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BKA had minimal metabolic effects in RCC cells, suggesting its role in preserving mitochondrial function without significantly altering metabolic pathways. In contrast, STAU induced substantial metabolic reprogramming in RCC cells, disrupting energy production, redox balance, and biosynthesis, thereby triggering apoptotic pathways. The combined treatment of BKA and STAU primarily mirrored the effects of STAU alone, with BKA showing little capacity to counteract the pro-apoptotic effects. In non-cancerous HK2 cells, the metabolic alterations were far less pronounced, highlighting key differences in the metabolic responses of cancerous and non-cancerous cells. RCC cells displayed greater metabolic flexibility, while HK2 cells maintained a more regulated metabolic state. These findings emphasize the potential for targeting cancer-specific metabolic vulnerabilities while sparing non-cancerous cells, underscoring the value of metabolomics in understanding apoptotic and anti-apoptotic mechanisms. Future studies should validate these results in vivo and explore their potential for personalized treatment strategies.<\/jats:p>","DOI":"10.3390\/cells14050367","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T09:04:49Z","timestamp":1740992689000},"page":"367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring Metabolic Shifts in Kidney Cancer and Non-Cancer Cells Under Pro- and Anti-Apoptotic Treatments Using NMR Metabolomics"],"prefix":"10.3390","volume":"14","author":[{"given":"Lucia","family":"Trisolini","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7799-5155","authenticated-orcid":false,"given":"Biagia","family":"Musio","sequence":"additional","affiliation":[{"name":"Department of Civil, Environmental, Land, Building Engineering and Chemistry (DICATECh), Polytechnic University of Bari, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0869-3568","authenticated-orcid":false,"given":"Beatriz","family":"Teixeira","sequence":"additional","affiliation":[{"name":"CICECO-Aveiro Institute of Materials and LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6916-325X","authenticated-orcid":false,"given":"Maria Noemi","family":"Sgobba","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8947-9733","authenticated-orcid":false,"given":"Anna Lucia","family":"Francavilla","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-3881","authenticated-orcid":false,"given":"Mariateresa","family":"Volpicella","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-9405","authenticated-orcid":false,"given":"Lorenzo","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-4263","authenticated-orcid":false,"given":"Anna","family":"De Grassi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2926-3106","authenticated-orcid":false,"given":"Vito","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Civil, Environmental, Land, Building Engineering and Chemistry (DICATECh), Polytechnic University of Bari, Via Orabona, 4, 70125 Bari, Italy"},{"name":"Innovative Solutions S.r.l.\u2014Spin-Off Company of the Polytechnic University of Bari, Zona H 150\/B, 70015 Noci, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-9256","authenticated-orcid":false,"given":"Iola F.","family":"Duarte","sequence":"additional","affiliation":[{"name":"CICECO-Aveiro Institute of Materials and LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-548X","authenticated-orcid":false,"given":"Ciro Leonardo","family":"Pierri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Pharmaceutical Sciences, University of Bari \u201cAldo Moro\u201d, Via Orabona, 4, 70125 Bari, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"941","DOI":"10.37349\/etat.2023.00175","article-title":"Biomarkers in Renal Cell Carcinoma and Their Targeted Therapies: A Review","volume":"4","author":"Gupta","year":"2023","journal-title":"Explor. 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Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/ja.2008.4","article-title":"Chemical Biology of Natural Indolocarbazole Products: 30 Years since the Discovery of Staurosporine","volume":"62","author":"Nakano","year":"2009","journal-title":"J. Antibiot."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1038\/sj.cdd.4401290","article-title":"Cathepsin D Mediates Cytochrome c Release and Caspase Activation in Human Fibroblast Apoptosis Induced by Staurosporine","volume":"10","author":"Johansson","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/S0026-895X(24)12510-2","article-title":"Multiple Kinetics of Mitochondrial Cytochrome c Release in Drug-Induced Apoptosis","volume":"60","author":"Luetjens","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_8","first-page":"131","article-title":"Granzymes and Mitochondria","volume":"85","author":"Kiselevsky","year":"2020","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yadav, N., Gogada, R., O\u2019Malley, J., Gundampati, R.K., Jayanthi, S., Hashmi, S., Lella, R., Zhang, D., Wang, J., and Kumar, R. (2020). Molecular Insights on Cytochrome c and Nucleotide Regulation of Apoptosome Function and Its Implication in Cancer. Biochim. Biophys. Acta Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2019.118573"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bcp.2015.11.019","article-title":"Identification of New Highly Selective Inhibitors of the Human ADP\/ATP Carriers by Molecular Docking and in Vitro Transport Assays","volume":"100","author":"Todisco","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamem.2008.04.011","article-title":"The ADP and ATP Transport in Mitochondria and Its Carrier","volume":"1778","author":"Klingenberg","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Trisolini, L., Laera, L., Favia, M., Muscella, A., Castegna, A., Pesce, V., Guerra, L., De