{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:00:25Z","timestamp":1789038025342,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PUT1465"],"award-info":[{"award-number":["PUT1465"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG1189"],"award-info":[{"award-number":["PRG1189"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Translational Genomics of University of Tartu","award":["SP1GVARENG"],"award-info":[{"award-number":["SP1GVARENG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The melanocortin system is a major regulator of stress responses in the skin and is responsible for the induction of melanin synthesis through activation of melanogenesis enzymes. The expression of both melanocortin system genes and melanogenesis enzyme genes is altered in psoriasis, and the focus here was on twelve genes related to the signal transduction between them. Additionally, five endogenous opioid system genes that are involved in cutaneous inflammation were examined. Quantitative real-time-PCR was utilized to measure mRNA expression in punch biopsies from lesional and non-lesional skin of psoriasis patients and from the skin of healthy control subjects. Most of the genes related to melanogenesis were down-regulated in patients (CREB1, MITF, LEF1, USF1, MAPK14, ICAM1, PIK3CB, RPS6KB1, KIT, and ATRN). Conversely, an up-regulation occurred in the case of opioids (PENK, PDYN, and PNOC). The suppression of genes related to melanogenesis is in agreement with the reported reduction in pigmentation signaling in psoriatic skin and potentially results from the pro-inflammatory environment. The increase in endogenous opioids can be associated with their involvement in inflammatory dysregulation in psoriasis.<\/jats:p>","DOI":"10.3390\/ijms222313056","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:19:08Z","timestamp":1638479948000},"page":"13056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Expression Pattern of Genes Related to Melanogenesis and Endogenous Opioids in Psoriasis"],"prefix":"10.3390","volume":"22","author":[{"given":"Ulvi","family":"Loite","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7348-2125","authenticated-orcid":false,"given":"Liisi","family":"Raam","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"},{"name":"Dermatology Clinic, Tartu University Hospital, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5410-4433","authenticated-orcid":false,"given":"Ene","family":"Reimann","sequence":"additional","affiliation":[{"name":"Institute of Genomics, University of Tartu, 23b\/2 Riia, 51010 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Reemann","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ele","family":"Prans","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Tartu University Hospital, 8 L. Puusepa, 51014 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-8534","authenticated-orcid":false,"given":"Tanel","family":"Traks","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-345X","authenticated-orcid":false,"given":"Eero","family":"Vasar","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi","family":"Silm","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"},{"name":"Dermatology Clinic, Tartu University Hospital, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fclli","family":"Kingo","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, University of Tartu, 31 Raja, 50417 Tartu, Estonia"},{"name":"Dermatology Clinic, Tartu University Hospital, 31 Raja, 50417 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-6643","authenticated-orcid":false,"given":"Sulev","family":"K\u00f5ks","sequence":"additional","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, 8 Verdun St., Nedlands, WA 6009, Australia"},{"name":"Centre for Comparative Genomics, Murdoch University, 90 South St., Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jaad.2008.09.022","article-title":"The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: Results from NHANES 2003\u20132004","volume":"60","author":"Kurd","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/jid.2012.339","article-title":"Global epidemiology of psoriasis: A systematic review of incidence and prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/bjd.12355","article-title":"Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis","volume":"169","author":"Dowlatshahi","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/1346-8138.14139","article-title":"Pathogenesis of psoriasis and development of treatment","volume":"45","author":"Ogawa","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"adv00030","DOI":"10.2340\/00015555-3384","article-title":"Psoriasis and Genetics","volume":"100","author":"Dand","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17705","DOI":"10.3390\/ijms151017705","article-title":"Local melatoninergic system as the protector of skin integrity","volume":"15","author":"Slominski","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-19683-6_1","article-title":"Sensing the environment: Regulation of local and global homeostasis by the skin\u2019s neuroendocrine system","volume":"212","author":"Slominski","year":"2012","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri3646","article-title":"Mechanisms regulating skin immunity and inflammation","volume":"14","author":"Pasparakis","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000087012","article-title":"Neuroendocrine system of the skin","volume":"211","author":"Slominski","year":"2005","journal-title":"Dermatology"},{"key":"ref_10","first-page":"985815","article-title":"Curbing Inflammation through Endogenous Pathways: Focus on Melanocortin Peptides","volume":"2013","author":"Ahmed","year":"2013","journal-title":"Int. J. Inflam."