{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:06:45Z","timestamp":1779271605520,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2209-A University Students Research Projects Support Program","award":["1919B012108968"],"award-info":[{"award-number":["1919B012108968"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hypericum species are known for their phytochemical richness and diverse pharmacological activities; however, the biological potential and underlying mechanisms of Hypericum triquetrifolium remain unclear. This study aimed to investigate the phytochemical profile and bioactivities of Hypericum triquetrifolium hydroalcoholic extract (HTE). Plant samples collected from Gelibolu (\u00c7anakkale, T\u00fcrkiye) were analyzed by HPTLC, revealing the presence of rutin, hyperoside, chlorogenic acid, neochlorogenic acid, and hypericin. Antioxidant activity was evaluated using DPPH, CUPRAC, and FRAP assays, demonstrating strong activity across all tests. Anti-inflammatory effects were assessed in LPS-stimulated RAW264.7 macrophages. HTE significantly reduced nitrite, PGE2, IL-6, ROS, and MDA levels, with the most pronounced effect observed at 0.5 mg\/mL (p &lt; 0.05). Cytotoxic and anticancer activities were evaluated in MIA PaCa-2 pancreatic cancer cells and healthy human dermal fibroblasts. The extract exhibited selective cytotoxicity toward cancer cells (IC50 = 0.16 mg\/mL), with approximately fivefold lower toxicity in healthy cells. Cell cycle analysis demonstrated G0\/G1 arrest, while the Annexin V assay revealed dose-dependent apoptosis (p &lt; 0.0001). DNA damage analysis further supported its anticancer potential. Overall, HTE exhibits potent antioxidant, anti-inflammatory, and selective anticancer activities by reducing oxidative stress, inducing cell cycle arrest, and promoting apoptosis, highlighting its potential as a therapeutic agent.<\/jats:p>","DOI":"10.3390\/molecules31101628","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:33:37Z","timestamp":1778589217000},"page":"1628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Evidence for the Dual Antioxidant and Anti-Inflammatory Roles of Hypericum triquetrifolium in Cancer Therapy: Selective Cytotoxicity Against Pancreatic Cancer Cells"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1992-619X","authenticated-orcid":false,"given":"Ece","family":"Sabuncu","sequence":"first","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u011fmur","family":"\u00d6zhan","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"},{"name":"Department of Toxicology, Hamidiye Faculty of Pharmacy, University of Health Sciences Turkey, 34668 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4833-655X","authenticated-orcid":false,"given":"Dilara","family":"G\u00fcre\u015f\u00e7i","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-651X","authenticated-orcid":false,"given":"Gizem","family":"Inetas Yengin","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-0572","authenticated-orcid":false,"given":"Merve G\u00fcd\u00fcl","family":"Bacanl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, G\u00fclhane Faculty of Pharmacy, University of Health Sciences Turkey, 06018 Ankara, T\u00fcrkiye"},{"name":"Health Institutes of T\u00fcrkiye (T\u00dcSEB), Turkish Vaccine Institute, 06270 Ankara, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etil","family":"G\u00fczelmeri\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-6533","authenticated-orcid":false,"given":"Dilek","family":"Telci","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-3143","authenticated-orcid":false,"given":"Hande","family":"Sipahi","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, Yeditepe University, 34755 \u0130stanbul, T\u00fcrkiye"},{"name":"Department of Toxicology, Hamidiye Faculty of Pharmacy, University of Health Sciences Turkey, 34668 \u0130stanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0378-8741(02)00044-2","article-title":"Hypericum triquetrifolium Turra. extract exhibits antiinflammatory activity in the rat","volume":"80","author":"Ozturk","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"El-Elimat, T., El-Qaderi, H.S., Hananeh, W.M., Abu AlSamen, M.M., Al Sharie, A.H., Alshehabat, M.A., Al-Gharaibeh, M., and