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A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-\u03b1 and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1\u03b2 into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.<\/jats:p>","DOI":"10.1007\/s00535-019-01657-8","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T08:02:36Z","timestamp":1576915356000},"page":"481-495","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review"],"prefix":"10.1007","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-0585","authenticated-orcid":false,"given":"Toshio","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis K. 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