{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:25:46Z","timestamp":1789122346158,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["5U01AI148308-05"],"award-info":[{"award-number":["5U01AI148308-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["5U01AI189442-02"],"award-info":[{"award-number":["5U01AI189442-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["5U01AI133561-04"],"award-info":[{"award-number":["5U01AI133561-04"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["1P01AI186817-01"],"award-info":[{"award-number":["1P01AI186817-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["P30GM159561"],"award-info":[{"award-number":["P30GM159561"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5U01AI148308-05"],"award-info":[{"award-number":["5U01AI148308-05"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5U01AI189442-02"],"award-info":[{"award-number":["5U01AI189442-02"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5U01AI133561-04"],"award-info":[{"award-number":["5U01AI133561-04"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1P01AI186817-01"],"award-info":[{"award-number":["1P01AI186817-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30GM159561"],"award-info":[{"award-number":["P30GM159561"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Radiological emergencies necessitate biomarkers that not only estimate absorbed ionizing radiation (IR) dose but also guide timely interventions to prevent or delay multi-organ injury. Conventional LC\u2013MS-based metabolomics of bulk plasma is constrained by matrix effects that mask low-abundance species. Extracellular vesicles (EVs) constitute a metabolically enriched, underexplored compartment that can provide complementary insight into systemic metabolic and redox responses to IR. Female WAG\/RijCmcr rats were exposed to 13.0 Gy leg-out partial-body X-rays and treated with one of three activated protein C (APC) variants\u2014rat wild-type (WT), rat 3K3A-APC, or human WT APC\u2014administered 24- and 48 h post-irradiation. Longitudinal plasma collections (days 1, 14, 30, and 90) were subjected to metabolomic and lipidomic profiling of whole plasma and matched EV-enriched fractions to define signatures of acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and their modulation by APC. ARS was marked by early dyslipidemia and widespread metabolic disruption, evolving into DEARE with persistent alterations in energy metabolism, and nucleotide biosynthesis, consistent with sustained oxidative and inflammatory stress. EV profiles showed matrix-specific, time-dependent trajectories distinct from plasma, with prominent lipid dysregulation and enrichment of fatty acid \u03b2-oxidation, sphingolipid, and cholesterol pathway metabolites at day 90. Rat 3K3A-APC promoted early EV metabolic normalization, whereas rat WT APC more effectively mitigated late DEARE-associated changes. Elevated sphingomyelins in plasma EVs at day 90 may suggest a compensatory or anti-inflammatory lipid response. These findings suggest that plasma-derived EVs may provide a sensitive matrix for radiation biomarker discovery and may help elucidate APC-mediated modulation of IR-induced metabolic and redox disturbances.<\/jats:p>","DOI":"10.3390\/antiox15091160","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:09:40Z","timestamp":1789117780000},"page":"1160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma-Derived Extracellular Vesicles as Systemic Mediators of Radiation Response and Radiation Mitigation by Activated Protein C in a Rat Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-5687","authenticated-orcid":false,"given":"Shivani","family":"Bansal","sequence":"first","affiliation":[{"name":"Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8410-9928","authenticated-orcid":false,"given":"Sunain","family":"Deol","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9391","authenticated-orcid":false,"given":"Meth","family":"Jayatilake","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-1016","authenticated-orcid":false,"given":"Yaoxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Brian L.","family":"Fish","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Xiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0804-1865","authenticated-orcid":false,"given":"Jose A.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-2547","authenticated-orcid":false,"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Tracy","family":"Gasperetti","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Meetha","family":"Medhora","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2249-5203","authenticated-orcid":false,"given":"Marjan","family":"Boerma","sequence":"additional","affiliation":[{"name":"Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9676-6371","authenticated-orcid":false,"given":"Heather A.","family":"Himburg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-7583","authenticated-orcid":false,"given":"Amrita K.","family":"Cheema","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA"},{"name":"Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA"},{"name":"Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/HP.0000000000000357","article-title":"Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation","volume":"109","author":"Unthank","year":"2015","journal-title":"Health Phys."