{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:50:26Z","timestamp":1791557426351,"version":"4.3.4"},"reference-count":165,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08822-7","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:44:31Z","timestamp":1787561071000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyamine metabolism in ischemia reperfusion injury: common mitochondrial mechanisms and organ-specific differences"],"prefix":"10.1186","volume":"24","author":[{"given":"Yangqi","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangwen","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"8822_CR1","doi-asserted-by":"publisher","first-page":"114299","DOI":"10.1016\/j.intimp.2025.114299","volume":"150","author":"DO Thc","year":"2025","unstructured":"Thc DO, Gkn G. Liver ischemia reperfusion injury: mechanisms, cellular pathways, and therapeutic approaches. Int Immunopharmacol. 2025;150:114299. https:\/\/doi.org\/10.1016\/j.intimp.2025.114299.","journal-title":"Int Immunopharmacol"},{"key":"8822_CR2","doi-asserted-by":"publisher","first-page":"101382","DOI":"10.1016\/j.mam.2025.101382","volume":"104","author":"W Li","year":"2025","unstructured":"Li W, Liao Y, Chen J, Kang W, Wang X, Zhai X, et al. Ischemia - reperfusion injury: a roadmap to precision therapies. Mol Aspects Med. 2025;104:101382. https:\/\/doi.org\/10.1016\/j.mam.2025.101382.","journal-title":"Mol Aspects Med"},{"key":"8822_CR3","doi-asserted-by":"publisher","first-page":"4299","DOI":"10.1002\/ptr.7620","volume-title":"Protective effects of curcumin on ischemia\/reperfusion injury","author":"M Mohamadian","year":"2022","unstructured":"Mohamadian M, Parsamanesh N, Chiti H, Sathyapalan T, Sahebkar A. Protective effects of curcumin on ischemia\/reperfusion injury. Vol. 36. Phytother Res: PTR; 2022. p. 4299\u2013324. https:\/\/doi.org\/10.1002\/ptr.7620."},{"key":"8822_CR4","doi-asserted-by":"publisher","first-page":"681504","DOI":"10.3389\/fimmu.2021.681504","volume":"12","author":"PM Patel","year":"2021","unstructured":"Patel PM, Connolly MR, Coe TM, Calhoun A, Pollok F, Markmann JF, et al. Minimizing ischemia reperfusion injury in xenotransplantation. Front Immunol. 2021;12:681504. https:\/\/doi.org\/10.3389\/fimmu.2021.681504.","journal-title":"Front Immunol"},{"key":"8822_CR5","doi-asserted-by":"publisher","first-page":"102884","DOI":"10.1016\/j.ebiom.2020.102884","volume":"57","author":"CJA Ramachandra","year":"2020","unstructured":"Ramachandra CJA, Hernandez-Resendiz S, Crespo-Avilan GE, Lin Y-H, Hausenloy DJ. Mitochondria in acute myocardial infarction and cardioprotection. Ebiomedicine. 2020;57:102884. https:\/\/doi.org\/10.1016\/j.ebiom.2020.102884.","journal-title":"Ebiomedicine"},{"issue":"10","key":"8822_CR6","doi-asserted-by":"publisher","first-page":"5253","DOI":"10.1007\/s12035-021-02494-8","volume":"58","author":"M Wu","year":"2021","unstructured":"Wu M, Gu X, Ma Z. Mitochondrial quality control in cerebral ischemia\u2013reperfusion injury. Mol Neurobiol. 2021;58(10):5253\u201371. https:\/\/doi.org\/10.1007\/s12035-021-02494-8.","journal-title":"Mol Neurobiol"},{"issue":"24","key":"8822_CR7","doi-asserted-by":"publisher","first-page":"5365","DOI":"10.1111\/febs.17130","volume":"291","author":"R Huang","year":"2024","unstructured":"Huang R, Zhang C, Xiang Z, Lin T, Ling J, Hu H. Role of mitochondria in renal ischemia\u2013reperfusion injury. FEBS J. 2024;291(24):5365\u201378. https:\/\/doi.org\/10.1111\/febs.17130.","journal-title":"The FEBS J"},{"issue":"29","key":"8822_CR8","doi-asserted-by":"publisher","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","volume":"291","author":"AE Pegg","year":"2016","unstructured":"Pegg AE. Functions of polyamines in mammals. J Biol Chem. 2016;291(29):14904\u201312. https:\/\/doi.org\/10.1074\/jbc.R116.731661.","journal-title":"J Biol Chem"},{"issue":"1","key":"8822_CR9","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1146\/annurev-biochem-071322-021330","volume":"92","author":"S Vrijsen","year":"2023","unstructured":"Vrijsen S, Houdou M, Cascalho A, Eggermont J, Vangheluwe P. Polyamines in Parkinson\u2019s disease: balancing between neurotoxicity and neuroprotection. Annu Rev Biochem. 2023;92(1):435\u201364. https:\/\/doi.org\/10.1146\/annurev-biochem-071322-021330.","journal-title":"Annu Rev Biochem"},{"key":"8822_CR10","doi-asserted-by":"publisher","unstructured":"Xuan M, Gu X, Li J, Huang D, Xue C, He Y. Polyamines: their significance for maintaining health and contributing to diseases. In: Cell commun signaling [Internet]. Springer Science and Business Media LLC; 2023 [cited 2025 July 24];21. https:\/\/doi.org\/10.1186\/s12964-023-01373-0.","DOI":"10.1186\/s12964-023-01373-0"},{"issue":"37","key":"8822_CR11","doi-asserted-by":"publisher","first-page":"27115","DOI":"10.1074\/jbc.M704066200","volume":"282","author":"J Lee","year":"2007","unstructured":"Lee J, Michael AJ, Martynowski D, Goldsmith EJ, Phillips MA. Phylogenetic diversity and the structural basis of substrate specificity in the \u03b2\/\u03b1-barrel Fold basic amino acid decarboxylases. J Biol Chem. 2007;282(37):27115\u201325. https:\/\/doi.org\/10.1074\/jbc.M704066200.","journal-title":"J Biol Chem"},{"issue":"3","key":"8822_CR12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1042\/BJ20090598","volume":"421","author":"RA Casero","year":"2009","unstructured":"Casero RA, Pegg AE. Polyamine catabolism and disease. Biochemical J. 2009;421(3):323\u201338. https:\/\/doi.org\/10.1042\/BJ20090598.","journal-title":"The Biochemical J"},{"key":"8822_CR13","doi-asserted-by":"publisher","unstructured":"Wu R, Chen X, Kang S, Wang T, Gnanaprakasam JR, Yao Y, et al. De Novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function. Sci Adv. 2020;6(51):eabc4275. https:\/\/doi.org\/10.1126\/sciadv.abc4275.","DOI":"10.1126\/sciadv.abc4275"},{"issue":"1","key":"8822_CR14","doi-asserted-by":"publisher","first-page":"9923","DOI":"10.1038\/s41467-025-65441-4","volume":"16","author":"Y Bian","year":"2025","unstructured":"Bian Y, Shan G, Bi G, Xu Z, Liang J, Yan Y, et al. Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status. Nat Commun. 2025;16(1):9923. https:\/\/doi.org\/10.1038\/s41467-025-65441-4.","journal-title":"Nat Commun"},{"issue":"10","key":"8822_CR15","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.tplants.2021.05.007","volume":"26","author":"L Gerlin","year":"2021","unstructured":"Gerlin L, Baroukh C, Genin S. Polyamines: double agents in disease and plant immunity. Trends Plant Sci. 2021;26(10):1061\u201371. https:\/\/doi.org\/10.1016\/j.tplants.2021.05.007.","journal-title":"Trends Plant Sci"},{"issue":"19","key":"8822_CR16","doi-asserted-by":"publisher","first-page":"11140","DOI":"10.1073\/pnas.95.19.11140","volume":"95","author":"HC Ha","year":"1998","unstructured":"Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA. The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA. 1998;95(19):11140\u201345. https:\/\/doi.org\/10.1073\/pnas.95.19.11140.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"8822_CR17","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.cell.2025.11.034","volume":"189","author":"J Gu","year":"2026","unstructured":"Gu J, Li Y, Chen Q, Song Z, Qian Q, Liang Y, et al. Tumor-produced ammonia is metabolized by regulatory T cells to further impede anti-tumor immunity. Cell. 2026;189(2):418\u201334.e24. https:\/\/doi.org\/10.1016\/j.cell.2025.11.034.","journal-title":"Cell"},{"issue":"12","key":"8822_CR18","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.3390\/antiox13121482","volume":"13","author":"L Szabo","year":"2024","unstructured":"Szabo L, Lejri I, Grimm A, Eckert A. Spermidine enhances mitochondrial bioenergetics in young and aged human-induced pluripotent stem cell-derived neurons. Antioxidants. 2024;13(12):1482. https:\/\/doi.org\/10.3390\/antiox13121482.","journal-title":"Antioxidants"},{"issue":"11","key":"8822_CR19","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1038\/s43587-023-00498-8","volume":"3","author":"Y Zhang","year":"2023","unstructured":"Zhang Y, Bai J, Cui Z, Li Y, Gao Q, Miao Y, et al. Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging. Nat Aging. 2023;3(11):1372\u201386. https:\/\/doi.org\/10.1038\/s43587-023-00498-8.","journal-title":"Nat Aging"},{"key":"8822_CR20","doi-asserted-by":"publisher","first-page":"1462777","DOI":"10.3389\/fimmu.2024.1462777","volume":"15","author":"X Guo","year":"2024","unstructured":"Guo X, Feng X, Yang Y, Zhang H, Bai L. Spermidine attenuates chondrocyte inflammation and cellular pyroptosis through the AhR\/NF-\u03baB axis and the NLRP3\/caspase-1\/GSDMD pathway. Front Immunol. 