DD, Yilmaz SU, Oztatlici M, Oztatlici H, Ozer S, Tumentemur G, Baykal AT, Ovali E. Lentiviral micro-dystrophin gene treatment into late-stage mdx mice for Duchene Muscular Dystrophy disease. Curr. Gene Ther. 2023;23:304–315.
  • Birinci, H., Vatansever, H. S., Yüncü, M. Effect of kisspeptin-54 on ovarian levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in an experimental model of ovarian hyperstimulation syndrome (OHSS). Reprod Fertil Dev. 2021;33(16):799-809. https://doi.org/10.1071/RD21140.
  • Özbilgin, M. K., Demirören, S., Üçöz, M., Oztatlici, M. Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c. Andrologia. 2012;53(7):e14071. https://doi.org/10.1111/and.14071.
  • Liu, M. W., Su, M. X., Tang, D. Y., Hao, L., Xun, X. H., Huang, Y. Q. Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression. BMC Pulm Med. 2019;19(1):35. https://doi.org/10.1186/s12890-019-0799-5.
  • Abolaban, F. A., Djouider, F.M. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development. Open Life Sci. 2021;16(1), 558-570. https://doi.org/10.1515/biol-2021-0051.
  • Jansen J, Reimer KC, Nagai JS, Varghese FS, Overheul GJ, de Beer M, Roverts R, Daviran D, Fermin LAS, Willemsen B, Beukenboom M, Djudjaj S, von Stillfried S, van Eijk LE, Mastik M, Bulthuis M, Dunnen WD, van Goor H, Hillebrands JL, Triana SH, Alexandrov T, Timm MC, van den Berge BT, van den Broek M, Nlandu Q, Heijnert J, Bindels EMJ, Hoogenboezem RM, Mooren F, Kuppe C, Miesen P, Grünberg K, Ijzermans T, Steenbergen EJ, Czogalla J, Schreuder MF, Sommerdijk N, Akiva A, Boor P, Puelles VG, Floege J, Huber TB. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 2021;29(2):217-231. https://doi.org/10.1016/j.stem.2021.12.010
  • Milross, L., Majo, J., Cooper, N., Kaye, P. M., Bayraktar, O., Filby, A., Fisher, A. J. Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19. Lancet Respir Med. 2022;10(1):95-106. https://doi.org/10.1016/s2213-2600(21)00408-2.
  • Shang C, Zhuang X, Zhang H, Li Y, Zhu Y, Lu J, Ge C, Cong J, Li T, Li N, Tian M, Jin N, Li X. Inhibition of Autophagy Suppresses SARS-CoV-2 Replication and Ameliorates Pneumonia in hACE2 Transgenic Mice and Xenografted Human Lung Tissues. J Virol. 2021;95(24):e0153721. https://doi.org/10.1128/JVI.01537-21.
  • Halfmann PJ, Iida S, Iwatsuki-Horimoto K, Maemura T, Kiso M, Scheaffer SM, Darling TL, Joshi A, Loeber S, Singh G, Foster SL, Ying B, Case JB, Chong Z, Whitener B, Moliva J, Floyd K, Ujie M, Nakajima N, Ito M, Wright R, Uraki R, Warang P, Gagne M, Li R, Sakai-Tagawa Y, Liu Y, Larson D, Osorio JE, Hernandez-Ortiz JP, Henry AR, Ciuoderis K, Florek KR, Patel M, Odle A, Wong LR, Bateman AC, Wang Z, Edara VV, Chong Z, Franks J, Jeevan T, Fabrizio T, DeBeauchamp J, Kercher L, Seiler P, Gonzalez-Reiche AS, Sordillo EM, Chang LA, van Bakel H, Simon V; Consortium Mount Sinai Pathogen Surveillance (PSP) study group; Douek DC, Sullivan NJ, Thackray LB, Ueki H, Yamayoshi S, Imai M, Perlman S, Webby RJ, Seder RA, Suthar MS, García-Sastre A, Schotsaert M, Suzuki T, Boon ACM, Diamond MS, Kawaoka Y. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature. 2022 Mar;603(7902):687-692. https://doi.org/10.1038/s41586-022-04441-6.
  • Hartmann, C., Miggiolaro, A. F. R. D. S., Motta, J. D. S. J., Baena Carstens, L., Busatta Vaz De Paula, C., Fagundes Grobe, S., de Souza Nunes, L. H., Marques, G. L., Libby, P., Moura, L. Z., de Noronha, L., Pellegrino Baena, C. The Pathogenesis of COVID-19 myocardial injury: An immunohistochemical study of postmortem biopsies. Front Immunol. 2021;12:748417. https://doi.org/10.3389/fimmu.2021.748417.
  • Pessolani, T. G., de Legaria, M. M. F., Apellániz, M. E., Moreno, S. S., Cortés, M. D. M. L., Sánchez, S. G. Multi-organ pathological findings associated with COVID-19 in postmortem needle core biopsies in four patients and a review of the current literature. Rev Esp Patol. 2021;54(4), 275-280. https://doi.org/10.1016/j.patol.2020.09.003