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Menon, S.S., Uppal, M., Randhawa, S., Cheema, M.S., Aghdam, N., Usala, R.L., Ghosh, S.P., Cheema, A.K., and Dritschilo, A. (2016). Radiation Metabolomics: Current Status and Future Directions. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00020"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"802","DOI":"10.3109\/09553002.2011.556177","article-title":"Radiation metabolomics and its potential in biodosimetry","volume":"87","author":"Coy","year":"2011","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cheema, A.K., Li, Y., Girgis, M., Jayatilake, M., Fatanmi, O.O., Wise, S.Y., Seed, T.M., and Singh, V.K. (2020). Alterations in Tissue Metabolite Profiles with Amifostine-Prophylaxed Mice Exposed to Gamma Radiation. Metabolites, 10.","DOI":"10.3390\/metabo10050211"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Upadhyay, M., Rajagopal, M., Gill, K., Li, Y., Bansal, S., Sridharan, V., Tyburski, J.B., Boerma, M., and Cheema, A.K. (2020). Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model. Metabolites, 10.","DOI":"10.3390\/metabo10060252"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.2147\/OTT.S142149","article-title":"Biomarkers for early diagnosis, prognosis, prediction, and recurrence monitoring of non-small cell lung cancer","volume":"10","author":"Tang","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.21037\/tcr.2018.01.24","article-title":"Potential biomarkers to evaluate therapeutic response in advanced pancreatic cancer","volume":"7","author":"Yang","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meehan, J., Gray, M., Martinez-Perez, C., Kay, C., Pang, L.Y., Fraser, J.A., Poole, A.V., Kunkler, I.H., Langdon, S.P., and Argyle, D. (2020). Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00628"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1080\/09553002.2023.2182001","article-title":"Analysis of the urinary metabolic profiles in irradiated rats treated with Activated Protein C (APC), a potential mitigator of radiation toxicity","volume":"99","author":"Bansal","year":"2023","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ceb.2004.06.003","article-title":"Exosomes: Endosomal-derived vesicles shipping extracellular messages","volume":"16","author":"Fevrier","year":"2004","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMra1704286","article-title":"Circulating Extracellular Vesicles in Human Disease","volume":"379","author":"Shah","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.biocel.2012.08.007","article-title":"Exosomes: New players in cell-cell communication","volume":"44","author":"Bang","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8545347","DOI":"10.1155\/2018\/8545347","article-title":"Isolation of Extracellular Vesicles: General Methodologies and Latest Trends","volume":"2018","author":"Konoshenko","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.molmed.2014.03.002","article-title":"Extracellular vesicles: Emerging targets for cancer therapy","volume":"20","author":"Vader","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1479-5876-7-4","article-title":"Can urinary exosomes act as treatment response markers in prostate cancer?","volume":"7","author":"Mitchell","year":"2009","journal-title":"J. Transl. Med."},{"key":"ref_16","unstructured":"Szajnik, M., Derbis, M., Lach, M., Patalas, P., Michalak, M., Drzewiecka, H., Szpurek, D., Nowakowski, A., Spaczynski, M., and Baranowski, W. (2013). Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy. Gynecol. Obstet., 3."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41392-020-00258-9","article-title":"Application of exosomes as liquid biopsy in clinical diagnosis","volume":"5","author":"Zhou","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Altadill, T., Campoy, I., Lanau, L., Gill, K., Rigau, M., Gil-Moreno, A., Reventos, J., Byers, S., Colas, E., and Cheema, A.K. (2016). Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151339"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s12967-022-03414-7","article-title":"An optimized method for the isolation of urinary extracellular vesicles for molecular phenotyping: Detection of biomarkers for radiation exposure","volume":"20","author":"Hinzman","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1538-7836.2007.02491.x","article-title":"Activated protein C","volume":"5","author":"Griffin","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/nm.2813","article-title":"Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity","volume":"18","author":"Geiger","year":"2012","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.2174\/138161212802430413","article-title":"Preclinical safety and pharmacokinetic profile of 3K3A-APC, a novel, modified activated protein C for ischemic stroke","volume":"18","author":"Williams","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1182\/blood-2004-01-0110","article-title":"Activated protein C variants with normal cytoprotective but reduced anticoagulant activity","volume":"104","author":"Mosnier","year":"2004","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bansal, S., Li, Y., Bansal, S., Klotzbier, W., Singh, B., Jayatilake, M., Sridharan, V., Fernandez, J.A., Griffin, J.H., and Weiler, H. (2024). Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma. Metabolites, 14.","DOI":"10.20944\/preprints202403.1819.