2024;15:1462777. https:\/\/doi.org\/10.3389\/fimmu.2024.1462777.","journal-title":"Front Immunol"},{"issue":"12","key":"8822_CR21","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1038\/s12276-020-00545-z","volume":"52","author":"AR Baek","year":"2020","unstructured":"Baek AR, Hong J, Song KS, Jang AS, Kim DJ, Chin SS, et al. Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice. Exp Mol Med. 2020;52(12):2034\u201345. https:\/\/doi.org\/10.1038\/s12276-020-00545-z.","journal-title":"Exp Mol Med"},{"issue":"8121","key":"8822_CR22","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41586-026-10597-2","volume":"655","author":"M Li","year":"2026","unstructured":"Li M, Yu X, Ouyang S, Chen X, Yu H, Liu Y, et al. Spermine is an endogenous iron chelator that inhibits ferroptosis. Nature. 2026;655(8121):240\u201350. https:\/\/doi.org\/10.1038\/s41586-026-10597-2.","journal-title":"Nature"},{"issue":"2","key":"8822_CR23","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.cmet.2019.05.003","volume":"30","author":"DJ Puleston","year":"2019","unstructured":"Puleston DJ, Buck MD, Klein Geltink RI, Kyle RL, Caputa G, O\u2019Sullivan D, et al. Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation. Cell MetabCell Metab. 2019;30(2):352\u201363.e8. https:\/\/doi.org\/10.1016\/j.cmet.2019.05.003.","journal-title":"Cell MetabCell Metab"},{"issue":"6","key":"8822_CR24","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.tcm.2022.02.005","volume":"33","author":"M Algoet","year":"2023","unstructured":"Algoet M, Janssens S, Himmelreich U, Gsell W, Pusovnik M, Van den Eynde J, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends Cardiovasc Med. 2023;33(6):357\u201366. https:\/\/doi.org\/10.1016\/j.tcm.2022.02.005.","journal-title":"Trends Cardiovasc Med"},{"issue":"1","key":"8822_CR25","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41392-023-01688-x","volume":"9","author":"M Zhang","year":"2024","unstructured":"Zhang M, Liu Q, Meng H, Duan H, Liu X, Wu J, et al. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Sig Transduct Target Ther. 2024;9(1):12. https:\/\/doi.org\/10.1038\/s41392-023-01688-x.","journal-title":"Sig Transduct Target Ther"},{"issue":"12","key":"8822_CR26","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/nm.4222","volume":"22","author":"T Eisenberg","year":"2016","unstructured":"Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428\u201338. https:\/\/doi.org\/10.1038\/nm.4222.","journal-title":"Nat Med"},{"issue":"6","key":"8822_CR27","doi-asserted-by":"publisher","first-page":"5297","DOI":"10.3390\/ijms24065297","volume":"24","author":"LH Fairley","year":"2023","unstructured":"Fairley LH, Lejri I, Grimm A, Eckert A. Spermidine rescues bioenergetic and mitophagy deficits induced by disease-associated tau protein. IJMS. 2023;24(6):5297. https:\/\/doi.org\/10.3390\/ijms24065297.","journal-title":"IJMS"},{"issue":"3","key":"8822_CR28","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.3892\/mmr.2017.7030","volume":"16","author":"R Zhang","year":"2017","unstructured":"Zhang R, Ma X-N, Liu K, Zhang L, Yao M. Exogenous spermine preserves mitochondrial bioenergetics via regulating src kinase signaling in the spinal cord. Mol Med Rep. 2017;16(3):3619\u201326. https:\/\/doi.org\/10.3892\/mmr.2017.7030.","journal-title":"Mol Med Rep"},{"issue":"12","key":"8822_CR29","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1021\/tx400316s","volume":"26","author":"AE Pegg","year":"2013","unstructured":"Pegg AE. Toxicity of polyamines and their metabolic products. Chem Res Toxicol. 2013;26(12):1782\u2013800. https:\/\/doi.org\/10.1021\/tx400316s.","journal-title":"Chem Res Toxicol"},{"issue":"48","key":"8822_CR30","doi-asserted-by":"publisher","first-page":"18736","DOI":"10.1074\/jbc.TM118.003337","volume":"293","author":"T Murray Stewart","year":"2018","unstructured":"Murray Stewart T, Dunston TT, Woster PM, Casero RA. Polyamine catabolism and oxidative damage. J Biol Chem. 2018;293(48):18736\u201345. https:\/\/doi.org\/10.1074\/jbc.TM118.003337.","journal-title":"J Biol Chem"},{"issue":"6","key":"8822_CR31","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.chembiol.2023.05.002","volume":"30","author":"M Rodr\u00edguez-Prados","year":"2023","unstructured":"Rodr\u00edguez-Prados M, Huang K-T, M\u00e1rta K, Paillard M, Csord\u00e1s G, Joseph SK, et al. MICU1 controls the sensitivity of the mitochondrial Ca2+ uniporter to activators and inhibitors. Cell Chem Biol. 2023;30(6):606\u201317.e4. https:\/\/doi.org\/10.1016\/j.chembiol.2023.05.002.","journal-title":"Cell Chem Biol"},{"issue":"3","key":"8822_CR32","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1042\/bj3470875","volume":"347","author":"C Stefanelli","year":"2000","unstructured":"Stefanelli C, Stanic I, Zini M, Bonavita F, Flamigni F, Zambonin L, et al. Polyamines directly induce release of cytochrome c from heart mitochondria. Biochemical J. 2000;347(3):875\u201380. https:\/\/doi.org\/10.1042\/bj3470875.","journal-title":"The Biochemical J"},{"key":"8822_CR33","doi-asserted-by":"publisher","first-page":"850688","DOI":"10.3389\/fcvm.2022.850688","volume":"9","author":"X Xiong","year":"2022","unstructured":"Xiong X, Li J, Zhang S, Jia X, Xiao C. Involvement of polyamines from cardiac mast cells in myocardial remodeling induced by pressure overload through mitochondrial permeability transition pore opening. Front Cardiovasc Med. 2022;9:850688. https:\/\/doi.org\/10.3389\/fcvm.2022.850688.","journal-title":"Front Cardiovasc Med"},{"issue":"21","key":"8822_CR34","doi-asserted-by":"publisher","first-page":"7429","DOI":"10.3390\/molecules28217429","volume":"28","author":"M \u0160ebela","year":"2023","unstructured":"\u0160ebela M, Ra\u0161kov\u00e1 M. Polyamine-derived aminoaldehydes and acrolein: cytotoxicity, reactivity and analysis of the induced protein modifications. Molecules. 2023;28(21):7429. https:\/\/doi.org\/10.3390\/molecules28217429.","journal-title":"Molecules"},{"key":"8822_CR35","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.bbrc.2023.05.029","volume":"666","author":"S Aihara","year":"2023","unstructured":"Aihara S, Torisu K, Hirashima Y, Kitazono T, Nakano T. Acrolein produced during acute kidney injury promotes tubular cell death. Biochem Bioph Res Co. 2023;666:137\u201345. https:\/\/doi.org\/10.1016\/j.bbrc.2023.05.029.","journal-title":"Biochem Bioph Res Co"},{"key":"8822_CR36","doi-asserted-by":"publisher","unstructured":"Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):R453\u201362. https:\/\/doi.org\/10.1016\/j.cub.2014.03.034.","DOI":"10.1016\/j.cub.2014.03.034"},{"issue":"2","key":"8822_CR37","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.molcel.2012.09.025","volume":"48","author":"LA Sena","year":"2012","unstructured":"Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158\u201367. https:\/\/doi.org\/10.1016\/j.molcel.2012.09.025.","journal-title":"Mol Cell"},{"issue":"7527","key":"8822_CR38","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/nature13909","volume":"515","author":"ET Chouchani","year":"2014","unstructured":"Chouchani ET, Pell VR, Gaude E, Aksentijevi\u0107 D, Sundier SY, Robb EL, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515(7527):431\u201335. https:\/\/doi.org\/10.1038\/nature13909.","journal-title":"Nature"},{"key":"8822_CR39","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.redox.2015.08.020","volume":"6","author":"DN Granger","year":"2015","unstructured":"Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 2015;6:524\u201351. https:\/\/doi.org\/10.1016\/j.redox.2015.08.020.","journal-title":"Redox Biol"},{"issue":"11\u201312","key":"8822_CR40","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.bbabio.2013.03.009","volume":"1827","author":"P Lanciano","year":"2013","unstructured":"Lanciano P, Khalfaoui-Hassani B, Selamoglu N, Ghelli A, Rugolo M, Daldal F. Molecular mechanisms of superoxide production by complex III: a bacterial versus human mitochondrial comparative case study. Biochim et Biophys Acta (BBA) - Bioenerg. 2013;1827(11\u201312):1332\u201339. https:\/\/doi.org\/10.1016\/j.bbabio.2013.03.009.","journal-title":"Biochim et Biophys Acta (BBA) - Bioenerg"},{"key":"8822_CR41","doi-asserted-by":"publisher","unstructured":"Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y, et al. ROS and ROS-mediated cellular signaling. 2025 Oct 14; https:\/\/doi.org\/10.1155\/2016\/4350965.","DOI":"10.1155\/2016\/4350965"},{"issue":"3","key":"8822_CR42","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1152\/physrev.00026.2013","volume":"94","author":"DB Zorov","year":"2014","unstructured":"Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909\u201350. https:\/\/doi.org\/10.1152\/physrev.00026.2013.","journal-title":"Physiol Rev"},{"issue":"49","key":"8822_CR43","doi-asserted-by":"publisher","first-page":"31198","DOI":"10.1073\/pnas.1922342117","volume":"117","author":"S Vrijsen","year":"2020","unstructured":"Vrijsen S, Besora-Casals L, van Veen S, Zielich J, Van den Haute C, Hamouda NN, et al. ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress. Proc Natl Acad Sci USA. 2020;117(49):31198\u2013207. https:\/\/doi.org\/10.1073\/pnas.1922342117.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"8822_CR44","doi-asserted-by":"publisher","first-page":"2485666","DOI":"10.1080\/13510002.2025.2485666","volume":"30","author":"Z-Q Du","year":"2025","unstructured":"Du Z-Q, Xie J-B, Ji S-Y, Zhou W, Tao Z-S. Spermidine prevents iron overload-induced impaired bone mass by activating SIRT1\/SOD2 signaling in senile rat model. Redox Rep. 2025;30(1):2485666. https:\/\/doi.org\/10.1080\/13510002.2025.2485666.","journal-title":"Redox Rep"},{"key":"8822_CR45","doi-asserted-by":"publisher","unstructured":"Zhu G, Xie Y, Wang J, Wang M, Qian Y, Sun Q, et al. Multifunctional copper-phenolic nanopills achieve comprehensive polyamines depletion to provoke enhanced pyroptosis and cuproptosis for cancer immunotherapy. Adv Mater. 2024;36(45):e2409066. https:\/\/doi.org\/10.1002\/adma.202409066.","DOI":"10.1002\/adma.202409066"},{"issue":"1","key":"8822_CR46","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s10020-022-00533-1","volume":"28","author":"X Li","year":"2022","unstructured":"Li X, Zhou X, Liu X, Li X, Jiang X, Shi B, et al. Spermidine protects against acute kidney injury by modulating macrophage NLRP3 inflammasome activation and mitochondrial respiration in an eIF5A hypusination-related pathway. Mol Med Cambridge, Mass.; 2022;28(1):103. https:\/\/doi.org\/10.1186\/s10020-022-00533-1.","journal-title":"Mol Med Cambridge"},{"key":"8822_CR47","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.theriogenology.2021.03.026","volume":"168","author":"D Jiang","year":"2021","unstructured":"Jiang D, Jiang Y, Long S, Chen Z, Li Y, Mo G, et al. Spermidine at supraphysiological doses induces oxidative stress and granulosa cell apoptosis in mouse ovaries. Theriogenology. 2021;168:25\u201332. https:\/\/doi.org\/10.1016\/j.theriogenology.2021.03.026.","journal-title":"Theriogenology"},{"key":"8822_CR48","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1038\/s41467-024-46776-w","volume-title":"Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer","author":"G Bi","year":"2024","unstructured":"Bi G, Liang J, Bian Y, Shan G, Huang Y, Lu T, et al. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Vol. 15. Nat Commun. Nature Publishing Group; 2024. p. 2461. https:\/\/doi.org\/10.1038\/s41467-024-46776-w."},{"issue":"9","key":"8822_CR49","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nrm3412","volume":"13","author":"R Rizzuto","year":"2012","unstructured":"Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012;13(9):566\u201378. https:\/\/doi.org\/10.1038\/nrm3412.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"12","key":"8822_CR50","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.3390\/biom11121876","volume":"11","author":"A Takeuchi","year":"2021","unstructured":"Takeuchi A, Matsuoka S. Physiological and pathophysiological roles of mitochondrial na+-Ca2+ exchanger, NCLX, in hearts. Biomolecules. 2021;11(12):1876. https:\/\/doi.org\/10.3390\/biom11121876.","journal-title":"Biomolecules"},{"issue":"9","key":"8822_CR51","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.3390\/biom13091304","volume":"13","author":"D D\u2019Angelo","year":"2023","unstructured":"D\u2019Angelo D, Rizzuto R. The mitochondrial calcium uniporter (MCU): molecular identity and role in human diseases. Biomolecules. 2023;13(9):1304. https:\/\/doi.org\/10.3390\/biom13091304.","journal-title":"Biomolecules"},{"issue":"4","key":"8822_CR52","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1042\/BST20230012","volume":"51","author":"SH Lee","year":"2023","unstructured":"Lee SH, Duron HE, Chaudhuri D. Beyond the TCA cycle: new insights into mitochondrial calcium regulation of oxidative phosphorylation. Biochem Soc Trans. 2023;51(4):1661\u201373. https:\/\/doi.org\/10.1042\/BST20230012.","journal-title":"Biochem Soc Trans"},{"key":"8822_CR53","doi-asserted-by":"publisher","unstructured":"Gherardi G, Monticelli H, Rizzuto R, Mammucari C. The mitochondrial Ca2+ uptake and the fine-tuning of aerobic metabolism. In: Front physiol [Internet]. Frontiers; 2020 [cited 2025 Oct 16];11. https:\/\/doi.org\/10.3389\/fphys.2020.554904.","DOI":"10.3389\/fphys.2020.554904"},{"key":"8822_CR54","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/s41418-023-01187-0","volume-title":"Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell death Differ","author":"P Bernardi","year":"2023","unstructured":"Bernardi P, Gerle C, Halestrap AP, Jonas EA, Karch J, Mnatsakanyan N, et al. Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell death Differ. Vol. 30. Nature Publishing Group; 2023. p. 1869\u201385. https:\/\/doi.org\/10.1038\/s41418-023-01187-0."},{"issue":"3","key":"8822_CR55","doi-asserted-by":"publisher","first-page":"108218","DOI":"10.1016\/j.jbc.2025.108218","volume":"301","author":"Y-C Tu","year":"2025","unstructured":"Tu Y-C, Lee I-C, Chang T-W, Lee V, Chao F-Y, Geltser ER, et al. Mechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex. J Biol Chem. 2025;301(3):108218. https:\/\/doi.org\/10.1016\/j.jbc.2025.108218.","journal-title":"J Biol Chem"},{"issue":"35","key":"8822_CR56","doi-asserted-by":"publisher","first-page":"16478","DOI":"10.1016\/S0021-9258(18)66591-3","volume":"261","author":"S Lenzen","year":"1986","unstructured":"Lenzen S, Hickethier R, Panten U. Interactions between spermine and Mg2+ on mitochondrial Ca2+ transport. J Biol Chem. 1986;261(35):16478\u201383. https:\/\/doi.org\/10.1016\/S0021-9258(18)66591-3.","journal-title":"J Biol Chem"},{"issue":"2","key":"8822_CR57","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bbamem.2003.12.005","volume":"1661","author":"M Salvi","year":"2004","unstructured":"Salvi M, Toninello A. Effects of polyamines on mitochondrial Ca2+ transport. Biochim et Biophys Acta (BBA) - Biomembr. 2004;1661(2):113\u201324. https:\/\/doi.org\/10.1016\/j.bbamem.2003.12.005.","journal-title":"Biochim et Biophys Acta (BBA) - Biomembr"},{"issue":"1","key":"8822_CR58","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/s42003-024-06933-9","volume":"7","author":"G Dematteis","year":"2024","unstructured":"Dematteis G, Tapella L, Casali C, Talmon M, Tonelli E, Reano S, et al. ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism. Commun Biol Nat Publishing Group. 2024;7(1):1294. https:\/\/doi.org\/10.1038\/s42003-024-06933-9.","journal-title":"Commun Biol Nat Publishing Group"},{"issue":"3","key":"8822_CR59","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1006\/bbrc.1993.2604","volume":"197","author":"LG Sayers","year":"1993","unstructured":"Sayers LG, Michelangeli F. The inhibition of the inositol 1, 4, 5-trisphosphate receptor from rat cerebellum by spermine and other polyamines. Biochem Bioph Res Co. 1993;197(3):1203\u201308. https:\/\/doi.org\/10.1006\/bbrc.1993.2604.","journal-title":"Biochem Bioph Res Co"},{"issue":"1","key":"8822_CR60","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0005-2736(92)90109-y","volume":"1108","author":"A Zarka","year":"1992","unstructured":"Zarka A, Shoshan-Barmatz V. The interaction of spermine with the ryanodine receptor from skeletal muscle. Biochim et Biophys Acta (BBA) - Biomembr. 1992;1108(1):13\u201320. https:\/\/doi.org\/10.1016\/0005-2736(92)90109-y.","journal-title":"Biochim et Biophys Acta (BBA) - Biomembr"},{"key":"8822_CR61","doi-asserted-by":"publisher","unstructured":"Ahumada-Castro U, Bustos G, Silva-Pavez E, Puebla-Huerta A, Lovy A, C\u00e1rdenas C. In the right place at the right time: regulation of cell metabolism by IP3R-mediated inter-organelle Ca2+ fluxes. In: Front cell Dev Biol [Internet]. Frontiers; 2021 [cited 2025 Oct 18];9. https:\/\/doi.org\/10.3389\/fcell.2021.629522.","DOI":"10.3389\/fcell.2021.629522"},{"issue":"6","key":"8822_CR62","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1083\/jcb.200608073","volume":"175","author":"G Szabadkai","year":"2006","unstructured":"Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR, Cavagna D, et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol. 2006;175(6):901\u201311. https:\/\/doi.org\/10.1083\/jcb.200608073.","journal-title":"J Cell Biol"},{"issue":"1","key":"8822_CR63","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12882-018-0940-3","volume":"19","author":"H Xu","year":"2018","unstructured":"Xu H, Guan N, Ren Y-L, Wei Q-J, Tao Y-H, Yang G-S, et al. IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an adriamycin nephropathy rat model. BMC Nephrol. 