{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:17:13Z","timestamp":1788715033318,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Chemistry","award":["451-03-47\/2023-01\/200168"],"award-info":[{"award-number":["451-03-47\/2023-01\/200168"]}]},{"name":"Faculty of Chemistry","award":["451-03-47\/2023-01\/200026"],"award-info":[{"award-number":["451-03-47\/2023-01\/200026"]}]},{"name":"Institute for Chemistry, Technology, and Metallurgy","award":["451-03-47\/2023-01\/200168"],"award-info":[{"award-number":["451-03-47\/2023-01\/200168"]}]},{"name":"Institute for Chemistry, Technology, and Metallurgy","award":["451-03-47\/2023-01\/200026"],"award-info":[{"award-number":["451-03-47\/2023-01\/200026"]}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200168"],"award-info":[{"award-number":["451-03-47\/2023-01\/200168"]}]},{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-47\/2023-01\/200026"],"award-info":[{"award-number":["451-03-47\/2023-01\/200026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van\u2019t Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near \u03b1\u03b2 interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~104 M\u22121), the highest observed for clozapine (2.2 \u00d7 104 M\u22121 at 25 \u00b0C). The clozapine binding showed \u201cfriendly\u201d effects: increased \u03b1-helical content, a higher melting point, and protein protection from free radical-mediated oxidation. On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible \u201cfoe\u201d. Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed.<\/jats:p>","DOI":"10.3390\/ijms24108921","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:09:44Z","timestamp":1684397384000},"page":"8921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?"],"prefix":"10.3390","volume":"24","author":[{"given":"Lena","family":"Platani\u0107 Arizanovi\u0107","sequence":"first","affiliation":[{"name":"University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8691-2486","authenticated-orcid":false,"given":"Nikola","family":"Gligorijevi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technology, and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, Njego\u0161eva 12, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-6172","authenticated-orcid":false,"given":"Ilija","family":"Cvijeti\u0107","sequence":"additional","affiliation":[{"name":"University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Mijatovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Mining and Geology, University of Belgrade, \u0110u\u0161ina 7, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-9408","authenticated-orcid":false,"given":"Maja Krsti\u0107","family":"Ristivojevi\u0107","sequence":"additional","affiliation":[{"name":"University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon","family":"Mini\u0107","sequence":"additional","affiliation":[{"name":"University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1116-2035","authenticated-orcid":false,"given":"Aleksandra Nikoli\u0107","family":"Koki\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u010cedo","family":"Miljevi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Mental Health, Palmoti\u0107eva 37, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1056\/NEJM199801223380407","article-title":"Respiratory function of hemoglobin","volume":"338","author":"Hsia","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/bmb\/ldv017","article-title":"Antipsychotic medication in schizophrenia: A review","volume":"114","author":"Lally","year":"2015","journal-title":"Br. Med. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1080\/14740338.2016.1191468","article-title":"Clozapine\u2019s critical role in treatment resistant schizophrenia: Ensuring both safety and use","volume":"15","author":"Remington","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_4","first-page":"CD006627","article-title":"Ziprasidone versus other atypical antipsychotics for schizophrenia","volume":"4","author":"Komossa","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/schbul\/sbaa191","article-title":"Does Switching Antipsychotics Ameliorate Weight Gain in Patients With Severe Mental Illness? A Systematic Review and Meta-analysis","volume":"47","author":"Siskind","year":"2021","journal-title":"Schizophr. Bull."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/JCP.0000000000000305","article-title":"Efficacy and safety of sertindole in schizophrenia: A clinical review","volume":"35","author":"Zoccali","year":"2015","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/jps.2600660532","article-title":"Uptake of acetazolamide by human erythrocytes in vitro","volume":"66","author":"Wallace","year":"1977","journal-title":"J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.addr.2016.02.007","article-title":"Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems","volume":"106","author":"Villa","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1021\/ja00265a036","article-title":"Hemoglobin as a receptor of drugs and peptides: X-ray studies of the stereochemistry of binding","volume":"108","author":"Perutz","year":"1986","journal-title":"J. Am. Chem. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nedi\u0107, O., Penezi\u0107, A., Mini\u0107, S., Radomirovi\u0107, M., Nikoli\u0107, M., \u0106irkovi\u0107 Veli\u010dkovi\u0107, T., and Gligorijevi\u0107, N. (2023). Food Antioxidants and Their Interaction with Human Proteins. Antioxidants, 12.","DOI":"10.3390\/antiox12040815"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1751-1097.1980.tb03674.x","article-title":"Tryptophan emission from human haemoglobin and its isolated subunits","volume":"31","author":"Alpert","year":"1980","journal-title":"J. Photochem. Photobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15353","DOI":"10.1021\/bi0012944","article-title":"Interface sliding as illustrated by the multiple quaternary structures of liganded hemoglobin","volume":"39","author":"Mueser","year":"2000","journal-title":"Biochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/S0021-9258(19)69925-4","article-title":"Conformational studies of hemoglobins using intrinsic fluorescence measurements","volume":"256","author":"Hirsch","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2841","DOI":"10.1002\/jmr.2841","article-title":"Esterase activity and interaction of human hemoglobin with diclofenac sodium: A spectroscopic and molecular docking study","volume":"33","author":"Dohare","year":"2020","journal-title":"J. Mol. Recognit."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lakowicz, J.R. (2006). Principles of Fluorescence Spectroscopy, Springer.","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1021\/j100809a020","article-title":"Oxygen quenching of fluorescence in solution: An experimental study of the diffusion process","volume":"66","author":"Ware","year":"1962","journal-title":"J. Phys. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jphotobiol.2011.07.004","article-title":"Studies on the interaction between docetaxel and human hemoglobin by spectroscopic analysis and molecular docking","volume":"105","author":"Cheng","year":"2011","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jphotobiol.2013.01.011","article-title":"Spectroscopic investigations of the interactions of tramadol hydrochloride and 5-azacytidine drugs with human serum albumin and human hemoglobin proteins","volume":"120","author":"Cetinkaya","year":"2013","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jlumin.2013.03.015","article-title":"Studies on the interactions of chloroquine diphosphate and phenelzine sulfate drugs with human serum albumin and human hemoglobin proteins by spectroscopic techniques","volume":"140","author":"Duman","year":"2013","journal-title":"J. Lumines"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.saa.2018.03.023","article-title":"Interaction of promethazine and adiphenine to human hemoglobin: A comparative spectroscopic and computational analysis","volume":"199","author":"Maurya","year":"2018","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbagen.2004.10.013","article-title":"Flavonoid-serum albumin complexation: Determination of binding constants and binding sites by fluorescence spectroscopy","volume":"1721","author":"Dufour","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1021\/jf030560s","article-title":"Hemoglobin-mediated oxidation of washed minced cod muscle phospholipids: Effect of pH and hemoglobin source","volume":"52","author":"Undeland","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1080\/07391102.2016.1180262","article-title":"Acetaminophen interacts with human hemoglobin: Optical, physical and molecular modeling studies","volume":"35","author":"Seal","year":"2017","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_24","first-page":"203","article-title":"Recent advances in molecular luminescence analysis","volume":"16","author":"Miller","year":"1979","journal-title":"Proc. Anal. Div. Chem. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1021\/bi00514a017","article-title":"Thermodynamics of protein association reactions: Forces contributing to stability","volume":"20","author":"Ross","year":"1981","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/978-3-030-41769-7_15","article-title":"Serum Albumin, Lipid and Drug Binding","volume":"94","author":"Nishi","year":"2020","journal-title":"Subcell. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.dyepig.2008.12.008","article-title":"A fluorimetric study of the interaction of C.I. Solvent Red 24 with haemoglobin","volume":"82","author":"Zhang","year":"2009","journal-title":"Dye. Pigm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1038\/nprot.2006.202","article-title":"Using circular dichroism spectra to estimate protein secondary structure","volume":"1","author":"Greenfield","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bbapap.2005.06.005","article-title":"How to study proteins by circular dichroism","volume":"1751","author":"Kelly","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1098\/rsif.2012.0364","article-title":"Thermal fluctuations of haemoglobin from different species: Adaptation to temperature via conformational dynamics","volume":"9","author":"Stadler","year":"2012","journal-title":"J. R. Soc. Interface"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9311","DOI":"10.1021\/bi00492a002","article-title":"Multiple heme pocket subconformations of methemoglobin associated with distal histidine interactions","volume":"29","author":"Levy","year":"1990","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1042\/bj2200685","article-title":"Oxidative interactions between haemoglobin and membrane lipid. A liposome model","volume":"220","author":"Szebeni","year":"1984","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10715769800300171","article-title":"Antioxidant properties of clozapine and related neuroleptics","volume":"29","author":"Scutari","year":"1998","journal-title":"Free Radic. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Caruso, G., Grasso, M., Fidilio, A., Tascedda, F., Drago, F., and Caraci, F. (2020). Antioxidant Properties of Second-Generation Antipsychotics: Focus on Microglia. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120457"},{"key":"ref_35","first-page":"1575","article-title":"Alternate and additional functions of erythrocyte hemoglobin","volume":"83","author":"Kosmachevskaya","year":"2018","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.eurpsy.2008.09.003","article-title":"The use of ziprasidone in clinical practice: Analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey","volume":"24","author":"Vogel","year":"2009","journal-title":"Eur. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4137\/JCNSD.S5729","article-title":"Sertindole in the Management of Schizophrenia","volume":"3","author":"Juruena","year":"2011","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s11095-004-1199-x","article-title":"Use of 2,2\u2032-azobis(2-amidinopropane) dihydrochloride as a reagent tool for evaluation of oxidative stability of drugs","volume":"22","author":"Betigeri","year":"2005","journal-title":"Pharm. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.biopha.2016.02.047","article-title":"Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models","volume":"81","author":"Brinholi","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijbiomac.2020.03.119","article-title":"Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation","volume":"154","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ijbiomac.2021.04.155","article-title":"Antipsychotic clozapine binding to alpha-2-macroglobulin protects interacting partners against oxidation and preserves the anti-proteinase activity of the protein","volume":"183","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_43","first-page":"599","article-title":"Clozapine dosages and plasma drug concentrations","volume":"96","author":"Chang","year":"1997","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_44","first-page":"14","article-title":"Review and management of clozapine side effects","volume":"61","author":"Miller","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"ref_45","unstructured":"Antonini, E., Rossi-Bernardi, L., and Hiancone, E. (1981). Methods in Enzymology, Academic Press."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119483","DOI":"10.1016\/j.saa.2021.119483","article-title":"Nutraceutical phycocyanobilin binding to catalase protects the pigment from oxidation without affecting catalytic activity","volume":"251","author":"Papadimitriou","year":"2021","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.foodchem.2017.07.066","article-title":"Characterization and effects of binding of food-derived bioactive phycocyanobilin to bovine serum albumin","volume":"239","author":"Minic","year":"2018","journal-title":"Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jmb.2005.12.018","article-title":"R-State Haemoglobin with Low Oxygen Affinity: Crystal Structures of Deoxy Human and Carbonmonoxy Horse Haemoglobin Bound to the Effector Molecule L35","volume":"356","author":"Yokoyama","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable Molecular Dynamics on CPU and GPU Architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1093\/bioinformatics\/btaa774","article-title":"The VEGA Suite of Programs: An Versatile Platform for Cheminformatics and Drug Design Projects","volume":"37","author":"Pedretti","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00894-012-1667-x","article-title":"Optimization of Parameters for Semiempirical Methods VI: More Modifications to the NDDO Approximations and Re-Optimization of Parameters","volume":"19","author":"Stewart","year":"2013","journal-title":"J. Mol. Model."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00128336","article-title":"MOPAC: A Semiempirical Molecular Orbital Program","volume":"4","author":"Stewart","year":"1990","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1021\/bi00745a020","article-title":"Quenching of fluorescence by oxygen. A probe for structural fluctuations in macromolecules","volume":"12","author":"Lakowicz","year":"1973","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molstruc.2004.05.026","article-title":"Investigation of the interaction between flavonoids and human serum albumin","volume":"703","author":"Bi","year":"2004","journal-title":"J. Mol. Struct."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.febslet.2014.05.006","article-title":"Forces Stabilizing Proteins","volume":"588","author":"Pace","year":"2014","journal-title":"FEBS Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:37:16Z","timestamp":1760125036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24108921"],"URL":"https:\/\/doi.org\/10.3390\/ijms24108921","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}