{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T09:56:09Z","timestamp":1770717369711,"version":"3.49.0"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,16]],"date-time":"2016-04-16T00:00:00Z","timestamp":1460764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The regulation of melanin production is important for managing skin darkness and hyperpigmentary disorders. Numerous anti-melanogenic agents that target tyrosinase activity\/stability, melanosome maturation\/transfer, or melanogenesis-related signaling pathways have been developed. As a rate-limiting enzyme in melanogenesis, tyrosinase has been the most attractive target, but tyrosinase-targeted treatments still pose serious potential risks, indicating the necessity of developing lower-risk anti-melanogenic agents. Sugars are ubiquitous natural compounds found in humans and other organisms. Here, we review the recent advances in research on the roles of sugars and sugar-related agents in melanogenesis and in the development of sugar-based anti-melanogenic agents. The proposed mechanisms of action of these agents include: (a) (natural sugars) disturbing proper melanosome maturation by inducing osmotic stress and inhibiting the PI3 kinase pathway and (b) (sugar derivatives) inhibiting tyrosinase maturation by blocking N-glycosylation. Finally, we propose an alternative strategy for developing anti-melanogenic sugars that theoretically reduce melanosomal pH by inhibiting a sucrose transporter and reduce tyrosinase activity by inhibiting copper incorporation into an active site. These studies provide evidence of the utility of sugar-based anti-melanogenic agents in managing skin darkness and curing pigmentary disorders and suggest a future direction for the development of physiologically favorable anti-melanogenic agents.<\/jats:p>","DOI":"10.3390\/ijms17040583","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T10:37:17Z","timestamp":1460975837000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Development of Sugar-Based Anti-Melanogenic Agents"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-9873","authenticated-orcid":false,"given":"Bum-Ho","family":"Bin","sequence":"first","affiliation":[{"name":"AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhyuk","family":"Bhin","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, POSTECH, Pohang 790-784, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3615-5763","authenticated-orcid":false,"given":"Eun-Gyung","family":"Cho","sequence":"additional","affiliation":[{"name":"AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1006\/jtbi.1993.1142","article-title":"Melanocytes as \u201csensory\u201d and regulatory cells in the epidermis","volume":"164","author":"Slominski","year":"1993","journal-title":"J. Theor. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1210\/er.2012-1092","article-title":"Key role of crf in the skin stress response system","volume":"34","author":"Slominski","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1046\/j.1523-1747.1999.00653.x","article-title":"The role of melanin in the induction of oxidative DNA base damage by ultraviolet a irradiation of DNA or melanoma cells","volume":"113","author":"Kvam","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1038\/jid.2014.161","article-title":"UV signaling pathways within the skin","volume":"134","author":"Chen","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_5","first-page":"1","article-title":"Unraveling the melanocyte","volume":"52","author":"Hearing","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1600-0749.1989.tb00170.x","article-title":"l-tyrosine, l-dopa, and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in bomirski ab amelanotic melanoma cells","volume":"2","author":"Slominski","year":"1989","journal-title":"Pigment Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1755-148X.2011.00898.x","article-title":"l-Tyrosine and l-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions","volume":"25","author":"Slominski","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_8","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_9","first-page":"457","article-title":"Neuroendocrinology of the skin","volume":"21","author":"Slominski","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_10","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_11","first-page":"20","article-title":"Postinflammatory hyperpigmentation: A review of the epidemiology, clinical features, and treatment options in skin of color","volume":"3","author":"Davis","year":"2010","journal-title":"J. Clin. Aesth. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/bjd.13059","article-title":"Risk factors for facial melasma in women: A case-control study","volume":"171","author":"Handel","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin pigmentation in mammalian skin and its hormonal regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/biof.29","article-title":"Physiological factors that regulate skin pigmentation","volume":"35","author":"Yamaguchi","year":"2009","journal-title":"Biofactors"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1755-148X.2010.00800.x","article-title":"Wnt\/\u03b2-catenin signaling is stimulated by \u03b1-melanocyte-stimulating hormone in melanoma and melanocyte cells: Implication in cell differentiation","volume":"24","author":"Bellei","year":"2011","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1038\/jid.2012.324","article-title":"Tyrosinase: A central regulatory protein for cutaneous pigmentation","volume":"132","author":"Park","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.biocel.2010.03.023","article-title":"Signaling pathways in melanosome biogenesis and