{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T10:34:55Z","timestamp":1788690895673,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["000106_22_RS__SEVER PROGETTI ATENEO MEDI 2021"],"award-info":[{"award-number":["000106_22_RS__SEVER PROGETTI ATENEO MEDI 2021"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["RM122181620497CF PROGETTI ATENEO MEDI 2022"],"award-info":[{"award-number":["RM122181620497CF PROGETTI ATENEO MEDI 2022"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex\u2010vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction\u2010relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF\u20101 was detected in both muscle and mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion &amp; Inferences<\/jats:title><jats:p>The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14850","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T09:40:55Z","timestamp":1719222055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance"],"prefix":"10.1111","volume":"36","author":[{"given":"Lucia","family":"Pallotta","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalinda","family":"Pisano","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Vona","sequence":"additional","affiliation":[{"name":"Center for Gender\u2010Specific Medicine Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-7314","authenticated-orcid":false,"given":"Martina","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gemma","family":"Pignataro","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Tattoli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Maselli","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology Laboratory National Institute of Gastroenterology \u201cS.\u00a0de Bellis\u201d, Research Hospital  Castellana Grotte Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Tarallo","sequence":"additional","affiliation":[{"name":"Department of Surgical Science Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Casella","sequence":"additional","affiliation":[{"name":"Department of Surgical Science Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Caronna","sequence":"additional","affiliation":[{"name":"Department of Surgical Science Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tancredi","sequence":"additional","affiliation":[{"name":"Department of Methods and Models for Economy, Territory and Finance Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia Burrelli","family":"Scotti","sequence":"additional","affiliation":[{"name":"Department of Surgical Science Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scalese","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Center for Gender\u2010Specific Medicine Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-4303","authenticated-orcid":false,"given":"Carla","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Severi","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.15140"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126698"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2019.07.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/003591576305600916"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.26.3.258"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.10.5.344"},{"key":"e_1_2_10_8_1","first-page":"147","article-title":"Zur Pathogenese de Divertikelerkrankung des Kolons [Pathogenesis of colon diverticular disease (author's transl)]","volume":"11","author":"Raguse T","year":"1981","journal-title":"Leber Magen Darm"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0886-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2005.026112"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04586.x"},{"key":"e_1_2_10_12_1","first-page":"76","article-title":"Morphologic basis for developing diverticular disease, diverticulitis, and diverticular bleeding","volume":"31","author":"Wedel T","year":"2015","journal-title":"Viszeralmedizin"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057023"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171416"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0203-z"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317619"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2022.02.001"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e3180653ca2"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.05.051"},{"key":"e_1_2_10_20_1","first-page":"747","article-title":"Medical hypothesis: speculating on the pathogenesis of acute diverticulitis","volume":"31","author":"Zullo A","year":"2018","journal-title":"Ann Gastroenterol"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1324-0"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01927.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2004.06.016"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14637"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003840100310"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10350-003-0050-5"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.031121"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-018-0032-9"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2852"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01445.x"},{"key":"e_1_2_10_31_1","first-page":"147","article-title":"Ultrastructural changes of the human enteric nervous system and interstitial cells of Cajal in diverticular disease","volume":"35","author":"Alaburda P","year":"2020","journal-title":"Histol Histopathol"},{"key":"e_1_2_10_32_1","first-page":"202","article-title":"Diverticolosi diverticolite del colon: note per una revisione critica [Diverticulosis and diverticulitis of the colon: notes for a critical review]","volume":"33","author":"Torsoli A","year":"1966","journal-title":"Arch Ital Mal Appar Dig"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb04831.x"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13583-0"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1318.2006.01160.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2018.09.006"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm20110"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081537"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e318265ea7d"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.09.022"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25105"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.004"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02234460"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-013-1716-7"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15092119"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2018.03.005"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1547-0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129934"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312377"},{"key":"e_1_2_10_50_1","first-page":"13","article-title":"Detection of endoscopic and histological inflammation after an attack of colonic diverticulitis is associated with higher diverticulitis recurrence","volume":"22","author":"Tursi A","year":"2013","journal-title":"J Gastrointestin Liver Dis"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S340929"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000580"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.14850","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T15:47:50Z","timestamp":1723477670000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.14850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/nmo.14850"],"URL":"https:\/\/doi.org\/10.1111\/nmo.14850","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]},"assertion":[{"value":"2023-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14850"}}