{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:00:25Z","timestamp":1771261225703,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["16K08395"],"award-info":[{"award-number":["16K08395"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin (cis-diamminedichloro-platinum; CDDP) is a chemotherapeutic agent that frequently induces peripheral neuropathy characterized by mechanical allodynia. Herein, we aimed to determine the effects of valproic acid (VPA) on cisplatin-induced mechanical allodynia in rats and elucidate the underlying mechanisms. A single administration of VPA (150 mg\/kg) transiently suppressed CDDP-induced mechanical allodynia, correlating with serum VPA concentrations. Repeated VPA administration before or after the onset of CDDP-induced mechanical allodynia significantly attenuated allodynia even after VPA discontinuation, suggesting fundamental treatment potential. Mechanistically, CDDP increased the expression of neurokinin 1 receptor (NK1R) mRNA in the dorsal horn of the spinal cord, and this increased expression was suppressed by repeated VPA administration. Treatment with an NK1R antagonist alleviated CDDP-induced mechanical allodynia, indicating the involvement of NK1R in allodynia. In vitro assays revealed that VPA did not affect the cytotoxicity of CDDP in Walker 256 cells, suggesting that VPA does not interfere with the antitumor activity of CDDP. Overall, repeated VPA administration may fundamentally ameliorate CDDP-induced peripheral neuropathy by suppressing the CDDP-induced increased NK1R expression without compromising the antitumor effects of CDDP. These findings provide insights into the potential use of VPA as a therapeutic agent for managing CDDP-induced peripheral neuropathy.<\/jats:p>","DOI":"10.3390\/ijms26114977","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T07:04:28Z","timestamp":1747897468000},"page":"4977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repeated Valproic Acid Administration Fundamentally Ameliorated Cisplatin-Induced Mechanical Allodynia in Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Yoshihiro","family":"Seto","sequence":"first","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Ohara","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Tachi","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Tomonari","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-4331","authenticated-orcid":false,"given":"Daisuke","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiyasu","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"},{"name":"Department of Drug Analysis, Daiichi University of Pharmacy, Fukuoka 815-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7967-2947","authenticated-orcid":false,"given":"Yasuhiro","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacometrics, School of Pharmacy, Nihon University, Chiba 274-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideto","family":"To","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5242","DOI":"10.1200\/JCO.23.00179","article-title":"Five-Year Overall Survival Analysis of the JIPANG Study: Pemetrexed or Vinorelbine Plus Cisplatin for Resected Stage II-IIIA Nonsquamous Non-Small-Cell Lung Cancer","volume":"41","author":"Kenmotsu","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1056\/NEJMoa0802656","article-title":"Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer","volume":"359","author":"Vermorken","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1056\/NEJMoa052985","article-title":"Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer","volume":"354","author":"Armstrong","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1200\/JCO.2012.46.2408","article-title":"Randomized Phase II Study of the Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Cetuximab with Cisplatin versus Cisplatin Alone in Patients with Metastatic Triple-Negative Breast Cancer","volume":"31","author":"Baselga","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1634\/theoncologist.2014-0044","article-title":"Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future","volume":"20","author":"Avan","year":"2015","journal-title":"Oncologist"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0162-0134(99)00135-X","article-title":"Platinum Neurotoxicity: Clinical Profiles, Experimental Models and Neuroprotective Approaches","volume":"77","author":"Screnci","year":"1999","journal-title":"J. Inorg. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s00520-013-2075-1","article-title":"Oral Alpha-Lipoic Acid to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"22","author":"Guo","year":"2014","journal-title":"Support. Care Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1212\/WNL.0b013e31822e045c","article-title":"Retinoic Acid Reduces Chemotherapy-Induced Neuropathy in an Animal Model and Patients with Lung Cancer","volume":"77","author":"Arrieta","year":"2011","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, L., Nan, G., Kim, H.Y., Cha, M., and Lee, B.H. (2024). Modulation of Chemotherapy-Induced Peripheral Neuropathy by JZL195 through Glia and the Endocannabinoid System. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.117515"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1124\/jpet.124.002165","article-title":"Chronic Administration of Cannabinoid Agonists ACEA (CB1), AM1241 (CB2), and CP55940 (Mixed CB1\/CB2) Induce Sex-Specific Differences in Tolerance and Sex Hormone Changes in a Chemotherapy-Induced Peripheral Neuropathy","volume":"391","author":"Barnes","year":"2024","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Seddiek, H., Hanna, M., Hamoud, A.E.M., Elbaset, M.A., Akabawy, A.M.A., Kotb, M.Z., and Khalifa, M.M. (2025). Deferiprone Ameliorates Cisplatin Induced Peripheral Neurotoxicity via Ferritinophagy Adjustment. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-87628-x"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1158\/1535-7163.MCT-08-0840","article-title":"Platinum Neurotoxicity Pharmacogenetics","volume":"8","author":"McWhinney","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/1097-0142(19920101)69:1<203::AID-CNCR2820690133>3.0.CO;2-1","article-title":"Cisplatin-Induced Peripheral Neurotoxicity Is Dependent on TotaI-Dose Intensity and Single-Dose Intensity","volume":"69","author":"Cavaletti","year":"1992","journal-title":"Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/BF00694340","article-title":"Progressive Paresthesias after Cessation of Therapy with Very High-Dose Cisplatin","volume":"25","author":"Grunberg","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1007\/s00520-010-1018-3","article-title":"The Use of Vitamin E for the Prevention of Chemotherapy-Induced Peripheral Neuropathy: Results of a Randomized Phase III Clinical Trial","volume":"19","author":"Kottschade","year":"2011","journal-title":"Support. Care Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1002\/cncr.23482","article-title":"Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial, N01C3","volume":"112","author":"Rao","year":"2008","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00228-025-03807-9","article-title":"Adjunctive Treatment for Pediatric Focal Epilepsy: A Systematic Review","volume":"81","author":"Wang","year":"2025","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/s41380-021-01334-4","article-title":"Pharmacological Treatment for Bipolar Mania: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials","volume":"27","author":"Kishi","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s11910-024-01361-y","article-title":"Migraine Management in Medically Complex Patients: A Narrative Review","volume":"24","author":"Hird","year":"2024","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/bph.12366","article-title":"HDAC Inhibitors Restore C-Fibre Sensitivity in Experimental Neuropathic Pain Model","volume":"170","author":"Matsushita","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.intimp.2019.01.050","article-title":"Inhibitory Effect of Valproate Sodium on Pain Behavior in Diabetic Mice Involves Suppression of Spinal Histone Deacetylase 1 and Inflammatory Mediators","volume":"70","author":"Elsherbiny","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","first-page":"20","article-title":"The Involvement of Taurine in the Action Mechanism of Sodium Valproate (VPA) in the Treatment of Epilspey","volume":"43","author":"Anyanwu","year":"1993","journal-title":"Acta Physiol. Pharmacol. Ther. Latinoam."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neulet.2014.12.054","article-title":"Valproic Acid Prevents Retinal Degeneration in a Murine Model of Normal Tension Glaucoma","volume":"588","author":"Kimura","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.biopha.2017.11.066","article-title":"Valproic Acid Attenuates Inflammation of Optic Nerve and Apoptosis of Retinal Ganglion Cells in a Rat Model of Optic Neuritis","volume":"96","author":"Liu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s12035-020-02126-7","article-title":"HDAC1 Expression, Histone Deacetylation, and Protective Role of Sodium Valproate in the Rat Dorsal Root Ganglia After Sciatic Nerve Transection","volume":"58","author":"Dzreyan","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Biso, L., Carli, M., Kolachalam, S., Monticelli, G., Calabr\u00f2, P.F., di Paolo, A., Giorgi, F.S., Bocci, G., and Scarselli, M. (2023). A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center. Pharmaceuticals, 16.","DOI":"10.3390\/ph16070945"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"442","DOI":"10.2165\/00003088-199529060-00005","article-title":"Therapeutic Drug Monitoring for the Treatment of Psychiatric Disorders: Clinical Use and Cost Effectiveness","volume":"29","author":"Eilers","year":"1995","journal-title":"Clin. Pharmacokinet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.neuron.2024.11.021","article-title":"Tachykinin Signaling in the Right Parabrachial Nucleus Mediates Early-Phase Neuropathic Pain Development","volume":"113","author":"Li","year":"2025","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, J.Y., Zhang, J.L., Chen, S.P., Gao, Y.H., Zhang, J.L., Chen, Y., Zhang, Y., Rong, P.J., and Liu, J.L. (2022). Electroacupuncture Relieves Hyperalgesia by Regulating Neuronal-Glial Interaction and Glutamate Transporters of Spinal Dorsal Horns in Rats with Acute Incisional Neck Pain. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.885107"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/BF00839140","article-title":"Cisplatin Neuropathy: Clinical Course and Neurophysiological Findings","volume":"239","author":"LoMonaco","year":"1992","journal-title":"J. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.phrs.2016.11.030","article-title":"Sec-Butylpropylacetamide (SPD), a New Amide Derivative of Valproic Acid for the Treatment of Neuropathic and Inflammatory Pain","volume":"117","author":"Kaufmann","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_32","first-page":"335","article-title":"Valproate Protective Effects on Cisplatin-Induced Peripheral Neuropathy: An in Vitro and in Vivo Study","volume":"28","author":"Gilardini","year":"2008","journal-title":"Anticancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2174\/156800908784533508","article-title":"Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors: Two Birds with One Stone?","volume":"8","author":"Tremolizzo","year":"2008","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"176067","DOI":"10.1016\/j.ejphar.2023.176067","article-title":"Novel HDAC inhibitors provide neuroprotection in MPTP-induced Parkinson\u2019s disease model of rats","volume":"959","author":"Meka","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100409","DOI":"10.1016\/j.dmpk.2021.100409","article-title":"Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and folate metabolism-related genes in the placenta of rats","volume":"40","author":"Furugen","year":"2021","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Seto, Y., Okazaki, F., Horikawa, K., Zhang, J., Sasaki, H., and To, H. (2016). Influence of Dosing Times on Cisplatin-Induced Peripheral Neuropathy in Rats. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2777-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107598","DOI":"10.1016\/j.neuropharm.2019.04.004","article-title":"The Bivalent Ligand MCC22 Potently Attenuates Hyperalgesia in a Mouse Model of Cisplatin-Evoked Neuropathic Pain without Tolerance or Reward","volume":"158","author":"Cataldo","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2017.10.011","article-title":"Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Dependent Microglial Activation Promotes Cisplatin-Induced Peripheral Neuropathy in Mice","volume":"68","author":"Hu","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and Central Sensitization in Chronic and Widespread Pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8S","DOI":"10.1097\/PRS.0000000000000682","article-title":"Pathophysiology of Pain: A Practical Primer","volume":"134","author":"Fong","year":"2014","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1046\/j.1471-4159.2003.01802.x","article-title":"Valproic Acid Inhibits Substance P-Induced Activation of Protein Kinase C Epsilon and Expression of the Substance P Receptor","volume":"86","author":"Lieb","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.npep.2005.10.007","article-title":"Changes in Tracheo-Bronchial Sensory Neuropeptide Receptor Gene Expression Pattern in Rats with Cisplatin-Induced Sensory Neuropathy","volume":"40","author":"Peitl","year":"2006","journal-title":"Neuropeptides"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zacky Ariffin, M., Yun Ng, S., Nadia, H., Koh, D., Loh, N., Michiko, N., and Khanna, S. (2024). Neurokinin1\u2014Cholinergic Receptor Mechanisms in the Medial Septum-Dorsal Hippocampus Axis Mediates Experimental Neuropathic Pain. Neurobiol. Pain., 16.","DOI":"10.1016\/j.ynpai.2024.100162"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1200\/JCO.2007.13.5251","article-title":"Use of Calcium and Magnesium Salts to Reduce Oxaliplatin-Related Neurotoxicity","volume":"25","author":"Hochster","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e000195","DOI":"10.1136\/jitc-2019-000195","article-title":"Histone Deacetylase Inhibitors Valproic Acid and Vorinostat Enhance Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Phagocytosis","volume":"8","author":"Laengle","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nevi, L., Pollanen, N., Penna, F., and Caretti, G. (2023). Targeting Epigenetic Regulators with HDAC and BET Inhibitors to Modulate Muscle Wasting. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216404"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Du, Y., He, C., An, Y., Huang, Y., Zhang, H., Fu, W., Wang, M., Shan, Z., Xie, J., and Yang, Y. (2024). The Role of Short Chain Fatty Acids in Inflammation and Body Health. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137379"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hatamnejad, M.R., Medzikovic, L., Dehghanitafti, A., Rahman, B., Vadgama, A., and Eghbali, M. (2025). Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052242"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/jat.727","article-title":"European Federation of Pharmaceutical Industries A, European Centre for the Validation of Alternative M. A good practice guide to the administration of substances and removal of blood, including routes and volumes","volume":"21","author":"Diehl","year":"2001","journal-title":"J. Appl. Toxicol."},{"key":"ref_50","first-page":"378","article-title":"HPLC Determination of Valproic Acid in Human Serum","volume":"58","author":"Kishore","year":"2003","journal-title":"Pharmazie"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"175519","DOI":"10.1016\/j.ejphar.2023.175519","article-title":"Time Dependent Cisplatin Dosing Differences on Hypoalgesia Focusing on Oxidative Stress","volume":"942","author":"Seto","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jphs.2017.06.003","article-title":"Pregabalin Reduces Cisplatin-Induced Mechanical Allodynia in Rats","volume":"134","author":"Seto","year":"2017","journal-title":"J. Pharmacol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4977\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:15Z","timestamp":1760031495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26114977"],"URL":"https:\/\/doi.org\/10.3390\/ijms26114977","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}