{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:26:11Z","timestamp":1787909171048,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2014\/13\/B\/NZ7\/02247"],"award-info":[{"award-number":["2014\/13\/B\/NZ7\/02247"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB\/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal hapten provocation. The mice were treated intraperitoneally with NT, SR 142948 (NTR1 receptor antagonist) + NT or NaCl. Twenty-four hours after the challenge, airway responsiveness to nebulized methacholine was measured. Bronchoalveolar lavage fluid (BALF) and lungs were collected for biochemical and immunohistological analysis. NT alleviated airway hyperreactivity and reduced the number of inflammatory cells in BALF. These beneficial effects were inhibited by pretreatment with the NTR1 antagonist. Additionally, NT reduced levels of IL-13 and TNF-\u03b1 in BALF and IL-17A, IL12p40, RANTES, mouse mast cell protease and malondialdehyde in lung homogenates. SR 142948 reverted only a post-NT TNF-\u03b1 decrease. NT exhibited anti-inflammatory activity in the hapten-induced asthma. Reduced leukocyte accumulation and airway hyperresponsiveness indicate that this beneficial NT action is mediated through NTR1 receptors. A lack of effect by the NTR1 blockade on mast cell activation, oxidative stress marker and pro-inflammatory cytokine production suggests that other pathways can be involved, which requires further research.<\/jats:p>","DOI":"10.3390\/ijms20205025","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T10:53:03Z","timestamp":1570791183000},"page":"5025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Beneficial Effects of Neurotensin in Murine Model of Hapten-Induced Asthma"],"prefix":"10.3390","volume":"20","author":[{"given":"Ewelina","family":"Russjan","sequence":"first","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawi\u0144skiego Street, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9608-4736","authenticated-orcid":false,"given":"Katarzyna","family":"Kaczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawi\u0144skiego Street, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1016\/S0021-9258(19)43429-7","article-title":"The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami","volume":"248","author":"Carraway","year":"1973","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000076632","article-title":"Developmental expression of neurotensin in thyrotropes and gonadotropes of male and female rats","volume":"79","author":"Bello","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/262607a0","article-title":"Hypothermia and intolerance to cold induced by intracisternal administration of the hypothalamic peptide neurotensin","volume":"262","author":"Bissette","year":"1976","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0014-2999(77)90236-9","article-title":"Neurotensin administered intracisternally inhibits responsiveness of mice to noxious stimuli","volume":"46","author":"Clineschmidt","year":"1977","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fendo.2013.00036","article-title":"Diverse roles of neurotensin agonists in the central nervous system","volume":"4","author":"Boules","year":"2013","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1749-6632.1995.tb17496.x","article-title":"Anatomy and mechanisms of neurotensin-dopamine interactions in the central nervous system","volume":"757","author":"Lambert","year":"1995","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0165-6147(99)01357-7","article-title":"Neurotensin and neurotensin receptors","volume":"20","author":"Vincent","year":"1999","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0896-6273(90)90137-5","article-title":"Structure and functional expression of the cloned rat neurotensin receptor","volume":"4","author":"Tanaka","year":"1990","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-5793(93)81509-X","article-title":"Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor","volume":"317","author":"Vita","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0014-5793(96)00397-3","article-title":"Molecular cloning of a levocabastine-sensitive neurotensin binding site","volume":"386","author":"Chalon","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejphar.2013.03.004","article-title":"Neurotensin and neurotensin receptors: Characteristic, structure-activity relationship and pain modulation\u2014A review","volume":"716","author":"Kleczkowska","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26273","DOI":"10.1074\/jbc.273.41.26273","article-title":"The 100-kDa neurotensin receptor is gp95\/sortilin, a non-G-protein-coupled receptor","volume":"273","author":"Mazella","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22788","DOI":"10.1074\/jbc.M100857200","article-title":"Activation and functional characterization of the mosaic receptor SorLA\/LR11","volume":"276","author":"Jacobsen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1535370213510665","article-title":"The effect of neurotensin in human keratinocytes-implication on impaired wound healing in diabetes","volume":"239","author":"Moura","year":"2014","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/039463200802100201","article-title":"Biology of neurotensin: Revisited study","volume":"21","author":"Katsanos","year":"2008","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_16","first-page":"1107","article-title":"Neuropeptides: Mediators of inflammation and tissue repair?","volume":"133","author":"Beiter","year":"1998","journal-title":"Arch. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/intimm\/dxx040","article-title":"Neuro-immune interactions in allergic diseases: Novel targets for therapeutics","volume":"29","author":"Voisin","year":"2017","journal-title":"Int. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0140-6736(86)90777-4","article-title":"Asthma as an axon reflex","volume":"1","author":"Barnes","year":"1986","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11515","DOI":"10.1073\/pnas.1411032111","article-title":"Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways","volume":"111","author":"Hahne","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1523\/JNEUROSCI.09-02-00466.1989","article-title":"Association of neurotensin binding sites with sensory and visceromotor components of the vagus nerve","volume":"9","author":"Kessler","year":"1989","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1172\/JCI4217","article-title":"Neurotensin is a proinflammatory neuropeptide in colonic inflammation","volume":"103","author":"Castagliuolo","year":"1999","journal-title":"Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/MOG.0b013e328331b69e","article-title":"Neuropeptides and inflammatory bowel disease","volume":"25","author":"Margolis","year":"2009","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm1738","article-title":"Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis","volume":"14","author":"Piliponsky","year":"2008","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Barchetta, I., Cimini, F.A., Capoccia, D., Bertoccini, L., Ceccarelli, V., Chiappetta, C., Leonetti, F., Di Cristofano, C., Silecchia, G., and Orho-Melander, M. (2018). Neurotensin Is a Lipid-Induced Gastrointestinal Peptide Associated with Visceral Adipose Tissue Inflammation in Obesity. Nutrients, 10.","DOI":"10.3390\/nu10040526"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1136\/gutjnl-2014-307329","article-title":"Neurotensin--regulated miR-133\u03b1 is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis","volume":"64","author":"Law","year":"2015","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1016\/j.peptides.2005.12.016","article-title":"Effects of NT on gastrointestinal motility and secretion, and role in intestinal inflammation","volume":"27","author":"Zhao","year":"2006","journal-title":"Peptides"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"G621","DOI":"10.1152\/ajpgi.00140.2004","article-title":"Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation","volume":"288","author":"Brun","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3748\/wjg.14.1222","article-title":"Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats","volume":"14","author":"Akcan","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbadis.2013.10.009","article-title":"Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice","volume":"1842","author":"Moura","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/j.bbamcr.2011.06.018","article-title":"Neurotensin downregulates the pro-inflammatory properties of skin dendritic cells and increases epidermal growth factor expression","volume":"1813","author":"Neves","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","first-page":"248240","article-title":"Neurotensin decreases the proinflammatory status of human skin fibroblasts and increases epidermal growth factor expression","volume":"2014","author":"Moura","year":"2014","journal-title":"Int. J. Inflam."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1023\/B:IFLA.0000039557.33267.65","article-title":"Murine model for non-IgE-mediated asthma","volume":"28","author":"Kraneveld","year":"2004","journal-title":"Inflammation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.pupt.2017.12.001","article-title":"Neuropeptides and breathing in health and disease","volume":"48","author":"Wojciechowski","year":"2018","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/0024-3205(95)00088-7","article-title":"Neurotensin stimulates neutrophil adherence to bronchial epithelial cells in vitro","volume":"56","author":"Robbins","year":"1995","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0167-0115(82)90063-5","article-title":"Neurotensin receptors in the rat bronchi","volume":"3","author":"Aas","year":"1982","journal-title":"Regul. Pept."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1152\/jappl.1989.66.5.2338","article-title":"Neutral endopeptidase modulates neurotensin-induced airway contraction","volume":"66","author":"Djokic","year":"1989","journal-title":"J. Appl. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0143-4179(94)90125-2","article-title":"Neurotensin modulates cholinergic and noncholinergic neurotransmission in guinea-pig main bronchi in vitro","volume":"26","author":"Martin","year":"1994","journal-title":"Neuropeptides"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0167-0115(00)00183-X","article-title":"Neurotensin: Peptide for the next millennium","volume":"93","author":"Boules","year":"2000","journal-title":"Regul. Pept."