{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:24:44Z","timestamp":1792794284443,"version":"4.5.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council Project","award":["APP1125392"],"award-info":[{"award-number":["APP1125392"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human intestinal biopsies were collected from Crohn\u2019s disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P &amp;lt; .0001) and unaffected CD (P &amp;lt; .0001), with transitional CD specimens also showing greater staining than controls (P &amp;lt; .05) and unaffected CD (P &amp;lt; .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P &amp;lt; .0001) and unaffected CD (P &amp;lt; .0001) and was significantly higher in transitional CD than in controls (P &amp;lt; .0001) and unaffected CD (P &amp;lt; .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P &amp;lt; .05), unaffected CD (P &amp;lt; .0001) and transitional CD (P &amp;lt; .05), with transitional CD specimens showing greater staining than unaffected CD (P &amp;lt; .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izab239","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T13:44:59Z","timestamp":1635774299000},"page":"586-598","source":"Crossref","is-referenced-by-count":63,"title":["Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn\u2019s Disease"],"prefix":"10.1093","volume":"28","author":[{"given":"Angie L","family":"Schroder","sequence":"first","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Charles Perkins Centre, The University of Sydney , NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belal","family":"Chami","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Charles Perkins Centre, The University of Sydney , NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Liu","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Charles Perkins Centre, The University of Sydney , NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulfam","family":"Ahmad","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Charles Perkins Centre, The University of Sydney , NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimalan","family":"Pathma-Nathan","sequence":"additional","affiliation":[{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"},{"name":"Centre for Virus Research, The Westmead Institute for Medical Research , Westmead, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Collins","sequence":"additional","affiliation":[{"name":"Centre for Virus Research, The Westmead Institute for Medical Research , Westmead, NSW, Australia"},{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Toh","sequence":"additional","affiliation":[{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"},{"name":"Centre for Virus Research, The Westmead Institute for Medical Research , Westmead, NSW, Australia"},{"name":"Department of Colorectal Surgery , Westmead Hospital, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Harman","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Byrne","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grahame","family":"Ctercteko","sequence":"additional","affiliation":[{"name":"Westmead Institute for Medical Research , Centre for Immunology and Allergy Research, Westmead, NSW, Australia"},{"name":"Centre for Virus Research, The Westmead Institute for Medical Research , Westmead, NSW, Australia"},{"name":"Department of Colorectal Surgery , Westmead Hospital, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-7004","authenticated-orcid":false,"given":"Paul K","family":"Witting","sequence":"additional","affiliation":[{"name":"The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health , NSW, Australia"},{"name":"Charles Perkins Centre, The University of Sydney , NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"2023112422080801100_CIT0001","doi-asserted-by":"crossref","first-page":"29239","DOI":"10.1038\/srep29239","article-title":"Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging","volume":"6","author":"Chernavskaia","year":"2016","journal-title":"Sci Rep."},{"key":"2023112422080801100_CIT0002","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.abb.2018.03.012","article-title":"Myeloperoxidase in the inflamed colon: A novel target for treating inflammatory bowel disease","volume":"645","author":"Chami","year":"2018","journal-title":"Arch Biochem 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