{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:34:53Z","timestamp":1791491693854,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["02-0058\/07"],"award-info":[{"award-number":["02-0058\/07"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["01-0422\/08"],"award-info":[{"award-number":["01-0422\/08"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"Young Researcher\u2019s grant of the Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["02-0058\/07"],"award-info":[{"award-number":["02-0058\/07"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010609","name":"Young Researcher\u2019s grant of the Medical University of Gda\u0144sk","doi-asserted-by":"publisher","award":["01-0422\/08"],"award-info":[{"award-number":["01-0422\/08"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Hashimoto\u2019s thyroiditis (HT) is an autoimmune disease mediated by T cells. It is characterized by the presence of thyroid autoantibodies in the serum, such as anti-thyroid peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab). The essential oil extracted from Nigella sativa seeds is rich in bioactive substances, such as thymoquinone and cymene. Methods: Therefore, we examined the effect of essential oil from Nigella sativa (NSEO) on T cells from HT patients, especially their proliferation capacity, ability to produce cytokines, and susceptibility to apoptosis. Results: The lowest ethanol (EtOH) dilution (1:10) of NSEO significantly inhibited the proliferation of CD4+ and CD8+ T cells from HT patients and healthy women by affecting the percentage of dividing cells and the number of cell divisions. In addition, 1:10 and 1:50 NSEO dilutions induced cell death. Different dilutions of NSEO also reduced the concentration of IL-17A and IL-10. In healthy women, the level of IL-4 and IL-2 significantly increased in the presence of 1:10 and 1:50 NSEO dilutions. NSEO did not influence the concentration of IL-6 and IFN-\u03b3. Conclusions: Our study demonstrates that NSEO has a strong immunomodulatory effect on the lymphocytes of HT patients.<\/jats:p>","DOI":"10.3390\/antiox12061246","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T08:37:33Z","timestamp":1686299853000},"page":"1246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Impact of Nigella sativa Essential Oil on T Cells in Women with Hashimoto\u2019s Thyroiditis"],"prefix":"10.3390","volume":"12","author":[{"given":"Klaudia","family":"Ciesielska-Figlon","sequence":"first","affiliation":[{"name":"Department of Physiopathology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Wojciechowicz","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-3090","authenticated-orcid":false,"given":"Agnieszka","family":"Daca","sequence":"additional","affiliation":[{"name":"Division of Pathology and Experimental Rheumatology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kokotkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"\u0141uczkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek Maciej","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6086-0024","authenticated-orcid":false,"given":"Katarzyna Aleksandra","family":"Lisowska","sequence":"additional","affiliation":[{"name":"Department of Physiopathology, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/PAP.0b013e3182534868","article-title":"Hashimoto Thyroiditis","volume":"19","author":"Ahmed","year":"2017","journal-title":"Adv. Anat. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1056\/NEJM199607113350206","article-title":"Chronic Autoimmune Thyroiditis","volume":"335","author":"Dayan","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101367","DOI":"10.1016\/j.beem.2019.101367","article-title":"Hashimotos\u2019 thyroiditis: Epidemiology, pathogenesis, clinic and therapy","volume":"33","author":"Ragusa","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jaut.2015.07.009","article-title":"Immunogenetics of autoimmune thyroid diseases: A comprehensive review","volume":"64","author":"Lee","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_5","first-page":"536","article-title":"A population-based study of chronic autoimmune hypothyroidism in Danish twins","volume":"85","author":"Brix","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","unstructured":"Janeway, C.A., Travers, P., Walport, M., and Shlomchik, M.J. (2001). Immunobiology: The Immune System in Health and Disease, Garland Science. [5th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/thy.1992.2.247","article-title":"T cells and human autoimmune thyroid disease: Emerging data show lack of need to invoke suppressor T cell problems","volume":"2","author":"Martin","year":"1992","journal-title":"Thyroid"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s12519-013-0398-0","article-title":"The differences in T and B cell subsets in thyroid of children with Graves\u2019 disease and Hashimoto\u2019s thyroiditis","volume":"9","author":"Szewczyk","year":"2013","journal-title":"World J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.275.5302.960","article-title":"Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto\u2019s thyroiditis","volume":"275","author":"Giordano","year":"1997","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1084\/jem.173.5.1099","article-title":"Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes","volume":"173","author":"Peters","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nri750","article-title":"Autoimmune thyroid disease: New models of cell death in autoimmunity","volume":"2","author":"Stassi","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1365-2249.1994.tb05515.x","article-title":"Perforin