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1073\/pnas.90.1.65","article-title":"Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor","volume":"90","author":"Gully","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/j.1476-5381.1994.tb13077.x","article-title":"The nonpeptide neurotensin antagonist, SR 48692, used as a tool to reveal putative neurotensin receptor subtypes","volume":"112","author":"Dubuc","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/00005344-199804000-00012","article-title":"SR142948A is a potent antagonist of the cardiovascular effects of neurotensin","volume":"31","author":"Schaeffer","year":"1998","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ejphar.2012.07.020","article-title":"Cardio-respiratory effects of systemic neurotensin injection are mediated through activation of neurotensin NTS1 receptors","volume":"691","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1007\/s00018-005-5128-x","article-title":"Multitasking with neurotensin in the central nervous system","volume":"62","author":"Dobner","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","first-page":"229","article-title":"The role of neurotensin in central nervous system pathophysiology: What is the evidence?","volume":"31","author":"Jomphe","year":"2006","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S1074-7613(03)00296-6","article-title":"The IL-12 family of heterodimeric cytokines: New players in the regulation of T cell responses","volume":"19","author":"Trinchieri","year":"2003","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.4049\/jimmunol.177.9.6460","article-title":"IL-12 contributes to allergen-induced airway inflammation in experimental asthma","volume":"177","author":"Meyts","year":"2006","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1164\/ajrccm.154.6.8970374","article-title":"Expression of RANTES mRNA and protein in airways of patients with mild asthma","volume":"154","author":"Berkman","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.rmed.2008.03.010","article-title":"RANTES in exhaled breath condensate of stable and unstable asthma patients","volume":"102","author":"Zietkowski","year":"2008","journal-title":"Respir. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.rmed.2010.02.018","article-title":"Increased serum IL-17 is an independent risk factor for severe asthma","volume":"104","author":"Agache","year":"2010","journal-title":"Respir. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1465-9921-7-135","article-title":"IL-17 mRNA in sputum of asthmatic patients: Linking T cell driven inflammation and granulocytic influx?","volume":"7","author":"Bullens","year":"2006","journal-title":"Respir. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"L1023","DOI":"10.1152\/ajplung.00306.2006","article-title":"IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells","volume":"292","author":"Dragon","year":"2007","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1084\/jem.183.6.2593","article-title":"T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines","volume":"183","author":"Fossiez","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.2174\/092986706777935140","article-title":"IL-13: A promising therapeutic target for bronchial asthma","volume":"13","author":"Izuhara","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.0105-2896.2004.00215.x","article-title":"Interleukin-13 in asthma pathogenesis","volume":"202","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1164\/ajrccm.152.1.7599866","article-title":"Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects","volume":"152","author":"Thomas","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1136\/thorax.57.9.774","article-title":"Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma","volume":"57","author":"Thomas","year":"2002","journal-title":"Thorax"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/eji.200636612","article-title":"Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-alpha in a murine model of asthma","volume":"37","author":"Kim","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1046\/j.1440-1711.2001.00980.x","article-title":"Tumour necrosis factor-alpha: The role of this multifunctional cytokine in asthma","volume":"79","author":"Thomas","year":"2001","journal-title":"Immunol. Cell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ddmod.2011.06.004","article-title":"Mast Cell Proteases and Inflammation","volume":"8","author":"Dai","year":"2011","journal-title":"Drug Discov. Today Dis. Models"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.4049\/jimmunol.169.4.2044","article-title":"Key role for mast cells in nonatopic asthma","volume":"169","author":"Kraneveld","year":"2002","journal-title":"J. Immunol."},{"key":"ref_61","first-page":"80","article-title":"Rola stresu oksydacyjnego w patogenezie astmy oskrzelowej","volume":"16","year":"2011","journal-title":"Alergia Astma Immunologia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cbi.2018.07.001","article-title":"Flavocoxid attenuates airway inflammation in ovalbumin-induced mouse asthma model","volume":"292","author":"Abdelaziz","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_63","first-page":"499","article-title":"Vitamin E effect in a rat model of toluene diisocyanate-induced asthma","volume":"89","author":"Muti","year":"2016","journal-title":"Clujul. Med."},{"key":"ref_64","first-page":"PA1407","article-title":"Opioid-neurotensin hybrid influences pulmonary inflammatory process in murine model of non-atopic asthma","volume":"50","author":"Kogut","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1046\/j.1365-2222.2000.00772.x","article-title":"Airway eosinophilia is not arequirement for allergen-induced airway hyperresponsiveness","volume":"30","author":"Tournoy","year":"2000","journal-title":"Clin. Exp. Allergy"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/20\/5025\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:03Z","timestamp":1760189103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/20\/5025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,11]]},"references-count":65,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["ijms20205025"],"URL":"https:\/\/doi.org\/10.3390\/ijms20205025","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,11]]}}}