{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:48:03Z","timestamp":1790887683846,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["Department of Biochemistry"],"award-info":[{"award-number":["Department of Biochemistry"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conde de Valenciana Foundation","award":["Researh Unit"],"award-info":[{"award-number":["Researh Unit"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Allergic conjunctivitis (AC) is one of the most common ophthalmological disorders seen in clinical practice. Growing evidence from recent years suggests that a subset of IL-10-expressing B cells is involved in inflammatory allergic diseases. In this study, we aimed to evaluate the potential involvement of blood Bregs cells in perennial allergic conjunctivitis (PAC), and interleukins (IL)-1\u03b2, IL-6, IL-8, IL-10, and IL-12, and tumor necrosis factor (TNF)-\u03b1, were measured in tear samples and compared with healthy controls (HC) using flow cytometry. Non-significant differences in CD19+IL-10+ cell frequency between PAC patients and healthy controls (HC) were observed. Nevertheless, when we analyzed the mean fluorescence intensity (MFI) of IL-10 on CD19+CD38Lo\/Med\/Hi-gated cells, we observed a significant decrease in MFI in all Bregs subsets in PAC patients. Additionally, tear cytokines showed 2.8 times lower levels of IL-10 than TNF-\u03b1 in PAC patients when compared to HC. Our findings demonstrate an immunological dysregulation in patients with allergic conjunctivitis, characterized by the low expression of IL-10 in circulating CD19+CD38+ Bregs subsets and an inverted tear IL-10\/TNF-\u03b1 ratio, promoting a local pro-inflammatory microenvironment. These findings highlight the novel pathologic changes involved in ocular allergic diseases. Understanding systemic and local mechanisms will aid the design of immunomodulating therapeutics at different levels.<\/jats:p>","DOI":"10.3390\/ijms20051035","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T11:41:03Z","timestamp":1551267663000},"page":"1035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Low Expression of IL-10 in Circulating Bregs and Inverted IL-10\/TNF-\u03b1 Ratio in Tears of Patients with Perennial Allergic Conjunctivitis: A Preliminary Study"],"prefix":"10.3390","volume":"20","author":[{"given":"Alberto","family":"Salazar","sequence":"first","affiliation":[{"name":"Departamento de Inmunolog\u00eda, ENCB, Instituto Polit\u00e9cnico Nacional, 11340 Ciudad de M\u00e9xico, Mexico"},{"name":"Department of Immunology and Research Unit, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Casanova-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Research Unit, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Pacheco-Quito","sequence":"additional","affiliation":[{"name":"Cornea and Refractive Surgery Department, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-4875","authenticated-orcid":false,"given":"Henry","family":"Vel\u00e1zquez-Soto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Research Unit, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Ayala-Balboa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Research Unit, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique O.","family":"Graue-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Cornea and Refractive Surgery Department, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanet","family":"Seraf\u00edn-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, ENCB, Instituto Polit\u00e9cnico Nacional, 11340 Ciudad de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3982-9097","authenticated-orcid":false,"given":"Mar\u00eda C.","family":"Jim\u00e9nez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Research Unit, Institute of Ophthalmology \u201cConde de Valenciana Foundation\u201d, 06800 Mexico City, Mexico"},{"name":"Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico. P.O. Box 70159, 04510 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.pcl.2014.03.009","article-title":"Allergic eye disease","volume":"61","author":"Kaufman","year":"2014","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/ACI.0b013e32834a9676","article-title":"Epidemiology of allergic conjunctivitis","volume":"11","author":"Rosario","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.atmosenv.2018.05.006","article-title":"Pollen in the atmosphere of Mexico City and its impact on the health of the pediatric population","volume":"186","year":"2018","journal-title":"Atmos. Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.5415\/apallergy.2018.8.e7","article-title":"The International Study of the Allergic Rhinitis Survey: Outcomes from 4 geographical regions","volume":"8","author":"Passali","year":"2018","journal-title":"Asia Pac. Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/ACI.0000000000000299","article-title":"An update on ocular allergy","volume":"16","author":"Shaker","year":"2016","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_6","first-page":"443","article-title":"Intracellular IL-4, IL-5 and IFN-g as the main characteristic of CD4+CD30+ T cells after allergen-stimulation, in patients with vernal keratoconjunctivitis","volume":"21","author":"Aguilar","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1111\/j.1365-2222.2009.03320.x","article-title":"Seasonal changes in suppressive capacity of CD4+ CD25+ T cells from patients with hayfever are allergen-specific and may result in part from expansion of effector T cells among the CD25+ population","volume":"39","author":"Anderson","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Galicia-Carre\u00f3n, J., Santacruz, C., Ayala-Balboa, J., Robles-Contreras, A., Perez-Tapia, S.M., Garfias, Y., Hong, E., and