{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:51:45Z","timestamp":1768035105082,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an \u03b1,\u03b2-unsaturated aldehyde, is a common dietary and environmental pollutant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet\/ streptozotocin-induced DN mice and in vitro DN cellular models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin\u2013angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1530\/eje-22-0493","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T15:37:25Z","timestamp":1661355445000},"page":"579-592","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":20,"title":["Acrolein plays a culprit role in the pathogenesis of diabetic nephropathy <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1093","volume":"187","author":[{"given":"Zhen-Jie","family":"Tong","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-Wei","family":"Kuo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Cheng","family":"Yen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Ching","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital , Taipei, Taiwan"},{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Tsun","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital , Taipei, Taiwan"},{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shing-Hwa","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Urology, Taipei Veterans General Hospital, Taoyuan Branch , Taoyuan, Taiwan"},{"name":"Department of Urology, School of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Taoyuan Branch of Taipei Veterans General Hospital , Taoyuan, Taiwan"},{"name":"Department of Healthcare Information and Management, Ming Chuan University , Taoyuan, Taiwan"},{"name":"Department of Business Administration, Ming Chuan University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"},{"name":"Division of Nephrology, Department of Medicine, Taipei City Hospital, Zhongxing Branch , Taipei, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University , Taipei, Taiwan"},{"name":"College of Science and Engineering, Fu Jen Catholic University , New Taipei City, Taiwan"},{"name":"Department of Special Education, University of Taipei , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Hsing","family":"Tsou","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University , Taipei, Taiwan"},{"name":"Kim Forest Enterprise Co., Ltd. , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4443-0670","authenticated-orcid":false,"given":"Hsiang-Tsui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University , Taipei, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University , Taipei, Taiwan"},{"name":"Toxicology, Kaohsiung Medical University , Kaohsiung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"2023010809172134400_bib1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11154-017-9422-3","article-title":"Novel insights into the pathophysiology and clinical aspects of diabetic nephropathy","volume":"18","author":"Ilyas","year":"2017","journal-title":"Reviews in Endocrine and Metabolic Disorders"},{"key":"2023010809172134400_bib2","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2011.861","article-title":"Temporal trends in the prevalence of diabetic kidney disease in the United States","volume":"305","author":"de Boer","year":"2011","journal-title":"JAMA"},{"key":"2023010809172134400_bib3","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2147\/IJNRD.S40172","article-title":"Diabetic nephropathy \u2013 complications and treatment","volume":"7","author":"Lim","year":"2014","journal-title":"International Journal of Nephrology and Renovascular Disease"},{"key":"2023010809172134400_bib4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3803\/EnM.2016.31.2.245","article-title":"Current challenges in diabetic nephropathy: early diagnosis and ways to improve outcomes","volume":"31","author":"Kim","year":"2016","journal-title":"Endocrinology and Metabolism"},{"key":"2023010809172134400_bib5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13098-019-0403-4","article-title":"Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary management","volume":"11","author":"Sulaiman","year":"2019","journal-title":"Diabetology and Metabolic Syndrome"},{"key":"2023010809172134400_bib6","first-page":"63","article-title":"Chapter 2: Definition, identification, and prediction of CKD progression","volume":"3","year":"2013","journal-title":"Kidney International Supplements 2011"},{"key":"2023010809172134400_bib7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2337\/dc06-1688","article-title":"How reliable is estimation of glomerular filtration rate at diagnosis of type 2 diabetes?","volume":"30","author":"Chudleigh","year":"2007","journal-title":"Diabetes Care"},{"key":"2023010809172134400_bib8","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.2337\/diabetes.52.4.1036","article-title":"Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions","volume":"52","author":"Caramori","year":"2003","journal-title":"Diabetes"},{"key":"2023010809172134400_bib9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ki.2009.399","article-title":"In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria","volume":"77","author":"Perkins","year":"2010","journal-title":"Kidney International"},{"key":"2023010809172134400_bib10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.diabres.2017.12.007","article-title":"Potential serum biomarkers for early detection of diabetic nephropathy","volume":"136","author":"Motawi","year":"2018","journal-title":"Diabetes Research and Clinical Practice"},{"key":"2023010809172134400_bib11","doi-asserted-by":"crossref","first-page":"850","DOI":"10.4239\/wjd.v6.i6.850","article-title":"Diabetes mellitus: the epidemic of the century","volume":"6","author":"Kharroubi","year":"2015","journal-title":"World Journal of