{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T21:53:18Z","timestamp":1771365198101,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["FIS\/IMSS\/PROT\/PRIO\/16\/058"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/PRIO\/16\/058"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["271815"],"award-info":[{"award-number":["271815"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2\u2032-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects.<\/jats:p>","DOI":"10.3390\/molecules26071909","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T16:01:57Z","timestamp":1617033717000},"page":"1909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["5-Aza-2\u2032-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Alain","family":"Aguirre-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Noreste, Departamento de Biolog\u00eda Molecular, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Le\u00f3n 64720, Mexico"},{"name":"Departamento de Biolog\u00eda Molecular, Instituto Potosino de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, San Luis Potos\u00ed, San Luis Potos\u00ed 78216, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6906-4561","authenticated-orcid":false,"given":"Luis A.","family":"Salazar-Olivo","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Instituto Potosino de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, San Luis Potos\u00ed, San Luis Potos\u00ed 78216, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X\u00f3chitl","family":"Flores-Ponce","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular-Neurociencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Laboratorio de Reprogramaci\u00f3n Celular, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda \u201cManuel Velasco Su\u00e1rez\u201d, Ciudad de M\u00e9xico14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L.","family":"Arriaga-Guerrero","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Noreste, Departamento de Biolog\u00eda Molecular, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Le\u00f3n 64720, Mexico"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, UANL, San Nicol\u00e1s de los Garza, Nuevo Le\u00f3n 66451, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dariela","family":"Garza-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Noreste, Departamento de Biolog\u00eda Molecular, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Le\u00f3n 64720, Mexico"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, UANL, San Nicol\u00e1s de los Garza, Nuevo Le\u00f3n 66451, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-6574","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Camacho-Moll","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Noreste, Departamento de Biolog\u00eda Molecular, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Le\u00f3n 64720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-6578","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Velasco","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular-Neurociencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"},{"name":"Laboratorio de Reprogramaci\u00f3n Celular, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda \u201cManuel Velasco Su\u00e1rez\u201d, Ciudad de M\u00e9xico14269, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Castorena-Torres","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Tecnologico de Monterrey, Monterrey, Nuevo Le\u00f3n 64710, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7155-0486","authenticated-orcid":false,"given":"Nidheesh","family":"Dadheech","sequence":"additional","affiliation":[{"name":"Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0993-2969","authenticated-orcid":false,"given":"Mario","family":"Berm\u00fadez de Le\u00f3n","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica del Noreste, Departamento de Biolog\u00eda Molecular, Instituto Mexicano del Seguro Social, Monterrey, Nuevo Le\u00f3n 64720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1242\/dev.092551","article-title":"Induced pluripotent stem cells in medicine and biology","volume":"140","author":"Takahashi","year":"2013","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.32607\/20758251-2010-2-2-18-27","article-title":"Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine","volume":"2","author":"Medvedev","year":"2010","journal-title":"Acta Nat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1089\/scd.2015.0366","article-title":"Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells","volume":"25","author":"Galat","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nbt.3070","article-title":"A comparison of non-integrating reprogramming methods","volume":"33","author":"Schlaeger","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1126\/science.1239278","article-title":"Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds","volume":"341","author":"Hou","year":"2013","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/jmcb\/mjr028","article-title":"Global epigenetic changes during somatic cell reprogramming to iPS cells","volume":"3","author":"Mattout","year":"2011","journal-title":"J. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"A160","DOI":"10.1289\/ehp.114-a160","article-title":"Epigenetics: The science of change","volume":"114","author":"Weinhold","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.mehy.2008.10.039","article-title":"Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology","volume":"73","author":"Csoka","year":"2009","journal-title":"Med. Hypotheses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1038\/sj.onc.1205699","article-title":"5-Azacytidine and 5-aza-2\u2032-deoxycytidine as inhibitors of DNA methylation: Mechanistic studies and their implications for cancer therapy","volume":"21","author":"Christman","year":"2002","journal-title":"Oncogene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/03602532.2018.1437446","article-title":"Effects of 5-Aza-2\u2032-deoxycytidine (decitabine) on gene expression","volume":"50","author":"Seelan","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1158\/0008-5472.CAN-04-2478","article-title":"Valproic acid alters chromatin structure by regulation of chromatin modulation proteins","volume":"65","author":"Marchion","year":"2005","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"Phiel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/jcp.25270","article-title":"Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence","volume":"231","author":"Chen","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nmeth.1591","article-title":"A more efficient method to generate integration-free human iPS cells","volume":"8","author":"Okita","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-1-61779-201-4_8","article-title":"Traditional human embryonic stem cell culture","volume":"767","author":"Schwartz","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Biswas, D., and Jiang, P. (2016). Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020226"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1002\/stem.240","article-title":"Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2","volume":"27","author":"Li","year":"2009","journal-title":"Stem Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.stem.2010.11.015","article-title":"Reprogramming of human primary somatic cells by OCT4 and chemical compounds","volume":"7","author":"Zhu","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.cell.2015.11.017","article-title":"A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming","volume":"163","author":"Zhao","year":"2015","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1089\/scd.2012.0261","article-title":"Basal expression of pluripotency-associated genes can contribute to stemness property and differentiation potential","volume":"22","author":"Dadheech","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1089\/clo.2009.0015","article-title":"Induction of stem cell gene expression in adult human fibroblasts without transgenes","volume":"11","author":"Page","year":"2009","journal-title":"Cloning Stem Cells"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature09342","article-title":"Epigenetic memory in induced pluripotent stem cells","volume":"467","author":"Kim","year":"2010","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nbt.1502","article-title":"Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2","volume":"26","author":"Huangfu","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.theriogenology.2008.04.042","article-title":"Increased pre-implantation development of cloned bovine embryos treated with 5-aza-2\u2032-deoxycytidine and trichostatin A","volume":"70","author":"Ding","year":"2008","journal-title":"Theriogenology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1074\/jbc.M309002200","article-title":"Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells","volume":"279","author":"Hattori","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.5966\/sctm.2015-0225","article-title":"Linking Pluripotency Reprogramming and Cancer","volume":"6","author":"Iglesias","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3892\/or.2013.2456","article-title":"OCT4 is epigenetically regulated by DNA hypomethylation of promoter and exon in primary gliomas","volume":"30","author":"Shi","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cao, L., Li, C., Shen, S., Yan, Y., Ji, W., Wang, J., Qian, H., Jiang, X., Li, Z., and Wu, M. (2013). OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-82"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, K.Y., Wang, L.T., Hsu, S.H., and Wang, S.N. (2019). Homeobox Genes and Hepatocellular Carcinoma. Cancers (Basel), 11.","DOI":"10.20944\/preprints201904.0224.v1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M502573200","article-title":"Transcriptional regulation of nanog by OCT4 and SOX2","volume":"280","author":"Rodda","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.stem.2008.06.019","article-title":"Wnt signaling promotes reprogramming of somatic cells to pluripotency","volume":"3","author":"Marson","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ai, Z., Shao, J., Wu, Y., Yu, M., Du, J., Shi, X., Shi, X., Zhang, Y., and Guo, Z. (2016). CHIR99021 enhances Klf4 Expression through beta-Catenin Signaling and miR-7a Regulation in J1 Mouse Embryonic Stem Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150936"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1093\/nar\/gnh146","article-title":"Hypervariable genes--experimental error or hidden dynamics","volume":"32","author":"Dozmorov","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt950","article-title":"Capturing and profiling adult hair follicle stem cells","volume":"22","author":"Morris","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3892\/ijo.2016.3556","article-title":"S100A4 influences cancer stem cell-like properties of MGC803 gastric cancer cells by regulating GDF15 expression","volume":"49","author":"Guo","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Zhou, Y., Zhou, X., Guo, Y., Huang, D., Zhang, J., Wang, C., and Cai, L. (2018). S100A4 suppresses cancer stem cell proliferation via interaction with the IKK\/NF-kappaB signaling pathway. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4563-7"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1158\/0008-5472.CAN-17-1294","article-title":"S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma","volume":"77","author":"Chow","year":"2017","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/nn.3510","article-title":"Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake","volume":"16","author":"Flavahan","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nrc1877","article-title":"Fibroblasts in cancer","volume":"6","author":"Kalluri","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1038\/oncsis.2014.44","article-title":"Deficiency of Kruppel-like factor KLF4 in myeloid-derived suppressor cells inhibits tumor pulmonary metastasis in mice accompanied by decreased fibrocytes","volume":"3","author":"Shi","year":"2014","journal-title":"Oncogenesis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1053\/j.gastro.2006.08.041","article-title":"The metastasis-associated gene S100A4 is a novel target of beta-catenin\/T-cell factor signaling in colon cancer","volume":"131","author":"Stein","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00109-007-0301-3","article-title":"S100A4: A common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?","volume":"86","author":"Schneider","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1007\/s13277-015-3709-3","article-title":"S100A4 participates in epithelial-mesenchymal transition in breast cancer via targeting MMP2","volume":"37","author":"Xu","year":"2016","journal-title":"Tumour. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jim-2017-000542","article-title":"S100A4 amplifies TGF-beta-induced epithelial-mesenchymal transition in a pleural mesothelial cell line","volume":"66","author":"Ning","year":"2018","journal-title":"J. Investig. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.7150\/jca.25469","article-title":"S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-beta-Mediated Epithelial-Mesenchymal Transition","volume":"9","author":"Li","year":"2018","journal-title":"J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.3892\/or.2016.4760","article-title":"S100A4 promotes endometrial cancer progress through epithelial-mesenchymal transition regulation","volume":"35","author":"Hua","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.1172482","article-title":"Human induced pluripotent stem cells free of vector and transgene sequences","volume":"324","author":"Yu","year":"2009","journal-title":"Science"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/7\/1909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:10:19Z","timestamp":1760364619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/7\/1909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["molecules26071909"],"URL":"https:\/\/doi.org\/10.3390\/molecules26071909","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]}}}