{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:12:36Z","timestamp":1776795156138,"version":"3.51.2"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET\/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET\/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET\/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.<\/jats:p>","DOI":"10.3390\/ijms22179225","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"9225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-5270","authenticated-orcid":false,"given":"Rosa","family":"Estrada-Reyes","sequence":"first","affiliation":[{"name":"Laboratorio de Fitofarmacolog\u00eda, Direcci\u00f3n de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel B.","family":"Quero-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6567-3538","authenticated-orcid":false,"given":"Citlali","family":"Trueta","sequence":"additional","affiliation":[{"name":"Departamento de Neurofisiolog\u00eda, Direcci\u00f3n de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-6055","authenticated-orcid":false,"given":"Armida","family":"Miranda","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-7321","authenticated-orcid":false,"given":"Marcela","family":"Vald\u00e9s-Tovar","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0760-4192","authenticated-orcid":false,"given":"Salvador","family":"Alarc\u00f3n-Elizalde","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1736-1112","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Oikawa-Sala","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3668-1066","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argueta","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0773-2581","authenticated-orcid":false,"given":"Luis A.","family":"Constantino-Jonapa","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Mu\u00f1oz-Estrada","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita L.","family":"Dubocovich","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), 955 Main Street, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-6851","authenticated-orcid":false,"given":"Gloria","family":"Ben\u00edtez-King","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Subdirecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","first-page":"35","article-title":"Signaling pathways underlying the rapid antidepressant actions of ketamine","volume":"62","author":"Duman","year":"2012","journal-title":"Neuro Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a019026","DOI":"10.1101\/cshperspect.a019026","article-title":"Adult neurogenesis and psychiatric disorders","volume":"8","author":"Kang","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9104","DOI":"10.1523\/JNEUROSCI.20-24-09104.2000","article-title":"Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus","volume":"20","author":"Malberg","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: Sources, regulation, and potential functions","volume":"71","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1358\/dnp.1998.11.5.863675","article-title":"Melatonin, active oxygen species and neurological damage","volume":"11","author":"Reiter","year":"1998","journal-title":"Drug News Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0197-0186(94)00154-M","article-title":"Melatonin stimulates brain glutathione peroxidase activity","volume":"26","year":"1995","journal-title":"Neurochem. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1034\/j.1600-079X.2001.280204.x","article-title":"Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brain","volume":"28","author":"Okatani","year":"2000","journal-title":"J. Pineal. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1600-079X.2009.00739.x","article-title":"The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-\u03b1 toxicity involves membrane melatonin receptors","volume":"48","author":"Das","year":"2010","journal-title":"J. Pineal. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/nn.4661","article-title":"Viewpoints: How the hippocampus contributes to memory, navigation and cognition","volume":"20","author":"Lisman","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bcp.2019.02.010","article-title":"Melatonin protects against methotrexate-induced memory deficit and hippocampal neurogenesis impairment in a rat model","volume":"163","author":"Sirichoat","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1600-079X.2011.00957.x","article-title":"Melatonin increases dendritogenesis in the hilus of hippocampal organotypic cultures","volume":"52","year":"2012","journal-title":"J. Pineal. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/jpi.12023","article-title":"Melatonin potentiates running wheel-induced neurogenesis in the dentate gyrus of adult C3H\/HeN mice hippocampus","volume":"54","author":"Liu","year":"2013","journal-title":"J. Pineal. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1600-079X.2010.00802.x","article-title":"Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice","volume":"50","author":"Kempermann","year":"2011","journal-title":"J. Pineal. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejphar.2009.02.037","article-title":"Antidepressant-like effects of melatonin in the mouse chronic mild stress model","volume":"607","author":"Detanico","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Estrada-Reyes, R. (2018). The Timing of Melatonin Administration Is Crucial for Its Antidepressant-Like Effect in Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082278"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.brainresbull.2017.07.013","article-title":"The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices","volume":"134","author":"Rebai","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.etp.2017.05.002","article-title":"Protective effects of melatonin on long-term administration of fluoxetine in rats","volume":"69","author":"Khaksar","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jpi.12136","article-title":"Melatonin synergizes with citalopram to induce antidepressant-like behavior and to promote hippocampal neurogenesis in adult mice","volume":"56","year":"2014","journal-title":"J. Pineal. Res."