{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:29:23Z","timestamp":1785432563154,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2023-04780"],"award-info":[{"award-number":["RGPIN-2023-04780"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RGPIN-2023-04780"],"award-info":[{"award-number":["RGPIN-2023-04780"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT175226"],"award-info":[{"award-number":["PJT175226"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PJT175226"],"award-info":[{"award-number":["PJT175226"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, leading to deregulated gene expression. The expression of the KMT2A-MLLT3 protein, resulting from a chromosomal translocation in mixed-lineage leukemia (MLL), a subtype of acute myeloid leukemia, augments transcription elongation, promoting the expression of HOXA9 and MEIS1, genes that play critical roles in MLL development. Bortezomib, a proteasome inhibitor, has been effective at treating various cancers. In this study, we compared the impact of bortezomib on histone PTMs in the MLL cell line MOLM-13 and the chronic myeloid leukemic (CML) cell line K562. We report that MOLM-13 had a greater level of histone H2B monoubiquitinated at lysine 120 (H2BK120ub) and histone H3 dimethylated at lysine 79 (H3K79me2) (modifications involved in elongation) and similar levels of histone H2A monoubiquitinated at lysine 119 (H2AK119ub). Bortezomib treatment resulted in significant reductions in H2BK120ub and H2AK119ub levels, as well as in transcript levels of genes involved in MLL development.<\/jats:p>","DOI":"10.3390\/ijms27156597","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:38:41Z","timestamp":1784889521000},"page":"6597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-0781","authenticated-orcid":false,"given":"Hedieh","family":"Sattarifard","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvellous","family":"Oyeyode","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3525-0267","authenticated-orcid":false,"given":"Dhanvi","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Duaqui","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurlovleen","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishdeep","family":"Muker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Luo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analysis Laboratory, College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6625-6717","authenticated-orcid":false,"given":"Ted M.","family":"Lakowski","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analysis Laboratory, College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-6888","authenticated-orcid":false,"given":"James R.","family":"Davie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3343\/alm.2016.36.2.85","article-title":"Systematic Classification of Mixed-Lineage Leukemia Fusion Partners Predicts Additional Cancer Pathways","volume":"36","author":"Marschalek","year":"2016","journal-title":"Ann. Lab. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1128\/MCB.00182-12","article-title":"The super elongation complex family of RNA polymerase II elongation factors: Gene target specificity and transcriptional output","volume":"32","author":"Luo","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"szae089","DOI":"10.1093\/stcltm\/szae089","article-title":"Targeting chromatin modifying complexes in acute myeloid leukemia","volume":"14","author":"Schurer","year":"2025","journal-title":"Stem Cells Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.celrep.2015.12.034","article-title":"Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis","volume":"14","author":"Maat","year":"2016","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-58971-4_1","article-title":"Structure, Dynamics and Function of the 26S Proteasome","volume":"96","author":"Mao","year":"2021","journal-title":"Subcell. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1083\/jcb.200510071","article-title":"A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling","volume":"173","author":"Dantuma","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14418","DOI":"10.1021\/bi970998j","article-title":"Rapid deubiquitination of nucleosomal histones in human tumor cells caused by proteasome inhibitors and stress response inducers: Effects on replication, transcription, translation, and the cellular stress response","volume":"36","author":"Mimnaugh","year":"1997","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41467-023-36370-x","article-title":"Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia","volume":"14","author":"Kamens","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.tig.2020.12.005","article-title":"Histone Ubiquitination: An Integrative Signaling Platform in Genome Stability","volume":"37","author":"Mattiroli","year":"2021","journal-title":"Trends Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117122","DOI":"10.1016\/j.bcp.2025.117122","article-title":"Regulation, functions and therapeutic strategies of H2AK119ub1","volume":"240","author":"Zhang","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-031-75980-2_1","article-title":"Basic Epigenetic Mechanisms","volume":"108","author":"Davie","year":"2025","journal-title":"Subcell. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11684-026-1209-z","article-title":"Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): Its multifaceted role in biology and implication in diseases","volume":"20","author":"Wu","year":"2026","journal-title":"MedScience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9978","DOI":"10.1093\/nar\/gkae698","article-title":"Ubiquitinated histone H2B as gatekeeper of the nucleosome acidic patch","volume":"52","author":"Hicks","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13072-025-00635-0","article-title":"Mechanistic basis for the opposing effects of H2A and H2B ubiquitination on nucleosome stability and dynamics","volume":"18","author":"Baweja","year":"2025","journal-title":"Epigenet. Chromatin"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Marsh, D.J., Ma, Y., and Dickson, K.A. (2020). Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer. Cancers, 12.","DOI":"10.3390\/cancers12113462"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110369","DOI":"10.1016\/j.celrep.2022.110369","article-title":"DOT1L activity in leukemia cells requires interaction with ubiquitylated H2B that promotes productive nucleosome binding","volume":"38","author":"Spangler","year":"2022","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1101\/gad.323790.118","article-title":"Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase","volume":"33","author":"Jang","year":"2019","journal-title":"Genes Dev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Delcuve, G.P., and Davie, J.R. (2002). Protein Blotting of Basic Proteins Resolved on Acid-Urea-Triton-Polyacrylamide Gels. The Protein Protocols Handbook, Springer.","DOI":"10.1385\/1-59259-169-8:337"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17284","DOI":"10.1038\/s41598-025-01657-0","article-title":"Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia","volume":"15","author":"Jenkins","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4161\/epi.6.5.15623","article-title":"An acetylation-mono-ubiquitination switch on lysine 120 of H2B","volume":"6","author":"Gatta","year":"2011","journal-title":"Epigenetics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wood, K., Tellier, M., and Murphy, S. (2018). DOT1L