{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T01:14:57Z","timestamp":1773710097179,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["18\/12"],"award-info":[{"award-number":["18\/12"]}]},{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["UID\/NEU\/04539\/2013"],"award-info":[{"award-number":["UID\/NEU\/04539\/2013"]}]},{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}]},{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["SFRH\/BD\/145531\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145531\/2019"]}]},{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["18\/12"],"award-info":[{"award-number":["18\/12"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["UID\/NEU\/04539\/2013"],"award-info":[{"award-number":["UID\/NEU\/04539\/2013"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["SFRH\/BD\/145531\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145531\/2019"]}]},{"name":"Foundation for Science and Technology (FCT), Portugal","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]},{"name":"COMPETE-FEDER","award":["18\/12"],"award-info":[{"award-number":["18\/12"]}]},{"name":"COMPETE-FEDER","award":["UID\/NEU\/04539\/2013"],"award-info":[{"award-number":["UID\/NEU\/04539\/2013"]}]},{"name":"COMPETE-FEDER","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}]},{"name":"COMPETE-FEDER","award":["SFRH\/BD\/145531\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145531\/2019"]}]},{"name":"COMPETE-FEDER","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphoid malignancies are a group of highly heterogeneous diseases frequently associated with constitutive activation of the nuclear factor kappa B (NF-\u03baB) signaling pathway. Parthenolide is a natural compound used to treat migraines and arthritis and found to act as a potent NF-\u03baB signaling inhibitor. This study evaluated in vitro parthenolide efficacy in lymphoid neoplasms. We assessed parthenolide metabolic activity in NCI-H929 (MM), Farage (GCB-DLBCL), Raji (BL), 697 and KOPN-8 (B-ALL), and CEM and MOLT-4 (T-ALL), by resazurin assay. Cell death, cell cycle, mitochondrial membrane potential (\u0394\u03a8mit), reactive oxygen species (ROS) and reduced glutathione (GSH) levels, activated caspase-3, FAS-ligand, and phosphorylated NF-\u03baB p65 were evaluated using flow cytometry. CMYC, TP53, GPX1, and TXRND1 expression levels were assessed using qPCR. Our results showed that parthenolide promoted a metabolic activity decrease in all cell lines in a time-, dose-, and cell-line-dependent manner. The mechanism induced by parthenolide was demonstrated to be cell line dependent. Nonetheless, parthenolide promoted cell death by apoptosis with significant ROS increase (peroxides and superoxide anion) and GSH decrease combined with a \u0394\u03a8mit reduction across all studied cell lines. Despite the need to further understand parthenolide mechanisms, parthenolide should be considered as a possible new therapeutic approach for B- and T-lymphoid malignancies.<\/jats:p>","DOI":"10.3390\/ijms24119167","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T01:29:26Z","timestamp":1684891766000},"page":"9167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-8077","authenticated-orcid":false,"given":"Joana","family":"Jorge","sequence":"first","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9340-1086","authenticated-orcid":false,"given":"Joana","family":"Neves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-6433","authenticated-orcid":false,"given":"Raquel","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"}]},{"given":"Catarina","family":"Geraldes","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-4841","authenticated-orcid":false,"given":"Ana Bela","family":"Sarmento-Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6386","DOI":"10.3389\/fonc.2022.1046307","article-title":"Incidence and survival of lymphoid neoplasms in Spain, 2002\u20132013: A population-based study from the Spanish Network of Cancer Registries (REDECAN)","volume":"12","author":"Pla","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/bjh.14136","article-title":"Guidelines for the management of diffuse large B-cell lymphoma","volume":"174","author":"Chaganti","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e28371","DOI":"10.1002\/pbc.28371","article-title":"Acute lymphoblastic leukemia","volume":"68","author":"Chang","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1159\/000520504","article-title":"Current Treatment Approaches to Newly Diagnosed Multiple Myeloma","volume":"44","author":"Ghandili","year":"2021","journal-title":"Oncol. Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1600-065X.2012.01106.x","article-title":"NF-\u03baB function in B lymphocytes","volume":"246","author":"Kaileh","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"239368","DOI":"10.1155\/2012\/239368","article-title":"A Key Role for NF-\u03baB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions","volume":"2012","author":"Visekruna","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grondona, P., Bucher, P., Schulze-Osthoff, K., Hailfinger, S., and Schmitt, A. (2018). NF-\u03baB Activation in Lymphoid Malignancies: Genetics, Signaling, and Targeted Therapy. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020038"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"936149","DOI":"10.3389\/ftox.2022.936149","article-title":"Parthenolide induces rapid thiol oxidation that leads to ferroptosis in hepatocellular carcinoma cells","volume":"4","author":"LoBianco","year":"2022","journal-title":"Front. Toxicol."},{"key":"ref_11","first-page":"8346","article-title":"Parthenolide targets NF-\u03baB (P50) to inhibit HIF-1\u03b1-mediated metabolic reprogramming of HCC","volume":"14","author":"Liu","year":"2022","journal-title":"Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120610","DOI":"10.1016\/j.lfs.2022.120610","article-title":"Parthenolide reverses the epithelial to mesenchymal transition process in breast cancer by targeting TGFbeta1: In vitro and in silico studies","volume":"301","author":"Sufian","year":"2022","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.chembiol.2019.03.016","article-title":"Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells","volume":"26","author":"Berdan","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Darwish, N.H.E., Sudha, T., Godugu, K., Bharali, D.J., Elbaz, O., El-ghaffar, H.A.A., Azmy, E., Anber, N., and Mousa, S.A. (2019). Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia. Molecules, 24.","DOI":"10.3390\/molecules24112103"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.7150\/jca.52641","article-title":"Suppression Of Aberrant Activation Of NF-\u03baB Pathway In Drug-resistant Leukemia Stem Cells Contributes To Parthenolide-potentiated Reversal Of Drug Resistance In Leukemia","volume":"12","author":"Yi","year":"2021","journal-title":"J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1039\/C9MD00297A","article-title":"Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia","volume":"10","author":"Li","year":"2019","journal-title":"MedChemComm"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1039\/C9NP00049F","article-title":"Advances in chemistry and bioactivity of parthenolide","volume":"37","author":"Freund","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S1074-5521(01)00049-7","article-title":"The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits I\u03baB kinase","volume":"8","author":"Kwok","year":"2001","journal-title":"Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.lfs.2004.01.024","article-title":"Role of cysteine residues of p65\/NF-\u03baB on the inhibition by the sesquiterpene lactone parthenolide and N-ethyl maleimide, and on its transactivating potential","volume":"75","author":"Lindenmeyer","year":"2004","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.3892\/or.2020.7649","article-title":"Parthenolide inhibits human lung cancer cell growth by modulating the IGF-1R\/PI3K\/Akt signaling pathway","volume":"44","author":"Sun","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23436","DOI":"10.18632\/oncotarget.15584","article-title":"Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf\/MAPK\/Erk pathway","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1182\/blood-2004-10-4135","article-title":"The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells","volume":"105","author":"Guzman","year":"2005","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1158\/0008-5472.CAN-09-4572","article-title":"A NADPH Oxidase\u2013Dependent Redox Signaling Pathway Mediates the Selective Radiosensitization Effect of Parthenolide in Prostate Cancer Cells","volume":"70","author":"Sun","year":"2010","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3109\/10428194.2011.555891","article-title":"The natural products parthenolide and andrographolide exhibit anticancer stem cell activity in multiple myeloma","volume":"52","author":"Gunn","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.3324\/haematol.2017.186700","article-title":"Investigating chemoresistance to improve sensitivity of childhood T-cell acute lymphoblastic leukemia to parthenolide","volume":"103","author":"Benjamin","year":"2018","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cui, M., Wang, Z., Huang, L.-T., and Wang, J.-H. (2022). Parthenolide leads to proteomic differences in thyroid cancer cells and promotes apoptosis. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03579-0"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"38954","DOI":"10.1074\/jbc.M203842200","article-title":"Oxidative Stress-mediated Apoptosis: The anticancer effect of the sesquiterpene lactone parthenolide*","volume":"277","author":"Wen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e891","DOI":"10.1038\/cddis.2013.415","article-title":"Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer","volume":"4","author":"Carlisi","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2147\/OTT.S117250","article-title":"Parthenolide suppresses pancreatic cell growth by autophagy-mediated apoptosis","volume":"10","author":"Liu","year":"2017","journal-title":"Onco Targets Therapy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.3390\/ijms24031823","article-title":"Role of NF-&kappa;B Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells","volume":"24","author":"Cippitelli","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s11596-008-0508-8","article-title":"Inhibitory effects of parthenolide on the angiogenesis induced by human multiple myeloma cells and the mechanism","volume":"28","author":"Kong","year":"2008","journal-title":"J. Huazhong Univ. Sci. Technol. [Med. Sci.]"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.canlet.2011.11.035","article-title":"Bcl-XL, but not Bcl-2, can protect human B-lymphoma cell lines from parthenolide-induced apoptosis","volume":"318","author":"Yeo","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature07968","article-title":"Mutations of multiple genes cause deregulation of NF-\u03baB in diffuse large B-cell lymphoma","volume":"459","author":"Compagno","year":"2009","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3892\/ijo_00000782","article-title":"Parthenolide treatment activates stress signaling proteins in high-risk acute lymphoblastic leukemia cells with chromosomal translocation t(4;11)","volume":"37","author":"Zunino","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1182\/blood-2012-08-448852","article-title":"Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia","volume":"121","author":"Diamanti","year":"2013","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Alves, R., Gon\u00e7alves, A.C., Jorge, J., Almeida, A.M., and Sarmento-Ribeiro, A.B. (2022). Combination of Elacridar with Imatinib Modulates Resistance Associated with Drug Efflux Transporters in Chronic Myeloid Leukemia. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051158"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s12032-020-01394-6","article-title":"Acute myeloid leukemia sensitivity to metabolic inhibitors: Glycolysis showed to be a better therapeutic target","volume":"37","author":"Lapa","year":"2020","journal-title":"Med. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jorge, J., Magalh\u00e3es, N., Alves, R., Lapa, B., Gon\u00e7alves, A.C., and Sarmento-Ribeiro, A.B. (2022). Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092207"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10637-019-00796-2","article-title":"Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines","volume":"38","author":"Jorge","year":"2020","journal-title":"Investig. New Drugs"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:37Z","timestamp":1760125237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119167"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119167","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}