},{"key":"ref_19","first-page":"27","article-title":"Major depressive disorder: Remission of associated symptoms","volume":"67","author":"Trivedi","year":"2006","journal-title":"J. Clin. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/sltb.12022","article-title":"Treatment-resistant depression and risk of suicide","volume":"43","author":"Pfeiffer","year":"2013","journal-title":"Suicide Life-Threat. Behav."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jad.2013.10.036","article-title":"Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression","volume":"155","author":"Shiroma","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/nyas.12223","article-title":"New paradigms for treatment-resistant depression","volume":"1292","author":"Zarate","year":"2013","journal-title":"Ann. N. Y. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbb.2015.11.009","article-title":"Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test","volume":"141","author":"Kordjazy","year":"2016","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","article-title":"A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression","volume":"63","author":"Zarate","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1176\/appi.ajp.2013.13030392","article-title":"Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial","volume":"170","author":"Murrough","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3109\/15622975.2016.1139747","article-title":"Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: A narrative review","volume":"18","author":"Cooper","year":"2017","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1001\/archpsyc.1994.03950030035004","article-title":"Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses","volume":"51","author":"Krystal","year":"1994","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_28","unstructured":"Elliott, J.M., Heal, D.J., and Marsden, C.A. (1992). Behavioural models of depression. Experimental Approaches to Anxiety and Depression, Wiley."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0006-3223(00)01028-3","article-title":"Genetic differences in the tail-suspension test and its relationship to imipramine response among 11 inbred strains of mice","volume":"49","author":"Liu","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jep.2012.03.028","article-title":"Neuropharmacological study of Dracocephalum moldavica L. (Lamiaceae) in mice: Sedative effect and chemical analysis of an aqueous extract","volume":"141","author":"Heinze","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00441-019-03043-5","article-title":"Neurogenesis and antidepressant action","volume":"377","author":"Park","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3940(03)00306-9","article-title":"Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: Evidence for involvement of N-methyl-D-aspartate receptors and the L-arginine-nitric oxide pathway","volume":"343","author":"Mantovani","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11317","DOI":"10.1523\/JNEUROSCI.1491-10.2010","article-title":"The NADPH oxidase NOX2 controls glutamate release: A novel mechanism involved in psychosis-like ketamine responses","volume":"30","author":"Sorce","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e858","DOI":"10.4088\/JCP.17f11802","article-title":"Ketamine for depression, 5: Potential pharmacokinetic and pharmacodynamic drug interactions","volume":"78","author":"Andrade","year":"2017","journal-title":"J. Clin. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/BF01923947","article-title":"The melatonin rhythm: Both a clock and a calendar","volume":"49","author":"Reiter","year":"1993","journal-title":"Experientia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.pharep.2016.04.003","article-title":"Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity","volume":"68","author":"Just","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s12264-017-0189-z","article-title":"Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF\u2013TrkB Signaling","volume":"34","author":"Li","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1038\/npp.2009.46","article-title":"Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice","volume":"34","author":"Klempin","year":"2009","journal-title":"Neuro Psycho Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1038\/s41380-019-0400-x","article-title":"Neurobiology of rapid-acting antidepressants: Convergent effects on GluA1-synaptic function","volume":"24","author":"Duman","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/syn.21892","article-title":"Melatonin receptor activation increases glutamatergic synaptic transmission in the rat medial lateral habenula","volume":"70","author":"Evely","year":"2016","journal-title":"Synapse"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/gbb.12369","article-title":"Role of the MT1 and MT2 melatonin receptors in mediating depressive- and anxiety-like behaviors in C3H\/HeN mice","volume":"16","author":"Liu","year":"2017","journal-title":"Genes Brain Behav."},{"key":"ref_42","first-page":"327","article-title":"Behavioral despair in mice: A primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.neubiorev.2005.03.009","article-title":"The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice","volume":"29","author":"Cryan","year":"2005","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jep.2013.12.057","article-title":"Central nervous system effects and chemical composition of two subspecies of Agastache mexicana; An ethnomedicine of Mexico","volume":"153","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.pharmthera.2009.02.010","article-title":"Ketamine and the next generation of antidepressants with a rapid onset of action","volume":"123","author":"Salvadore","year":"2009","journal-title":"Pharmacol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:54Z","timestamp":1760165574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":46,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179225"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179225","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]}}}