  • De Maio, F., Cascio, E. L., Babini, G., Sali, M., Della Longa, S., Tilocca, B., Roncada, P., Arcovito, A., Sanguinetti, M., Scambia, G., Urbani, A. Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis. Microbes Infect. 2020;22(10):592-597. https://doi.org/10.1016/j.micinf.2020.08.006.
  • Shepley-McTaggart A, Sagum CA, Oliva I, Rybakovsky E, DiGuilio K, Liang J, Bedford MT, Cassel J, Sudol M, Mullin JM, Harty RN. SARS-CoV-2 Envelope (E) protein interacts with PDZ-domain-2 of host tight junction protein ZO1. PLoS One 2021;16(6):e0251955. https://doi.org/10.1371/journal.pone.0251955.
  • Stewart CA, Gay CM, Ramkumar K, Cargill KR, Cardnell RJ, Nilsson MB, Heeke S, Park EM, Kundu ST, Diao L, Wang Q, Shen L, Xi Y, Zhang B, Della Corte CM, Fan Y, Kundu K, Gao B, Avila K, Pickering CR, Johnson FM, Zhang J, Kadara H, Minna JD, Gibbons DL, Wang J, Heymach JV, Byers LA. Lung cancer models reveal SARS-CoV-2-induced EMT contributes to COVID-19 pathophysiology. bioRxiv. 2021;2020.05.28.122291. https://doi.org/10.1101/2020.05.28.122291. Update in: J Thorac Oncol. 2021 Nov;16(11):1821-1839.
  • Herrero, R., Sanchez, G., Lorente, J. A. New insights into the mechanisms of pulmonary edema in acute lung injury. Ann Transl Med. 2018;6(2):32. https://doi.org/10.21037/atm.2017.12.18.
  • Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, Sepe PA, Resasco T, Camporotondo R, Bruno R, Baldanti F, Paolucci S, Pelenghi S, Iotti GA, Mojoli F, Arbustini E. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911-915. https://doi.org/10.1002/ejhf.1828.
  • Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, Shen J, Zhou Y, Shi ZL, Zhou P, Peng K. SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther. 2020;5(1):235. https://doi.org/10.1038/s41392-020-00334-0.
  • Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, Bucci E, Piacentini M, Ippolito G, Melino,G. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020;27(5):1451-1454. https://doi.org/10.1038/s41418-020-0530-3.
  • Ho HT, Peischard S, Strutz-Seebohm N, Klingel K, Seebohm G. Myocardial damage by sars-cov-2: Emerging mechanisms and therapies. Viruses. 2021;13(9):1880. https://doi.org/10.3390/v13091880
  • Lindner D, Fitzek A, Bräuninger H. Association of cardiac infection with sars-cov-2 in confirmed covid-19 autopsy cases. JAMA Cardiol. 2020;5(11):1281-1285. https://doi.org/10.1001/jamacardio.2020.3551.
  • DeDiego, M. L., Nieto-Torres, J. L., Regla-Nava, J. A., Jimenez-Guardeño, J. M., Fernandez-Delgado, R., Fett, C., Castano-Rodriguez, C., Perlman, S., Enjuanes, L. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913-24. https://doi.org/10.1128/JVI.02576-13.
  • Delgado-Roche, L., Mesta, F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch Med Res. 2020;51(5):384-387. https://doi.org/10.1016/j.arcmed.2020.04.019.
  • Chernyak, B. V., Popova, E. N., Prikhodko, A. S., Grebenchikov, O. A., Zinovkina, L. A., Zinovkin, R. A. COVID-19 and Oxidative Stress. Biochemistry (Mosc). 2020;85(12):1543-1553. https://doi.org/10.1134/S0006297920120068.
  • Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0.
  • Carvacho I, Piesche M. RGD-binding integrins and TGF-β in SARS-CoV-2 infections - novel targets to treat COVID-19 patients? Clin Transl Immunology. 2021;10(3):e1240. https://doi.org/10.1002/cti2.1240.
  • Vaz de Paula CB, Nagashima S, Liberalesso V, Collete M, da Silva FPG, Oricil AGG, Barbosa GS, da Silva GVC, Wiedmer DB, da Silva Dezidério F, Noronha L. COVID-19: Immunohistochemical analysis of tgf-β signaling pathways in pulmonary fibrosis. Int J Mol Sci. 2021;23(1):168. https://doi.org/10.3390/ijms23010168.
  • Xu L, Tan B, Huang D, Yuan M, Li T, Wu M, Ye C. Remdesivir inhibits tubulointerstitial fibrosis in obstructed kidneys. Front Pharmacol. 2021;12:626510. https://doi.org/10.3389/fphar.2021.626510.
There are 36 citations in total.