2018;19(1):140. https:\/\/doi.org\/10.1186\/s12882-018-0940-3.","journal-title":"BMC Nephrol"},{"key":"8822_CR64","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.yjmcc.2022.11.003","volume":"174","author":"DJ Robichaux","year":"2023","unstructured":"Robichaux DJ, Harata M, Murphy E, Karch J. Mitochondrial permeability transition pore-dependent necrosis. J Mol Cellular Cardiol. 2023;174:47\u201355. https:\/\/doi.org\/10.1016\/j.yjmcc.2022.11.003.","journal-title":"J Mol Cellular Cardiol"},{"issue":"4","key":"8822_CR65","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.bbamcr.2010.09.013","volume":"1813","author":"KW Kinnally","year":"2011","unstructured":"Kinnally KW, Peixoto PM, Ryu S-Y, Dejean LM. Is mPTP the gatekeeper for necrosis, apoptosis, or both? Biochim et Biophys Acta (BBA) - Mol Cell Res. 2011;1813(4):616\u201322. https:\/\/doi.org\/10.1016\/j.bbamcr.2010.09.013.","journal-title":"Biochim et Biophys Acta (BBA) - Mol Cell Res"},{"issue":"9","key":"8822_CR66","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.3390\/cells12091273","volume":"12","author":"R Endlicher","year":"2023","unstructured":"Endlicher R, Drahota Z, \u0160tefkov\u00e1 K, \u010cervinkov\u00e1 Z, Ku\u010dera O. The mitochondrial permeability transition pore\u2014current knowledge of its structure, function, and regulation, and optimized methods for evaluating its functional state. Cells. 2023;12(9):1273. https:\/\/doi.org\/10.3390\/cells12091273.","journal-title":"Cells"},{"key":"8822_CR67","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3389\/fphys.2013.00076","volume":"4","author":"S Javadov","year":"2013","unstructured":"Javadov S, Kuznetsov A. Mitochondrial permeability transition and cell death: the role of cyclophilin d. Front Physiol. 2013;4:76. https:\/\/doi.org\/10.3389\/fphys.2013.00076.","journal-title":"Front Physiol"},{"key":"8822_CR68","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.yjmcc.2014.09.023","volume":"78","author":"P Bernardi","year":"2015","unstructured":"Bernardi P, Di Lisa F. The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection. J Mol Cellular Cardiol. 2015;78:100\u201306. https:\/\/doi.org\/10.1016\/j.yjmcc.2014.09.023.","journal-title":"J Mol Cellular Cardiol"},{"issue":"6","key":"8822_CR69","doi-asserted-by":"publisher","first-page":"186","DOI":"10.4330\/wjc.v3.i6.186","volume":"3","author":"M-G Perrelli","year":"2011","unstructured":"Perrelli M-G. Ischemia\/Reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. WJC. 2011;3(6):186\u2013200. https:\/\/doi.org\/10.4330\/wjc.v3.i6.186.","journal-title":"WJC"},{"key":"8822_CR70","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.yjmcc.2014.08.018","volume":"78","author":"AP Halestrap","year":"2015","unstructured":"Halestrap AP, Richardson AP. The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia\/reperfusion injury. J Mol Cellular Cardiol. 2015;78:129\u201341. https:\/\/doi.org\/10.1016\/j.yjmcc.2014.08.018.","journal-title":"J Mol Cellular Cardiol"},{"issue":"2","key":"8822_CR71","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.bbabio.2014.10.007","volume":"1847","author":"PA Elustondo","year":"2015","unstructured":"Elustondo PA, Negoda A, Kane CL, Kane DA, Pavlov EV. Spermine selectively inhibits high-conductance, but not low-conductance calcium-induced permeability transition pore. Biochim et Biophys Acta (BBA) - Bioenerg. 2015;1847(2):231\u201340. https:\/\/doi.org\/10.1016\/j.bbabio.2014.10.007.","journal-title":"Biochim et Biophys Acta (BBA) - Bioenerg"},{"issue":"14","key":"8822_CR72","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1177\/1535370216643417","volume":"241","author":"C Wei","year":"2016","unstructured":"Wei C, Li H, Wang Y, Peng X, Shao H, Li H, et al. Exogenous spermine inhibits hypoxia\/ischemia-induced myocardial apoptosis via regulation of mitochondrial permeability transition pore and associated pathways. Exp Biol Med (Maywood). 2016;241(14):1505\u201315. https:\/\/doi.org\/10.1177\/1535370216643417.","journal-title":"Exp Biol Med (Maywood)"},{"key":"8822_CR73","doi-asserted-by":"publisher","unstructured":"Li R, Wu X, Zhu Z, Lv Y, Zheng Y, Lu H, et al. Polyamines protect boar sperm from oxidative stress in vitro. J Anim Sci. 2022;100(4):skac069. https:\/\/doi.org\/10.1093\/jas\/skac069.","DOI":"10.1093\/jas\/skac069"},{"issue":"17","key":"8822_CR74","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.2174\/0929867043364559","volume":"11","author":"A Toninello","year":"2004","unstructured":"Toninello A, Salvi M, Mondov\u00ec B. Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. CMC. 2004;11(17):2349\u201374. https:\/\/doi.org\/10.2174\/0929867043364559.","journal-title":"CMC"},{"issue":"3","key":"8822_CR75","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/medsci10030038","volume":"10","author":"K Zahedi","year":"2022","unstructured":"Zahedi K, Barone S, Soleimani M. Polyamines and their metabolism: from the maintenance of physiological homeostasis to the mediation of disease. Med Sci. 2022;10(3):38. https:\/\/doi.org\/10.3390\/medsci10030038.","journal-title":"Med Sci"},{"issue":"9","key":"8822_CR76","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/s41556-018-0176-2","volume":"20","author":"K Palikaras","year":"2018","unstructured":"Palikaras K, Lionaki E, Tavernarakis N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat Cell Biol. 2018;20(9):1013\u201322. https:\/\/doi.org\/10.1038\/s41556-018-0176-2.","journal-title":"Nat Cell Biol"},{"key":"8822_CR77","doi-asserted-by":"publisher","first-page":"105433","DOI":"10.1016\/j.phrs.2021.105433","volume":"165","author":"X-L Wang","year":"2021","unstructured":"Wang X-L, Feng S-T, Wang Z-Z, Chen N-H, Zhang Y. Role of mitophagy in mitochondrial quality control: mechanisms and potential implications for neurodegenerative diseases. Pharmacological Res. 2021;165:105433. https:\/\/doi.org\/10.1016\/j.phrs.2021.105433.","journal-title":"Pharmacological Res"},{"issue":"4","key":"8822_CR78","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","volume":"147","author":"N Mizushima","year":"2011","unstructured":"Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728\u201341. https:\/\/doi.org\/10.1016\/j.cell.2011.10.026.","journal-title":"Cell"},{"issue":"1","key":"8822_CR79","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","volume":"132","author":"B Levine","year":"2008","unstructured":"Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27\u201342. https:\/\/doi.org\/10.1016\/j.cell.2007.12.018.","journal-title":"Cell"},{"key":"8822_CR80","doi-asserted-by":"publisher","first-page":"102288","DOI":"10.1016\/j.redox.2022.102288","volume":"52","author":"C Cai","year":"2022","unstructured":"Cai C, Guo Z, Chang X, Li Z, Wu F, He J, et al. Empagliflozin attenuates cardiac microvascular ischemia\/reperfusion through activating the AMPK\u03b11\/ULK1\/FUNDC1\/mitophagy pathway. Redox Biol. 2022;52:102288. https:\/\/doi.org\/10.1016\/j.redox.2022.102288.","journal-title":"Redox Biol"},{"key":"8822_CR81","doi-asserted-by":"publisher","first-page":"154111","DOI":"10.1016\/j.phymed.2022.154111","volume":"101","author":"Z Mao","year":"2022","unstructured":"Mao Z, Tian L, Liu J, Wu Q, Wang N, Wang G, et al. Ligustilide ameliorates hippocampal neuronal injury after cerebral ischemia reperfusion through activating PINK1\/parkin-dependent mitophagy. Phytomedicine. 2022;101:154111. https:\/\/doi.org\/10.1016\/j.phymed.2022.154111.","journal-title":"Phytomedicine"},{"issue":"1","key":"8822_CR82","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s11658-025-00713-x","volume":"30","author":"L Tang","year":"2025","unstructured":"Tang L, Zhang W, Liao Y, Wang W, Deng X, Wang C, et al. Autophagy: a double-edged sword in ischemia\u2013reperfusion injury. Cell Mol Biol Lett. 2025;30(1):42. https:\/\/doi.org\/10.1186\/s11658-025-00713-x.","journal-title":"Cell Mol Biol Lett"},{"key":"8822_CR83","doi-asserted-by":"publisher","first-page":"176292","DOI":"10.1016\/j.ejphar.2023.176292","volume":"963","author":"Z Wang","year":"2024","unstructured":"Wang Z, Lin D, Cui B, Zhang D, Wu J, Ma J. Melatonin protects against myocardial ischemia-reperfusion injury by inhibiting excessive mitophagy through the apelin\/SIRT3 signaling axis. Eur J PharmacolEuropean J Pharmacol. 