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"683","DOI":"10.3389\/fendo.2019.00683","article-title":"Melanocortin Regulation of Inflammation","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_12","first-page":"1421","article-title":"Roles of inflammation factors in melanogenesis (Review)","volume":"21","author":"Fu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1159\/000447535","article-title":"Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin","volume":"232","author":"Liakou","year":"2016","journal-title":"Dermatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1038\/jid.2013.237","article-title":"IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: Potential relevance to psoriasis","volume":"133","author":"Wang","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/j.1365-2230.2011.04088.x","article-title":"Postinflammatory hypopigmentation","volume":"36","author":"Vachiramon","year":"2011","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.2340\/00015555-1524","article-title":"Gene expression analysis of the corticotrophin-releasing hormone-proopiomelanocortin system in psoriasis skin biopsies","volume":"93","author":"Loite","year":"2013","journal-title":"Acta Derm. Venereol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"444","DOI":"10.2340\/00015555-3137","article-title":"Polymorphisms in Corticotrophin-releasing Hormone-proopiomelanocortin (CRH-POMC) System Genes are Associated with Plaque Psoriasis","volume":"99","author":"Traks","year":"2019","journal-title":"Acta Derm. Venereol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1600-0625.2009.00844.x","article-title":"Opioids and the skin\u2014Where do we stand?","volume":"18","author":"Bigliardi","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/physrev.2000.80.3.979","article-title":"Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress","volume":"80","author":"Slominski","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2045-8118-12-3","article-title":"The effects of beta-endorphin: State change modification","volume":"12","author":"Veening","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"ref_21","first-page":"4014","article-title":"beta-Endorphin attenuates collagen-induced arthritis partially by inhibiting peripheral pro-inflammatory mediators","volume":"15","author":"He","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/exd.13021","article-title":"Opioids and skin homeostasis, regeneration and ageing\u2014What\u2019s the evidence?","volume":"25","author":"Bigliardi","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s11926-007-0081-3","article-title":"Leukocytes as mediators of pain and analgesia","volume":"9","author":"Rittner","year":"2007","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jdermsci.2010.08.004","article-title":"Analysis of the expression profile of CRH-POMC system genes in vitiligo skin biopsies","volume":"60","author":"Reimann","year":"2010","journal-title":"J. Dermatol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, S.A., Finlay, G.J., Baguley, B.C., and Askarian-Amiri, M.E. (2016). Signaling Pathways in Melanogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071144"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1034\/j.1600-0749.2000.130203.x","article-title":"Cyclic AMP a key messenger in the regulation of skin pigmentation","volume":"13","author":"Busca","year":"2000","journal-title":"Pigment. Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1093\/emboj\/21.11.2703","article-title":"Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling","volume":"21","author":"Yasumoto","year":"2002","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1600-0749.2006.00348.x","article-title":"Activation of the Mitf promoter by lipid-stimulated activation of p38-stress signalling to CREB","volume":"19","author":"Saha","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6877","DOI":"10.4049\/jimmunol.166.11.6877","article-title":"The p38 mitogen-activated protein kinase mediates cytoskeletal remodeling in pulmonary microvascular endothelial cells upon intracellular adhesion molecule-1 ligation","volume":"166","author":"Wang","year":"2001","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/1523-1747.ep12460991","article-title":"Interleukins 1 alpha and 6 and tumor necrosis factor-alpha are paracrine inhibitors of human melanocyte proliferation and melanogenesis","volume":"96","author":"Swope","year":"1991","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.immuni.2006.02.014","article-title":"IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB\/AP-1 proteins","volume":"24","author":"Hu","year":"2006","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1016\/j.jaci.2020.12.657","article-title":"Cross-talk between IFN-\u03b3 and TWEAK through miR-149 amplifies skin inflammation in psoriasis","volume":"147","author":"Srivastava","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/pcmr.12190","article-title":"IFN-\u03b3 inhibits basal and \u03b1-MSH-induced melanogenesis","volume":"27","author":"Son","year":"2014","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jdermsci.2008.03.013","article-title":"Expressional changes in the intracellular melanogenesis pathways and their possible role in the pathogenesis of