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/09553002.2018.1554921","article-title":"WAG\/RijCmcr rat models for injuries to multiple organs by single high dose ionizing radiation: Similarities to nonhuman primates (NHP)","volume":"96","author":"Fish","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1667\/RR13425.1","article-title":"Model development and use of ACE inhibitors for preclinical mitigation of radiation-induced injury to multiple organs","volume":"182","author":"Medhora","year":"2014","journal-title":"Radiat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1471-4159.2009.05921.x","article-title":"Species-dependent neuroprotection by activated protein C mutants with reduced anticoagulant activity","volume":"109","author":"Guo","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6931","DOI":"10.1021\/ac500734c","article-title":"Interactive XCMS Online: Simplifying advanced metabolomic data processing and subsequent statistical analyses","volume":"86","author":"Gowda","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W652","DOI":"10.1093\/nar\/gkp356","article-title":"MetaboAnalyst: A web server for metabolomic data analysis and interpretation","volume":"37","author":"Xia","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nprot.2011.335","article-title":"Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry","volume":"6","author":"Dunn","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41420-025-02654-y","article-title":"Redox mechanism of glycerophospholipids and relevant targeted therapy in ferroptosis","volume":"11","author":"Chang","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.freeradbiomed.2006.01.035","article-title":"Sphingolipid signaling and redox regulation","volume":"40","author":"Won","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s10522-017-9710-z","article-title":"Lipid (per) oxidation in mitochondria: An emerging target in the ageing process?","volume":"18","author":"Ademowo","year":"2017","journal-title":"Biogerontology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1002\/rcm.6997","article-title":"Improved identification of multiple drugs of abuse and relative metabolites in urine samples using liquid chromatography\/triple quadrupole mass spectrometry coupled with a library search","volume":"28","author":"Lin","year":"2014","journal-title":"Rapid Commun. Mass. Spectrom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13924","DOI":"10.1021\/acs.analchem.9b03415","article-title":"Hybrid Search: A Method for Identifying Metabolites Absent from Tandem Mass Spectrometry Libraries","volume":"91","author":"Cooper","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0163-7827(91)90005-P","article-title":"Sphingomyelin and derivatives as cellular signals","volume":"30","author":"Kolesnick","year":"1991","journal-title":"Progress. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, S., Park, Y., Duraisingham, S., Strobel, F.H., Khan, N., Soltow, Q.A., Jones, D.P., and Pulendran, B. (2013). Predicting network activity from high throughput metabolomics. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003123"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1182\/blood-2006-09-003004","article-title":"The cytoprotective protein C pathway","volume":"109","author":"Mosnier","year":"2007","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Livnat, T., Weinberger, Y., Fernandez, J.A., Bashir, A., Ben-David, G., Palevski, D., Levy-Mendelovich, S., Kenet, G., Budnik, I., and Nisgav, Y. (2021). Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction. Biomolecules, 11.","DOI":"10.3390\/biom11030358"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1182\/blood-2015-02-355974","article-title":"Activated protein C: Biased for translation","volume":"125","author":"Griffin","year":"2015","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1182\/blood-2017-10-810895","article-title":"PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke","volume":"131","author":"Sinha","year":"2018","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1021\/acs.jproteome.5b00576","article-title":"Serum Dyslipidemia Is Induced by Internal Exposure to Strontium-90 in Mice, Lipidomic Profiling Using a Data-Independent Liquid Chromatography-Mass Spectrometry Approach","volume":"14","author":"Goudarzi","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9777","DOI":"10.1038\/s41598-017-10299-w","article-title":"Lipidomic Signatures of Nonhuman Primates with Radiation-Induced Hematopoietic Syndrome","volume":"7","author":"Pannkuk","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41569-021-00536-1","article-title":"Ceramides and other sphingolipids as drivers of cardiovascular disease","volume":"18","author":"Choi","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1002\/1878-0261.13063","article-title":"Sphingolipid metabolism in the development and progression of cancer: One cancer\u2019s help is another\u2019s hindrance","volume":"15","author":"Piazzesi","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5897","DOI":"10.1038\/sj.onc.1206702","article-title":"Radiation and ceramide-induced apoptosis","volume":"22","author":"Kolesnick","year":"2003","journal-title":"Oncogene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:23:25Z","timestamp":1789118605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antiox15091160"],"URL":"https:\/\/doi.org\/10.3390\/antiox15091160","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}