Grassi, A., Volpicella, M., and Pierri, C.L. (2021). Differential Expression of ADP\/ATP Carriers as a Biomarker of Metabolic Remodeling and Survival in Kidney Cancers. Biomolecules, 11.","DOI":"10.3390\/biom11010038"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/s41418-023-01187-0","article-title":"Identity, Structure, and Function of the Mitochondrial Permeability Transition Pore: Controversies, Consensus, Recent Advances, and Future Directions","volume":"30","author":"Bernardi","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.bbamem.2009.06.007","article-title":"Cardiolipin and Mitochondrial Carriers","volume":"1788","author":"Klingenberg","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1023\/A:1005568630151","article-title":"Control of the Mitochondrial Permeability Transition Pore by High-Affinity ADP Binding at the ADP\/ATP Translocase in Permeabilized Mitochondria","volume":"32","author":"Haworth","year":"2000","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ki.1994.6","article-title":"HK-2: An Immortalized Proximal Tubule Epithelial Cell Line from Normal Adult Human Kidney","volume":"45","author":"Ryan","year":"1994","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1177\/1091581820942534","article-title":"In Vitro to In Vivo Concordance of Toxicity Using the Human Proximal Tubule Cell Line HK-2","volume":"39","author":"Mossoba","year":"2020","journal-title":"Int. J. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1038\/s41467-019-11311-9","article-title":"A Metabolic Profile of All-Cause Mortality Risk Identified in an Observational Study of 44,168 Individuals","volume":"10","author":"Deelen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vignoli, A., Tenori, L., Giusti, B., Takis, P.G., Valente, S., Carrabba, N., Balzi, D., Barchielli, A., Marchionni, N., and Gensini, G.F. (2019). NMR-Based Metabolomics Identifies Patients at High Risk of Death within Two Years after Acute Myocardial Infarction in the AMI-Florence II Cohort. BMC Med., 10.","DOI":"10.1186\/s12916-018-1240-2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.18632\/oncotarget.2081","article-title":"TRIM8 Anti-Proliferative Action against Chemo-Resistant Renal Cell Carcinoma","volume":"5","author":"Caratozzolo","year":"2014","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1006\/excr.1994.1093","article-title":"Induction of a Common Pathway of Apoptosis by Staurosporine","volume":"211","author":"Bertrand","year":"1994","journal-title":"Exp. Cell Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11306-008-0137-z","article-title":"A Direct Cell Quenching Method for Cell-Culture Based Metabolomics","volume":"5","author":"Teng","year":"2009","journal-title":"Metabolomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D608","DOI":"10.1093\/nar\/gkx1089","article-title":"HMDB 4.0: The Human Metabolome Database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1585","DOI":"10.1038\/cddis.2014.545","article-title":"Primary Clear Cell Renal Carcinoma Cells Display Minimal Mitochondrial Respiratory Capacity Resulting in Pronounced Sensitivity to Glycolytic Inhibition by 3-Bromopyruvate","volume":"6","author":"Nilsson","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19642","DOI":"10.1074\/jbc.M116.734814","article-title":"ATP\/ADP Turnover and Import of Glycolytic ATP into Mitochondria in Cancer Cells Is Independent of the Adenine Nucleotide Translocator","volume":"291","author":"Maldonado","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3892\/ol.2012.928","article-title":"Energy Metabolism of Cancer: Glycolysis versus Oxidative Phosphorylation (Review)","volume":"4","author":"Zheng","year":"2012","journal-title":"Oncol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kennedy, L., Sandhu, J.K., Harper, M.E., and Cuperlovic-culf, M. (2020). Role of Glutathione in Cancer: From Mechanisms to Therapies. Biomolecules, 10.","DOI":"10.3390\/biom10101429"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1016\/j.bbamcr.2016.04.011","article-title":"AGC1\/2, the Mitochondrial Aspartate-Glutamate Carriers","volume":"1863","author":"Amoedo","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/972913","article-title":"Role of Glutathione in Cancer Progression and Chemoresistance","volume":"2013","author":"Traverso","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bonilla, D.A., Kreider, R.B., Stout, J.R., Forero, D.A., Kerksick, C.M., Roberts, M.D., and Rawson, E.S. (2021). Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients, 13.","DOI":"10.3390\/nu13041238"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00726-011-0877-3","article-title":"The Creatine Kinase System and Pleiotropic Effects of Creatine","volume":"40","author":"Wallimann","year":"2011","journal-title":"Amino Acids"},{"key":"ref_32","first-page":"4279","article-title":"SLC18A3 Promoted Renal Cancer Development through Acetylcholine\/CAMP Signaling","volume":"12","author":"Tie","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mori, N., Wildes, F., Takagi, T., Glunde, K., and Bhujwalla, Z.M. (2016). The Tumor Microenvironment Modulates Choline and Lipid Metabolism. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00262"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chakraborty, S., Balan, M., Sabarwal, A., Choueiri, T.K., and Pal, S. (2021). Metabolic Reprogramming in Renal Cancer: Events of a Metabolic Disease. Biochim. Biophys. Acta Rev. Cancer, 1876.","DOI":"10.1016\/j.bbcan.2021.188559"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ctrv.2015.07.002","article-title":"Metabolic Alterations in Renal Cell Carcinoma","volume":"41","author":"Massari","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.freeradbiomed.2024.08.022","article-title":"A Comparative Study of the Efficiency of Mitochondria-Targeted Antioxidants MitoTEMPO and SKQ1 under Oxidative Stress","volume":"224","author":"Liu","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"F686","DOI":"10.1152\/ajprenal.00049.2020","article-title":"Protein Disulfide Isomerase Inhibition Impairs Keap1\/Nrf2 Signaling and Mitochondrial Function and Induces Apoptosis in Renal Proximal Tubular Cells","volume":"319","author":"Pokkunuri","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41419-024-06939-5","article-title":"Oxidative Cell Death in Cancer: Mechanisms and Therapeutic Opportunities","volume":"15","author":"An","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1432-1033.1976.tb10377.x","article-title":"The State of ADP or ATP Fixed to the Mitochondria by Bongkrekate","volume":"65","author":"Klingenberg","year":"1976","journal-title":"Eur. J. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6311","DOI":"10.1016\/j.febslet.2006.10.036","article-title":"Interaction of Peroxidized Cardiolipin with Rat-Heart Mitochondrial Membranes: Induction of Permeability Transition and Cytochrome c Release","volume":"580","author":"Petrosillo","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.2174\/0929867033457278","article-title":"The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death","volume":"10","author":"Halestrap","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.celrep.2018.12.033","article-title":"ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore","volume":"26","author":"Neginskaya","year":"2019","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tibs.2018.02.013","article-title":"A Lethal Channel between the ATP Synthase Monomers","volume":"43","author":"Nesci","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Malsy, M., Bitzinger, D., Graf, B., and Bundscherer, A. (2019). Staurosporine Induces Apoptosis in Pancreatic Carcinoma Cells PaTu 8988t and Panc-1 via the Intrinsic Signaling Pathway. Eur. J. Med. Res., 24.","DOI":"10.1186\/s40001-019-0365-x"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1158\/1535-7163.187.3.2","article-title":"Staurosporine Induces Apoptosis of Melanoma by Both Caspase-Dependent and -Independent Apoptotic Pathways","volume":"3","author":"Zhang","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1038\/sj.onc.1204436","article-title":"Staurosporine Induces Apoptosis through Both Caspase-Dependent and Caspase-Independent Mechanisms","volume":"20","author":"Belmokhtar","year":"2001","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/emboj\/17.1.37","article-title":"Mitochondrial Cytochrome c Release in Apoptosis Occurs Upstream of DEVD-Specific Caspase Activation and Independently of Mitochondrial Transmembrane Depolarization","volume":"17","author":"Newmeyer","year":"1998","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S0092-8674(00)80301-3","article-title":"Mitochondria Are Excitable Organelles Capable of Generating and Conveying Electrical and Calcium Signals","volume":"89","author":"Ichas","year":"1997","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Todisco, S., Musio, B., Pesce, V., Cavalluzzi, M.M., Petrosillo, G., La Piana, G., Sgobba, M.N., Schlosserov\u00e1, N., Cafferati Beltrame, L., and Di Lorenzo, R. (2023). Targeting Mitochondrial Impairment for the Treatment of Cardiovascular Diseases: From Hypertension to Ischemia-Reperfusion Injury, Searching for New Pharmacological Targets. Biochem. Pharmacol., 208.","DOI":"10.1016\/j.bcp.2022.115405"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.yjmcc.2014.08.018","article-title":"The Mitochondrial Permeability Transition: A Current Perspective on Its Identity and Role in Ischaemia\/Reperfusion Injury","volume":"78","author":"Halestrap","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0300-9084(02)01375-5","article-title":"The Permeability Transition Pore Complex: Another View","volume":"84","author":"Halestrap","year":"2002","journal-title":"Biochimie"},{"key":"ref_52","first-page":"2893","article-title":"Induction of Apoptosis by Staurosporine Involves the Inhibition of Expression of the Major Cell Cycle Proteins at the G2\/M Checkpoint Accompanied by Alterations in Erk and Akt Kinase Activities","volume":"29","author":"Antonsson","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.freeradbiomed.2007.10.054","article-title":"Proline Modulates the Intracellular Redox Environment and Protects Mammalian Cells against Oxidative Stress","volume":"44","author":"Krishnan","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1357-2725(01)00143-1","article-title":"Glutamine and Its Relationship with Intracellular Redox Status, Oxidative Stress and Cell Proliferation\/Death","volume":"34","author":"Asenjo","year":"2002","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/35014006","article-title":"Changes in Intramitochondrial and Cytosolic PH: Early Events That Modulate Caspase Activation during Apoptosis","volume":"2","author":"Matsuyama","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.biocel.2009.12.024","article-title":"The Fourth Isoform of the Adenine Nucleotide Translocator Inhibits Mitochondrial Apoptosis in Cancer Cells","volume":"42","author":"Gallerne","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/5\/367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:45:56Z","timestamp":1760028356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/5\/367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,2]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cells14050367"],"URL":"https:\/\/doi.org\/10.3390\/cells14050367","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,2]]}}}