{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:49:55Z","timestamp":1761130195518,"version":"3.41.2"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Blood proteomics offers a powerful approach for identifying disease-specific biomarkers. However, no reliable blood markers are currently available for the diagnosis stroke. Nervonic acid (NA), a vital long-chain monounsaturated fatty acid found in mammalian nervous tissue, shows promising therapeutic potential in neurological disorders. This study aimed to develop a reliable methodology for whole blood proteomics to identify early warning biomarkers and evaluate drug treatment efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After modeling via the classic thread embolization method, whole blood samples were collected from the rats. Morphological assessments of brain tissue indicated that NA significantly mitigated brain and neuronal damage in rats. The differential protein expression profile was analyzed using Liquid Chromatography\u2014Tandem Mass Spectrometry (LC-MS\/MS) whole blood proteomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene Ontology (GO) analysis revealed that, compared to ginkgo biloba extract (EGb), the proteins differentially expressed under NA intervention were predominantly involved in oxidative stress response and calcium-dependent adhesion processes. Key targets of NA in the treatment of middle cerebral artery occlusion (MCAO) models included ENO1, STAT3, NME2, VCL, and CCT3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This whole blood proteomic approach provides a comprehensive understanding of protein profiles associated with disease states, offering valuable insights into potential therapeutic targets and enabling the evaluation of NA and EGb intervention efficacy. Our findings underscore the protective effects of NA against cerebral ischemia-reperfusion injury and highlight its potential as a treatment for stroke.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1546073","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:43:54Z","timestamp":1738046634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic analysis of whole blood to investigate the therapeutic effects of nervonic acid on cerebral ischemia-reperfusion injury in rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Qingqing","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengrong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e30219","DOI":"10.1371\/journal.pone.0030219","article-title":"Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion","volume":"7","author":"Brentnall","year":"2012","journal-title":"Public Libr. Sci. One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"115930","DOI":"10.1016\/j.jpba.2023.115930","article-title":"UPLC-Q-TOF\/MS based serum and urine metabolomics strategy to analyze the mechanism of nervonic acid in treating Alzheimer\u2019s disease","volume":"240","author":"Chen","year":"","journal-title":"J. Pharm. Biomed. Analysis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"115930","DOI":"10.1016\/j.jpba.2023.115930","article-title":"UPLC-Q-TOF\/MS based serum and urine metabolomics strategy to analyze the mechanism of nervonic acid in treating Alzheimer\u2019s disease","volume":"240","author":"Chen","year":"","journal-title":"J. Pharm. Biomed. Analysis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41582-021-00605-6","article-title":"Pharmacological brain cytoprotection in acute ischaemic stroke \u2014 renewed hope in the reperfusion era","volume":"18","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13223-019-0382-x","article-title":"Whole blood vs PBMC: compartmental differences in gene expression profiling exemplified in asthma","volume":"15","author":"He","year":"2019","journal-title":"Allergy, Asthma and Clin. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1161\/CIRCRESAHA.122.320110","article-title":"Stroke proteomics: from discovery to diagnostic and therapeutic applications","volume":"130","author":"Hochrainer","year":"2022","journal-title":"Circulation Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5821","DOI":"10.1002\/ptr.7988","article-title":"Ginkgo biloba extract promotes Treg differentiation to ameliorate ischemic stroke via inhibition of HIF-1\u03b1\/HK2 pathway","volume":"37","author":"Hui","year":"2023","journal-title":"Phytotherapy Res."},{"key":"B8","first-page":"684","article-title":"Chinese guideline for endovascular treatment of acute ischemic stroke 2023","volume":"18","author":"Huo","year":"2023","journal-title":"Chin. J. Stroke"},{"key":"B9","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1002\/glia.22953","article-title":"Traumatically injured astrocytes release a proteomic signature modulated by STAT3-dependent cell survival","volume":"64","author":"Levine","year":"2016","journal-title":"Glia"},{"key":"B10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12943-015-0320-6","article-title":"Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up-regulation of N-myc downstream regulated gene 2","volume":"14","author":"Li","year":"2015","journal-title":"Mol. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"125286","DOI":"10.1016\/j.foodchem.2019.125286","article-title":"A mini review of nervonic acid: source, production, and biological functions","volume":"301","author":"Li","year":"2019","journal-title":"Food Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e20149","DOI":"10.1016\/j.heliyon.2023.e20149","article-title":"Angong niuhuang wan attenuates LPS-induced acute lung injury by inhibiting PIK3CG\/p65\/MMP9 signaling in mice based on proteomics","volume":"9","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"B13","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s12192-019-00977-1","article-title":"Antioxidant effects of ginkgolides and bilobalide against cerebral ischemia injury by activating the Akt\/Nrf2 pathway in vitro and in vivo","volume":"24","author":"Liu","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"B14","doi-asserted-by":"publisher","first-page":"112362","DOI":"10.1016\/j.jep.2019.112362","article-title":"In-depth transcriptomic and proteomic analyses of the hippocampus and cortex in a rat model after cerebral ischemic injury and repair by Shuxuetong (SXT) injection","volume":"249","author":"Liu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1161\/01.str.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"B16","doi-asserted-by":"publisher","first-page":"150696","DOI":"10.1016\/j.bbrc.2024.150696","article-title":"Nervonic acid improves depression like behaviors and demyelination of medial prefrontal cortex in chronic restraint stress mice","volume":"733","author":"Ma","year":"2024","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"713124","DOI":"10.3389\/fneur.2021.713124","article-title":"Proteomics-based approach to identify novel blood biomarker candidates for differentiating intracerebral hemorrhage from ischemic stroke-A pilot study","volume":"12","author":"Malicek","year":"2021","journal-title":"Front. Neurology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1161\/CIRCULATIONAHA.121.058615","article-title":"Targeting of scavenger receptors stabilin-1 and stabilin-2 ameliorates atherosclerosis by a plasma proteome switch mediating monocyte\/macrophage suppression","volume":"146","author":"Manta","year":"2022","journal-title":"Circulation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"12888","DOI":"10.3390\/ijms222312888","article-title":"Effect of 2-cys peroxiredoxins inhibition on redox modifications of bull sperm proteins","volume":"22","author":"Mostek-Majewska","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"12888","DOI":"10.3390\/ijms222312888","article-title":"Effect of 2-cys peroxiredoxins inhibition on redox modifications of bull sperm proteins","volume":"22","author":"Mostek-Majewska","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1161\/STROKEAHA.122.038466","article-title":"Clinically ineffective reperfusion after endovascular therapy in acute ischemic stroke","volume":"54","author":"Nie","year":"2023","journal-title":"Stroke"},{"key":"B22","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1007\/s13311-019-00720-9","article-title":"High-throughput profiling of circulating antibody signatures for stroke diagnosis using small volumes of whole blood","volume":"16","author":"O\u2019Connell","year":"2019","journal-title":"Neurotherapeutics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1152\/japplphysiol.91415.2008","article-title":"Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells","volume":"106","author":"Ou","year":"2009","journal-title":"J. Appl. Physiology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.3390\/biom14091130","article-title":"The influence of oxidative stress markers in patients with ischemic stroke","volume":"14","author":"Pawluk","year":"2024","journal-title":"Biomolecules"},{"key":"B25","doi-asserted-by":"publisher","first-page":"932383","DOI":"10.3389\/fimmu.2022.932383","article-title":"Natural fish oil improves the differentiation and maturation of oligodendrocyte precursor cells to oligodendrocytes in vitro after interaction with the blood\u2013brain barrier","volume":"13","author":"Piatek","year":"2022","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/s41419-021-04234-1","article-title":"Requirement of transcription factor NME2 for the maintenance of the stemness of gastric cancer stem-like cells","volume":"12","author":"Qi","year":"2021","journal-title":"Cell Death Dis."},{"key":"B27","first-page":"272","volume":"17","year":"2020","journal-title":"Chin. J. Cerebrovasc. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1161\/STROKEAHA.117.017283","article-title":"Reconsidering neuroprotection in the reperfusion era","volume":"48","author":"Savitz","year":"2017","journal-title":"Stroke"},{"key":"B29","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/ana.21127","article-title":"Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials","volume":"61","author":"Savitz","year":"2007","journal-title":"Ann. Neurology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1476-4598-13-65","article-title":"Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma","volume":"13","author":"Song","year":"2014","journal-title":"Mol. Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"542976","DOI":"10.1155\/2012\/542976","article-title":"Hypoxic-ischemic injury in the developing brain: the role of reactive oxygen species originating in mitochondria","volume":"2012","author":"Ten","year":"2012","journal-title":"Neurological Res. Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"14450","DOI":"10.1038\/s41598-023-41766-2","article-title":"Proteome profiling of hippocampus reveals the neuroprotective effect of mild hypothermia on global cerebral ischemia-reperfusion injury in rats","volume":"13","author":"Wang","year":"","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"154911","DOI":"10.1016\/j.phymed.2023.154911","article-title":"Nervonic acid improves liver inflammation in a mouse model of Parkinson\u2019s disease by inhibiting proinflammatory signaling pathways and regulating metabolic pathways","volume":"117","author":"Wang","year":"","journal-title":"Phytomedicine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fnmol.2020.00028","article-title":"Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury","volume":"13","author":"Wu","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"154845","DOI":"10.1016\/j.phymed.2023.154845","article-title":"Calycosin alleviates cerebral ischemia\/reperfusion injury by repressing autophagy via STAT3\/FOXO3a signaling pathway","volume":"115","author":"Xu","year":"2023","journal-title":"Phytomedicine"},{"key":"B36","doi-asserted-by":"publisher","first-page":"116230","DOI":"10.1016\/j.biopha.2024.116230","article-title":"Natural compounds efficacy in Ophthalmic Diseases: a new twist impacting ferroptosis","volume":"172","author":"Yuan","year":"2024","journal-title":"Biomed. and Pharmacother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"154934","DOI":"10.1016\/j.phymed.2023.154934","article-title":"Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia\/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology","volume":"118","author":"Yuan","year":"2023","journal-title":"Phytomedicine"},{"key":"B38","doi-asserted-by":"publisher","first-page":"578101","DOI":"10.1016\/j.jneuroim.2023.578101","article-title":"Ginkgo biloba extract (EGb-761) confers neuroprotection against ischemic stroke by augmenting autophagic\/lysosomal signaling pathway","volume":"382","author":"Zang","year":"2023","journal-title":"J. Neuroimmunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1114663","DOI":"10.3389\/fimmu.2023.1114663","article-title":"Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model","volume":"14","author":"Zeng","year":"2023","journal-title":"Front. Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"00371","DOI":"10.1016\/j.jare.2024.08.028","article-title":"Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3\/IL-1\u03b2 pathway","author":"Zeng","year":"2024","journal-title":"J. Adv. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10571-024-01483-4","article-title":"Urine proteomic signatures of mild hypothermia treatment in cerebral ischemia\u2013reperfusion injury in rats","volume":"44","author":"Zhang","year":"","journal-title":"Cell Mol. Neurobiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.hlife.2024.08.001","article-title":"Nervonic acid alleviates stroke and its associated poststroke depression behaviors","volume":"2","author":"Zhang","year":"","journal-title":"hLife"},{"key":"B43","doi-asserted-by":"publisher","first-page":"118791","DOI":"10.1016\/j.jep.2024.118791","article-title":"Bailixiang tea, an herbal medicine formula, co-suppresses TLR2\/MAPK8 and TLR2\/NF-\u03baB signaling pathways to protect against LPS-triggered cytokine storm in mice","volume":"337","author":"Zhang","year":"","journal-title":"J. Ethnopharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.19540\/j.cnki.cjcmm.20240815.601","article-title":"Progress in the study of proteomics in the prevention and treatment of heart failure and myocardial infarction diseases in traditional Chinese medicine","author":"Zhang","year":"","journal-title":"China J. Chin. Materia medica"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2300671","DOI":"10.1002\/mnfr.202300671","article-title":"Dietary supplementation with nervonic acid ameliorates cerebral ischemia-reperfusion injury by modulating of gut microbiota composition-fecal metabolites interaction","volume":"68","author":"Zhou","year":"","journal-title":"Mol. Nutr. and Food Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1016\/j.cmet.2024.05.016","article-title":"Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation","volume":"36","author":"Zhou","year":"","journal-title":"Cell Metab."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1546073\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:21:59Z","timestamp":1748337719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1546073\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":46,"alternative-id":["10.3389\/fcell.2025.1546073"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1546073","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"article-number":"1546073"}}