{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:04:17Z","timestamp":1788537857947,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Krebshilfe","award":["70112392"],"award-info":[{"award-number":["70112392"]}]},{"name":"Deutsche Krebshilfe","award":["DJCLS 17R\/2018"],"award-info":[{"award-number":["DJCLS 17R\/2018"]}]},{"name":"Deutsche Krebshilfe","award":["KH331\/2-3"],"award-info":[{"award-number":["KH331\/2-3"]}]},{"name":"Deutsche Krebshilfe","award":["Kha2\/002\/20"],"award-info":[{"award-number":["Kha2\/002\/20"]}]},{"name":"Deutsche Krebshilfe","award":["FKZ 01KD2103A"],"award-info":[{"award-number":["FKZ 01KD2103A"]}]},{"name":"Jose Carreras Leuk\u00e4mie Stiftung","award":["70112392"],"award-info":[{"award-number":["70112392"]}]},{"name":"Jose Carreras Leuk\u00e4mie Stiftung","award":["DJCLS 17R\/2018"],"award-info":[{"award-number":["DJCLS 17R\/2018"]}]},{"name":"Jose Carreras Leuk\u00e4mie Stiftung","award":["KH331\/2-3"],"award-info":[{"award-number":["KH331\/2-3"]}]},{"name":"Jose Carreras Leuk\u00e4mie Stiftung","award":["Kha2\/002\/20"],"award-info":[{"award-number":["Kha2\/002\/20"]}]},{"name":"Jose Carreras Leuk\u00e4mie Stiftung","award":["FKZ 01KD2103A"],"award-info":[{"award-number":["FKZ 01KD2103A"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["70112392"],"award-info":[{"award-number":["70112392"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["DJCLS 17R\/2018"],"award-info":[{"award-number":["DJCLS 17R\/2018"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["KH331\/2-3"],"award-info":[{"award-number":["KH331\/2-3"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["Kha2\/002\/20"],"award-info":[{"award-number":["Kha2\/002\/20"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["FKZ 01KD2103A"],"award-info":[{"award-number":["FKZ 01KD2103A"]}]},{"name":"Medicine at University Hospital of Muenster","award":["70112392"],"award-info":[{"award-number":["70112392"]}]},{"name":"Medicine at University Hospital of Muenster","award":["DJCLS 17R\/2018"],"award-info":[{"award-number":["DJCLS 17R\/2018"]}]},{"name":"Medicine at University Hospital of Muenster","award":["KH331\/2-3"],"award-info":[{"award-number":["KH331\/2-3"]}]},{"name":"Medicine at University Hospital of Muenster","award":["Kha2\/002\/20"],"award-info":[{"award-number":["Kha2\/002\/20"]}]},{"name":"Medicine at University Hospital of Muenster","award":["FKZ 01KD2103A"],"award-info":[{"award-number":["FKZ 01KD2103A"]}]},{"name":"OUTLIVE-CRC","award":["70112392"],"award-info":[{"award-number":["70112392"]}]},{"name":"OUTLIVE-CRC","award":["DJCLS 17R\/2018"],"award-info":[{"award-number":["DJCLS 17R\/2018"]}]},{"name":"OUTLIVE-CRC","award":["KH331\/2-3"],"award-info":[{"award-number":["KH331\/2-3"]}]},{"name":"OUTLIVE-CRC","award":["Kha2\/002\/20"],"award-info":[{"award-number":["Kha2\/002\/20"]}]},{"name":"OUTLIVE-CRC","award":["FKZ 01KD2103A"],"award-info":[{"award-number":["FKZ 01KD2103A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML.<\/jats:p>","DOI":"10.3390\/ijms26178301","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"8301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8298-4135","authenticated-orcid":false,"given":"Helal","family":"Ahmed","sequence":"first","affiliation":[{"name":"Medical Department A, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"},{"name":"Faculty of Medicine and Health Sciences, Amran University, Amran 00967, Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2605-4475","authenticated-orcid":false,"given":"Pradeep Kumar","family":"Patnana","sequence":"additional","affiliation":[{"name":"Medical Department A, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya S.","family":"Al-Matary","sequence":"additional","affiliation":[{"name":"Clinic for Oral and Maxillofacial Surgery, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Fiori","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen-M\u00fcnster (WTZ), University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Vorwerk","sequence":"additional","affiliation":[{"name":"Medical Department A, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marah H.","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-2261","authenticated-orcid":false,"given":"Eva","family":"Dazert","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8960-5040","authenticated-orcid":false,"given":"Lorenz","family":"Oelschl\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229-3039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-2105","authenticated-orcid":false,"given":"Axel","family":"K\u00fcnstner","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Group, L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Opalka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen-M\u00fcnster (WTZ), University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"von Bubnoff","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-6269","authenticated-orcid":false,"given":"Cyrus","family":"Khandanpour","sequence":"additional","affiliation":[{"name":"Medical Department A, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","article-title":"Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the european leukemianet","volume":"115","author":"Estey","year":"2010","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/bjh.17940","article-title":"Dexamethasone-mediated inhibition of notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells","volume":"196","author":"Ahmed","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e90036","DOI":"10.1172\/jci.insight.90036","article-title":"Aml-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth","volume":"2","author":"Battula","year":"2017","journal-title":"JCI Insight"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Brenner, A.K., Nepstad, I., and Bruserud, \u00d8. (2017). Mesenchymal stem cells support survival and proliferation of primary human acute myeloid leukemia cells through heterogeneous molecular mechanisms. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00106"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.leukres.2015.01.013","article-title":"Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors","volume":"39","author":"Chandran","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1158\/0008-5472.CAN-14-3379","article-title":"Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia","volume":"75","author":"Kim","year":"2015","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.blre.2017.03.004","article-title":"The bone marrow microenvironment\u2014Home of the leukemic blasts","volume":"31","author":"Shafat","year":"2017","journal-title":"Blood Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ccell.2019.06.003","article-title":"Mubritinib targets the electron transport chain complex i and reveals the landscape of oxphos dependency in acute myeloid leukemia","volume":"36","author":"Baccelli","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1158\/2159-8290.CD-16-0441","article-title":"Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism","volume":"7","author":"Farge","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.cmet.2020.09.001","article-title":"Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy","volume":"32","author":"Forte","year":"2020","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1182\/blood-2015-01-621870","article-title":"Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with bcl-2 inhibition","volume":"126","author":"Jacque","year":"2015","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.stem.2012.12.013","article-title":"Bcl-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells","volume":"12","author":"Lagadinou","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1182\/blood-2017-03-772939","article-title":"Nadph oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts","volume":"130","author":"Marlein","year":"2017","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1182\/blood-2015-07-655860","article-title":"Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy","volume":"128","author":"Moschoi","year":"2016","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e75908","DOI":"10.7554\/eLife.75908","article-title":"Crosstalk between aml and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells","volume":"11","author":"Cuminetti","year":"2022","journal-title":"eLife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.exphem.2016.04.001","article-title":"Gfi1(36n) as a therapeutic and prognostic marker for myelodysplastic syndrome","volume":"44","author":"Botezatu","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/leu.2016.11","article-title":"Gfi1 as a novel prognostic and therapeutic factor for aml\/mds","volume":"30","author":"Botezatu","year":"2016","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3324\/haematol.2017.167288","article-title":"Gfi1b: A key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome","volume":"103","author":"Thivakaran","year":"2018","journal-title":"Haematologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1182\/blood-2009-03-206672","article-title":"Pd-1\/pd-l1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model","volume":"114","author":"Zhang","year":"2009","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/s41467-018-03408-4","article-title":"Expansion of functional personalized cells with specific transgene combinations","volume":"9","author":"Lipps","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/leu.2015.325","article-title":"Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia","volume":"30","author":"Geyh","year":"2016","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute myeloid leukemia","volume":"373","author":"Weisdorf","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1126\/science.1164390","article-title":"Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells","volume":"322","author":"Colmone","year":"2008","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e302","DOI":"10.1038\/bcj.2015.17","article-title":"Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration","volume":"5","author":"Huang","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5573","DOI":"10.1172\/JCI96221","article-title":"Notch signaling suppresses glucose metabolism in mesenchymal progenitors to restrict osteoblast differentiation","volume":"128","author":"Lee","year":"2018","journal-title":"J. Clin. Invest."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41586-024-08439-0","article-title":"Immune evasion through mitochondrial transfer in the tumour microenvironment","volume":"638","author":"Ikeda","year":"2025","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"215582","DOI":"10.1016\/j.canlet.2022.215582","article-title":"Metformin sensitizes aml cells to chemotherapy through blocking mitochondrial transfer from stromal cells to aml cells","volume":"532","author":"You","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3324\/haematol.2019.242974","article-title":"Daratumumab inhibits acute myeloid leukaemia metabolic capacity by blocking mitochondrial transfer from mesenchymal stromal cells","volume":"106","author":"Mistry","year":"2021","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1038\/s41591-018-0233-1","article-title":"Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia","volume":"24","author":"Pollyea","year":"2018","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1182\/bloodadvances.2020003661","article-title":"Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate aml resistance to oxphos inhibition","volume":"5","author":"Saito","year":"2021","journal-title":"Blood Adv."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zampieri, L.X., Silva-Almeida, C., Rondeau, J.D., and Sonveaux, P. (2021). Mitochondrial transfer in cancer: A comprehensive review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063245"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/nature04980","article-title":"Transformation from committed progenitor to leukaemia stem cell initiated by mll-af9","volume":"442","author":"Krivtsov","year":"2006","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/nm1443","article-title":"A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis","volume":"12","author":"Yan","year":"2006","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1200\/JCO.2010.31.0904","article-title":"Leukemia stem cells and microenvironment: Biology and therapeutic targeting","volume":"29","author":"Konopleva","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.stem.2017.11.002","article-title":"Dye-independent methods reveal elevated mitochondrial mass in hematopoietic stem cells","volume":"21","author":"Luchsinger","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1038\/s41375-022-01635-9","article-title":"Gfi1b acts as a metabolic regulator in hematopoiesis and acute myeloid leukemia","volume":"36","author":"Liu","year":"2022","journal-title":"Leukemia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/bjh.18939","article-title":"Dose-dependent expression of gfi1 alters metabolism in the haematopoietic progenitors and mll::Af9-induced leukaemic cells","volume":"202","author":"Patnana","year":"2023","journal-title":"Br. J. Haematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:41Z","timestamp":1760034821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178301"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178301","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]}}}