{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:33:23Z","timestamp":1792460003757,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress is no longer viewed as a random imbalance between reactive oxygen species and antioxidants, but as a failure of an integrated redox network that connects metabolism, immunity, and metal homeostasis. Classical markers such as malondialdehyde and 4-hydroxynonenal define oxidative damage, yet they cannot explain how redox adaptation occurs or fails. Over the past decade, the discovery of regulated cell-death pathways (ferroptosis, cuproptosis) and emerging metabolic signals has revealed a new generation of adaptive redox mediators\u2014including itaconate, nitro-fatty acids, reactive sulfur species and succinate\u2014that act as electrophilic or persulfidating regulators rather than passive by-products of oxidation. This review integrates mechanistic, biochemical and clinical evidence to define how these mediators remodel the nuclear factor erythroid 2-related factor 2\/Kelch-like ECH-associated protein 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and hypoxia-inducible factor 1-alpha axes, coordinate lipid\u2013metal\u2013sulfur cross-talk, and shape vulnerability or resistance to ferroptosis and cuproptosis. By combining deep molecular research with translational perspectives, we propose a unifying framework for predictive redox medicine based on composite biomarker panels and AI-assisted phenotyping. Understanding and quantifying these next-generation mediators will open new avenues for precision nutrition, drug development, and disease prevention\u2014transforming oxidative-stress biology from a descriptive field into an actionable platform for human health.<\/jats:p>","DOI":"10.3390\/antiox15040427","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Next-Generation Redox Mediators: Itaconate, Nitro-Fatty Acids, Reactive Sulfur Species and Succinate as Emerging Switches in Predictive Redox Medicine"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7524-0103","authenticated-orcid":false,"given":"Luca","family":"Gammeri","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Science and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-8239","authenticated-orcid":false,"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-158X","authenticated-orcid":false,"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Gangemi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.bbadis.2015.01.015","article-title":"On the Role of 4-Hydroxynonenal in Health and Disease","volume":"1852","author":"Csala","year":"2015","journal-title":"Biochim. 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