{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:35:27Z","timestamp":1781001327293,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University","award":["000106_22_RS__SEVER PROGETTI ATENEO MEDI 2021 SEVERI"],"award-info":[{"award-number":["000106_22_RS__SEVER PROGETTI ATENEO MEDI 2021 SEVERI"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathophysiology of diverticular disease (DD) is not well outlined. Recent studies performed on the DD human ex vivo model have shown the presence of a predominant transmural oxidative imbalance whose origin remains unknown. Considering the central role of mitochondria in oxidative stress, the present study evaluates their involvement in the alterations of DD clinical phenotypes. Colonic surgical samples of patients with asymptomatic diverticulosis, complicated DD, and controls were analyzed. Electron microscopy, protein expression, and cytofluorimetric analyses were performed to assess the contribution of mitochondrial oxidative stress. Functional muscle activity was tested on cells in response to contractile and relaxant agents. To assess the possibility of reverting oxidative damages, N-acetylcysteine was tested on an in vitro model. Compared with the controls, DD tissues showed a marketed increase in mitochondrial number and fusion accompanied by the altered mitochondrial electron transport chain complexes. In SMCs, the mitochondrial mass increase was accompanied by altered mitochondrial metabolic activity supported by a membrane potential decrease. Ulteriorly, a decrease in antioxidant content and altered contraction\u2013relaxation dynamics reverted by N-acetylcysteine were observed. Therefore, the oxidative stress-driven alterations resulted in mitochondrial impairment. The beneficial effects of antioxidant treatments open new possibilities for tailored therapeutic strategies that have not been tested for this disease.<\/jats:p>","DOI":"10.3390\/ijms25179680","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T11:53:11Z","timestamp":1725623591000},"page":"9680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Unexplored Role of Mitochondria-Related Oxidative Stress in Diverticular Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-7314","authenticated-orcid":false,"given":"Martina","family":"Cappelletti","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9693-1613","authenticated-orcid":false,"given":"Lucia","family":"Pallotta","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-8661","authenticated-orcid":false,"given":"Rosa","family":"Vona","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7697-814X","authenticated-orcid":false,"given":"Antonella","family":"Tinari","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena 299, 00161 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, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-7198","authenticated-orcid":false,"given":"Giovanni","family":"Casella","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-3553","authenticated-orcid":false,"given":"Daniele","family":"Crocetti","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominga","family":"Carlomagno","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7925-4609","authenticated-orcid":false,"given":"Ivan","family":"Tattoli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 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, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-3752","authenticated-orcid":false,"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9249-1318","authenticated-orcid":false,"given":"Carola","family":"Severi","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/codi.15140","article-title":"European Society of Coloproctology: Guidelines for the Management of Diverticular Disease of the Colon","volume":"22","author":"Schultz","year":"2020","journal-title":"Color. 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