expression by thyroid-infiltrating T cells in autoimmune thyroid disease","volume":"98","author":"Wu","year":"1994","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1210\/jc.2011-2178","article-title":"Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto\u2019s thyroiditis","volume":"97","author":"Ehlers","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","first-page":"358","article-title":"Immunological Mechanisms Implicated in the Pathogenesis of Chronic Urticaria and Hashimoto Thyroiditis","volume":"16","author":"Berghi","year":"2017","journal-title":"Iran J. Allergy Asthma Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cyto.2019.01.003","article-title":"Immunological aspects of autoimmune thyroid disease\u2014Complex interplay between cells and cytokines","volume":"116","author":"Luty","year":"2019","journal-title":"Cytokine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S2221-1691(13)60075-1","article-title":"A review on therapeutic potential of Nigella sativa: A miracle herb","volume":"3","author":"Ahmad","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0731-7085(98)00300-8","article-title":"High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.)","volume":"19","author":"Ghosheh","year":"1999","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000285289","article-title":"Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients","volume":"19","author":"Kiran","year":"2010","journal-title":"Med. Princ. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3109\/08820139.2016.1153649","article-title":"Immunomodulatory Effect of Nigella sativa Oil on T Lymphocytes in Patients with Rheumatoid Arthritis","volume":"45","author":"Kheirouri","year":"2016","journal-title":"Immunol. Investig."},{"key":"ref_20","first-page":"1","article-title":"Improvement of Th17\/Treg balance and asthma control test score by Nigella sativa supplementation in asthmatic children: A new approach to managing asthma","volume":"6","author":"Barlianto","year":"2018","journal-title":"Tur. J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1515\/pteridines.2007.18.1.8","article-title":"Effects of methanolic extract and commercial oil of Nigella sativa L. on blood glucose and antioxidant capacity in alloxan-induced diabetic rats","volume":"18","author":"Houcher","year":"2007","journal-title":"Pteridines"},{"key":"ref_22","first-page":"16","article-title":"Evaluation of antioxidant effects of Nigella sativa on the ultrastructure of neural tube defects in diabetic rats offspring","volume":"6","author":"Panahi","year":"2011","journal-title":"Jundishapur J. Nat. Pharm. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Farhangi, M.A., Dehghan, P., Tajmiri, S., and Abbasi, M.M. (2016). The effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF)\u20141, Nesfatin-1 and anthropometric features in patients with Hashimoto\u2019s thyroiditis: A randomized controlled trial. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1432-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.eujim.2016.03.003","article-title":"Nigella Sativa treatment and serum concentrations of thyroid hormones, transforming growth factor \u03b2 (TGF-\u03b2) and interleukin 23 (IL-23) in patients with Hashimoto\u2019s Thyroiditis","volume":"8","author":"Tajmiri","year":"2016","journal-title":"Eur. J. Integr. Med."},{"key":"ref_25","first-page":"802","article-title":"Can Nigella sativa Oil (NSO) Reverse Hypothyroid Status Induced by PTU in Rat? Biochemical and Histological Studies","volume":"10","year":"2013","journal-title":"Life Sci. J."},{"key":"ref_26","first-page":"980","article-title":"Immunomodulatory effect of Nigella sativa oil in the disease process of type 1 diabetic rats","volume":"4","author":"Hmza","year":"2013","journal-title":"Res. J. Pharm. Biol. Chem. Sci."},{"key":"ref_27","first-page":"6269","article-title":"Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats","volume":"8","author":"Noor","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_28","first-page":"e13801","article-title":"The positive effect of black seed (Nigella sativa L.) essential oil on thyroid hormones in rats with hypothyroidism and hyperthyroidism","volume":"46","author":"Avci","year":"2021","journal-title":"J. Food Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113349","DOI":"10.1016\/j.biopha.2022.113349","article-title":"The influence of Nigella sativa essential oil on proliferation, activation, and apoptosis of human T lymphocytes in vitro","volume":"153","author":"Daca","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","first-page":"9.25.1","article-title":"Advanced application of CFSE for cellular tracking","volume":"44","author":"Witkowski","year":"2008","journal-title":"Curr. Protoc. Cytom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4110\/in.2016.16.1.1","article-title":"Regulation of Th2 Cell Immunity by Dendritic Cells","volume":"16","author":"Na","year":"2016","journal-title":"Immune Netw."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1210\/jc.2005-2337","article-title":"Regulatory T cells in human autoimmune thyroid disease","volume":"91","author":"Marazuela","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1472-8206.2007.00509.x","article-title":"The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients","volume":"21","author":"Boskabady","year":"2007","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.amjoto.2010.07.019","article-title":"Herbal treatment of allergic rhinitis: The use of Nigella sativa","volume":"32","author":"Nikakhlagh","year":"2011","journal-title":"Am. J. Otolaryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S628","DOI":"10.4103\/pm.pm_93_17","article-title":"Apoptotic Effect of Nigella sativa on Human Lymphoma U937 Cells","volume":"13","author":"Arslan","year":"2017","journal-title":"Pharmacogn. Mag."