pathology","volume":"42","author":"Schiaffino","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.humpath.2013.02.022","article-title":"Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma","volume":"44","author":"Brozyna","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/exd.12618","article-title":"The role of melanin pigment in melanoma","volume":"24","author":"Slominski","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.mayocp.2014.02.009","article-title":"Melanoma resistance: A bright future for academicians and a challenge for patient advocates","volume":"89","author":"Slominski","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.autrev.2015.12.006","article-title":"Vitiligo: Pathogenesis, clinical variants and treatment approaches","volume":"15","author":"Iannella","year":"2015","journal-title":"Autoimmun. Rrev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jdermsci.2015.07.010","article-title":"Effects of rhododendrol and its metabolic products on melanocytic cell growth","volume":"80","author":"Okura","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/jid.2011.321","article-title":"Six decades of vitiligo genetics: Genome-wide studies provide insights into autoimmune pathogenesis","volume":"132","author":"Spritz","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jdermsci.2015.01.002","article-title":"An immune pathological and ultrastructural skin analysis for rhododenol-induced leukoderma patients","volume":"77","author":"Tanemura","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8293","DOI":"10.3390\/ijms15058293","article-title":"Inhibitors of intracellular signaling pathways that lead to stimulated epidermal pigmentation: Perspective of anti-pigmenting agents","volume":"15","author":"Imokawa","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1096\/fj.04-2079rev","article-title":"The cutaneous serotoninergic\/melatoninergic system: Securing a place under the sun","volume":"19","author":"Slominski","year":"2005","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/ng584","article-title":"Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka","volume":"28","author":"Fukamachi","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bin, B.H., Bhin, J., Yang, S.H., Choi, D.H., Park, K., Shin, D.W., Lee, A.Y., Hwang, D., Cho, E.G., and Lee, T.R. (2014). Hyperosmotic stress reduces melanin production by altering melanosome formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105965"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1242\/jcs.082024","article-title":"Identification of an animal sucrose transporter","volume":"124","author":"Meyer","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1600-0749.2005.00288.x","article-title":"Tyrosinase maturation through the mammalian secretory pathway: Bringing color to life","volume":"19","author":"Wang","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1093\/hmg\/ddp003","article-title":"Molecular genetics of human pigmentation diversity","volume":"18","author":"Sturm","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1242\/jcs.01154","article-title":"Carbohydrates act as sorting determinants in er-associated degradation of tyrosinase","volume":"117","author":"Svedine","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/jez.1402680216","article-title":"Molecular basis for osmoregulation of organic osmolytes in renal medullary cells","volume":"268","author":"Burg","year":"1994","journal-title":"J. Exp. Zool."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/j.1600-0625.2008.00746.x","article-title":"Ultraviolet a induces transport of compatible organic osmolytes in human dermal fibroblasts","volume":"17","author":"Warskulat","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.0022-202X.2004.23313.x","article-title":"The osmolyte strategy of normal human keratinocytes in maintaining cell homeostasis","volume":"123","author":"Warskulat","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01868535","article-title":"Role of organic osmolytes in adaptation of renal cells to high osmolality","volume":"119","author":"Burg","year":"1991","journal-title":"J. Membr. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/jcp.22840","article-title":"Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea","volume":"227","author":"Mavrogonatou","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bin, B.H., Bhin, J., Yang, S.H., Shin, M., Nam, Y.J., Choi, D.H., Shin, D.W., Lee, A.Y., Hwang, D., and Cho, E.G. (2015). Membrane-associated transporter protein (MATP) regulates melanosomal ph and influences tyrosinase activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129273"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12188","DOI":"10.3390\/ijms150712188","article-title":"Novel inhibitory effect of N-(2-hydroxycyclohexyl)valiolamine on melanin production in a human skin model","volume":"15","author":"Bin","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/exd.12195","article-title":"Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis","volume":"22","author":"Bin","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1007\/s00253-012-4184-z","article-title":"Enzymatic production of 3,6-anhydro-l-galactose from agarose and its purification and in vitro skin whitening and anti-inflammatory activities","volume":"97","author":"Yun","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1271\/bbb.61.162","article-title":"Neoagarobiose as a novel moisturizer with whitening effect","volume":"61","author":"Kobayashi","year":"1997","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/jcp.1040920107","article-title":"Effects of sugars on melanogenesis in cultured melanoma cells","volume":"92","author":"Nakayasu","year":"1977","journal-title":"J.Cell. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/1523-1747.ep12524388","article-title":"Importance of glycoproteins in the initiation of melanogenesis: An electron microscopic study of b-16 melanoma cells after release from inhibition of glycosylation","volume":"87","author":"Imokawa","year":"1986","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mrfmmm.2004.06.053","article-title":"Hypertonic stress response","volume":"569","author":"Dmitrieva","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1046\/j.1523-1747.2002.01710.x","article-title":"Functional expression of AQP3 in human skin epidermis and reconstructed epidermis","volume":"118","author":"Sougrat","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/1523-1747.ep12462252","article-title":"Electron probe analysis of human skin: Determination of the water concentration profile","volume":"90","author":"Warner","year":"1988","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1242\/jcs.110.17.2027","article-title":"Dense core lysosomes can fuse with late endosomes and are re-formed from the resultant hybrid organelles","volume":"110","author":"Bright","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1034\/j.1600-0854.2001.20906.x","article-title":"The relationship between lumenal and limiting membranes in swollen late endocytic compartments formed after wortmannin treatment or sucrose accumulation","volume":"2","author":"Bright","year":"2001","journal-title":"Traffic"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1242\/jcs.040667","article-title":"Melanosomes at a glance","volume":"121","author":"Wasmeier","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8169","DOI":"10.1074\/jbc.275.11.8169","article-title":"Mutations at critical n-glycosylation sites reduce tyrosinase activity by altering folding and quality control","volume":"275","author":"Negroiu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1600-0625.2006.00515.x","article-title":"Influence of N-glycan processing disruption on tyrosinase and melanin synthesis in HM3KO melanoma cells","volume":"16","author":"Choi","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"15796","DOI":"10.1074\/jbc.272.25.15796","article-title":"Inhibition of N-glycan processing in B16 melanoma cells results in inactivation of tyrosinase but does not prevent its transport to the melanosome","volume":"272","author":"Petrescu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5924","DOI":"10.1074\/jbc.M009203200","article-title":"Translation rate of human tyrosinase determines its N-linked glycosylation level","volume":"276","author":"Ujvari","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1034\/j.1600-0749.2003.00029.x","article-title":"Chemical and instrumental approaches to treat hyperpigmentation","volume":"16","author":"Briganti","year":"2003","journal-title":"Pigment Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/sj.jid.5700683","article-title":"Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase","volume":"127","author":"Ando","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_57","first-page":"1994","article-title":"Loss of melanogenic properties in tyrosinases induced by glucosylation inhibitors within malignant melanoma cells","volume":"42","author":"Imokawa","year":"1982","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1021\/jm00156a023","article-title":"Synthesis and \u03b1-d-glucosidase inhibitory activity of N-substituted valiolamine derivatives as potential oral antidiabetic agents","volume":"29","author":"Horii","year":"1986","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bin, B.H., Kim, S.T., Bhin, J., Byoun, K., Lee, T.R., and Cho, E.G. (2016). Synergistic effect of maltose enhances the anti-melanogenic activity of acarbose, Unpublished work.","DOI":"10.1007\/s00403-017-1717-4"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"905472","DOI":"10.1155\/2014\/905472","article-title":"Mutational analysis of oculocutaneous albinism: A compact review","volume":"2014","author":"Kamaraj","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1750-1172-2-43","article-title":"Oculocutaneous albinism","volume":"2","author":"Gronskov","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1360\/yc-006-1149","article-title":"A new form of oculocutaneous albinism, OCA4","volume":"28","author":"Li","year":"2006","journal-title":"Yi Chuan"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1086\/324340","article-title":"Mutations in the human orthologue of the mouse underwhite gene (UW) underlie a new form of oculocutaneous albinism, oca4","volume":"69","author":"Newton","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1042\/BJ20140572","article-title":"Proton-associated sucrose transport of mammalian solute carrier family 45: An analysis in saccharomyces cerevisiae","volume":"464","author":"Bartolke","year":"2014","journal-title":"Biochem. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nature07163","article-title":"Cell-specific atp7a transport sustains copper-dependent tyrosinase activity in melanosomes","volume":"454","author":"Setty","year":"2008","journal-title":"Nature"},{"key":"ref_66","first-page":"729","article-title":"The involvement of histidine at the active site of harding-passey mouse melanoma tyrosinase","volume":"11","author":"Martinez","year":"1985","journal-title":"Biochem. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/excr.2001.5251","article-title":"Melanosomal ph controls rate of melanogenesis, eumelanin\/phaeomelanin ratio and melanosome maturation in melanocytes and melanoma cells","volume":"268","author":"Ancans","year":"2001","journal-title":"Exp. Cell Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/4\/583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:22:23Z","timestamp":1760210543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/4\/583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,16]]},"references-count":67,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4]]}},"alternative-id":["ijms17040583"],"URL":"https:\/\/doi.org\/10.3390\/ijms17040583","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,16]]}}}