{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:20Z","timestamp":1787028560465,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Nacional de Lujan","award":["DISP CDD-CD 243-21"],"award-info":[{"award-number":["DISP CDD-CD 243-21"]}]},{"name":"Universidad Nacional de Lujan","award":["DISP CDD-CB 490-23"],"award-info":[{"award-number":["DISP CDD-CB 490-23"]}]},{"name":"Universidad Nacional de Lujan","award":["BID PICT 2021 GRFTI507"],"award-info":[{"award-number":["BID PICT 2021 GRFTI507"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a metabolic condition of epidemic scale. Previously, we showed that antioxidant extracts from Ribes nigrum had antioxidant and anti-adipogenic effects in mature adipocytes (AD). Here, we evaluated an aqueous extract from Peumus boldus (Boldo) in AD and studied its effect on reactive oxygen species (ROS) and lipid production. We analyzed the antioxidant activity (AA) of the Boldo extract using the DPPH technique and polyphenol (Pph) content via Folin\u2019s reagent. In AD, we evaluated ROS production, catalase (CAT) activity, intracellular triglyceride (Tg) and cholesterol (Chol) contents, nitric oxide (NO) production via Griess reagent, and the levels of glycerol (Gly) and TNF-\u03b1 released in the culture medium. We showed that the Boldo extract has high AA. In vitro, Boldo treatment decreased ROS intracellular production and CAT activity. In addition, the Boldo extract was effective in reducing Tg and Chol levels and NO production. We did not identify significant differences in Gly released or TNF-\u03b1 secreted. We suggest that the Boldo extract has antioxidant and anti-adipogenic effects, but we did not observe lipolytic effects. Boldo did not modify inflammatory markers.<\/jats:p>","DOI":"10.3390\/ijms26094326","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:44:58Z","timestamp":1746171898000},"page":"4326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Peumus boldus Extract Inhibits Lipid Accumulation in 3T3-L1 Adipocytes"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-9325","authenticated-orcid":false,"given":"Laura","family":"Montaldo","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llerson","family":"Bendezu Meza","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"De Marzi","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"},{"name":"CONICET-INEDES, Grupo de Investigaciones Basicas y Aplicadas en Inmunolog\u0131a y Bioactivos (GIBAIB), Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-7358","authenticated-orcid":false,"given":"Liliana Noemi","family":"Guerra","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Basicas, Universidad Nacional de Lujan, Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"},{"name":"CONICET-INEDES, Grupo de Investigaciones Basicas y Aplicadas en Inmunolog\u0131a y Bioactivos (GIBAIB), Av Constitucion y Ruta 5, Lujan 6700, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-48382-5_1","article-title":"The Definition and Prevalence of Obesity and Metabolic Syndrome","volume":"Volume 960","author":"Engin","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0092-8674(74)90126-3","article-title":"Sublines of Mouse 3T3 Cells That Accumulate Lipid","volume":"1","author":"Green","year":"1974","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1258\/ebm.2010.010063","article-title":"Cell Line Models for Differentiation: Preadipocytes and Adipocytes","volume":"235","author":"Poulos","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Soto, D., Martini, C.N., Frontera, E.M., Montaldo, L.A., Vila, M.D.C., Calvo, J.C., and Guerra, L.N. (2020). N-Acetylcysteine Inhibits Lipids Production in Mature Adipocytes Through the Inhibition of Peroxisome Proliferator-Activated Receptor \u03b3. Int. J. Biochem. Res. Rev., 17\u201329.","DOI":"10.9734\/ijbcrr\/2020\/v29i430182"},{"key":"ref_5","unstructured":"Mallappa, K. (2020). Plant-Derived Bioactives: Production, Properties and Therapeutic Applications, Springer. [1st ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1080\/87559129.2020.1717523","article-title":"Immunomodulatory; Anti-Inflammatory\/antioxidant Effects of Polyphenols: A Comparative Review on the Parental Compounds and Their Metabolites","volume":"37","author":"Sobhani","year":"2021","journal-title":"Food Rev. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kiokias, S., Proestos, C., and Oreopoulou, V. (2020). Phenolic Acids of Plant Origin-A Review on Their Antioxidant Activity in Vitro (O\/W Emulsion Systems) along with Their in Vivo Health Biochemical Properties. Foods, 9.","DOI":"10.3390\/foods9040534"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s11626-021-00549-7","article-title":"3,5-Dimethoxy-4-Benzoic Acid (syringic Acid) a Natural Phenolic Acid Reduces Reactive Oxygen Species in Differentiated 3T3-L1 Adipocytes","volume":"57","author":"John","year":"2021","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Lee, S., and Cho, E.J. (2020). Flavonoids from Acer Okamotoanum Inhibit Adipocyte Differentiation and Promote Lipolysis in the 3T3-L1 Cells. Molecules, 25.","DOI":"10.3390\/molecules25081920"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s11130-012-0289-x","article-title":"Phenolic Compounds from Mat\u00e9 (Ilex paraguariensis) Inhibit Adipogenesis in 3T3-L1 Preadipocytes","volume":"67","author":"Gosmann","year":"2012","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_11","first-page":"911","article-title":"Separation Conditions and Evaluation of Antioxidant Properties of Boldo (Peumus boldus) Extracts","volume":"7","author":"Belmares","year":"2013","journal-title":"J. Med. Plants Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.chroma.2009.11.014","article-title":"Direct Identification of Phenolic Constituents in Boldo Folium (Peumus boldus Mol.) Infusions by High-Performance Liquid Chromatography with Diode Array Detection and Electrospray Ionization Tandem Mass Spectrometry","volume":"1217","author":"Simirgiotis","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/(SICI)1099-1573(200003)14:2<99::AID-PTR600>3.0.CO;2-4","article-title":"Toxicological Evaluation of the Hydro-Alcohol Extract of the Dry Leaves of Peumus boldus and Boldine in Rats","volume":"14","author":"Almeida","year":"2000","journal-title":"Phytother. Res. PTR"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/ptr.2746","article-title":"Effect of boldo (Peumus boldus Molina) infusion on lipoperoxidation induced by cisplatin in mice liver","volume":"23","author":"Fernandez","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10601","DOI":"10.1074\/jbc.M808742200","article-title":"Reactive Oxygen Species Facilitate Adipocyte Differentiation by Accelerating Mitotic Clonal Expansion","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.biocel.2012.10.007","article-title":"Dietary Polyphenols Preconditioning Protects 3T3-L1 Preadipocytes from Mitochondrial Alterations Induced by Oxidative Stress","volume":"45","author":"Baret","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3390\/cells1040976","article-title":"Redox Mechanisms in Regulation of Adipocyte Differentiation: Beyond a General Stress Response","volume":"1","author":"Liu","year":"2012","journal-title":"Cells"},{"key":"ref_18","unstructured":"Mayer, B. (2012). Nitric Oxide, Springer Science & Business Media."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11010-006-9369-2","article-title":"Nitric Oxide Suppresses Preadipocyte Differentiation in 3T3-L1 Culture","volume":"300","author":"Kawachi","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.febslet.2007.11.051","article-title":"TNF-Alpha and Adipocyte Biology","volume":"582","author":"Cawthorn","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/oby.2008.39","article-title":"Dietary Fatty Acids Differentially Regulate Production of TNF-Alpha and IL-10 by Murine 3T3-L1 Adipocytes","volume":"16","author":"Bradley","year":"2008","journal-title":"Obesity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-7-1","article-title":"Signaling Pathways Involved in LPS Induced TNFalpha Production in Human Adipocytes","volume":"7","author":"Hoareau","year":"2010","journal-title":"J. Inflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9165","DOI":"10.3892\/mmr.2017.7710","article-title":"Ginsenoside Rb1 Inhibits Free Fatty Acids-induced Oxidative