2024;963:176292. https:\/\/doi.org\/10.1016\/j.ejphar.2023.176292.","journal-title":"Eur J PharmacolEuropean J Pharmacol"},{"key":"8822_CR84","doi-asserted-by":"publisher","first-page":"123367","DOI":"10.1016\/j.lfs.2024.123367","volume":"362","author":"Y Li","year":"2025","unstructured":"Li Y, Gao Y, Yu G, Ye Y, Zhu H, Wang J, et al. G6PD protects against cerebral ischemia-reperfusion injury by inhibiting excessive mitophagy. Life Sci. 2025;362:123367. https:\/\/doi.org\/10.1016\/j.lfs.2024.123367.","journal-title":"Life Sci"},{"issue":"3","key":"8822_CR85","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/cdd.2014.215","volume":"22","author":"F Pietrocola","year":"2015","unstructured":"Pietrocola F, Lachkar S, Enot DP, Niso-Santano M, Bravo-San Pedro JM, Sica V, et al. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015;22(3):509\u201316. https:\/\/doi.org\/10.1038\/cdd.2014.215.","journal-title":"Cell Death Differ"},{"issue":"11","key":"8822_CR86","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/ncb1975","volume":"11","author":"T Eisenberg","year":"2009","unstructured":"Eisenberg T, Knauer H, Schauer A, B\u00fcttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305\u201314. https:\/\/doi.org\/10.1038\/ncb1975.","journal-title":"Nat Cell Biol"},{"issue":"2","key":"8822_CR87","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.bbrc.2019.08.162","volume":"519","author":"H Liu","year":"2019","unstructured":"Liu H, Dong J, Song S, Zhao Y, Wang J, Fu Z, et al. Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway. Biochem Bioph Res Co. 2019;519(2):227\u201333. https:\/\/doi.org\/10.1016\/j.bbrc.2019.08.162.","journal-title":"Biochem Bioph Res Co"},{"issue":"7","key":"8822_CR88","doi-asserted-by":"publisher","first-page":"6401","DOI":"10.18632\/aging.103035","volume":"12","author":"T-T Xu","year":"2020","unstructured":"Xu T-T, Li H, Dai Z, Lau GK, Li B-Y, Zhu W-L, et al. Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging (Milano). 2020;12(7):6401\u201314. https:\/\/doi.org\/10.18632\/aging.103035.","journal-title":"Aging (Milano)"},{"key":"8822_CR89","doi-asserted-by":"publisher","first-page":"176823","DOI":"10.1016\/j.ejphar.2024.176823","volume":"979","author":"S Satarker","year":"2024","unstructured":"Satarker S, Wilson J, Kolathur KK, Mudgal J, Lewis SA, Arora D, et al. Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders. Eur J PharmacolEuropean J Pharmacol. 2024;979:176823. https:\/\/doi.org\/10.1016\/j.ejphar.2024.176823.","journal-title":"Eur J PharmacolEuropean J Pharmacol"},{"issue":"1","key":"8822_CR90","doi-asserted-by":"publisher","first-page":"24700","DOI":"10.1038\/srep24700","volume":"6","author":"Y Qi","year":"2016","unstructured":"Qi Y, Qiu Q, Gu X, Tian Y, Zhang Y. ATM mediates spermidine-induced mitophagy via PINK1 and parkin regulation in human fibroblasts. Sci Rep. 2016;6(1):24700. https:\/\/doi.org\/10.1038\/srep24700.","journal-title":"Sci Rep"},{"issue":"2","key":"8822_CR91","doi-asserted-by":"publisher","first-page":"108985","DOI":"10.1016\/j.celrep.2021.108985","volume":"35","author":"S Schroeder","year":"2021","unstructured":"Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, et al. Dietary spermidine improves cognitive function. Cell Rep. 2021;35(2):108985. https:\/\/doi.org\/10.1016\/j.celrep.2021.108985.","journal-title":"Cell Rep"},{"issue":"18","key":"8822_CR92","doi-asserted-by":"publisher","first-page":"9920","DOI":"10.3390\/ijms25189920","volume":"25","author":"H Kim","year":"2024","unstructured":"Kim H, Massett MP. Effect of spermidine on endothelial function in systemic lupus erythematosus mice. IJMS. 2024;25(18):9920. https:\/\/doi.org\/10.3390\/ijms25189920.","journal-title":"IJMS"},{"key":"8822_CR93","doi-asserted-by":"publisher","unstructured":"Ou Y, Wang S-J, Li D, Chu B, Gu W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc Natl Acad Sci. Proceedings of the National Academy of Sciences. 2016: E6806\u201312. https:\/\/doi.org\/10.1073\/pnas.1607152113 113.","DOI":"10.1073\/pnas.1607152113"},{"key":"8822_CR94","doi-asserted-by":"publisher","unstructured":"Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. Vol. 375. New York, N.Y; 2022. p. 1254\u201361. https:\/\/doi.org\/10.1126\/science.abf0529.","DOI":"10.1126\/science.abf0529"},{"issue":"9","key":"8822_CR95","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1172\/JCI120849","volume":"128","author":"B Zhou","year":"2018","unstructured":"Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin InvestJournal Clin Investigation. 2018;128(9):3716\u201326. https:\/\/doi.org\/10.1172\/JCI120849.","journal-title":"J Clin InvestJournal Clin Investigation"},{"key":"8822_CR96","doi-asserted-by":"publisher","unstructured":"Tan L, Zeng C, Dong W, Huang H, Zhang Y, Song Q, et al. Spatial metabolomics reveals GLA -Mediated imbalance of gal 2 cer \/ GalCer as a therapeutic target in myocardial ischemia\u2013reperfusion injury. Faseb J. 2026;40(1):e71378. https:\/\/doi.org\/10.1096\/fj.202502961RR.","DOI":"10.1096\/fj.202502961RR"},{"key":"8822_CR97","doi-asserted-by":"publisher","unstructured":"Li Z, Jiang F, Chen Y, Li Z, Wu Y, He Z, et al. Spatial transcriptional heterogeneity in the infarct core and its surrounding regions targeting Piezo1 signals in rats with myocardial ischemia-reperfusion injury. MedComm (2020). 2026;7(1):e70537. https:\/\/doi.org\/10.1002\/mco2.70537.","DOI":"10.1002\/mco2.70537"},{"issue":"1\u20132","key":"8822_CR98","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s11010-009-0183-5","volume":"332","author":"Y-J Zhao","year":"2009","unstructured":"Zhao Y-J, Zhang W-H, Xu C-Q, Li H-Z, Wang L-N, Li H, et al. Involvement of the ornithine decarboxylase\/polyamine system in precondition-induced cardioprotection through an interaction with PKC in rat hearts. Mol Cell Biochem. 2009;332(1\u20132):135\u201344. https:\/\/doi.org\/10.1007\/s11010-009-0183-5.","journal-title":"Mol Cell Biochem"},{"issue":"3","key":"8822_CR99","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.ejphar.2007.01.096","volume":"562","author":"Y-J Zhao","year":"2007","unstructured":"Zhao Y-J, Xu C-Q, Zhang W-H, Zhang L, Bian S-L, Huang Q, et al. Role of polyamines in myocardial ischemia\/reperfusion injury and their interactions with nitric oxide. Eur J PharmacolEuropean J Pharmacol. 2007;562(3):236\u201346. https:\/\/doi.org\/10.1016\/j.ejphar.2007.01.096.","journal-title":"Eur J PharmacolEuropean J Pharmacol"},{"issue":"1","key":"8822_CR100","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.ijcard.2007.07.163","volume":"132","author":"L Han","year":"2009","unstructured":"Han L, Xu C, Guo Y, Li H, Jiang C, Zhao Y. Polyamine metabolism in rat myocardial ischemia-reperfusion injury. Int J Cardiol. 2009;132(1):142\u201344. https:\/\/doi.org\/10.1016\/j.ijcard.2007.07.163.","journal-title":"Int J Cardiol"},{"key":"8822_CR101","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/457429","volume":"2014","author":"W Wang","year":"2014","unstructured":"Wang W, Zhang H, Xue G, Zhang L, Zhang W, Wang L, et al. Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool. Oxidative Med Cellular Longevity. 2014;2014:1\u201314. https:\/\/doi.org\/10.1155\/2014\/457429.","journal-title":"Oxidative Med Cellular Longevity"},{"issue":"9","key":"8822_CR102","first-page":"3976","volume":"8","author":"Q Duan","year":"2016","unstructured":"Duan Q, Yang W, Jiang D, Tao K, Dong A, Cheng H. Spermine ameliorates ischemia\/reperfusion injury in cardiomyocytes via regulation of autophagy. Am J Transl Res. 2016;8(9):3976\u201385.","journal-title":"Am J Transl Res"},{"key":"8822_CR103","doi-asserted-by":"publisher","unstructured":"Chai N, Zheng H, Zhang H, Li L, Yu X, Wang L, et al. Spermidine alleviates intrauterine hypoxia-induced offspring newborn myocardial mitochondrial damage in rats by inhibiting oxidative stress and regulating mitochondrial quality control. Iran J Pharm Res: IJPR. 2023;21(1):e133776. https:\/\/doi.org\/10.5812\/ijpr-133776.","DOI":"10.5812\/ijpr-133776"},{"issue":"11","key":"8822_CR104","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41569-022-00703-y","volume":"19","author":"JM Quiles","year":"2022","unstructured":"Quiles JM, Gustafsson \u00c5B. The role of mitochondrial fission in cardiovascular health and disease. Nat Rev Cardiol. 2022;19(11):723\u201336. https:\/\/doi.org\/10.1038\/s41569-022-00703-y.","journal-title":"Nat Rev Cardiol"},{"issue":"2","key":"8822_CR105","doi-asserted-by":"publisher","first-page":"355","DOI":"10.34067\/KID.0004772020","volume":"2","author":"JA Schaub","year":"2021","unstructured":"Schaub JA, Venkatachalam MA, Weinberg JM. Proximal tubular oxidative metabolism in acute kidney injury and the transition to CKD. Kidney360. 