{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:02:47Z","timestamp":1779692567755,"version":"3.53.1"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by the ingestion of gluten in genetically predisposed individuals. While the adaptive immune response to deamidated gliadin peptides represents a central pathogenic mechanism, growing evidence suggests that epithelial stress and innate immune activation play a fundamental role in the onset and persistence of the disease. Heat shock proteins (Hsps), central regulators of cellular proteostasis, have emerged as potential mediators at the interface between epithelial distress and immune signaling. This review discusses the involvement of major Hsp families, including Hsp27, Hsp60, Hsp70, and Hsp90, in the pathophysiology of CD. The altered expression of Hsp27 and Hsp70 in the intestinal mucosa reflects a persistent state of epithelial stress that often persists despite a strict gluten-free diet (GFD). We focus specifically on Hsp60, whose extracellular release under stress conditions may allow it to function as a damage-associated molecular pattern (DAMP), engaging Toll-like receptors and promoting NF-\u03baB- and inflammasome-dependent inflammatory pathways. Although direct mechanistic evidence linking Hsp60 to CD remains limited, the convergence of epithelial stress signs, Toll-like receptor (TLR) upregulation, and prolonged innate immune activation supports the hypothesis of a stress-induced inflammatory amplification circuit in the coeliac mucosa. Further studies are essential to clarify the pathogenic relevance and potential therapeutic implications of this proposed axis.<\/jats:p>","DOI":"10.3390\/biology15100805","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular Stress and Immune Activation in Celiac Disease: Is the Chaperone System a Key Player?"],"prefix":"10.3390","volume":"15","author":[{"given":"Giuseppe","family":"Vergilio","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Vultaggio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia","family":"Gagliardo","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, National Research Council of Italy (CNR), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-7761","authenticated-orcid":false,"given":"Letizia","family":"Paladino","sequence":"additional","affiliation":[{"name":"Department of Theoretical and Applied Sciences, eCampus University, 22060 Novedrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-5268","authenticated-orcid":false,"given":"Francesca","family":"Rappa","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council of Italy (CNR), 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ilchmann-Diounou, H., and Menard, S. (2020). Psychological stress, intestinal barrier dysfunctions, and autoimmune disorders: An overview. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01823"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41581-023-00720-1","article-title":"Pathogenesis of autoimmune disease","volume":"19","author":"Pisetsky","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2020.03.007","article-title":"Challenges, progress, and prospects of developing therapies to treat autoimmune diseases","volume":"181","author":"Fugger","year":"2020","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1172\/JCI78086","article-title":"Genetic basis of autoimmunity","volume":"125","author":"Marson","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_5","first-page":"437231","article-title":"A potential link between environmental triggers and autoimmunity","volume":"2014","author":"Vojdani","year":"2014","journal-title":"Autoimmune Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tiffon, C. (2018). The impact of nutrition and environmental epigenetics on human health and disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113425"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e70262","DOI":"10.1002\/mco2.70262","article-title":"Autoimmune diseases: Molecular pathogenesis and therapeutic targets","volume":"6","author":"Song","year":"2025","journal-title":"MedComm"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6036","DOI":"10.3748\/wjg.v18.i42.6036","article-title":"Celiac disease: Prevalence, diagnosis, pathogenesis and treatment","volume":"18","author":"Gujral","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20587384211008709","DOI":"10.1177\/20587384211008709","article-title":"Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects","volume":"35","author":"Admou","year":"2021","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dunne, M.R., Byrne, G., Chirdo, F., and Feighery, C. (2020). Coeliac disease pathogenesis: The uncertainties of a well-known immune mediated disorder. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01374"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0140-6736(03)13803-2","article-title":"Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease","volume":"362","author":"Maiuri","year":"2003","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jcmgh.2016.12.006","article-title":"Celiac disease: Role of the epithelial barrier","volume":"3","author":"Schumann","year":"2017","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_13","first-page":"135","article-title":"Chapter 12\u2014Chaperone proteins and Chaperonopathies","volume":"Volume 3","author":"Fink","year":"2019","journal-title":"Handbook of Stress, Stress Physiology, Biochemistry, and Pathology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Caio, G., Volta, U., Sapone, A., Leffler, D.A., De Giorgio, R., Catassi, C., and Fasano, A. (2019). Celiac disease: A comprehensive current review. BMC Med., 