Alali, F.Q. (2023). Evaluation of the Wound Healing Potential of Hypericum triquetrifolium Turra: An Experimental Animal Study and Histopathological Examination. Sci. Pharm., 91.","DOI":"10.3390\/scipharm91010016"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.bse.2007.09.002","article-title":"Phenolic constituents of 17 Hypericum species from Turkey","volume":"36","author":"Smelcerovic","year":"2008","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.phytol.2017.05.003","article-title":"Comparative HPLC-DAD and UHPLC-ESI(-)-HRMS & MS\/MS profiling of Hypericum species and correlation with necrotic cell-death activity in human leukemic cells","volume":"20","author":"Sakavitsi","year":"2017","journal-title":"Phytochem. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0378-8741(03)00117-X","article-title":"The in vitro effects of Hypericum species on human leukocyte myeloperoxidase activity","volume":"87","author":"Meral","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114843","DOI":"10.1016\/j.jep.2021.114843","article-title":"A comprehensive study to evaluate the wound healing potential of okra (Abelmoschus esculentus) fruit","volume":"287","author":"Sipahi","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.foodchem.2004.03.049","article-title":"Phytochemical and antioxidant characterization of Hypericum perforatum alcoholic extracts","volume":"90","author":"Silva","year":"2005","journal-title":"Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"586470","DOI":"10.1093\/ecam\/nen056","article-title":"Hypericum triquetrifolium\u2014Derived Factors Downregulate the Production Levels of LPS-Induced Nitric Oxide and Tumor Necrosis Factor-\u03b1 in THP-1 Cells","volume":"2011","author":"Saad","year":"2011","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1590\/S0102-695X2013000500018","article-title":"Antiproliferative activity of the hexanic extract and phloroglucinols from Hypericum brasiliense","volume":"23","author":"Rocha","year":"2013","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_10","first-page":"14","article-title":"Morphological and phytochemical diversity among Hypericum species","volume":"5","author":"Crockett","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101238","DOI":"10.1016\/j.redox.2019.101238","article-title":"L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation","volume":"26","author":"Liu","year":"2019","journal-title":"Redox Biol."},{"key":"ref_12","unstructured":"Munjal, A., and Allam, A.E. (2025). Indomethacin. StatPearls, StatPearls Publishing."},{"key":"ref_13","unstructured":"Payne, S., and Miles, D. (2018). Mechanisms of anticancer drugs. Scott-Brown\u2019s Otorhinolaryngology and Head and Neck Surgery, CRC Press."},{"key":"ref_14","first-page":"203","article-title":"Synergistic effects of bleomycin and Hypericum triquetrifolium","volume":"10","author":"Mohammed","year":"2009","journal-title":"J. Glob. Pharm. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mahajna, S., Kadan, S., Tietel, Z., Saad, B., Khasib, S., Tumeh, A., Ginsberg, D., and Zaid, H. (2019). In vitro evaluation of chemically analyzed Hypericum triquetrifolium extract efficacy in apoptosis induction and cell cycle arrest of the HCT-116 colon cancer cell line. Molecules, 24.","DOI":"10.3390\/molecules24224139"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tili, E., and Michaille, J. (2016). Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs. Molecules, 21.","DOI":"10.3390\/molecules21091263"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Villar, V.H., V\u00f6gler, O., Barcel\u00f3, F., Mart\u00edn-Broto, J., Mart\u00ednez-Serra, J., Ru\u00edz-Guti\u00e9rrez, V., and Alemany, R. (2016). Down-Regulation of AKT Signalling by Ursolic Acid Induces Intrinsic Apoptosis and Sensitization to Doxorubicin in Soft Tissue Sarcoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155946"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154356","DOI":"10.1016\/j.phymed.2022.154356","article-title":"Hypericin and its anticancer effects: From mechanism of action to potential therapeutic application","volume":"105","author":"Choudhary","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dall\u2019Acqua, S., Ak, G., Sinan, K.I., Elbasan, F., Ferrarese, I., Sut, S., Y\u0131ld\u0131ztugay, E., Peron, G., Schievano, E., and Picot-Allain, M.C.N. (2021). Hypericum triquetrifolium and H. neurocalycinum as Sources of Antioxidants and Multi-Target Bioactive Compounds. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.660735"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.phytochem.2018.05.003","article-title":"Phytochemical Profiles, Phototoxic and Antioxidant Properties of Eleven Hypericum Species\u2014A Comparative Study","volume":"152","author":"Napoli","year":"2018","journal-title":"Phytochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"609","DOI":"10.55262\/fabadeczacilik.1785409","article-title":"Comparative Antioxidant Activities and Total Phenolic Content of Hypericum perforatum, H. scabrum and H. heterophyllum from Different Regions of T\u00fcrkiye","volume":"50","author":"Tosun","year":"2025","journal-title":"Fabad J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1038\/s41598-021-83409-4","article-title":"Harvest Time Affects Antioxidant Capacity and Polyphenol Content of Hypericum perforatum","volume":"11","author":"Makarova","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.repbio.2018.09.005","article-title":"The effect of lipopolysaccharide on anti-inflammatory and pro-inflammatory cytokines production of human amniotic epithelial cells","volume":"18","author":"Motedayyen","year":"2018","journal-title":"Reprod. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.18632\/oncotarget.28382","article-title":"Selective protection of normal cells from chemotherapy","volume":"14","author":"Blagosklonny","year":"2023","journal-title":"Oncotarget"},{"key":"ref_25","first-page":"7","article-title":"Origin, Synthesis and Various Mechanisms of Hypericin as Antidepressant, Photosensitizer and Antiviral","volume":"3","author":"Waqar","year":"2022","journal-title":"Pak. J. Health Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/14786410500356243","article-title":"Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra","volume":"21","author":"Conforti","year":"2007","journal-title":"Nat. Prod. Res."},{"key":"ref_27","first-page":"719","article-title":"Antioxidant and cytotoxic activities of Hypericum sp. on brine shrimps and human cancer cell lines","volume":"16","author":"Couladis","year":"2002","journal-title":"Phytother. Res. Int. J. Devoted Pharmacol. Toxicol. Eval. Nat. Prod. Deriv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.31557\/APJCP.2023.24.10.3599","article-title":"Cytotoxic activity of Hypericum triquetrifolium Turra methanolic extract against cancer cell lines","volume":"24","author":"Mousa","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_29","first-page":"113","article-title":"Investigation of In Vitro Cytotoxicity of Hypericum Perforatum in Pancreatic Cancer","volume":"21","author":"Yurt","year":"2025","journal-title":"Celal Bayar Univ. J. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/10286020.2024.2380744","article-title":"Polyprenylated acylphloroglucinols from Hypericum sampsonii with cytotoxicity against pancreatic carcinomas","volume":"27","author":"Wang","year":"2025","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7345","DOI":"10.1007\/s13277-015-4552-2","article-title":"Hyperoside induces apoptosis and inhibits growth in pancreatic cancer via Bcl-2 family and NF-\u03baB signaling pathway both in vitro and in vivo","volume":"37","author":"Li","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_32","unstructured":"Tumeh, A.M.A. (2015). In Vitro Evaluation of Apoptotic Induction of Hypericum triquetrifolium. [Ph.D. Thesis, An-Najah National University]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1016\/j.jsps.2020.10.013","article-title":"Prevalence of post-traumatic stress disorder during the COVID-19 pandemic in Saudi Arabia","volume":"28","author":"Alshehri","year":"2020","journal-title":"Saudi Pharm. J."},{"key":"ref_34","first-page":"87","article-title":"Anti-cancer potential of Hypericum spp. with focus on Hypericum perforatum: A review of the literature","volume":"9","author":"Khoshnazar","year":"2023","journal-title":"Curr. Tradit. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ion, V., Ielciu, I., C\u00e2rje, A.G., Muntean, D.L., Cri\u015fan, G., and P\u0103ltinean, R. (2022). Hypericum spp.