{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:32Z","timestamp":1785435572820,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016247","name":"Wroc\u0142aw University of Environmental and Life Sciences","doi-asserted-by":"publisher","award":["N070\/0015\/23"],"award-info":[{"award-number":["N070\/0015\/23"]}],"id":[{"id":"10.13039\/100016247","id-type":"DOI","asserted-by":"publisher"}]},{"award":["N070\/0015\/23"],"award-info":[{"award-number":["N070\/0015\/23"]}],"id":[{"id":"https:\/\/ror.org\/05cs8k179","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tretinoin (all-trans-retinoic acid, ATRA) is an established therapy for acute promyelocytic leukemia (APL) and neuroblastoma (NB); however, its broader oncological application is limited by poor bioavailability and rapid resistance development. In this study, we developed lipidic ester derivatives of ATRA as a potential prodrug approach aimed at modulating its physicochemical and biological properties. Three ATRA derivatives were evaluated in vitro in six human cancer cell lines: leukemia (MV4-11), gastric (AGS), colon (HT-29), lung (A549), and breast cancer cells (MCF-7, MDA-MB-468). Cytotoxicity toward normal human breast epithelial cells (MCF-10A) was also assessed. Among the synthesized derivatives, cetyl all-trans-retinoate (ATRA-CA) exhibited the strongest anticancer activity, showing up to threefold greater potency than ATRA, with inhibitory concentrations ranging from 1.34 to 23.1 \u00b5M and minimal toxicity toward normal cells. Moreover, ATRA-CA enhanced the efficacy of conventional chemotherapeutics. In A549 cells, treatment with 5 and 10 \u00b5M ATRA-CA reduced the cisplatin IC50 from 25.7 \u00b1 3.2 \u00b5M to 9.1 \u00b1 3.0 and 5.9 \u00b1 1.5 \u00b5M, corresponding to synergistic (CI = 0.63) and additive (CI = 0.88) effects, respectively. Similar effects were observed in MCF-7 cells and in combination with doxorubicin and paclitaxel.<\/jats:p>","DOI":"10.3390\/ijms27135982","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:39:11Z","timestamp":1783078751000},"page":"5982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cetyl All-Trans-Retinoate as a Lipidic ATRA Prodrug with Enhanced Anticancer and Chemosensitizing Activity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8857-8250","authenticated-orcid":false,"given":"Pawe\u0142","family":"Moroz","sequence":"first","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Muciek","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"\u015awitalska","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-6606","authenticated-orcid":false,"given":"Joanna","family":"Wietrzyk","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7315-1983","authenticated-orcid":false,"given":"Zbigniew","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Microbiology, Wroc\u0142aw University of Environmental and Life Sciences, Chelmonskiego 37, 51-630 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-6369","authenticated-orcid":false,"given":"Anna","family":"Gliszczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/neu.20242","article-title":"Overview of Retinoid Metabolism and Function","volume":"66","author":"Blomhoff","year":"2006","journal-title":"J. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/bs.apha.2015.04.006","article-title":"Chapter Eleven\u2014Role of Retinoic Acid-Metabolizing Cytochrome P450s, CYP26, in Inflammation and Cancer","volume":"Volume 74","author":"Hardwick","year":"2015","journal-title":"Advances in Pharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113451","DOI":"10.1016\/j.ejmech.2021.113451","article-title":"Overview of All-Trans-Retinoic Acid (ATRA) and Its Analogues: Structures, Activities, and Mechanisms in Acute Promyelocytic Leukaemia","volume":"220","author":"Liang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/0145-2126(86)90337-1","article-title":"Structure-Activity Relationships of Aromatic Retinoids on the Differentiation of the Human Histiocytic Lymphoma Cell Line U-937","volume":"10","author":"Chomienne","year":"1986","journal-title":"Leuk. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11430","DOI":"10.1002\/chem.200901952","article-title":"Synthetic Retinoids: Structure-Activity Relationships","volume":"15","author":"Barnard","year":"2009","journal-title":"Chemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.clml.2017.06.037","article-title":"Acute Promyelocytic Leukemia: A Perspective","volume":"17","author":"Ravandi","year":"2017","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_7","first-page":"391","article-title":"Retinoids as Preventive and Therapeutic Anticancer Agents (Part I)","volume":"71","author":"Lippman","year":"1987","journal-title":"Cancer Treat. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1056\/NEJM199710093371501","article-title":"All-Trans-Retinoic Acid in Acute Promyelocytic Leukemia","volume":"337","author":"Tallman","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia","volume":"369","author":"Avvisati","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Iyer, S.G., Elias, L., Stanchina, M., and Watts, J. (2022). The Treatment of Acute Promyelocytic Leukemia in 2023: Paradigm, Advances, and Future Directions. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1062524"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1089\/jir.2009.0036","article-title":"Differentiation of Human SH-SY5Y Neuroblastoma Cells by All-Trans Retinoic Acid Activates the Interleukin-18 System","volume":"30","author":"Sallmon","year":"2010","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bouriez, D., Giraud, J., Gronnier, C., and Varon, C. (2018). Efficiency of All-Trans Retinoic Acid on Gastric Cancer: A Narrative Literature Review. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113388"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hunsu, V.O., Facey, C.O.B., Fields, J.Z., and Boman, B.M. (2021). Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147731"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15074","DOI":"10.1038\/s41598-023-42177-z","article-title":"Combined Dandelion Extract and All-Trans Retinoic Acid Induces Cytotoxicity in Human Breast Cancer Cells","volume":"13","author":"Rezaie","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhu, Y.-H., Ye, N., Tang, X.-F., Khan, M.I., Liu, H.-L., Shi, N., and Hang, L.-F. (2019). Synergistic Effect of Retinoic Acid Polymeric Micelles and Prodrug for the Pharmacodynamic Evaluation of Tumor Suppression. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00447"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1093\/carcin\/21.7.1271","article-title":"Retinoids in Chemoprevention and Differentiation Therapy","volume":"21","author":"Hansen","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s002800050719","article-title":"All-Trans-Retinoic Acid Modulation of Drug-Metabolizing Enzyme Activities: Investigation with Selective Metabolic Drug Probes","volume":"41","author":"Adedoyin","year":"1998","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s002800050582","article-title":"A Phase II Trial of All-Trans-Retinoic Acid in Hormone-Refractory Prostate Cancer: A Clinical Trial with Detailed Pharmacokinetic Analysis","volume":"39","author":"Trump","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/10428190310001628158","article-title":"Treatment of Multiple Myeloma with All-Trans Retinoic Acid Alone and in Combination with Chemotherapy: A Phase I\/II Trial","volume":"45","author":"Koskela","year":"2004","journal-title":"Leuk. Lymphoma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1038\/sj.leu.2402719","article-title":"Retinoic Acid Resistance in Acute Promyelocytic Leukemia","volume":"16","author":"Gallagher","year":"2002","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1365-2710.2008.00935.x","article-title":"Retinoic Acid Syndrome: A Review","volume":"33","author":"Patatanian","year":"2008","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0003-9861(91)90482-X","article-title":"Solubility of Retinoids in Water","volume":"287","author":"Szuts","year":"1991","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Abdelaal, M.R., Soror, S.H., Elnagar, M.R., and Haffez, H. (2021). Revealing the Potential Application of EC-Synthetic Retinoid Analogues in Anticancer Therapy. Molecules, 26.","DOI":"10.3390\/molecules26020506"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3390\/pharmaceutics12080707","article-title":"Current Trends in ATRA Delivery for Cancer Therapy","volume":"12","author":"Giuli","year":"2020","journal-title":"Pharmaceutics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4755","DOI":"10.1002\/jps.22205","article-title":"Prodrugs: Some Thoughts and Current Issues","volume":"99","author":"Stella","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nrd2468","article-title":"Prodrugs: Design and Clinical Applications","volume":"7","author":"Rautio","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ejoc.200901128","article-title":"Isomerization of All-(E)-Retinoic Acid Mediated by Carbodiimide Activation\u2014Synthesis of ATRA Ether Lipid Conjugates","volume":"2010","author":"Christensen","year":"2010","journal-title":"Eur. J. Org. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1600397","DOI":"10.1002\/ejlt.201600397","article-title":"The Nonlinear Effect of Alkyl Chain Length in the Membrane Interactions of Phenolipids: Evidence by X-Ray Diffraction Analysis","volume":"119","author":"Durand","year":"2017","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10471","DOI":"10.1021\/acs.jmedchem.2c00629","article-title":"Escaping from the Cutoff Paradox by Accumulating Long-Chain Alcohols in the Cell Membrane","volume":"65","author":"Matsumoto","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"di Martino, O., and Welch, J.S. (2019). Retinoic Acid Receptors in Acute Myeloid Leukemia Therapy. Cancers, 11.","DOI":"10.3390\/cancers11121915"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dong, X., Peng, S., Ling, Y., Huang, B., Tu, W., Sun, X., Li, Q., Fang, Y., and Wu, J. (2023). ATRA Treatment Slowed P-Selectin-Mediated Rolling of Flowing HL60 Cells in a Mechano-Chemical-Dependent Manner. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1148543"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/gcc.23180","article-title":"Clinical and Genomic Characterization of an ATRA-Insensitive Acute Promyelocytic Leukemia Variant with a FNDC3B::RARB Fusion","volume":"62","author":"Kirkham","year":"2023","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115314","DOI":"10.1016\/j.biopha.2023.115314","article-title":"Targeting DHODH Reveals Therapeutic Opportunities in ATRA-Resistant Acute Promyelocytic Leukemia","volume":"166","author":"Yang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1158\/0008-5472.CAN-05-4048","article-title":"Synergistic Induction of Folate Receptor Beta by All-Trans Retinoic Acid and Histone Deacetylase Inhibitors in Acute Myelogenous Leukemia Cells: Mechanism and Utility in Enhancing Selective Growth Inhibition by Antifolates","volume":"66","author":"Qi","year":"2006","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"109182","DOI":"10.1016\/j.intimp.2022.109182","article-title":"All-Trans Retinoic Acid Enhanced the Antileukemic Efficacy of ABT-199 in Acute Myeloid Leukemia by Downregulating the Expression of S100A8","volume":"112","author":"Li","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Osmond, B., Facey, C.O.B., Zhang, C., and Boman, B.M. (2022). HOXA9 Overexpression Contributes to Stem Cell Overpopulation That Drives Development and Growth of Colorectal Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126799"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s10616-018-0199-3","article-title":"Combination Treatment of All-Trans Retinoic Acid (ATRA) and \u03b3-Secretase Inhibitor (DAPT) Cause Growth Inhibition and Apoptosis Induction in the Human Gastric Cancer Cell Line","volume":"70","author":"Patrad","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000068567","article-title":"N-(4-Hydroxyphenyl)-Retinamide Selectively Increases All-TRANS Retinoic Acid Inhibitory Effects in HER2\/NEU-Overexpressing Breast Cancer Cells","volume":"23","author":"Lim","year":"2002","journal-title":"Tumour Biol."},{"key":"ref_39","first-page":"579","article-title":"Anticancer Activity of Retinoic Acid against Breast Cancer Cells Derived from an Iraqi Patient","volume":"18","author":"Abdullah","year":"2023","journal-title":"J. Taibah Univ. Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Qu, Y., Han, B., Yu, Y., Yao, W., Bose, S., Karlan, B.Y., Giuliano, A.E., and Cui, X. (2015). Evaluation of MCF10A as a Reliable Model for Normal Human Mammary Epithelial Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131285"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1039\/D0MD00317D","article-title":"Normal Breast Epithelial MCF-10A Cells to Evaluate the Safety of Carbon Dots","volume":"12","author":"Vale","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1056\/NEJM199307153290307","article-title":"Acute Promyelocytic Leukemia","volume":"329","author":"Warrell","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S1357-2725(03)00247-4","article-title":"Leukemia: Beneficial Actions of Retinoids and Rexinoids","volume":"36","author":"Altucci","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/35106036","article-title":"The Promise of Retinoids to Fight against Cancer","volume":"1","author":"Altucci","year":"2001","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1023\/A:1015490627613","article-title":"Decryption of the Retinoid Death Code in Leukemia","volume":"22","author":"Altucci","year":"2002","journal-title":"J. Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8754","DOI":"10.1158\/0008-5472.CAN-04-3569","article-title":"Rexinoid-Triggered Differentiation and Tumor-Selective Apoptosis of Acute Myeloid Leukemia by Protein Kinase A\u2013Mediated Desubordination of Retinoid X Receptor","volume":"65","author":"Altucci","year":"2005","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.addr.2010.07.003","article-title":"Retinoid Pathway and Cancer Therapeutics","volume":"62","author":"Bushue","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_48","first-page":"938","article-title":"Retinoids as Anti-Cancer Agents and Their Mechanisms of Action","volume":"12","author":"Jin","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative Analysis of Dose-Effect Relationships: The Combined Effects of Multiple Drugs or Enzyme Inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12695","DOI":"10.2147\/IJN.S477512","article-title":"Multifunctional Indomethacin Conjugates for the Development of Nanosystems Targeting Cancer Treatment","volume":"19","author":"Thiruchenthooran","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_51","unstructured":"(2026, March 01). Available online: https:\/\/www.molinspiration.com\/."},{"key":"ref_52","unstructured":"(2026, March 01). Available online: http:\/\/biosig.unimelb.edu.au\/pkcsm\/."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_54","first-page":"367","article-title":"Synthesis of a Natural Gamma-Butyrolactone from Nerylacetone by Acremonium Roseum and Fusarium Oxysporum Cultures","volume":"6","author":"Switalska","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/cbdv.201500127","article-title":"Dehalogenation Activity of Selected Fungi Toward \u03b4-Iodo-\u03b3-Lactone Derived from Trans,Trans-Farnesol","volume":"13","author":"Wietrzyk","year":"2016","journal-title":"Chem. Biodivers."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nevozhay, D. (2014). Cheburator Software for Automatically Calculating Drug Inhibitory Concentrations from in Vitro Screening Assays. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106186"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5982\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:46:47Z","timestamp":1783079207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":56,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135982"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135982","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}