Diabetes"},{"key":"2023010809172134400_bib12","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circulation Research"},{"key":"2023010809172134400_bib13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1254\/jphs.12R03CR","article-title":"Renin-angiotensin system, hypertension, and chronic kidney disease: pharmacogenetic implications","volume":"120","author":"Santos","year":"2012","journal-title":"Journal of Pharmacological Sciences"},{"key":"2023010809172134400_bib14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.200700412","article-title":"Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease","volume":"52","author":"Stevens","year":"2008","journal-title":"Molecular Nutrition and Food Research"},{"key":"2023010809172134400_bib15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/toxsci\/kfu233","article-title":"Molecular mechanisms of acrolein toxicity: relevance to human disease","volume":"143","author":"Moghe","year":"2015","journal-title":"Toxicological Sciences"},{"key":"2023010809172134400_bib16","doi-asserted-by":"crossref","first-page":"16058","DOI":"10.1074\/jbc.273.26.16058","article-title":"Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins","volume":"273","author":"Uchida","year":"1998","journal-title":"Journal of Biological Chemistry"},{"key":"2023010809172134400_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envres.2016.03.015","article-title":"Acrolein metabolites, diabetes and insulin resistance","volume":"148","author":"Feroe","year":"2016","journal-title":"Environmental Research"},{"key":"2023010809172134400_bib18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1203\/01.PDR.0000076662.72100.74","article-title":"Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes","volume":"54","author":"Tsukahara","year":"2003","journal-title":"Pediatric Research"},{"key":"2023010809172134400_bib19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0006-291X(03)00716-2","article-title":"Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients","volume":"305","author":"Sakata","year":"2003","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2023010809172134400_bib20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1191\/0960327104ht416oa","article-title":"Glucose-stimulated acrolein production from unsaturated fatty acids","volume":"23","author":"Medina-Navarro","year":"2004","journal-title":"Human and Experimental Toxicology"},{"key":"2023010809172134400_bib21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.urolonc.2020.02.017","article-title":"Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease","volume":"38","author":"Hong","year":"2020","journal-title":"Urologic Oncology"},{"key":"2023010809172134400_bib22","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1158\/1541-7786.MCR-19-0402","article-title":"Targeting RNA polymerase I with hernandonine inhibits ribosomal RNA synthesis and tumor cell growth","volume":"17","author":"Chen","year":"2019","journal-title":"Molecular Cancer Research"},{"key":"2023010809172134400_bib23","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1681\/ASN.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"Journal of the American Society of Nephrology"},{"key":"2023010809172134400_bib24","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1159\/000431333","article-title":"A pathological scoring system to predict renal outcome in diabetic nephropathy","volume":"41","author":"Hoshino","year":"2015","journal-title":"American Journal of Nephrology"},{"key":"2023010809172134400_bib25","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/mnfr.201100149","article-title":"Acrolein scavengers: reactivity, mechanism and impact on health","volume":"55","author":"Zhu","year":"2011","journal-title":"Molecular Nutrition and Food Research"},{"key":"2023010809172134400_bib26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1507\/endocrj.50.61","article-title":"Increased urinary levels of pentosidine, pyrraline and acrolein adduct in type 2 diabetes","volume":"50","author":"Daimon","year":"2003","journal-title":"Endocrine Journal"},{"key":"2023010809172134400_bib27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2169\/internalmedicine.38.309","article-title":"Carbonyl stress in the pathogenesis of diabetic nephropathy","volume":"38","author":"Suzuki","year":"1999","journal-title":"Internal Medicine"},{"key":"2023010809172134400_bib28","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3109\/02713683.2012.713152","article-title":"A possible role of acrolein in diabetic retinopathy: involvement of a VEGF\/TGFbeta signaling pathway of the retinal pigment epithelium in hyperglycemia","volume":"37","author":"Grigsby","year":"2012","journal-title":"Current Eye Research"},{"key":"2023010809172134400_bib29","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.jdiacomp.2016.07.011","article-title":"Diabetes and increased lipid peroxidation are associated with systemic inflammation even in well-controlled patients","volume":"30","author":"de Souza Bastos","year":"2016","journal-title":"Journal of Diabetes and its Complications"},{"key":"2023010809172134400_bib30","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1006\/bbrc.2000.2601","article-title":"Polyamines: mysterious modulators of cellular functions","volume":"271","author":"Igarashi","year":"2000","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2023010809172134400_bib31","volume-title":"Polyamines, Uremia and Hemodialysis","author":"TY","year":"1978"},{"key":"2023010809172134400_bib32","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1080\/0886022X.2016.1229990","article-title":"Uremic toxins: some thoughts on acrolein and spermine","volume":"38","author":"Sindhu","year":"2016","journal-title":"Renal Failure"},{"key":"2023010809172134400_bib33","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/978-1-4939-7398-9_38","article-title":"Acrolein: an effective biomarker for tissue damage produced from