2021;2(2):355\u201364. https:\/\/doi.org\/10.34067\/KID.0004772020.","journal-title":"Kidney360"},{"key":"8822_CR106","doi-asserted-by":"publisher","unstructured":"Li Z, Ludwig N, Thomas K, Mersmann S, Lehmann M, Vestweber D, et al. The pathogenesis of ischemia-reperfusion induced acute kidney injury depends on renal neutrophil recruitment whereas sepsis-induced AKI does not. In: Front immunol [Internet]. Frontiers; 2022 [cited 2026 May 28];13. https:\/\/doi.org\/10.3389\/fimmu.2022.843782.","DOI":"10.3389\/fimmu.2022.843782"},{"issue":"1","key":"8822_CR107","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41420-024-02082-4","volume":"10","author":"S-S Chang","year":"2024","unstructured":"Chang S-S, Cheng C-C, Chen Y-R, Chen F-W, Cheng Y-M, Wang J-M. Epithelial CEBPD activates fibronectin and enhances macrophage adhesion in renal ischemia-reperfusion injury. Cell Death Discov. 2024;10(1):328. https:\/\/doi.org\/10.1038\/s41420-024-02082-4.","journal-title":"Cell Death Discov"},{"issue":"1","key":"8822_CR108","doi-asserted-by":"publisher","first-page":"30101","DOI":"10.1038\/s41598-024-81600-x","volume":"14","author":"W Li","year":"2024","unstructured":"Li W, Liu X, Li H, Zeng J, Chen Y, Xu B. Metabolomic and transcriptomic insights into the mechanisms of renal ischemia-reperfusion injury progression. Sci Rep. 2024;14(1):30101. https:\/\/doi.org\/10.1038\/s41598-024-81600-x.","journal-title":"Sci Rep"},{"key":"8822_CR109","doi-asserted-by":"publisher","unstructured":"Xu B, Li W, Zhang Y, Chen Y, Feng J, Song X. Untargeted and spatial-resolved metabolomics characterize serum and tissue-specific metabolic reprogramming in acute kidney injury. Heliyon. 2023;9(11):e21171. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e21171.","DOI":"10.1016\/j.heliyon.2023.e21171"},{"issue":"19","key":"8822_CR110","doi-asserted-by":"publisher","first-page":"4790","DOI":"10.3390\/ijms20194790","volume":"20","author":"K Zahedi","year":"2019","unstructured":"Zahedi K, Barone S, Soleimani M. Polyamine catabolism in acute kidney injury. IJMS. 2019;20(19):4790. https:\/\/doi.org\/10.3390\/ijms20194790.","journal-title":"IJMS"},{"key":"8822_CR111","doi-asserted-by":"publisher","unstructured":"Zahedi K, Wang Z, Barone S, Prada AE, Kelly CN, Casero RA, et al. Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. Am J Physiol-Renal Physiol. 2003;284(5):F1046\u201355. https:\/\/doi.org\/10.1152\/ajprenal.00318.2002.","DOI":"10.1152\/ajprenal.00318.2002"},{"key":"8822_CR112","doi-asserted-by":"publisher","unstructured":"Zahedi K, Barone S, Wang Y, Murray-Stewart T, Roy-Chaudhury P, Smith RD, et al. Proximal tubule epithelial cell specific ablation of the spermidine\/spermine N1-acetyltransferase gene reduces the severity of renal ischemia\/reperfusion injury. PLoS One. 2014;9(11):e110161. https:\/\/doi.org\/10.1371\/journal.pone.0110161.","DOI":"10.1371\/journal.pone.0110161"},{"key":"8822_CR113","doi-asserted-by":"publisher","unstructured":"Zahedi K, Lentsch AB, Okaya T, Barone S, Sakai N, Witte DP, et al. Spermidine\/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice. Am J Physiol-Gastr L. 2009;296(4):G899\u2013909. https:\/\/doi.org\/10.1152\/ajpgi.90507.2008.","DOI":"10.1152\/ajpgi.90507.2008"},{"key":"8822_CR114","doi-asserted-by":"publisher","unstructured":"Zahedi K, Bissler JJ, Wang Z, Josyula A, Lu L, Diegelman P, et al. Spermidine\/Spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest. Am J Physiol-Cell Physiol. 2007;292(3):C1204\u201315. https:\/\/doi.org\/10.1152\/ajpcell.00451.2006.","DOI":"10.1152\/ajpcell.00451.2006"},{"issue":"3","key":"8822_CR115","doi-asserted-by":"publisher","first-page":"200","DOI":"10.5115\/acb.2017.50.3.200","volume":"50","author":"J Kim","year":"2017","unstructured":"Kim J. Spermidine is protective against kidney ischemia and reperfusion injury through inhibiting DNA nitration and PARP1 activation. Anat Cell Biol. 2017;50(3):200\u201306. https:\/\/doi.org\/10.5115\/acb.2017.50.3.200.","journal-title":"Anat Cell Biol"},{"issue":"5","key":"8822_CR116","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.21037\/tau-21-280","volume":"10","author":"B Yan","year":"2021","unstructured":"Yan B, Min S-J, Xu B, Zhang C, Pei J, Zhang W, et al. The protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats. Transl Androl Urol. 2021;10(5):2051\u201366. https:\/\/doi.org\/10.21037\/tau-21-280.","journal-title":"Transl Androl Urol"},{"key":"8822_CR117","doi-asserted-by":"publisher","unstructured":"Zhao J, Hou L, Dery KJ, Yuan X, Kim KH, Kupiec-Weglinski JW, et al. Hepatic ischemia-reperfusion injury: underlying mechanisms and concepts in liver surgery and liver transplantation. Hepatology. 2025. https:\/\/doi.org\/10.1097\/HEP.0000000000001609.","DOI":"10.1097\/HEP.0000000000001609"},{"issue":"14","key":"8822_CR118","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.3390\/cells11142222","volume":"11","author":"C Kaltenmeier","year":"2022","unstructured":"Kaltenmeier C, Wang R, Popp B, Geller D, Tohme S, Yazdani HO. Role of immuno-inflammatory signals in liver ischemia-reperfusion injury. Cells. 2022;11(14):2222. https:\/\/doi.org\/10.3390\/cells11142222.","journal-title":"Cells"},{"issue":"9","key":"8822_CR119","doi-asserted-by":"publisher","first-page":"527","DOI":"10.14348\/molcells.2023.0099","volume":"46","author":"MJ Heo","year":"2023","unstructured":"Heo MJ, Suh JH, Poulsen KL, Ju C, Kim KH. Updates on the immune cell basis of hepatic ischemia-reperfusion injury. Mol Cells. 2023;46(9):527\u201334. https:\/\/doi.org\/10.14348\/molcells.2023.0099.","journal-title":"Mol Cells"},{"issue":"2","key":"8822_CR120","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1111\/jgh.16396","volume":"39","author":"D Yinzhi","year":"2024","unstructured":"Yinzhi D, Jianhua H, Hesheng L. The roles of liver sinusoidal endothelial cells in liver ischemia\/reperfusion injury. J Gastro Hepatol. 2024;39(2):224\u201330. https:\/\/doi.org\/10.1111\/jgh.16396.","journal-title":"J Gastro Hepatol"},{"issue":"1","key":"8822_CR121","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s42003-023-04564-0","volume":"6","author":"J Xin","year":"2023","unstructured":"Xin J, Yang T, Wu X, Wu Y, Liu Y, Liu X, et al. Spatial transcriptomics analysis of zone-dependent hepatic ischemia-reperfusion injury murine model. Commun Biol. 2023;6(1):194. https:\/\/doi.org\/10.1038\/s42003-023-04564-0.","journal-title":"Commun Biol"},{"issue":"2","key":"8822_CR122","doi-asserted-by":"publisher","first-page":"101465","DOI":"10.1016\/j.gendis.2024.101465","volume":"12","author":"Q Li","year":"2025","unstructured":"Li Q, Qin X, Wang L, Hu D, Liao R, Yu H, et al. Multi-time point transcriptomics and metabolomics reveal key transcription and metabolic features of hepatic ischemia-reperfusion injury in mice. Genes & Dis. 2025;12(2):101465. https:\/\/doi.org\/10.1016\/j.gendis.2024.101465.","journal-title":"Genes & Dis"},{"issue":"1","key":"8822_CR123","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.biocel.2009.07.009","volume":"42","author":"K Igarashi","year":"2010","unstructured":"Igarashi K, Kashiwagi K. Modulation of cellular function by polyamines. Int J Biochem Cell Biol. 2010;42(1):39\u201351. https:\/\/doi.org\/10.1016\/j.biocel.2009.07.009.","journal-title":"The Int J Biochem Cell Biol"},{"issue":"6","key":"8822_CR124","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1016\/j.biocel.2013.02.021","volume":"45","author":"T Yamashita","year":"2013","unstructured":"Yamashita T, Nishimura K, Saiki R, Okudaira H, Tome M, Higashi K, et al. Role of polyamines at the G1\/S boundary and G2\/M phase of the cell cycle. Int J Biochem Cell Biol. 2013;45(6):1042\u201350. https:\/\/doi.org\/10.1016\/j.biocel.2013.02.021.","journal-title":"The Int J Biochem Cell Biol"},{"key":"8822_CR125","doi-asserted-by":"publisher","first-page":"948","DOI":"10.3389\/fimmu.2018.00948","volume":"9","author":"S Zhou","year":"2018","unstructured":"Zhou S, Gu J, Liu R, Wei S, Wang Q, Shen H, et al. Spermine alleviates acute liver injury by inhibiting liver-resident macrophage pro-inflammatory response through ATG5-dependent autophagy. Front Immunol. 2018;9:948. https:\/\/doi.org\/10.3389\/fimmu.2018.00948.","journal-title":"Front Immunol"},{"issue":"5","key":"8822_CR126","doi-asserted-by":"publisher","first-page":"924","DOI":"10.14336\/AD.2017.1126","volume":"9","author":"F Liu","year":"2018","unstructured":"Liu F, Lu J, Manaenko A, Tang J, Hu Q. Mitochondria in ischemic stroke: new insight and implications. Aging Disease. 