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This study examined the protective role of natural flavone, acacetin (ACA), and a protease of <jats:italic>Bacillus cereus<\/jats:italic> bacteria (<jats:italic>B. cereus<\/jats:italic>) as well as the potential role of miR-155\/SIRT1\/FOXO1 network in DOX-induced testicular injury. Twenty-four male Wistar rats were randomly allocated into four groups and treated as follows: Control, DOX (1\u00a0mg\/kg, i.p) every other day for 21\u00a0days with a total dose equal to 10\u00a0mg\/kg throughout the experiment, and pre-treated groups that received ACA (5\u00a0mg\/kg\/day, p.o) or <jats:italic>B. cereus<\/jats:italic> protease (36\u00a0mg\/kg\/day, p.o) for a week prior to DOX administration. DOX challenge reduced the testis weight coefficient, serum testosterone, and testicular 17\u03b2-hydroxysteroid dehydrogenase (17\u03b2-HSD). DOX caused a significant increase in testicular oxidative stress, inflammatory, and apoptotic markers. Aberrant testicular miR-34c, a germ-specific miRNA, and miR-155 expressions were observed, along with decreased protein expression of sirtuin1 (SIRT1) dependent forkhead box 1 (FOXO1) acetylation which induces apoptosis. Besides, abnormal histopathological architecture and a marked reduction in the testicular expression of proliferating cell nuclear antigen (PCNA) were observed. ACA or protease administration significantly improved the histopathological and immunohistochemical pictures compared with DOX alone and renovated testicular functions. Interestingly, treatment with protease was more significant than treatment with ACA in ameliorating DOX-induced testicular injury. Taken together, this study reveals the prophylactic role of these two regimens on male fertility by exhibiting antioxidant, anti-inflammatory, and anti-apoptotic effects against DOX-elicited testicular damage, possibly via modulating miR-155\/SIRT1\/FOXO1 network.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12010-022-03992-8","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T02:02:31Z","timestamp":1655517751000},"page":"5196-5219","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Inflammatory Modulation of miR-155 Inhibits Doxorubicin-Induced Testicular Dysfunction via SIRT1\/FOXO1 Pathway: Insight into the Role of Acacetin and Bacillus cereus Protease"],"prefix":"10.1007","volume":"194","author":[{"given":"Hend Mohamed","family":"Anwar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherin Ramadan","family":"Hamad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad Elsayed Mohamed","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania Hassan Mohamed","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3919-2612","authenticated-orcid":false,"given":"Eman Maher","family":"Elbaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,18]]},"reference":[{"issue":"20","key":"3992_CR1","doi-asserted-by":"publisher","first-page":"12141","DOI":"10.1111\/jcmm.15859","volume":"24","author":"WY Wu","year":"2020","unstructured":"Wu, W. 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