Details

Primary Language English
Subjects Immunology (Other), Infectious Diseases
Journal Section Articles
Authors

Mustafa Öztatlıcı 0000-0001-9914-7122

Hülya Öztatlıcı 0000-0002-6749-9665

Derya Dilek Kançağı 0000-0003-4725-3200

Raife Dilek Turan 0000-0001-5159-4775

Gözde Yalçın 0000-0002-0682-5869

Bulut Yurtsever 0000-0002-9269-8383

Didem Çakirsoy 0000-0002-1293-9520

Selen Abanuz 0000-0002-6136-5033

Cihan Taştan 0000-0002-4173-6634

Samed Özer 0000-0003-1036-4046

Gamze Tumentemur 0000-0002-3114-634X

Murat Kasap 0000-0001-8527-2096

Gürler Akpınar 0000-0002-9675-3714

Büşra Şen Halıcıoğlu 0000-0003-4089-5243

Sevda Demir 0000-0003-0427-3519

Dilek Telci 0000-0002-2793-6533

Fikrettin Şahin 0000-0002-7208-8967

Mehmet İbrahim Tuğlu 0000-0002-0569-8415

Ercüment Ovalı 0000-0002-4782-5355

Early Pub Date September 30, 2025
Publication Date September 30, 2025
Submission Date July 10, 2024
Acceptance Date September 5, 2025
Published in Issue Year 2025 Volume: 15 Issue: 3

Cite

APA Öztatlıcı, M., Öztatlıcı, H., Dilek Kançağı, D., … Turan, R. D. (2025). Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model. Clinical and Experimental Health Sciences, 15(3), 504-516. https://doi.org/10.33808/clinexphealthsci.1512385
AMA Öztatlıcı M, Öztatlıcı H, Dilek Kançağı D, et al. Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model. Clinical and Experimental Health Sciences. September 2025;15(3):504-516. doi:10.33808/clinexphealthsci.1512385
Chicago Öztatlıcı, Mustafa, Hülya Öztatlıcı, Derya Dilek Kançağı, Raife Dilek Turan, Gözde Yalçın, Bulut Yurtsever, Didem Çakirsoy, et al. “Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model”. Clinical and Experimental Health Sciences 15, no. 3 (September 2025): 504-16. https://doi.org/10.33808/clinexphealthsci.1512385.
EndNote Öztatlıcı M, Öztatlıcı H, Dilek Kançağı D, Turan RD, Yalçın G, Yurtsever B, Çakirsoy D, Abanuz S, Taştan C, Özer S, Tumentemur G, Kasap M, Akpınar G, Şen Halıcıoğlu B, Demir S, Telci D, Şahin F, Tuğlu Mİ, Ovalı E (September 1, 2025) Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model. Clinical and Experimental Health Sciences 15 3 504–516.
IEEE M. Öztatlıcı et al., “Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model”, Clinical and Experimental Health Sciences, vol. 15, no. 3, pp. 504–516, 2025, doi: 10.33808/clinexphealthsci.1512385.
ISNAD Öztatlıcı, Mustafa et al. “Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model”. Clinical and Experimental Health Sciences 15/3 (September2025), 504-516. https://doi.org/10.33808/clinexphealthsci.1512385.
JAMA Öztatlıcı M, Öztatlıcı H, Dilek Kançağı D, Turan RD, Yalçın G, Yurtsever B, Çakirsoy D, Abanuz S, Taştan C, Özer S, Tumentemur G, Kasap M, Akpınar G, Şen Halıcıoğlu B, Demir S, Telci D, Şahin F, Tuğlu Mİ, Ovalı E. Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model. Clinical and Experimental Health Sciences. 2025;15:504–516.
MLA Öztatlıcı, Mustafa et al. “Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model”. Clinical and Experimental Health Sciences, vol. 15, no. 3, 2025, pp. 504-16, doi:10.33808/clinexphealthsci.1512385.
Vancouver Öztatlıcı M, Öztatlıcı H, Dilek Kançağı D, Turan RD, Yalçın G, Yurtsever B, et al. Post Challenge Effects of Ozg-38.61.3 Gamma Irradiated SARSCoV- 2 Vaccine on Organ Protection in Transgenic Mouse Model. Clinical and Experimental Health Sciences. 2025;15(3):504-16.
 Download Cover Image

14639   14640