{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:04:13Z","timestamp":1791651853202,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood\u2013brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research.<\/jats:p>","DOI":"10.3390\/jcm14196797","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T06:02:52Z","timestamp":1758866572000},"page":"6797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Fingolimod as a Neuroprotective Agent in Ischemic Stroke: A Review of Preclinical and Clinical Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2079-2383","authenticated-orcid":false,"given":"Alin","family":"Ciubotaru","sequence":"first","affiliation":[{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-0859","authenticated-orcid":false,"given":"Roxana","family":"Covali","sequence":"additional","affiliation":[{"name":"Department of Radiology, Biomedical Engineering Faculty, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Grosu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alexa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esthir Flavia","family":"Pil\u0103","sequence":"additional","affiliation":[{"name":"Department of the Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1441-1751","authenticated-orcid":false,"given":"Andrei Ionu\u021b","family":"Cucu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biological Sciences, University Stefan cel Mare of Suceava, 720229 Suceava, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2874-9227","authenticated-orcid":false,"given":"Amelian Madalin","family":"Bobu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Saint Spiridon Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8765-7426","authenticated-orcid":false,"given":"Gabriela Dumachita","family":"Sargu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Elena Doamna Obstetrics and Gynecology University Hospital, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Riscanu","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela Camelia","family":"Tirnovanu","sequence":"additional","affiliation":[{"name":"Mother and Child Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-3320","authenticated-orcid":false,"given":"Cristina","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Medical Specialties I, Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, Cardiovascular Rehabilitation Clinic, Pantelimon Halipa Street No. 14, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9741","authenticated-orcid":false,"given":"Emilian Bogdan","family":"Ignat","sequence":"additional","affiliation":[{"name":"Department of Neurology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1177\/17474930241307876","article-title":"World Stroke Organization (WSO): Global intracerebral hemorrhage factsheet 2025","volume":"20","author":"Krishnamurthi","year":"2025","journal-title":"Int. J. Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salaudeen, M.A., Bello, N., Danraka, R.N., and Ammani, M.L. (2024). Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones. Biomolecules, 14.","DOI":"10.3390\/biom14030305"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"C135","DOI":"10.1152\/ajpcell.00136.2018","article-title":"Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke","volume":"316","author":"Yang","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1055\/s-0043-1777721","article-title":"Reperfusion therapy for acute ischemic stroke: Where are we in 2023?","volume":"81","author":"Martins","year":"2023","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/2396987317733343","article-title":"Estimating the number of UK stroke patients eligible for endovascular thrombectomy","volume":"2","author":"McMeekin","year":"2017","journal-title":"Eur. Stroke J."},{"key":"ref_6","unstructured":"Anderson, T. (2025, August 01). EVT Effective, But Use for Acute Stroke Still Low in Europe, Medscape Medical News, Available online: https:\/\/www.medscape.com\/viewarticle\/evt-effective-use-acute-stroke-still-low-europe-2025a10001cr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113518","DOI":"10.1016\/j.expneurol.2020.113518","article-title":"Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies","volume":"335","author":"Paul","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1177\/1591019920925677","article-title":"Intra-arterial neuroprotective therapy as an adjunct to endovascular intervention in acute ischemic stroke: A review of the literature and future directions","volume":"26","author":"Link","year":"2020","journal-title":"Interv. Neuroradiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12987-021-00280-1","article-title":"Adjunctive cytoprotective therapies in acute ischemic stroke: A systematic review","volume":"18","author":"Mulder","year":"2021","journal-title":"Fluids Barriers CNS"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhao, M., Wang, J., Liu, G., Li, S., Ding, Y., Ji, X., and Zhao, W. (2024). Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era. Biomolecules, 14.","DOI":"10.3390\/biom14091181"},{"key":"ref_11","first-page":"413","article-title":"Efficacy of fingolimod combined with alteplase in acute ischemic stroke and rehabilitation nursing","volume":"32","author":"Zhang","year":"2019","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00972","DOI":"10.1002\/prp2.972","article-title":"The efficacy and safety of fingolimod plus standardized treatment versus standardized treatment alone for acute ischemic stroke: A systematic review and meta-analysis","volume":"10","author":"Bai","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/ana.25352","article-title":"Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow","volume":"84","author":"Tian","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1161\/CIRCULATIONAHA.115.016371","article-title":"Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial","volume":"132","author":"Zhu","year":"2015","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mizuma, A., and Yenari, M.A. (2017). Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00467"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1161\/STROKEAHA.112.679043","article-title":"Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model","volume":"44","author":"Cai","year":"2013","journal-title":"Stroke"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mazzantini, C., Venturini, M., Lana, D., Mulas, G., Santalmasi, C., Magni, G., Bruni, P., Pugliese, A.M., Cencetti, F., and Pellegrini-Giampietro, D.E. (2025). Dual action of sphingosine 1-phosphate pathway in in vitro models of global cerebral ischemia. Neurobiol. Dis., 208.","DOI":"10.1016\/j.nbd.2025.106865"},{"key":"ref_18","first-page":"101148","article-title":"Global, regional, and national burden of ischemic stroke, 1990\u20132021: An analysis of data from the Global Burden of Disease Study 2021","volume":"58","author":"Li","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12974-025-03492-6","article-title":"IFP35, a novel DAMP, aggravates neuroinflammation following acute ischemic stroke via TLR4\/NF-\u03baB\/NLRP3 signaling","volume":"22","author":"Zhang","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/WCO.0b013e32832b4db3","article-title":"Suppression of inflammation in ischemic and hemorrhagic stroke: Therapeutic options","volume":"22","author":"Kleinig","year":"2009","journal-title":"Curr. Opin. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.4103\/1673-5374.274331","article-title":"Autophagy and inflammation in ischemic stroke","volume":"15","author":"Mo","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e17986","DOI":"10.1016\/j.heliyon.2023.e17986","article-title":"Neuroinflammation and anti-inflammatory therapy for ischemic stroke","volume":"9","author":"Cao","year":"2023","journal-title":"Heliyon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12017-020-08614-2","article-title":"Sphingosine 1-Phosphate Receptors in Cerebral Ischemia","volume":"23","author":"Gaire","year":"2021","journal-title":"Neuromol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lian, Z., Luo, Y., Li, Y., Gao, Y., Xiong, X., and Gu, L. (2025). CD4\u207a T cells in ischemic stroke: Effects and therapeutic targets. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1512634"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neuroscience.2024.02.017","article-title":"New Perspectives in Neuroprotection for Ischemic Stroke","volume":"550","author":"Arias","year":"2024","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.31083\/j.jin2308142","article-title":"Fingolimod Alleviates Inflammation after Cerebral Ischemia via HMGB1\/TLR4\/NF-\u03baB Signaling Pathway","volume":"23","author":"Xing","year":"2024","journal-title":"J. Integr. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12974-021-02083-5","article-title":"The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia","volume":"18","author":"Malone","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2350370","DOI":"10.1002\/eji.202350370","article-title":"The impact of fingolimod on Treg function in brain ischaemia","volume":"53","author":"Malone","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"D\u00edaz D\u00edaz, A.C., Malone, K., Shearer, J.A., Moore, A.C., and Waeber, C. (2022). Preclinical evaluation of fingolimod in rodent models of stroke with age or atherosclerosis as comorbidities. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.920449"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/jmri.27914","article-title":"USPIO-SWI Shows Fingolimod Enhanced Alteplase Action on Angiographic Reperfusion in eMCAO Rats","volume":"55","author":"Fu","year":"2022","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, W., He, T., Jiang, L., Shi, R., Song, Y., Mamtilahun, M., Ma, Y., Zhang, Z., Tang, Y., and Yang, G.Y. (2020). Fingolimod inhibits inflammation but exacerbates brain edema in the acute phases of cerebral ischemia in diabetic mice. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00842"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s12975-020-00789-x","article-title":"FTY720 protects against ischemia-reperfusion injury by preventing the redistribution of tight junction proteins and decreases inflammation in the subacute phase in an experimental stroke model","volume":"11","author":"Wang","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"146509","DOI":"10.1016\/j.brainres.2019.146509","article-title":"Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization","volume":"1726","author":"Shang","year":"2020","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Salas-Perdomo, A., Mir\u00f3-Mur, F., Gallizioli, M., Brait, V.H., Justicia, C., Meissner, A., Urra, X., Chamorro, A., and Planas, A.M. (2019). Role of the S1P pathway and inhibition by fingolimod in preventing hemorrhagic transformation after stroke. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44845-5"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ji, J., Wang, J., Yang, J., Wang, X.P., Huang, J.J., Xue, T.F., and Sun, X.L. (2019). The intra-nuclear SphK2-S1P axis facilitates M1-to-M2 shift of microglia via suppressing HDAC1-mediated KLF4 deacetylation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01241"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, X., Wang, M.H., Qin, C., Fan, W.H., Tian, D.S., and Liu, J.L. (2017). Fingolimod suppresses neuronal autophagy through the mTOR\/p70S6K pathway and alleviates ischemic brain damage in mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188748"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1111\/jcmm.13596","article-title":"S1PR3 is essential for phosphorylated fingolimod to protect astrocytes against oxygen-glucose deprivation-induced neuroinflammation via inhibiting TLR2\/4-NF-\u03baB signalling","volume":"22","author":"Dong","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Herz, J., K\u00f6ster, C., Crasm\u00f6ller, M., Abberger, H., Hansen, W., Felderhoff-M\u00fcser, U., and Bendix, I. (2018). Peripheral T cell depletion by FTY720 exacerbates hypoxic-ischemic brain injury in neonatal mice. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01696"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492659","DOI":"10.1155\/2015\/492659","article-title":"Exogenous S1P exposure potentiates ischemic stroke damage that is reduced possibly by inhibiting S1P receptor signaling","volume":"2015","author":"Moon","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2174\/1567202613666160823152446","article-title":"Fingolimod (FTY720) reduces cortical infarction and neurological deficits during ischemic stroke through potential maintenance of microvascular patency","volume":"13","author":"Schuhmann","year":"2016","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.brainresbull.2016.04.004","article-title":"Fingolimod (FTY720) improves hippocampal synaptic plasticity and memory deficit in rats following focal cerebral ischemia","volume":"124","author":"Nazari","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18315","DOI":"10.1073\/pnas.1416166111","article-title":"Impact of an immune modulator fingolimod on acute ischemic stroke","volume":"111","author":"Fu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","unstructured":"(2025, August 01). Fingolimod in Endovascular Treatment of Ischemic Stroke. Available online: https:\/\/trial.medpath.com\/clinical-trial\/ce240e9813f079f0\/nct04629872-combinating-fingolimod-endovascular-treatment-acute-ischemic-stroke."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1177\/1747493017710340","article-title":"Rationale and Design of Combination of an Immune Modulator Fingolimod with Alteplase Bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) Trial","volume":"12","author":"Zhang","year":"2017","journal-title":"Int. J. Stroke"},{"key":"ref_45","first-page":"123","article-title":"The potential capacities of FTY720: Novel therapeutic functions, targets, and mechanisms against diseases","volume":"103","author":"Liu","year":"2025","journal-title":"J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2101526","DOI":"10.1002\/advs.202101526","article-title":"Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke","volume":"8","author":"Li","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2311803","DOI":"10.1002\/adma.202311803","article-title":"Neutrophil Membrane-Camouflaged Polyprodrug Nanomedicine for Inflammation Suppression in Ischemic Stroke Therapy","volume":"36","author":"Zhao","year":"2024","journal-title":"Adv. Mater"},{"key":"ref_48","first-page":"753","article-title":"Modular assembled biomimetic nanobubbles for synergistic therapy of ischemic stroke via cascade modulation of thrombo-inflammatory network","volume":"52","author":"Qin","year":"2025","journal-title":"Bioact. Mater."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/6797\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T12:55:36Z","timestamp":1759841736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/6797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":48,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcm14196797"],"URL":"https:\/\/doi.org\/10.3390\/jcm14196797","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]}}}