2018;9(5):924\u201337. https:\/\/doi.org\/10.14336\/AD.2017.1126.","journal-title":"Aging Disease"},{"issue":"15","key":"8822_CR127","doi-asserted-by":"publisher","first-page":"8512","DOI":"10.3390\/ijms23158512","volume":"23","author":"AE Sifat","year":"2022","unstructured":"Sifat AE, Nozohouri S, Archie SR, Chowdhury EA, Abbruscato TJ. Brain energy metabolism in ischemic stroke: effects of smoking and diabetes. IJMS. 2022;23(15):8512. https:\/\/doi.org\/10.3390\/ijms23158512.","journal-title":"IJMS"},{"key":"8822_CR128","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.2147\/JIR.S461795","volume":"17","author":"X Shui","year":"2024","unstructured":"Shui X, Chen J, Fu Z, Zhu H, Tao H, Li Z. Microglia in ischemic stroke: pathogenesis insights and therapeutic challenges. JIR. 2024;17:3335\u201352. https:\/\/doi.org\/10.2147\/JIR.S461795.","journal-title":"JIR"},{"issue":"5","key":"8822_CR129","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1161\/STROKEAHA.122.036946","volume":"53","author":"E Candelario-Jalil","year":"2022","unstructured":"Candelario-Jalil E, Dijkhuizen RM, Magnus T. Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities. Stroke. 2022;53(5):1473\u201386. https:\/\/doi.org\/10.1161\/STROKEAHA.122.036946.","journal-title":"Stroke"},{"key":"8822_CR130","doi-asserted-by":"publisher","first-page":"1613464","DOI":"10.3389\/fphar.2025.1613464","volume":"16","author":"M Yang","year":"2025","unstructured":"Yang M, Liu B, Chen B, Shen Y, Liu G. Cerebral ischemia-reperfusion injury: mechanisms and promising therapies. Front Pharmacol. 2025;16:1613464. https:\/\/doi.org\/10.3389\/fphar.2025.1613464.","journal-title":"Front Pharmacol"},{"issue":"1","key":"8822_CR131","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13024-023-00636-1","volume":"18","author":"SP Yu","year":"2023","unstructured":"Yu SP, Jiang MQ, Shim SS, Pourkhodadad S, Wei L. Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset alzheimer\u2019s disease. Mol Neurodegener. 2023;18(1):43. https:\/\/doi.org\/10.1186\/s13024-023-00636-1.","journal-title":"Mol Neurodegener"},{"key":"8822_CR132","doi-asserted-by":"publisher","first-page":"105954","DOI":"10.1016\/j.neuint.2025.105954","volume":"185","author":"Z-L Ren","year":"2025","unstructured":"Ren Z-L, Lan X, Cheng J-L, Zheng Y-X, Chen C-A, Liu Y, et al. Astrocyte-neuron metabolic crosstalk in ischaemic stroke. Neurochemistry Int. 2025;185:105954. https:\/\/doi.org\/10.1016\/j.neuint.2025.105954.","journal-title":"Neurochemistry Int"},{"key":"8822_CR133","doi-asserted-by":"publisher","first-page":"1091616","DOI":"10.3389\/fphar.2023.1091616","volume":"14","author":"Q Chen","year":"2023","unstructured":"Chen Q, Zhou T, Yuan J-J, Xiong X-Y, Liu X-H, Qiu Z-M, et al. Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice. Front Pharmacol. 2023;14:1091616. https:\/\/doi.org\/10.3389\/fphar.2023.1091616.","journal-title":"Front Pharmacol"},{"key":"8822_CR134","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s41419-025-08114-w","volume-title":"Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm. Cell death Dis","author":"Y Wang","year":"2025","unstructured":"Wang Y, Ge M, Wang J, Xu Y, Wang N, Xu S. Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm. Cell death Dis. Vol. 16. Nature Publishing Group; 2025. p. 788. https:\/\/doi.org\/10.1038\/s41419-025-08114-w."},{"issue":"1\u20132","key":"8822_CR135","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/0006-8993(91)91726-h","volume":"566","author":"W Paschen","year":"1991","unstructured":"Paschen W, Csiba L, R\u00f6hn G, Bereczki D. Polyamine metabolism in transient focal ischemia of rat brain. Brain Res. 1991;566(1\u20132):354\u201357. https:\/\/doi.org\/10.1016\/0006-8993(91)91726-h.","journal-title":"Brain Res"},{"key":"8822_CR136","doi-asserted-by":"publisher","unstructured":"Fan J, Chen M, Wang X, Tian Z, Wang J, Fan D, et al. Targeting smox is neuroprotective and ameliorates brain inflammation in cerebral ischemia\/reperfusion rats. 2025, Oct, 23. https:\/\/doi.org\/10.1093\/toxsci\/kfy300. Accessed 23 Oct 2025.","DOI":"10.1093\/toxsci\/kfy300"},{"issue":"1","key":"8822_CR137","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1017\/s0317167100006247","volume":"36","author":"GH Kim","year":"2009","unstructured":"Kim GH, Komotar RJ, McCullough-Hicks ME, Otten ML, Starke RM, Kellner CP, et al. The role of polyamine metabolism in neuronal injury following cerebral ischemia. Can J Neurol Sci. 2009;36(1):14\u201319. https:\/\/doi.org\/10.1017\/s0317167100006247.","journal-title":"Can J Neurol Sci"},{"issue":"2","key":"8822_CR138","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1046\/j.1471-4159.1999.0720765.x","volume":"72","author":"A Do\u011fan","year":"1999","unstructured":"Do\u011fan A, Rao AM, Hatcher J, Rao VL, Ba\u015fkaya MK, Dempsey RJ. Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral after occlusion. J Neurochem. 1999;72(2):765\u201370. https:\/\/doi.org\/10.1046\/j.1471-4159.1999.0720765.x.","journal-title":"J Neurochem"},{"issue":"5","key":"8822_CR139","doi-asserted-by":"publisher","first-page":"597","DOI":"10.22038\/IJBMS.2022.63733.14046","volume":"25","author":"N Cetin","year":"2022","unstructured":"Cetin N, Dasdelen D, Mogulkoc R, Menevse E, Baltaci AK. Role of exogenous putrescine in the status of energy, DNA damage, inflammation, and spermidine\/spermine-n(1)- acetyltransferase in brain ischemia-reperfusion in rats. Iran J Basic Med Sci. 2022;25(5):597\u2013603. https:\/\/doi.org\/10.22038\/IJBMS.2022.63733.14046.","journal-title":"Iran J Basic Med Sci"},{"key":"8822_CR140","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.neuroscience.2019.03.037","volume":"406","author":"T Sawano","year":"2019","unstructured":"Sawano T, Tsuchihashi R, Watanabe F, Niimi K, Yamaguchi W, Yamaguchi N, et al. Changes in L-arginine metabolism by Sema4D deficiency induce promotion of microglial proliferation in ischemic cortex. Neuroscience. 2019;406:420\u201331. https:\/\/doi.org\/10.1016\/j.neuroscience.2019.03.037.","journal-title":"Neuroscience"},{"key":"8822_CR141","doi-asserted-by":"publisher","DOI":"10.1556\/2060.2022.00138","volume-title":"Effects of putrescine on oxidative stress, spermidine\/spermine-N(1)-acetyltransferase, inflammation and energy levels in liver and serum in rats with brain ischemia-reperfusion","author":"D Dasdelen","year":"2023","unstructured":"Dasdelen D, Cetin N, Menevse E, Baltaci AK, Mogulkoc R. Effects of putrescine on oxidative stress, spermidine\/spermine-N(1)-acetyltransferase, inflammation and energy levels in liver and serum in rats with brain ischemia-reperfusion. 2023. 2025 July 12]; https:\/\/doi.org\/10.1556\/2060.2022.00138."},{"issue":"1","key":"8822_CR142","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3892\/etm.2017.4455","volume":"14","author":"H Du","year":"2017","unstructured":"Du H, Ming X, Zhou S. Pre-treatment with spermine for acute cerebral ischemia\/reperfusion injuries. Exp Ther Med. 2017;14(1):169\u201372. https:\/\/doi.org\/10.3892\/etm.2017.4455.","journal-title":"Exp Ther Med"},{"issue":"7","key":"8822_CR143","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.3390\/biomedicines10071756","volume":"10","author":"M Cervelli","year":"2022","unstructured":"Cervelli M, Averna M, Vergani L, Pedrazzi M, Amato S, Fiorucci C, et al. The involvement of polyamines catabolism in the crosstalk between neurons and astrocytes in neurodegeneration. Biomedicines. 2022;10(7):1756. https:\/\/doi.org\/10.3390\/biomedicines10071756.","journal-title":"Biomedicines"},{"issue":"9","key":"8822_CR144","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/lt.24471","volume":"22","author":"S Okumura","year":"2016","unstructured":"Okumura S, Teratani T, Fujimoto Y, Zhao X, Tsuruyama T, Masano Y, et al. Oral administration of polyamines ameliorates liver ischemia\/reperfusion injury and promotes liver regeneration in rats. Liver Transpl: Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc. 2016;22(9):1231\u201344. https:\/\/doi.org\/10.1002\/lt.24471.","journal-title":"Liver Transpl: Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc"},{"key":"8822_CR145","doi-asserted-by":"publisher","unstructured":"Zahedi K, Barone S, Kramer DL, Amlal H, Alhonen L, J\u00e4nne J, et al. The role of spermidine\/spermine N1-acetyltransferase in endotoxin-induced acute kidney injury. Am J Physiol-Cell Physiol. 2010;299(1):C164\u201374. https:\/\/doi.org\/10.1152\/ajpcell.00512.2009.","DOI":"10.1152\/ajpcell.00512.2009"},{"issue":"3","key":"8822_CR146","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/s0887-2333(97)00116-1","volume":"12","author":"UR Tipnis","year":"1998","unstructured":"Tipnis UR, He GY. Mechanism of polyamine toxicity in cultured cardiac myocytes. Toxicol Vitro. 