{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:24:26Z","timestamp":1776273866196,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T00:00:00Z","timestamp":1658534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood\u2013brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2\u2019,7\u2019-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax\/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 \u00b5M group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1\/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.<\/jats:p>","DOI":"10.3390\/jpm12081202","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"1202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress"],"prefix":"10.3390","volume":"12","author":[{"given":"Amogh","family":"Auti","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-2130","authenticated-orcid":false,"given":"Nicola","family":"Alessio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-3457","authenticated-orcid":false,"given":"Mario","family":"Dioguardi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-2521","authenticated-orcid":false,"given":"Stefania","family":"Cantore","sequence":"additional","affiliation":[{"name":"Independent Researcher, 70129 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-2489","authenticated-orcid":false,"given":"Salvatore","family":"Scacco","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari ALDO MORO, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Vitiello","sequence":"additional","affiliation":[{"name":"Pharmaceutical Department, Local Sanitary Unit Umbria 1, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucio","family":"Quagliuolo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-8124","authenticated-orcid":false,"given":"Luigi","family":"Santacroce","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Interdisciplinary Medicine, School of Medicine, University of Bari ALDO MORO, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122-6078, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6989-010X","authenticated-orcid":false,"given":"Mariarosaria","family":"Boccellino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative Stress and Antioxidant Defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3389\/fendo.2019.00540","article-title":"The Role of Oxidative Stress and Hormones in Controlling Obesity","volume":"10","author":"Pinto","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9345","DOI":"10.1002\/jcp.26427","article-title":"Effect of restriction vegan diet\u2019s on muscle mass, oxidative status, and myocytes differentiation: A pilot study","volume":"233","author":"Vanacore","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_4","first-page":"405","article-title":"Epigenetic Changes Induced by Green Tea Catechins are Associated with Prostate Cancer","volume":"17","author":"Giudice","year":"2017","journal-title":"Curr. Mol. Med."},{"key":"ref_5","first-page":"299","article-title":"Vascular endothelial growth factor: An important molecular target of curcumin","volume":"59","author":"Katsiki","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative Stress and the Central Nervous System","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1007\/s12035-015-9337-5","article-title":"Oxidative Stress in Neurodegenerative Diseases","volume":"53","author":"Niedzielska","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.brainresrev.2009.09.006","article-title":"The role and regulation of hypoxia-inducible factor-1\u03b1 expression in brain development and neonatal hypoxic\u2013ischemic brain injury","volume":"62","author":"Fan","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nrd1199","article-title":"HIF-1 as a target for drug development","volume":"2","author":"Giaccia","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.freeradbiomed.2013.01.026","article-title":"Hypoxia-inducible factor prolyl hydroxylases as targets for neuroprotection by \u201cantioxidant\u201d metal chelators: From ferroptosis to stroke","volume":"62","author":"Speer","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.brainres.2008.06.074","article-title":"Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical neurons","volume":"1229","author":"Patel","year":"2008","journal-title":"Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/j.1474-9726.2012.00870.x","article-title":"Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response","volume":"11","author":"Jurk","year":"2012","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.toxlet.2017.07.895","article-title":"PKA activity exacerbates hypoxia-induced ROS formation and hypoxic injury in PC-12 cells","volume":"279","author":"Gozal","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.2174\/0929867328666210810154732","article-title":"Another look at dietary polyphenols: Challenges in cancer prevention and treatment","volume":"29","author":"Arrigoni","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ballini, A., Scacco, S., Boccellino, M., Santacroce, L., and Arrigoni, R. (2020). Microbiota and Obesity: Where Are We Now?. Biology, 9.","DOI":"10.3390\/biology9120415"},{"key":"ref_16","first-page":"8835813","article-title":"Antioxidant Effect of Beer Polyphenols and Their Bioavailability in Dental-Derived Stem Cells (D-dSCs) and Human Intestinal Epithelial Lines (Caco-2) Cells","volume":"2020","author":"Feola","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Crocetto, F., Boccellino, M., Barone, B., Di Zazzo, E., Sciarra, A., Galasso, G., Settembre, G., Quagliuolo, L., Imbimbo, C., and Boffo, S. (2020). The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?. Nutrients, 12.","DOI":"10.3390\/nu12092648"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6813","DOI":"10.1002\/jcb.26905","article-title":"The enigmatic role of matrix metalloproteinases in epithelial-to-mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects","volume":"120","author":"Ricci","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s12031-021-01922-7","article-title":"Emerging Novel Approaches for the Enhanced Delivery of Natural Products for the Management of Neurodegenerative Diseases","volume":"72","author":"Bandiwadekar","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/15734064113096660053","article-title":"Chemistry, Stability and Bioavailability of Resveratrol","volume":"10","author":"Franciosoa","year":"2014","journal-title":"Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Boccellino, M., and D\u2019Angelo, S. (2020). Anti-Obesity Effects of Polyphenol Intake: Current Status and Future Possibilities. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165642"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ejmech.2019.07.033","article-title":"Protective effect of piceatannol and bioactive stilbene derivatives against hypoxia-induced toxicity in H9c2 cardiomyocytes and structural elucidation as 5-LOX inhibitors","volume":"180","author":"Boccellino","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1089\/jmf.2012.0076","article-title":"Effect of Annurca Apple Polyphenols on Human HaCaT Keratinocytes Proliferation","volume":"15","author":"Napolitano","year":"2012","journal-title":"J. Med. Food"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.2174\/138527210792927654","article-title":"Bioavailability and Recent Advances in the Bioactivity of Flavonoid and Stilbene Compounds","volume":"14","author":"Lim","year":"2010","journal-title":"Curr. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.201200589","article-title":"Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans","volume":"58","author":"Cottart","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1007\/s12031-014-0441-1","article-title":"Resveratrol Attenuates the Blood-Brain Barrier Dysfunction by Regulation of the MMP-9\/TIMP-1 Balance after Cerebral Ischemia Reperfusion in Rats","volume":"55","author":"Wei","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s12035-010-8111-y","article-title":"Resveratrol as a therapeutic agent for neurodegenerative diseases","volume":"41","author":"Sun","year":"2010","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.nut.2015.08.017","article-title":"Beneficial action of resveratrol: How and why?","volume":"32","author":"Repossi","year":"2016","journal-title":"Nutrition"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6874146","DOI":"10.1155\/2021\/6874146","article-title":"H9c2 Cardiomyocytes under Hypoxic Stress: Biological Effects Mediated by Sentinel Downstream Targets","volume":"2021","author":"Boccellino","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Boccellino, M., Di Domenico, M., Donniacuo, M., Bitti, G., Gritti, G., Ambrosio, P., Quagliuolo, L., and Rinaldi, B. (2018). AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202297"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/jcp.24548","article-title":"Definition of novel electrochemotherapy parameters and validation of their in vitro and in vivo effectiveness","volume":"229","author":"Spugnini","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10495-012-0771-9","article-title":"Peritoneal dialysis fluid activates calcium signaling and apoptosis in mesothelial cells","volume":"18","author":"Boccellino","year":"2013","journal-title":"Apoptosis"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Aprile, D., Alessio, N., Demirsoy, I.H., Squillaro, T., Peluso, G., Di Bernardo, G., and Galderisi, U. (2021). MUSE Stem Cells Can Be Isolated from Stromal Compartment of Mouse Bone Marrow, Adipose Tissue, and Ear Connective Tissue: A Comparative Study of Their In Vitro Properties. Cells, 10.","DOI":"10.3390\/cells10040761"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/15384101.2016.1175798","article-title":"Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: Hints for side effects following radiotherapy","volume":"16","author":"Alessio","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0002-9440(10)62367-X","article-title":"Platelet-activating factor regulates cadherin-catenin adhesion system expression and beta-catenin phosphorylation during Kaposi\u2019s sarcoma cell motility","volume":"166","author":"Boccellino","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/mc.20322","article-title":"3-O-methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating alphavbeta5 integrin and inhibiting metalloproteinase-9 secretion","volume":"46","author":"Buommino","year":"2007","journal-title":"Mol. Carcinog."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/carcin\/24.3.535","article-title":"Styrene-7,8-oxide activates a complex apoptotic response in neuronal PC12 cell line","volume":"24","author":"Boccellino","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbrc.2007.12.138","article-title":"Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD","volume":"367","author":"Robb","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Quoc Trung, L., Espinoza, J.L., Takami, A., and Nakao, S. (2013). Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2\/STAT3 pathway inhibition. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055183"},{"key":"ref_40","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1204\u20131222."},{"key":"ref_41","unstructured":"GBD 2016 Causes of Death Collaborators (2017). Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet, 390, 1151\u20131210."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1750-3639.2004.tb00085.x","article-title":"Ischemia leads to apoptosis-and necrosis-like neuron death in the ischemic rat hippocampus","volume":"14","author":"Stadelmann","year":"2004","journal-title":"Brain Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1212\/WNL.50.3.599","article-title":"Factors determining the therapeutic window for stroke","volume":"50","author":"Zivin","year":"1998","journal-title":"Neurology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s13346-011-0046-y","article-title":"Advances in stroke therapy","volume":"1","author":"Jaffer","year":"2011","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/jemt.23171","article-title":"Resveratrol treatment of spinal cord injury in rat model","volume":"82","author":"Liu","year":"2019","journal-title":"Microsc. Res. Tech."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neuroscience.2017.02.027","article-title":"Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1\/AMPK signaling pathway","volume":"348","author":"Zhao","year":"2017","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1152\/jn.00510.2016","article-title":"Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice","volume":"116","author":"Wang","year":"2016","journal-title":"J. Neurophysiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mukandala, G., Tynan, R., Lanigan, S., and O\u2019Connor, J.J. (2016). The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. Brain Sci., 6.","DOI":"10.3390\/brainsci6010006"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1177\/0963689718780930","article-title":"Resveratrol Treatment in Different Time-Attenuated Neuronal Apoptosis After Oxygen and Glucose Deprivation\/Reoxygenation via Enhancing the Activation of Nrf-2 Signaling Pathway In Vitro","volume":"27","author":"Yang","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4103\/0976-9668.71667","article-title":"Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe","volume":"1","author":"Hamad","year":"2010","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_51","first-page":"15","article-title":"Neuronal differentiation of adipose tissue-derived stromal cells","volume":"14","author":"Liu","year":"2010","journal-title":"Chin. J. Tissue Eng. Res."},{"key":"ref_52","first-page":"102","article-title":"Summarize of cell apoptosis mechanism","volume":"24","author":"Zhang","year":"2007","journal-title":"Environ. Occup. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neulet.2014.05.025","article-title":"The relationship between mitochondrial fusion\/fission and apoptosis in the process of adipose-derived stromal cells differentiation into astrocytes","volume":"575","author":"Zhang","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1038\/s41598-020-63577-5","article-title":"Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel","volume":"10","author":"Akyuva","year":"2020","journal-title":"Sci. Rep."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/8\/1202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:33Z","timestamp":1760140533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/8\/1202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,23]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["jpm12081202"],"URL":"https:\/\/doi.org\/10.3390\/jpm12081202","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,23]]}}}