},{"key":"ref_36","first-page":"213","article-title":"A Methanolic Extract of Nigella sativa Seed Inhibits SiHa Human Cervical Cancer Cell Proliferation Through Apoptosis","volume":"8","author":"Hasan","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9655","DOI":"10.7314\/APJCP.2014.15.22.9655","article-title":"Roles of p53 and caspases in induction of apoptosis in MCF-7 breast cancer cells treated with a methanolic extract of Nigella sativa seeds","volume":"15","author":"Alhazmi","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2324-9293.1000117","article-title":"Preventive Effects of Methanolic Extract of Seeds of Nigella sativa Linn. on PMA Induced Apoptosis in Human Blood Lymphocytes","volume":"4","author":"Tripathi","year":"2015","journal-title":"Cell Biol. Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0192-0561(00)00036-9","article-title":"Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection","volume":"22","author":"Salem","year":"2000","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Salim, L.Z., Othman, R., Abdulla, M.A., Al-Jashamy, K., Ali, H.M., Hassandarvish, P., Dehghan, F., Ibrahim, M.Y., Omer, F.A., and Mohan, S. (2014). Thymoquinone inhibits murine leukemia WEHI-3 cells in vivo and in vitro. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115340"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11219","DOI":"10.3390\/molecules180911219","article-title":"Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro","volume":"18","author":"Salim","year":"2013","journal-title":"Molecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.1021\/la4049902","article-title":"Domain formation and permeabilization induced by the saponin \u03b1-hederin and its aglycone hederagenin in a cholesterol-containing bilayer","volume":"30","author":"Lorent","year":"2014","journal-title":"Langmuir"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14000","DOI":"10.1074\/jbc.M112.407635","article-title":"Induction of highly curved structures in relation to membrane permeabilization and budding by the triterpenoid saponins, \u03b1- and \u03b4-Hederin","volume":"288","author":"Lorent","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_44","unstructured":"Gardner, J.F., and Peel, M.M. (1991). Principles of Chemical Disinfection: Introduction to Sterilization, Disinfection and Infection Control, Churchill Livingstone. [3rd ed.]."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13044-018-0046-9","article-title":"Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases","volume":"11","author":"Rydzewska","year":"2018","journal-title":"Thyroid Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"979167","DOI":"10.1155\/2015\/979167","article-title":"Immune disorders in Hashimoto\u2019s thyroiditis: What do we know so far?","volume":"2015","author":"Pyzik","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1210\/jc.2009-1719","article-title":"Increased Circulating Pro-Inflammatory Cytokines and Th17 Lymphocytes in Hashimoto\u2019s Thyroiditis","volume":"95","author":"Benedicto","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.it.2012.05.004","article-title":"Defining the human T helper 17 cell phenotype","volume":"33","author":"Annunziato","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Duechting, A., Przybyla, A., Kuerten, S., and Lehmann, P.V. (2017). Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells. Cells, 6.","DOI":"10.3390\/cells6030029"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ni887","article-title":"Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process","volume":"4","author":"Bruniquel","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1084\/jem.187.2.225","article-title":"A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism","volume":"187","author":"Khoruts","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6136","DOI":"10.4049\/jimmunol.172.10.6136","article-title":"IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition","volume":"172","author":"Sojka","year":"2004","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e67209","DOI":"10.7554\/eLife.67209","article-title":"Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model","volume":"10","author":"Fukasawa","year":"2021","journal-title":"Elife"},{"key":"ref_54","first-page":"S0190-9622(23)00516-9","article-title":"Interleukin-17 pathway inhibition with brodalumab in early systemic sclerosis: Analysis of a single-arm, open-label, phase 1 trial","volume":"29","author":"Fukasawa","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"223","DOI":"10.14238\/pi57.5.2017.223-8","article-title":"Effects of Nigella sativa oil on Th1\/Th2, cytokine balance, and improvement of asthma control in children","volume":"57","author":"Barlianto","year":"2017","journal-title":"Paediatr. Indones."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/6\/1246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:51:41Z","timestamp":1760125901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/6\/1246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,9]]},"references-count":55,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["antiox12061246"],"URL":"https:\/\/doi.org\/10.3390\/antiox12061246","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,9]]}}}