polyamines","volume":"1694","author":"Igarashi","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"2023010809172134400_bib34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11010-010-0439-0","article-title":"Does polyamine oxidase activity influence the oxidative metabolism of children who suffer of diabetes mellitus?","volume":"341","author":"Bjelakovic","year":"2010","journal-title":"Molecular and Cellular Biochemistry"},{"key":"2023010809172134400_bib35","doi-asserted-by":"crossref","first-page":"113066","DOI":"10.1016\/j.expneurol.2019.113066","article-title":"Acrolein is involved in ischemic stroke-induced neurotoxicity through spermidine\/spermine-N1-acetyltransferase activation","volume":"323","author":"Liu","year":"2020","journal-title":"Experimental Neurology"},{"key":"2023010809172134400_bib36","first-page":"2514","article-title":"Accumulation of acrolein-conjugated protein in the vitreous fluid of proliferative diabetic retinopathy","volume":"58","author":"Noda","year":"2017","journal-title":"Investigative Ophthalmology and Visual Science"},{"key":"2023010809172134400_bib37","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1007\/s00125-008-1071-3","article-title":"Evaluation of N (epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy","volume":"51","author":"Zhang","year":"2008","journal-title":"Diabetologia"},{"key":"2023010809172134400_bib38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3390\/jcm9020340","article-title":"Pharmacological inhibition of spermine oxidase reduces neurodegeneration and improves retinal function in diabetic mice","volume":"9","author":"Liu","year":"2020","journal-title":"Journal of Clinical Medicine"},{"key":"2023010809172134400_bib39","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1007\/s00125-018-4707-y","article-title":"Muller glial dysfunction during diabetic retinopathy in rats is reduced by the acrolein-scavenging drug, 2-hydrazino-4,6-dimethylpyrimidine","volume":"61","author":"McDowell","year":"2018","journal-title":"Diabetologia"},{"key":"2023010809172134400_bib40","first-page":"2524","article-title":"Evidence supporting a role for N-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy","volume":"16","author":"Yong","year":"2010","journal-title":"Molecular Vision"},{"key":"2023010809172134400_bib41","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1046\/j.1523-1755.2000.07715.x","article-title":"Role of angiotensin II in diabetic nephropathy","volume":"77","author":"Leehey","year":"2000","journal-title":"Kidney International: Supplement"},{"key":"2023010809172134400_bib42","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1093\/ndt\/gft320","article-title":"ACE2 alterations in kidney disease","volume":"28","author":"Soler","year":"2013","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"2023010809172134400_bib43","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1093\/ndt\/gfr600","article-title":"High-salt diet increases glomerular ACE\/ACE2 ratio leading to oxidative stress and kidney damage","volume":"27","author":"Bernardi","year":"2012","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"2023010809172134400_bib44","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/ki.2011.381","article-title":"Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy","volume":"81","author":"Batlle","year":"2012","journal-title":"Kidney International"},{"key":"2023010809172134400_bib45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2174\/138955708783955953","article-title":"Carbonyl-scavenging drugs and protection against carbonyl stress-associated cell injury","volume":"8","author":"Burcham","year":"2008","journal-title":"Mini Reviews in Medicinal Chemistry"},{"key":"2023010809172134400_bib46","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ejphar.2011.10.041","article-title":"Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: a comparison with N-acetylcysteine","volume":"674","author":"Ahmad","year":"2012","journal-title":"European Journal of Pharmacology"},{"key":"2023010809172134400_bib47","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1111\/j.1523-1755.2005.00677.x","article-title":"N-acetylcysteine attenuates the progression of chronic renal failure","volume":"68","author":"Shimizu","year":"2005","journal-title":"Kidney International"},{"key":"2023010809172134400_bib48","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1002\/ar.23618","article-title":"Acrolein scavenger hydralazine prevents streptozotocin-induced painful diabetic neuropathy and spinal neuroinflammation in rats","volume":"300","author":"Yao","year":"2017","journal-title":"Anatomical Record"},{"key":"2023010809172134400_bib49","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.2174\/0929867326666190326111851","article-title":"Carnosine and diabetic nephropathy","volume":"27","author":"Peters","year":"2020","journal-title":"Current Medicinal Chemistry"},{"key":"2023010809172134400_bib50","doi-asserted-by":"crossref","first-page":"44492","DOI":"10.1038\/srep44492","article-title":"Carnosine attenuates the development of both type 2 diabetes and diabetic nephropathy in BTBR ob\/ob mice","volume":"7","author":"Albrecht","year":"2017","journal-title":"Scientific Reports"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/187\/4\/EJE-22-0493.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/187\/4\/EJE-22-0493.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/4\/579\/48515994\/eje-22-0493.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/4\/579\/48515994\/eje-22-0493.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:18:15Z","timestamp":1676391495000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/187\/4\/579\/6972102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10,1]]}},"URL":"https:\/\/doi.org\/10.1530\/eje-22-0493","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10]]},"published":{"date-parts":[[2022,9,22]]}}}