and H3K79 Methylation in Transcription and Genomic Stability. Biomolecules, 8.","DOI":"10.3390\/biom8010011"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1038\/s41467-018-04329-y","article-title":"MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity","volume":"9","author":"Skucha","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/leu.2017.339","article-title":"SETD2-mediated crosstalk between H3K36me3 and H3K79me2 in MLL-rearranged leukemia","volume":"32","author":"Bu","year":"2018","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/ijc.35332","article-title":"Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions","volume":"158","author":"Perner","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.molcel.2022.02.013","article-title":"MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape","volume":"82","author":"Olsen","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.molcel.2019.03.029","article-title":"Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination","volume":"74","author":"Wang","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9565","DOI":"10.1038\/s41467-025-65439-y","article-title":"Molecular mechanism of co-transcriptional H3K36 methylation by SETD2","volume":"16","author":"Walshe","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1126\/science.adn6319","article-title":"Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription","volume":"387","author":"Markert","year":"2025","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3324\/haematol.2018.187708","article-title":"Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation","volume":"103","author":"Zhou","year":"2018","journal-title":"Haematologica"},{"key":"ref_30","first-page":"2308","article-title":"Overexpression of KDM4D promotes acute myeloid leukemia cell development by activating MCL-1","volume":"13","author":"Wu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1021\/bi00472a002","article-title":"Level of ubiquitinated histone H2B in chromatin is coupled to ongoing transcription","volume":"29","author":"Davie","year":"1990","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s12253-015-9977-9","article-title":"Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers","volume":"22","author":"Melling","year":"2016","journal-title":"Pathol. Oncol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22576","DOI":"10.1038\/s41598-025-06219-y","article-title":"Effect of defective H2B ubiquitination on the malignancy and repair of DNA double breaks and its significance in lung adenocarcinoma","volume":"15","author":"An","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00280-005-0135-z","article-title":"Bortezomib interactions with chemotherapy agents in acute leukemia in vitro","volume":"58","author":"Horton","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13046-017-0493-5","article-title":"Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells","volume":"36","author":"Bista","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13045-024-01604-y","article-title":"Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia","volume":"17","author":"Sedloev","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.1093\/nar\/9.13.3151","article-title":"Rapid turnover of the histone-ubiquitin conjugate, protein A24","volume":"9","author":"Seale","year":"1981","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/17501911.2025.2501524","article-title":"Ubiquitin proteasome system (UPS): A crucial determinant of the epigenetic landscape in cancer","volume":"17","author":"Roy","year":"2025","journal-title":"Epigenomics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1016\/j.apsb.2023.02.019","article-title":"Deubiquitination complex platform: A plausible mechanism for regulating the substrate specificity of deubiquitinating enzymes","volume":"13","author":"Fang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.febslet.2010.10.042","article-title":"The role of deubiquitinating enzymes in chromatin regulation","volume":"585","author":"Atanassov","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41467-023-36467-3","article-title":"H2B ubiquitination recruits FACT to maintain a stable altered nucleosome state for transcriptional activation","volume":"14","author":"Luo","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_42","first-page":"4513","article-title":"Rapid cytoplasmic turnover of c-myc mRNA: Requirement of the 3\u2019 untranslated sequences","volume":"7","author":"Jones","year":"1987","journal-title":"Mol. Cell. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1073\/pnas.1301045110","article-title":"Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1021\/acschembio.2c00887","article-title":"Effects of Histone H2B Ubiquitylations and H3K79me3 on Transcription Elongation","volume":"18","author":"Huynh","year":"2023","journal-title":"ACS Chem. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.3324\/haematol.2019.220962","article-title":"Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: A report from the Children\u2019s Oncology Group","volume":"105","author":"Aplenc","year":"2020","journal-title":"Haematologica"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"van Dijk, A.D., Hoff, F.W., Qiu, Y., Hubner, S.E., Go, R.L., Ruvolo, V.R., Leonti, A.R., Gerbing, R.B., Gamis, A.S., and Aplenc, R. (2024). Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial. Cancers, 16.","DOI":"10.3390\/cancers16081448"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jprot.2015.12.018","article-title":"HDAC inhibitors induce global changes in histone lysine and arginine methylation and alter expression of lysine demethylases","volume":"133","author":"Lillico","year":"2016","journal-title":"J. Proteom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1021\/acs.jproteome.8b00118","article-title":"Selective DOT1L, LSD1, and HDAC Class I Inhibitors Reduce HOXA9 Expression in MLL-AF9 Rearranged Leukemia Cells, But Dysregulate the Expression of Many Histone-Modifying Enzymes","volume":"17","author":"Lillico","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12943-023-01907-7","article-title":"Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia","volume":"22","author":"Jayavelu","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/bcb-2024-0264","article-title":"Doxorubicin, a DNA intercalator, inhibits transcription elongation","volume":"103","author":"Tempel","year":"2025","journal-title":"Biochem. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/bcb-2025-0335","article-title":"An improved version of the early histone HCl extraction protocol","volume":"104","author":"Analike","year":"2026","journal-title":"Biochem. Cell Biol."},{"key":"ref_52","unstructured":"Sattarifard, H., and Winnipeg, W. (2024). Role of DOT1L in Epigenetic Regulation of the HOXA9 Gene Expression in Mixed Lineage Leukemia. [Ph.D. Thesis, University of Manitoba]."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1158\/1535-7163.MCT-17-1209","article-title":"APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells","volume":"17","author":"Local","year":"2018","journal-title":"Mol. Cancer Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6597\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:42:49Z","timestamp":1784889769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":53,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156597"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156597","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}