1998;12(3):233\u201340. https:\/\/doi.org\/10.1016\/s0887-2333(97)00116-1.","journal-title":"Toxicol Vitro"},{"issue":"7","key":"8822_CR147","doi-asserted-by":"publisher","first-page":"102421","DOI":"10.1016\/j.clinre.2024.102421","volume":"48","author":"T Hu","year":"2024","unstructured":"Hu T, Tang W, Hong W, Huang Q, Sun X, Wu W, et al. Spermine oxidase regulates liver inflammation and fibrosis through \u03b2-catenin pathway. Clin ResearchHepatol Gastroenterol. 2024;48(7):102421. https:\/\/doi.org\/10.1016\/j.clinre.2024.102421.","journal-title":"Clin ResearchHepatol Gastroenterol"},{"issue":"3","key":"8822_CR148","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/medsci10030047","volume":"10","author":"AB Furbish","year":"2022","unstructured":"Furbish AB, Alford AS, Burger P, Peterson YK, Murray-Stewart T, Casero A, et al. Identification and characterization of novel small-molecule SMOX inhibitors. Med Sci. 2022;10(3):47. https:\/\/doi.org\/10.3390\/medsci10030047.","journal-title":"Med Sci"},{"issue":"1","key":"8822_CR149","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s42003-022-03735-9","volume":"5","author":"E Diaz","year":"2022","unstructured":"Diaz E, Adhikary S, Tepper AWJW, Riley D, Ortiz-Meoz R, Krosky D, et al. Structure of human spermine oxidase in complex with a highly selective allosteric inhibitor. Commun Biol Nat Publishing Group. 2022;5(1):787. https:\/\/doi.org\/10.1038\/s42003-022-03735-9.","journal-title":"Commun Biol Nat Publishing Group"},{"issue":"3","key":"8822_CR150","doi-asserted-by":"publisher","first-page":"140","DOI":"10.32607\/actanaturae.10992","volume":"12","author":"TT Dunston","year":"2020","unstructured":"Dunston TT, Khomutov MA, Gabelli SB, Stewart TM, Foley JR, Kochetkov SN, et al. Identification of a novel substrate-derived spermine oxidase inhibitor. Acta Naturae. 2020;12(3):140\u201344. https:\/\/doi.org\/10.32607\/actanaturae.10992.","journal-title":"Acta Naturae"},{"issue":"10","key":"8822_CR151","doi-asserted-by":"publisher","first-page":"3356","DOI":"10.1161\/STROKEAHA.109.553248","volume":"40","author":"R Saiki","year":"2009","unstructured":"Saiki R, Nishimura K, Ishii I, Omura T, Okuyama S, Kashiwagi K, et al. Intense correlation between brain infarction and protein-conjugated acrolein. Stroke. Am Heart Assoc. 2009;40(10):3356\u201361. https:\/\/doi.org\/10.1161\/STROKEAHA.109.553248.","journal-title":"Stroke. Am Heart Assoc"},{"issue":"11","key":"8822_CR152","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.3390\/molecules29112519","volume":"29","author":"M Kopera","year":"2024","unstructured":"Kopera M, Gwozdzinski K, Pieniazek A. Acrolein induces changes in cell membrane and cytosol proteins of erythrocytes. Mol. Multidiscip Digit Publishing Inst. 2024;29(11):2519. https:\/\/doi.org\/10.3390\/molecules29112519.","journal-title":"Mol. Multidiscip Digit Publishing Inst"},{"issue":"8","key":"8822_CR153","doi-asserted-by":"publisher","first-page":"5579","DOI":"10.1073\/pnas.082609299","volume":"99","author":"S Ivanova","year":"2002","unstructured":"Ivanova S, Batliwalla F, Mocco J, Kiss S, Huang J, Mack W, et al. Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal. Proc Natl Acad Sci USA. 2002;99(8):5579\u201384. https:\/\/doi.org\/10.1073\/pnas.082609299.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8822_CR154","doi-asserted-by":"publisher","unstructured":"Holbert CE, Foley JR, Yu A, Murray Stewart T, Phanstiel O, Oupicky D, et al. Polyamine-based nanostructures share polyamine transport mechanisms with native polyamines and their analogues: significance for polyamine-targeted therapy. In: Med Sci. Vol. 10. Basel, Switzerland; 2022. p. 44. https:\/\/doi.org\/10.3390\/medsci10030044.","DOI":"10.3390\/medsci10030044"},{"key":"8822_CR155","doi-asserted-by":"publisher","first-page":"114323","DOI":"10.1016\/j.jconrel.2025.114323","volume":"388","author":"X Li","year":"2025","unstructured":"Li X, Cantley LG, Xu L. Engineering polyamidoamine dendrimer nanoparticles for targeted drug delivery to proximal tubular cells after renal ischemia\/reperfusion injury. J Control Release. 2025;388:114323. https:\/\/doi.org\/10.1016\/j.jconrel.2025.114323.","journal-title":"J Control Release"},{"issue":"1","key":"8822_CR156","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.kint.2020.04.024","volume":"98","author":"ZH Endre","year":"2020","unstructured":"Endre ZH, Erlich JH. Targeted protection of proximal tubular cells by nanoparticle-enhanced delivery of a TLR9-antagonist. Kidney Int. 2020;98(1):48\u201350. https:\/\/doi.org\/10.1016\/j.kint.2020.04.024.","journal-title":"Kidney Int"},{"issue":"6","key":"8822_CR157","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/jcbfm.1993.131","volume":"13","author":"CA Muszynski","year":"1993","unstructured":"Muszynski CA, Robertson CS, Goodman JC, Henley CM. DFMO reduces cortical infarct volume after middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab. 1993;13(6):1033\u201337. https:\/\/doi.org\/10.1038\/jcbfm.1993.131.","journal-title":"J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab"},{"issue":"8","key":"8822_CR158","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1080\/15548627.2021.1933299","volume":"17","author":"SJ Hofer","year":"2021","unstructured":"Hofer SJ, Liang Y, Zimmermann A, Schroeder S, Dengjel J, Kroemer G, et al. Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging. Autophagy. 2021;17(8):2037\u201339. https:\/\/doi.org\/10.1080\/15548627.2021.1933299.","journal-title":"Autophagy"},{"key":"8822_CR159","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2788","volume-title":"Spermidine in health and disease","author":"F Madeo","year":"2018","unstructured":"Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. American Association for the Advancement of Science; 2018. 2025 July 1]; https:\/\/doi.org\/10.1126\/science.aan2788. Science [Internet]."},{"key":"8822_CR160","doi-asserted-by":"publisher","unstructured":"Wang Y, Chen P, Huang S, Chen L, Ge Y, Gu H, et al. Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5. J Adv Res. 2025;S2091\u20131232(25)1029\u2013X. https:\/\/doi.org\/10.1016\/j.jare.2025.12.039.","DOI":"10.1016\/j.jare.2025.12.039"},{"key":"8822_CR161","doi-asserted-by":"publisher","unstructured":"Schibalski RS, Shulha AS, Tsao BP, Palygin O, Ilatovskaya DV. The role of polyamine metabolism in cellular function and physiology. Am J Physiol-Cell Physiol. 2024;327(2):C341\u201356. https:\/\/doi.org\/10.1152\/ajpcell.00074.2024.","DOI":"10.1152\/ajpcell.00074.2024"},{"issue":"1","key":"8822_CR162","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00726-026-03497-2","volume":"58","author":"T Uemura","year":"2026","unstructured":"Uemura T, Takayama J, Oguro A, Terui Y. Polyamine metabolism as a regulator of cellular and organismal aging. Amino Acids. 2026;58(1):7. https:\/\/doi.org\/10.1007\/s00726-026-03497-2.","journal-title":"Amino Acids"},{"issue":"1","key":"8822_CR163","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s42003-022-03530-6","volume":"5","author":"ILMH Aye","year":"2022","unstructured":"Aye ILMH, Gong S, Avellino G, Barbagallo R, Gaccioli F, Jenkins BJ, et al. Placental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation. Commun Biol. 2022;5(1):586. https:\/\/doi.org\/10.1038\/s42003-022-03530-6.","journal-title":"Commun Biol"},{"key":"8822_CR164","doi-asserted-by":"publisher","unstructured":"Ramos-Molina B, Queipo-Ortu\u00f1o MI, Lambertos A, Tinahones FJ, Pe\u00f1afiel R. Dietary and gut microbiota polyamines in obesity- and age-related diseases. Front Nutr. 2019 [cited 2026 June 14];6. 6. https:\/\/doi.org\/10.3389\/fnut.2019.00024.","DOI":"10.3389\/fnut.2019.00024"},{"issue":"1","key":"8822_CR165","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3390\/cells9010082","volume":"9","author":"E Gaband\u00e9-Rodr\u00edguez","year":"2019","unstructured":"Gaband\u00e9-Rodr\u00edguez E, G\u00f3mez De Las Heras MM, Mittelbrunn M. Control of inflammation by calorie restriction mimetics: on the crossroad of autophagy and mitochondria. Cells. 2019;9(1):82. https:\/\/doi.org\/10.3390\/cells9010082.","journal-title":"Cells"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08822-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08822-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08822-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:06:35Z","timestamp":1791554795000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08822-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":165,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8822"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08822-7","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"assertion":[{"value":"3 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no known competing financial interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1275"}}