17.","DOI":"10.1186\/s12916-019-1380-z"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.autrev.2018.05.013","article-title":"Celiac disease and endocrine autoimmunity\u2014The genetic link","volume":"17","author":"Kahaly","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"389","DOI":"10.5152\/tjg.2018.18635","article-title":"Diagnosing celiac disease: A critical overview","volume":"30","author":"Ensari","year":"2019","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cappello, F., David, S., Rappa, F., Bucchieri, F., Maras\u00e0, L., Bartolotta, T.E., Farina, F., and Zummo, G. (2005). The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer, 5.","DOI":"10.1186\/1471-2407-5-139"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Caruso Bavisotto, C., Cipolla, C., Graceffa, G., Barone, R., Bucchieri, F., Bulone, D., Cabibi, D., Campanella, C., Marino Gammazza, A., and Pitruzzella, A. (2019). Immunomorphological pattern of molecular chaperones in normal and pathological thyroid tissues and circulating exosomes: Potential use in clinics. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184496"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, M., and Bi, X. (2024). Heat shock proteins and breast cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020876"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10735-023-10119-8","article-title":"The chaperone system in cancer therapies: Hsp90","volume":"54","author":"Basset","year":"2023","journal-title":"J. Mol. Histol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbapap.2014.12.019","article-title":"Small heat shock proteins: Role in cellular functions and pathology","volume":"1854","author":"Bakthisaran","year":"2015","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.tibs.2011.11.005","article-title":"Small heat shock proteins and \u03b1-crystallins: Dynamic proteins with flexible functions","volume":"37","author":"Basha","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1600-0404.2010.01475.x","article-title":"Elevated HSP27 levels during attacks in patients with multiple sclerosis","volume":"124","author":"Ce","year":"2011","journal-title":"Acta Neurol. Scand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7021","DOI":"10.4049\/jimmunol.176.11.7021","article-title":"Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis","volume":"176","author":"Roelofs","year":"2006","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ishida, R., Okamoto, T., Motojima, F., Kubota, H., Takahashi, H., Tanabe, M., Oka, T., Kitamura, A., Kinjo, M., and Yoshida, M. (2018). Physicochemical Properties of the Mammalian Molecular Chaperone HSP60. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020489"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"801","DOI":"10.4161\/cbt.7.6.6281","article-title":"Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy","volume":"7","author":"Cappello","year":"2008","journal-title":"Cancer Biol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100012","DOI":"10.1016\/j.mocell.2024.100012","article-title":"The structural basis of eukaryotic chaperonin TRiC\/CCT: Action and folding","volume":"47","author":"Kim","year":"2024","journal-title":"Mol. Cells"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11668","DOI":"10.3390\/cimb46100693","article-title":"Exploring the Gene Expression and Plasma Protein Levels of HSP90, HSP60, and GDNF in Multiple Sclerosis Patients and Healthy Controls","volume":"46","author":"Sokolowski","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s12192-010-0196-8","article-title":"Hsp60 and Hsp10 increase in colon mucosa of Crohn\u2019s disease and ulcerative colitis","volume":"15","author":"Rodolico","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s12192-018-0951-9","article-title":"Autoantibodies to heat shock proteins 60, 70, and 90 in patients with rheumatoid arthritis","volume":"24","author":"Mantej","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Brocchieri, L., de Macario, E.C., and Macario, A.J. (2008). hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions. BMC Evol. Biol., 8.","DOI":"10.1186\/1471-2148-8-19"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.4081\/ejh.2011.e38","article-title":"Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy","volume":"55","author":"Tomasello","year":"2011","journal-title":"Eur. J. Histochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/MPG.0b013e3181ea0092","article-title":"Increased heat shock protein 72 expression in celiac disease","volume":"51","author":"Sziksz","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hoter, A., El-Sabban, M.E., and Naim, H.Y. (2018). The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092560"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1379\/1466-1268(2000)005<0276:THAGSP>2.0.CO;2","article-title":"The hsp110 and Grp170 stress proteins: Newly recognized relatives of the Hsp70s","volume":"5","author":"Easton","year":"2000","journal-title":"Cell Stress Chaperones"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13045-024-01601-1","article-title":"Heat shock proteins as hallmarks of cancer: Insights from molecular mechanisms to therapeutic strategies","volume":"17","author":"Zuo","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cell.2006.04.014","article-title":"Molecular chaperones and protein quality control","volume":"125","author":"Bukau","year":"2006","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"525","DOI":"10.17219\/acem\/44144","article-title":"The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases","volume":"24","author":"Samborski","year":"2015","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1093\/rheumatology\/kew266","article-title":"Heat shock proteins and their immunomodulatory role in inflammatory arthritis","volume":"56","author":"Spierings","year":"2017","journal-title":"Rheumatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jcjd.2016.05.016","article-title":"Heat shock proteins and diabetes","volume":"40","author":"Zilaee","year":"2016","journal-title":"Can. J. Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s10571-011-9789-8","article-title":"The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis","volume":"32","author":"Gammazza","year":"2012","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hoter, A., and Naim, H.Y. (2019). The functions and therapeutic potential of heat shock proteins in inflammatory bowel disease\u2014An update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215331"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1007\/s00018-009-0086-3","article-title":"Heat shock protein 27 phosphorylation: Kinases, phosphatases, functions and pathology","volume":"66","author":"Kostenko","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1128\/MCB.22.3.816-834.2002","article-title":"Hsp27 as a negative regulator of cytochrome C release","volume":"22","author":"Paul","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1053\/j.gastro.2015.05.013","article-title":"Distinct and synergistic contributions of epithelial stress and adaptive immunity to functions of intraepithelial killer cells and active celiac disease","volume":"149","author":"Setty","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bavisotto, C.C., Alberti, G., Vitale, A.M., Paladino, L., Campanella, C., Rappa, F., Gorska, M., de Macario, E.C., Cappello, F., and Macario, A.J.L. (2020). Hsp60 post-translational modifications: Functional and pathological consequences. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00095"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1002\/mco2.161","article-title":"Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.3748\/wjg.v23.i44.7849","article-title":"Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations","volume":"23","author":"Pasko","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Barone, M.V., Auricchio, R., Nanayakkara, M., Greco, L., Troncone, R., and Auricchio, S. (2022). Pivotal role of inflammation in celiac disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137177"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Calderwood, S.K., Gong, J., and Murshid, A. (2016). Extracellular HSPs: The complicated roles of extracellular HSPs in immunity. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00159"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zininga, T., Ramatsui, L., and Shonhai, A. (2018). Heat shock proteins as immunomodulants. Molecules, 23.","DOI":"10.3390\/molecules23112846"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.it.2010.11.001","article-title":"The HSP60 immune system network","volume":"32","author":"Quintana","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12974-016-0486-x","article-title":"HSP60 plays a regulatory role in IL-1\u03b2-induced microglial inflammation via TLR4-p38 MAPK axis","volume":"13","author":"Swaroop","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12974-018-1214-5","article-title":"HSP60 critically regulates endogenous IL-1\u03b2 production in activated microglia by stimulating NLRP3 inflammasome pathway","volume":"15","author":"Swaroop","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhen, Y., and Zhang, H. (2019). NLRP3 inflammasome and inflammatory bowel disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00276"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"110542","DOI":"10.1016\/j.biopha.2020.110542","article-title":"Role of the NLRP3 inflammasome in autoimmune diseases","volume":"130","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.2353\/ajpath.2010.100371","article-title":"IL-1beta-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-kappaB pathway","volume":"177","author":"Ye","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kaminsky, L.W., Al-Sadi, R., and Ma, T.Y. (2021). IL-1\u03b2 and the intestinal epithelial tight junction barrier. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.767456"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e1251384","DOI":"10.1080\/21688370.2016.1251384","article-title":"Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases","volume":"4","author":"Sturgeon","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/MPG.0b013e318064514a","article-title":"Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in celiac disease","volume":"45","author":"Szebeni","year":"2007","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Talipova, D., Smagulova, A., and Poddighe, D. (2022). Toll-like receptors and celiac disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010265"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"31332","DOI":"10.1074\/jbc.M103217200","article-title":"Endocytotic HSP60s use the toll-like receptor 2 (TLR2) and TLR4 to activate the toll\/interleukin-1 receptor signaling pathway in innate immune cells","volume":"276","author":"Vabulas","year":"2001","journal-title":"J. Biol. Chem."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/10\/805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:05:30Z","timestamp":1779689130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/10\/805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":62,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biology15100805"],"URL":"https:\/\/doi.org\/10.3390\/biology15100805","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]}}}