Jim\u00e9nez-Mart\u00ednez, M.C. (2013). An Imbalance Between Frequency of CD4+CD25+FOXP3+ Regulatory T Cells, and CCR4+ and CCR9+ Circulating Helper T cells is Associated with Active Perennial Allergic Conjunctivitis. Clin. Dev. Immunol.","DOI":"10.1155\/2013\/919742"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/gene.2014.45","article-title":"Regulatory T cells and immune regulation of allergic diseases: Roles of IL-10 and TGF-\u03b2","volume":"15","author":"Palomares","year":"2014","journal-title":"Genes Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2353\/ajpath.2010.090936","article-title":"Control of Th2-Mediated Inflammation by Regulatory T Cells","volume":"177","author":"Poojary","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000106461","article-title":"Expansion of B cells is necessary for the induction of T-cell tolerance elicited through the anterior chamber of the eye","volume":"144","author":"Ashour","year":"2007","journal-title":"Int. Arch Allergy Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12598","DOI":"10.1523\/JNEUROSCI.1994-16.2016","article-title":"Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation","volume":"36","author":"Pennati","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_13","first-page":"173ra23","article-title":"CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation","volume":"5","author":"Bosma","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/ni833","article-title":"B cells regulate autoimmunity by provision of IL-10","volume":"3","author":"Fillatreau","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jaci.2016.07.006","article-title":"Role of regulatory B cells in immune tolerance to allergens and beyond","volume":"138","author":"Stanic","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s00011-005-1387-0","article-title":"Deficiency of regulatory B cells increases allergic airway inflammation","volume":"54","author":"Lundy","year":"2005","journal-title":"Inflamm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bekeredjian-Ding, I., Foermer, S., Kirschning, C.J., Parcina, M., and Heeg, K. (2012). Poke weed mitogen requires Toll-like receptor ligands for proliferative activity in human and murine B lymphocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029806"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1067\/mai.2000.111238","article-title":"Allergic and immunologic disorders of the eye. Part II: Ocular allergy","volume":"106","author":"Bielory","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","first-page":"172","article-title":"The ocular surface: From physiology to the ocular allergic diseases","volume":"60","author":"Santacruz","year":"2013","journal-title":"Rev. Alerg. Mexico"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1167\/iovs.08-2701","article-title":"Regulatory function of CpG-activated B cells in late-phase experimental allergic conjunctivitis","volume":"50","author":"Miyazaki","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF02789175","article-title":"Fundamentals of flow cytometry","volume":"11","author":"Jaroszeski","year":"1999","journal-title":"Mol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/clin.1994.1023","article-title":"Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements","volume":"70","author":"Hulstaert","year":"1994","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2249.2010.04206.x","article-title":"Reference values for B cell subpopulations from infancy to adulthood","volume":"162","author":"Morbach","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/sji.12413","article-title":"Effects of Ageing on the Immune System: Infants to Elderly","volume":"83","author":"Valiathan","year":"2016","journal-title":"Scand. J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2010-07-294249","article-title":"Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells","volume":"117","author":"Iwata","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.immuni.2009.11.009","article-title":"CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients","volume":"32","author":"Blair","year":"2010","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e12664","DOI":"10.1111\/sji.12664","article-title":"CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL-10 production by regulatory B cells","volume":"87","year":"2018","journal-title":"Scand. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s12967-014-0251-9","article-title":"Increased numbers of CD5+CD19+CD1dhighIL-10+ Bregs, CD4+Foxp3+ Tregs, CD4+CXCR5+Foxp3+ follicular regulatory T (TFR) cells in CHB or CHC patients","volume":"9","author":"Wang","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jeong, Y.I., Hong, S.H., Cho, S.H., Lee, W.J., and Lee, S.E. (2012). Induction of IL-10-producing CD1dhighCD5+ regulatory B cells following Babesia microti-infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046553"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/0304-4165(78)90366-5","article-title":"Carbohydrate-binding specificity of pokeweed mitogens","volume":"538","author":"Yokoyama","year":"1978","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dewald, J.H., Colomb, F., Bobowski-Gerard, M., Groux-Degroote, S., and Delannoy, P. (2016). Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer. Cells, 29.","DOI":"10.3390\/cells5040043"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cyto.2014.10.031","article-title":"Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy","volume":"74","author":"Saxena","year":"2014","journal-title":"Cytokine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.4049\/jimmunol.146.10.3444","article-title":"IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells","volume":"146","author":"Fiorentino","year":"1991","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1084\/jem.173.2.507","article-title":"Interleukin 10: A novel stimulatory factor for mast cells and their progenitors","volume":"173","author":"Dhar","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/all.13334","article-title":"Clinical implications of mast cell involvement in allergic conjunctivitis","volume":"73","author":"Rambasek","year":"2018","journal-title":"Allergy"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/j.1365-2222.2006.02499.x","article-title":"Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjunctival fibroblast cultures","volume":"36","author":"Leonardi","year":"2006","journal-title":"Clin. Exp. Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1136\/bjophthalmol-2011-301382","article-title":"Cytological changes in tears during the secondary conjunctival response induced by nasal allergy","volume":"96","author":"Pelikan","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3109\/02713683.2013.836542","article-title":"Cytokine profiles in tears accompanying the secondary conjunctival responses induced by nasal allergy","volume":"39","author":"Pelikan","year":"2014","journal-title":"Curr. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Skwor, T.A., Atik, B., Kandel, R.P., Adhikari, H.K., Sharma, B., and Dean, D. (2008). Role of secreted conjunctival mucosal cytokine and chemokine proteins in different stages of trachomatous disease. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000264"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"247.e1","DOI":"10.1016\/j.ajo.2013.04.003","article-title":"Analysis of tear cytokines and clinical correlations in Sj\u00f6gren syndrome dry eye patients and non-Sj\u00f6gren syndrome dry eye patients","volume":"156","author":"Lee","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1136\/bjo.2006.100180","article-title":"Interleukin 10 and transforming growth factor beta contribute to the development of experimentally induced allergic conjunctivitis in mice during the effector phase","volume":"90","author":"Fukushima","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exer.2017.10.019","article-title":"Unlike Th1\/Th17 cells, Th2\/Th9 cells selectively migrate to the limbus\/conjunctiva and initiate an eosinophilic infiltration process","volume":"166","author":"Tan","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1615\/CritRevImmunol.v37.i2-6.50","article-title":"Tumor Necrosis Factor: Function, Release and Clearance","volume":"37","author":"Bemelmans","year":"2017","journal-title":"Crit. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cyto.2008.07.007","article-title":"Cytokine responses by conjunctival epithelial cells: An in vitro model of ocular inflammation","volume":"44","author":"Calder","year":"2008","journal-title":"Cytokine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2249.2008.03716.x","article-title":"Allergy and the eye","volume":"153","author":"Leonardi","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2332\/allergolint.09-OA-0092","article-title":"Corneal and conjunctival fibroblasts are major sources of eosinophil-recruiting chemokines","volume":"58","author":"Fukagawa","year":"2009","journal-title":"Allergol. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s11882-002-0061-7","article-title":"The central role of conjunctival mast cells in the pathogenesis of ocular allergy","volume":"2","author":"Leonardi","year":"2002","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1097\/ICO.0000000000000989","article-title":"Bilateral Alterations in Corneal Nerves, Dendritic Cells, and Tear Cytokine Levels in Ocular Surface Disease","volume":"35","author":"Yamaguchi","year":"2016","journal-title":"Cornea"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.jaci.2013.01.014","article-title":"IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses","volume":"131","author":"Stanic","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/ACI.0000000000000400","article-title":"The role of regulatory B cells in allergen immunotherapy","volume":"17","year":"2017","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4168\/aair.2018.10.3.236","article-title":"Analysis of Peripheral B Cell Subsets in Patients With Allergic Rhinitis","volume":"10","author":"Luo","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.4049\/jimmunol.155.8.4090","article-title":"Paradoxical effects of IL-10 in endotoxin-induced uveitis","volume":"15","author":"Rosenbaum","year":"1995","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/bjo.85.7.861","article-title":"Ex vivo adenovirus mediated gene transfection of human conjunctival epithelium","volume":"85","author":"Shen","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/00003226-200203000-00018","article-title":"Expression of IL-10 and TNF-inhibitor genes in lacrimal gland epithelial cells suppresses their ability to activate lymphocytes","volume":"21","author":"Zhu","year":"2002","journal-title":"Cornea"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.3390\/ijms16034850","article-title":"Expression of IL-8, IL-6 and IL-1\u03b2 in tears as a main characteristic of the immune response in human microbial keratitis","volume":"16","author":"Santacruz","year":"2015","journal-title":"Int. J. Mol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/5\/1035\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:35:06Z","timestamp":1760186106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/5\/1035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["ijms20051035"],"URL":"https:\/\/doi.org\/10.3390\/ijms20051035","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]}}}