{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:57:11Z","timestamp":1789664231699,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/07256-4"],"award-info":[{"award-number":["2020\/07256-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["302733\/2022-1"],"award-info":[{"award-number":["302733\/2022-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["2020\/07256-4"],"award-info":[{"award-number":["2020\/07256-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302733\/2022-1"],"award-info":[{"award-number":["302733\/2022-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy of senolytics in idiopathic pulmonary fibrosis, a lung disease associated with the presence of senescent cells. Another approach to senotherapeutics consists of controlling inflammation related to cellular senescence or \u201cinflammaging\u201d, which participates, among other processes, in establishing pulmonary fibrosis. We evaluate whether polyphenols such as caffeic acid, chlorogenic acid, epicatechin, gallic acid, quercetin, or resveratrol combined with different senotherapeutics such as metformin or rapamycin, and antifibrotic drugs such as nintedanib or pirfenidone, could present beneficial actions in an in vitro model of senescent MRC-5 lung fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by the measurement of interleukin (IL)-6, IL-8, and IL-1\u03b2. The senescent-associated \u03b2-galactosidase (SA-\u03b2-gal) activity and cellular proliferation were assessed. Fibrosis was evaluated using a Picrosirius red assay and the gene expression of fibrosis-related genes. Epithelial-mesenchymal transition (EMT) was assayed in the A549 cell line exposed to Transforming Growth Factor (TGF)-\u03b2 in vitro. The combination that demonstrated the best results was metformin and caffeic acid, by inhibiting IL-6 and IL-8 in senescent MRC-5 cells. Metformin and caffeic acid also restore cellular proliferation and reduce SA-\u03b2-gal activity during senescence induction. The collagen production by senescent MRC-5 cells was inhibited by epicatechin alone or combined with drugs. Epicatechin and nintedanib were able to control EMT in A549 cells. In conclusion, caffeic acid and epicatechin can potentially increase the effectiveness of senotherapeutic drugs in controlling lung diseases whose pathophysiological component is the presence of senescent cells and fibrosis.<\/jats:p>","DOI":"10.3390\/ijms25137163","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Addition of Polyphenols to Drugs: The Potential of Controlling \u201cInflammaging\u201d and Fibrosis in Human Senescent Lung Fibroblasts In Vitro"],"prefix":"10.3390","volume":"25","author":[{"given":"Maria Carolina Ximenes de","family":"Godoy","sequence":"first","affiliation":[{"name":"School for Life Sciences, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, Campinas 13034-685, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Arruda","family":"Monteiro","sequence":"additional","affiliation":[{"name":"School for Life Sciences, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, Campinas 13034-685, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara Hakim de","family":"Moraes","sequence":"additional","affiliation":[{"name":"School for Life Sciences, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, Campinas 13034-685, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Alves","family":"Macedo","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, School of Food Engineering, State University of Campinas, Campinas 13083-862, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele Mara Silva","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"School for Life Sciences, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, Campinas 13034-685, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Gambero","sequence":"additional","affiliation":[{"name":"School for Life Sciences, Pontifical Catholic University of Campinas (PUC-Campinas), Av. John Boyd Dunlop, Campinas 13034-685, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.21037\/jtd.2019.02.11","article-title":"Cellular senescence and senescence-associated secretory phenotype: Comparison of idiopathic pulmonary fibrosis, connective tissue disease-associated interstitial lung disease, and chronic obstructive pulmonary disease","volume":"11","author":"Okuda","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/bs.apha.2023.04.001","article-title":"Senotherapy for lung diseases","volume":"98","author":"Barnes","year":"2023","journal-title":"Adv. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ncb1909","article-title":"Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion","volume":"11","author":"Rodier","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102315","DOI":"10.1016\/j.arr.2024.102315","article-title":"Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions","volume":"97","author":"Jha","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lushchak, O., Schosserer, M., and Grillari, J. (2023). Senopathies-Diseases Associated with Cellular Senescence. Biomolecules, 13.","DOI":"10.3390\/biom13060966"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nambiar, A., Kellogg, D., Justice, J., Goros, M., Gelfond, J., Pascual, R., Hashmi, S., Masternak, M., Prata, L., and LeBrasseur, N. (2023). Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: Results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. EBioMedicine, 90.","DOI":"10.1016\/j.ebiom.2023.104481"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41591-023-02543-w","article-title":"Senolytic therapy in mild Alzheimer\u2019s disease: A phase 1 feasibility trial","volume":"29","author":"Gonzales","year":"2023","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/bs.apcsb.2023.02.020","article-title":"Senolytic and senomorphic interventions to defy senescence-associated mitochondrial dysfunction","volume":"136","author":"Nehlin","year":"2023","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hansel, C., Barr, S., Schemann, A.V., Lauber, K., Hess, J., Unger, K., Zitzelsberger, H., Jendrossek, V., and Klein, D. (2021). Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137064"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/cbin.11536","article-title":"Metformin attenuates lipopolysaccharide-induced epithelial cell senescence by activating autophagy","volume":"45","author":"Wang","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12964-020-00533-w","article-title":"Rapamycin promotes endothelial-mesenchymal transition during stress-induced premature senescence through the activation of autophagy","volume":"18","author":"Sasaki","year":"2020","journal-title":"Cell Commun. Signal"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"242","DOI":"10.18632\/aging.102613","article-title":"Epithelial cell senescence induces pulmonary fibrosis through Nanog-mediated fibroblast activation","volume":"12","author":"Chen","year":"2019","journal-title":"Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102131","DOI":"10.1016\/j.arr.2023.102131","article-title":"On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert antiaging effects?","volume":"92","author":"Scisciola","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Luo, J., Si, H., Jia, Z., and Liu, D. (2021). Dietary Antiaging Polyphenols and Potential Mechanisms. Antioxidants, 10.","DOI":"10.3390\/antiox10020283"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s11033-019-05194-8","article-title":"Quercetin, caffeic acid and resveratrol regulate circadian clock genes and aging-related genes in young and old human lung fibroblast cells","volume":"47","author":"Okada","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, N., Wei, W.Y., Li, L.L., Hu, C., and Tang, Q.Z. (2018). Therapeutic Potential of Polyphenols in Cardiac Fibrosis. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00122"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1139\/cjpp-2012-0432","article-title":"Quercetin provides greater cardioprotective effect than its glycoside derivative rutin on isoproterenol-induced cardiac fibrosis in the rat","volume":"91","author":"Li","year":"2013","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3945\/jn.111.157263","article-title":"Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats","volume":"142","author":"Panchal","year":"2012","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.clnu.2014.08.014","article-title":"Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-beta1 signaling","volume":"34","author":"Zhang","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1080\/10717544.2022.2105445","article-title":"Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats","volume":"29","author":"Albanawany","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101953","DOI":"10.1016\/j.tice.2022.101953","article-title":"Resveratrol alleviates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition and down-regulating TLR4\/NF-kappaB and TGF-beta1\/smad3 signalling pathways in rats","volume":"79","author":"Wang","year":"2022","journal-title":"Tissue Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e170499","DOI":"10.1172\/JCI170499","article-title":"Pulmonary inflammation and fibroblast immunoregulation: From bench to bedside","volume":"133","author":"Ghonim","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41514-024-00135-7","article-title":"A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging","volume":"10","author":"Linders","year":"2024","journal-title":"NPJ Aging"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Saleh, T., Bloukh, S., Carpenter, V.J., Alwohoush, E., Bakeer, J., Darwish, S., Azab, B., and Gewirtz, D.A. (2020). Therapy-Induced Senescence: An \u201cOld\u201d Friend Becomes the Enemy. Cancers, 12.","DOI":"10.3390\/cancers12040822"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3291957","DOI":"10.1155\/2023\/3291957","article-title":"Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression","volume":"2023","author":"He","year":"2023","journal-title":"Can. Respir. J."},{"key":"ref_26","first-page":"1089","article-title":"Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology","volume":"79","author":"Adcock","year":"2023","journal-title":"Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ebiom.2018.12.052","article-title":"Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study","volume":"40","author":"Justice","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"18333","DOI":"10.1038\/s41598-021-97225-3","article-title":"Factors associated with inflamm-aging in institutionalized older people","volume":"11","author":"Tavares","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bogdanova, D.A., Kolosova, E.D., Pukhalskaia, T.V., Levchuk, K.A., Demidov, O.N., and Belotserkovskaya, E.V. (2024). The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074031"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107758","DOI":"10.1016\/j.jdiacomp.2020.107758","article-title":"Metformin alters peripheral blood mononuclear cells (PBMC) senescence biomarkers gene expression in type 2 diabetic patients","volume":"35","author":"Alshahrani","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sorrenti, V., Benedetti, F., Buriani, A., Fortinguerra, S., Caudullo, G., Davinelli, S., Zella, D., and Scapagnini, G. (2022). Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080912"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sreedharan, S., Nair, V., and Cisneros-Zevallos, L. (2023). Protective Role of Phenolic Compounds from Whole Cardamom (Elettaria cardamomum (L.) Maton) against LPS-Induced Inflammation in Colon and Macrophage Cells. Nutrients, 15.","DOI":"10.3390\/nu15132965"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"852","DOI":"10.3390\/cimb45020056","article-title":"Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1beta\/IL-6\/TNF-alpha Mediated Signaling Mechanisms in Type-2 Diabetic Rats","volume":"45","author":"Janaki","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Espindola, K.M.M., Ferreira, R.G., Narvaez, L.E.M., Silva Rosario, A.C.R., da Silva, A.H.M., Silva, A.G.B., Vieira, A.P.O., and Monteiro, M.C. (2019). Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00541"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s12272-017-0909-y","article-title":"Methyl caffeate and some plant constituents inhibit age-related inflammation: Effects on senescence-associated secretory phenotype (SASP) formation","volume":"40","author":"Lim","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.2337\/db19-1268","article-title":"Diabetic Kidney Disease Alters the Transcriptome and Function of Human Adipose-Derived Mesenchymal Stromal Cells but Maintains Immunomodulatory and Paracrine Activities Important for Renal Repair","volume":"70","author":"Hickson","year":"2021","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jang, J.Y., Im, E., and Kim, N.D. (2022). Mechanism of Resveratrol-Induced Programmed Cell Death and New Drug Discovery against Cancer: A Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213689"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3997190","DOI":"10.1155\/2022\/3997190","article-title":"Pharmacological Activity of Quercetin: An Updated Review","volume":"2022","author":"Wang","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12915","DOI":"10.1039\/D2FO02758E","article-title":"Component analysis and anti-pulmonary fibrosis effects of Rosa sterilis juice","volume":"13","author":"Wang","year":"2022","journal-title":"Food Funct."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6721958","DOI":"10.1155\/2022\/6721958","article-title":"Fibropreventive and Antifibrotic Effects of Uncaria gambir on Rats with Pulmonary Fibrosis","volume":"2022","author":"Desdiani","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shariati, S., Kalantar, H., Pashmforoosh, M., Mansouri, E., and Khodayar, M.J. (2019). Epicatechin protective effects on bleomycin-induced pulmonary oxidative stress and fibrosis in mice. Biomed. Pharmacother., 114.","DOI":"10.1016\/j.biopha.2019.108776"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1055\/s-2000-8599","article-title":"Oral absorption and bioavailability of tea catechins","volume":"66","author":"Zhu","year":"2000","journal-title":"Planta Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e35353","DOI":"10.1097\/MD.0000000000035353","article-title":"Efficacy and safety of caffeic acid tablets in the treatment of thrombocytopenia: A systematic review and meta-analysis","volume":"102","author":"Yu","year":"2023","journal-title":"Medicine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7291774","DOI":"10.1155\/2022\/7291774","article-title":"Epigallocatechin Gallate Relieved PM2.5-Induced Lung Fibrosis by Inhibiting Oxidative Damage and Epithelial-Mesenchymal Transition through AKT\/mTOR Pathway","volume":"2022","author":"Zhongyin","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.resinv.2020.01.003","article-title":"Nintedanib inhibits epithelial-mesenchymal transition in A549 alveolar epithelial cells through regulation of the TGF-beta\/Smad pathway","volume":"58","author":"Ihara","year":"2020","journal-title":"Respir. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"de Godoy, M.C.X., Macedo, J.A., and Gambero, A. (2024). Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010070"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-62703-239-1_8","article-title":"Colorimetric detection of senescence-associated beta galactosidase","volume":"965","author":"Itahana","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/978-1-4939-6430-7_39","article-title":"TGF-beta1- and CCN2-Stimulated Sirius Red Assay for Collagen Accumulation in Cultured Cells","volume":"1489","author":"Trackman","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s10020-021-00283-6","article-title":"TGF-beta-induced alpha-SMA expression is mediated by C\/EBPbeta acetylation in human alveolar epithelial cells","volume":"27","author":"Ding","year":"2021","journal-title":"Mol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7163\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:07:28Z","timestamp":1760108848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":49,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137163"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137163","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}