\u2014An overview of the extraction methods and analysis of compounds. Separations, 9.","DOI":"10.3390\/separations9010017"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Reich, E., and Schibli, A. (2007). High-Performance Thin-Layer Chromatography for the Analysis of Medicinal Plants, Thieme.","DOI":"10.1055\/b-002-66241"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109921","DOI":"10.1016\/j.lwt.2020.109921","article-title":"Importance of chromatographic and spectrophotometric methods in determining authenticity, classification and bioactivity of honey","volume":"132","year":"2020","journal-title":"LWT"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sen, N.B., Guzelmeric, E., Vovk, I., Glavnik, V., K\u0131rm\u0131z\u0131bekmez, H., and Yesilada, E. (2023). Phytochemical and bioactivity studies. Antioxidants, 12.","DOI":"10.3390\/antiox12071394"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7970","DOI":"10.1021\/jf048741x","article-title":"Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method","volume":"52","author":"Apak","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"\u00d6zhan, Y., G\u00fczelmeri\u00e7, E., \u00c7ok\u00e7eken, Z., Reis, R., Hamito\u011flu, M., Tugcu, G., and Sipahi, H. (2025). Cytoprotective potential of Sideritis congesta. Food Chem. Toxicol., 115825.","DOI":"10.1016\/j.fct.2025.115825"},{"key":"ref_41","first-page":"4282","article-title":"Examination of Guinea Pig Luteinizing Hormone-Releasing Hormone Gene Reveals a Unique Decapeptide and Existence of Two Transcripts in the Brain","volume":"138","author":"Rubin","year":"1997","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106377","DOI":"10.1016\/j.fitote.2025.106377","article-title":"Isolation of anti-inflammatory and cytotoxic secondary metabolites","volume":"181","author":"Tirpanlar","year":"2025","journal-title":"Fitoterapia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2400238","DOI":"10.1002\/ardp.202400238","article-title":"iNOS\/PGE2 inhibitors as a novel template for analgesic\/anti-inflammatory activity: Design, synthesis, in vitro biological activity and docking studies","volume":"357","author":"Erdogan","year":"2024","journal-title":"Arch. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","first-page":"440","article-title":"Anti-inflammatory effects of Origanum majorana","volume":"25","year":"2021","journal-title":"J. Res. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1006\/abio.1994.1355","article-title":"Assay of malondialdehyde in biological fluids","volume":"220","author":"Yeo","year":"1994","journal-title":"Anal. Biochem."},{"key":"ref_47","first-page":"495","article-title":"Uranyl acetate induces oxidative stress and mitochondrial membrane potential collapse in the human dermal fibroblast primary cells","volume":"11","author":"Daraie","year":"2012","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1177\/0960327121997986","article-title":"Modulation of cigarette smoke extract-induced human bronchial epithelial damage by eucalyptol and curcumin","volume":"40","author":"Reis","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Turnalar \u00dclger, T., O\u00e7kun, M.A., Guzelmeric, E., Sen, N.B., Sipahi, H., \u00d6zhan, Y., and Yesilada, E. (2023). Chemical and bioactivity profiles. Molecules, 28.","DOI":"10.3390\/molecules28186520"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.2147\/CMAR.S163747","article-title":"Comparison of NSAIDs activity in COX-2 expressing and non-expressing 2D and 3D pancreatic cancer cell cultures","volume":"10","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_52","first-page":"2317","article-title":"Anti-cancer effects of Tilia species","volume":"15","author":"Bedir","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.fct.2015.04.015","article-title":"Antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin","volume":"81","year":"2015","journal-title":"Food Chem. Toxicol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T09:12:59Z","timestamp":1779268379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/10\/1628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31101628"],"URL":"https:\/\/doi.org\/10.3390\/molecules31101628","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]}}}