vitiligo","volume":"52","author":"Kingo","year":"2008","journal-title":"J. Dermatol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1365-2133.2004.06304.x","article-title":"The mitogen-activated protein kinases p38 and ERK1\/2 are increased in lesional psoriatic skin","volume":"152","author":"Johansen","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jaci.2019.06.019","article-title":"Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis","volume":"144","author":"Sakurai","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1242\/jcs.093773","article-title":"Classes of phosphoinositide 3-kinases at a glance","volume":"127","author":"Jean","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/sj.leu.2404245","article-title":"Phosphoinositide 3-kinase\/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia","volume":"20","author":"Martelli","year":"2006","journal-title":"Leukemia"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wu, P.Y., You, Y.J., Liu, Y.J., Hou, C.W., Wu, C.S., Wen, K.C., Lin, C.Y., and Chiang, H.M. (2018). Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041108"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1046\/j.1440-1711.2000.00928.x","article-title":"Cellular function of p70S6K: A role in regulating cell motility","volume":"78","author":"Berven","year":"2000","journal-title":"Immunol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"31824","DOI":"10.1074\/jbc.271.50.31824","article-title":"Inhibition of the phosphatidylinositol 3-kinase\/p70(S6)-kinase pathway induces B16 melanoma cell differentiation","volume":"271","author":"Busca","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/labinvest.2013.84","article-title":"Melanoma genotypes and phenotypes get personal","volume":"93","author":"Pimiento","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/path.1538","article-title":"Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: Role of SCF\/KIT protein interactions and the downstream effector, MITF-M","volume":"202","author":"Kitamura","year":"2004","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/ics.12466","article-title":"Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation","volume":"40","author":"Serre","year":"2018","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mce.2013.01.022","article-title":"Involvement of Nurr-1\/Nur77 in corticotropin-releasing factor\/urocortin1-induced tyrosinase-related protein 1 gene transcription in human melanoma HMV-II cells","volume":"370","author":"Watanuki","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/1529-0131(200104)44:4<782::AID-ANR134>3.0.CO;2-H","article-title":"Involvement of the nuclear orphan receptor NURR1 in the regulation of corticotropin-releasing hormone expression and actions in human inflammatory arthritis","volume":"44","author":"Murphy","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/sj.jid.5701023","article-title":"Increased expression of the orphan nuclear receptor NURR1 in psoriasis and modulation following TNF-alpha inhibition","volume":"128","author":"Markham","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/18217","article-title":"The mouse mahogany locus encodes a transmembrane form of human attractin","volume":"398","author":"Gunn","year":"1999","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1755-148X.2009.00582.x","article-title":"Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: A cAMP-independent pathway","volume":"22","author":"Hida","year":"2009","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/jid.2010.376","article-title":"Regulated proenkephalin expression in human skin and cultured skin cells","volume":"131","author":"Slominski","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00403-011-1169-1","article-title":"Innate immunity in the pathogenesis of psoriasis","volume":"303","author":"Sweeney","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2133.2011.10347.x","article-title":"Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch","volume":"165","author":"Taneda","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhang, L., Stuber, F., and Stamer, U.M. (2013). Inflammatory mediators influence the expression of nociceptin and its receptor in human whole blood cultures. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074138"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"836569","DOI":"10.4061\/2011\/836569","article-title":"NOP Receptor Ligands as Potential Agents for Inflammatory and Autoimmune Diseases","volume":"2011","author":"Gavioli","year":"2011","journal-title":"J. Amino Acids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18045","DOI":"10.1038\/s41598-017-18404-9","article-title":"RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin","volume":"7","author":"Swindell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2340\/00015555-3066","article-title":"Keratinocyte Transcriptome in Psoriasis: Pathways Related to Immune Responses, Cell Cycle and Keratinization","volume":"99","author":"Pasquali","year":"2019","journal-title":"Acta Derm. Venereol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00403-010-1080-1","article-title":"Definition of treatment goals for moderate to severe psoriasis: A European consensus","volume":"303","author":"Mrowietz","year":"2011","journal-title":"Arch. Dermatol. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:55Z","timestamp":1760168335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":57,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222313056"],"URL":"https:\/\/doi.org\/10.3390\/ijms222313056","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]}}}