Stress and Inflammation in 3T3-L1 Adipocytes","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lin, D., Xiao, M., Zhao, J., Li, Z., Xing, B., Li, X., Kong, M., Li, L., Zhang, Q., and Liu, Y. (2016). An Overview of Plant Phenolic Compounds and Their Importance in Human Nutrition and Management of Type 2 Diabetes. Molecules, 21.","DOI":"10.3390\/molecules21101374"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kowalska, K., Olejnik, A., Szwajgier, D., and Olkowicz, M. (2017). Inhibitory Activity of Chokeberry, Bilberry, Raspberry and Cranberry Polyphenol-Rich Extract Towards Adipogenesis and Oxidative Stress in Differentiated 3T3-L1 Adipose Cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188583"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"675","DOI":"10.4155\/tde-2023-0018","article-title":"Anthocyanin-Enriched Extract from Ribes Nigrum Inhibits Triglyceride and Cholesterol Accumulation in Adipocytes","volume":"14","author":"Montaldo","year":"2023","journal-title":"Ther. Deliv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.foodchem.2008.08.008","article-title":"DPPH Antioxidant Assay Revisited","volume":"113","author":"Sharma","year":"2009","journal-title":"Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Udomwasinakun, N., Pirak, T., and Chanput, W.P. (2022). Identification of Polyphenols in White Mugwort (Artemisia lactiflora Wall.) Ethanolic Extracts and Their Anti-Inflammatory and Anti-Adipogenic Activity Potential. Food Biosci., 47.","DOI":"10.1016\/j.fbio.2022.101761"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Torres, I., Castrej\u00f3n-T\u00e9llez, V., Soto, M.E., Rubio-Ruiz, M.E., Manzano-Pech, L., and Guarner-Lans, V. (2021). Oxidative Stress, Plant Natural Antioxidants, and Obesity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041786"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1161\/CIRCULATIONAHA.115.018585","article-title":"Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Shabbir, U., Rubab, M., Daliri EB, M., Chelliah, R., Javed, A., and Oh, D.H. (2021). Curcumin, Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota. Nutrients, 13.","DOI":"10.3390\/nu13010206"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100485","DOI":"10.1016\/j.jlr.2023.100485","article-title":"From NAFLD to MASLD: Updated Naming and Diagnosis Criteria for Fatty Liver Disease","volume":"65","author":"Rinella","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tarantino, G., Balsano, C., Santini, S.J., Brienza, G., Clemente, I., Cosimini, B., and Sinatti, G. (2021). It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413424"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.fbp.2013.06.002","article-title":"Effect of Extraction Conditions on Total Phenolic Content and Antioxidant Capacity of Pretreated Wild Peumus boldus Leaves from Chile","volume":"92","author":"Soto","year":"2014","journal-title":"Food Bioprod. Process."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"C371","DOI":"10.1111\/j.1365-2621.2004.tb10700.x","article-title":"Antioxidant Activity of Crude Extract, Alkaloid Fraction, and Flavonoid Fraction from Boldo (Peumus boldus Molina) Leaves","volume":"69","author":"Quezada","year":"2004","journal-title":"J. Food Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3839\/jksabc.2009.012","article-title":"Production of Reactive Oxygen Species and Changes in Antioxidant Enzyme Activities During Differentiation of 3T3-L1 Adipocyte","volume":"52","author":"Lee","year":"2009","journal-title":"J. Korean Soc. Appl. Biol. Chem."},{"key":"ref_37","first-page":"210","article-title":"N-Acetylcysteine Affects Obesity-Related Protein Expression in 3T3-L1 Adipocytes","volume":"18","author":"Calzadilla","year":"2013","journal-title":"Redox Rep. Commun. Free Radic. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, L., Zheng, M., Cai, H., Chen, J., Lin, Y., Wang, F., Wang, L., Zhang, X., and Liu, J. (2023). The Activity Comparison of Six Dietary Flavonoids Identifies That Luteolin Inhibits 3T3-L1 Adipocyte Differentiation through Reducing ROS Generation. J. Nutr. Biochem., 112.","DOI":"10.1016\/j.jnutbio.2022.109208"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Donaldson, L. (2020). Autofluorescence in Plants. Molecules, 25.","DOI":"10.3390\/molecules25102393"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104332","DOI":"10.1016\/j.phrs.2019.104332","article-title":"The Beneficial Effects of N-Acetyl Cysteine (NAC) Against Obesity Associated Complications: A Systematic Review of Pre-Clinical Studies","volume":"146","author":"Dludla","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.3390\/ijms12106936","article-title":"N-Acetylcysteine Reduces Markers of Differentiation in 3T3-L1 Adipocytes","volume":"12","author":"Calzadilla","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4014\/jmb.1910.10040","article-title":"Antioxidant and Anti-Obesity Activities of Polygonum cuspidatum Extract Through Alleviation of Lipid Accumulation on 3T3-L1 Adipocytes","volume":"30","author":"Choi","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1006\/bbrc.2002.6444","article-title":"Insulin Stimulates Nitric Oxide Production in Rat Adipocytes","volume":"291","author":"Jaubert","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Munteanu, I.G., and Apetrei, C. (2021). Analytical Methods Used in Determining Antioxidant Activity: A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073380"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1021\/jf048396b","article-title":"Rapid Determination of Polyphenols and Vitamin C in Plant-Derived Products","volume":"53","author":"Brat","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","first-page":"530","article-title":"Automatic Aluminum Chloride Method for Routine Estimation of Total Flavonoids in Red Wines and Teas","volume":"5","author":"Almeida","year":"2011","journal-title":"Food Anal. Methods"},{"key":"ref_47","first-page":"265","article-title":"N-Acetylcysteine Inhibits Kinase Phosphorylation during 3T3-L1 Adipocyte Differentiation","volume":"22","author":"Soto","year":"2017","journal-title":"Redox Rep. Commun. Free Radic. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s13105-021-00826-9","article-title":"Alendronate Inhibits Triglyceride Accumulation and Oxidative Stress in Adipocytes and the Inflammatory Response of Macrophages Which Are Associated with Adipose Tissue Dysfunction","volume":"77","author":"Martini","year":"2021","journal-title":"J. Physiol. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"287","DOI":"10.4155\/tde-2020-0093","article-title":"N-Acetylcysteine Delivery with Silica Nanoparticles into 3T3-L1 Adipocytes","volume":"12","author":"Frontera","year":"2021","journal-title":"Ther. Deliv."},{"key":"ref_51","first-page":"185","article-title":"Thyroid Hormone Effect in Human Hepatocytes","volume":"13","author":"Miler","year":"2008","journal-title":"Redox Rep. Commun. Free Radic. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.redox.2016.05.006","article-title":"N-Acetylcysteine Inhibits Lipid Accumulation in Mouse Embryonic Adipocytes","volume":"9","author":"Pieralisi","year":"2016","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3390\/s30800276","article-title":"Measurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay","volume":"3","author":"Sun","year":"2003","journal-title":"Sensors"},{"key":"ref_54","unstructured":"(2020). Oliveira S\u00e1, A; Pimentel, T; Oliveira, N. Boldo-Induced Hepatotoxicity: A Case of Unexplained Jaundice. Eur. J. Case Rep. Intern. Med., 7, 002116."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijcard.2003.06.039","article-title":"Cardiovascular pharmacotherapy and herbal medicines: The risk of drug interaction","volume":"98","author":"Izzo","year":"2005","journal-title":"Int. J. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1016\/j.transproceed.2014.01.021","article-title":"Case report: Boldo (Peumus boldus) and tacrolimus interaction in a renal transplant patient","volume":"46","author":"Carbajal","year":"2014","journal-title":"Transpl. Proc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:26:14Z","timestamp":1760030774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26094326"],"URL":"https:\/\/doi.org\/10.3390\/ijms26094326","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]}}}