{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:27:36Z","timestamp":1778686056994,"version":"3.51.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["21K07929"],"award-info":[{"award-number":["21K07929"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["22K15363"],"award-info":[{"award-number":["22K15363"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["21KK0291"],"award-info":[{"award-number":["21KK0291"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["22K08047"],"award-info":[{"award-number":["22K08047"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare, Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Crohn\u2019s disease (CD) is a refractory inflammatory bowel disease with an unclear etiology. CircularRNA (circRNA) has been highlighted as a novel class of functional noncoding RNAs associated with the pathogenesis of various diseases. However, the functions of circRNA in CD remain unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Biopsies were obtained from noninflammatory sites in the terminal ileum of the CD group (n\u2005=\u20054) and non-CD group (n\u2005=\u20054) and analyzed for circRNA expression using RNA sequencing. The significantly altered circRNAs were validated in the CD group (n\u2005=\u200545) and non-CD group (n\u2005=\u200515) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transcriptome analysis was conducted using circRNA-downregulated macrophage-like THP-1 cells. Reactive oxygen species (ROS) levels, cytokine mRNA expression, phagocytosis, and migration were evaluated in circRNA-downregulated THP-1 cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CircularRNA sequencing analysis revealed significant differences in 31 circRNAs between the CD group and non-CD group. Quantitative reverse transcriptase-polymerase chain reaction analysis for each circRNA demonstrated significant upregulation of hsa_circ_0015388 in the CD group. Hsa_circ_0015388 was expressed in THP-1 cells, but not in HCEC-1CT and Caco-2\/bbe. Transcriptome analysis in THP-1 cells transfected with scramble or hsa_circ_0015388 siRNA (small interfering RNA) showed a significant alteration in innate immune response related pathway. Reactive oxygen species production was significantly increased in the hsa_circ_0015388 downregulated THP-1 cells. Reactive oxygen species induction in the hsa_circ_0015388 knocked down THP-1 was diminished by the inhibition of TNFSF10.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A comprehensive analysis of circRNA expression revealed that 31 circRNAs were dysregulated in the CD group. Hsa_circ_0015388 is expressed in macrophages and negatively regulates ROS function inhibiting the TNFSF10 pathway. This study first revealed that hsa_circ_0015388 plays a role in the pathogenesis of CD by suppressing ROS production in macrophages.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izae317","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T08:54:12Z","timestamp":1736844852000},"page":"1355-1365","source":"Crossref","is-referenced-by-count":1,"title":["hsa_circ_0015388 Reduces Macrophage Derived Reactive Oxygen Species in Crohn\u2019s Disease"],"prefix":"10.1093","volume":"31","author":[{"given":"Yuya","family":"Sugiyama","sequence":"first","affiliation":[{"name":"Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology\/Oncology, Department of Medicine, Asahikawa Medical University , Midorigaoka-Higashi 2-1-1-1, Asahikawa Hokkaido, 078-8510 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