{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:13:06Z","timestamp":1788333186319,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274028"],"award-info":[{"award-number":["82274028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["LH2023H032"],"award-info":[{"award-number":["LH2023H032"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["PL2025H098"],"award-info":[{"award-number":["PL2025H098"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Arsenic trioxide (ATO) therapy for acute promyelocytic leukaemia (APL) can induce neurological disorders, including cognitive impairment (CI) and depression, severely impacting patient quality of life, yet effective interventions are lacking. Clinical observations indicate ATO treatment is associated with gut microbiota dysbiosis. Given the crucial role of gut microbes and their metabolites in neurological health, this study investigated indole\u20103\u2010propionic acid (IPA), a neuroprotective microbiota\u2010derived metabolite capable of crossing the blood\u2013brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In ATO\u2010treated mice, behavioural tests confirmed significant cognitive decline. 16S rRNA genotyping revealed a reduction in Bifidobacterium abundance, and metabolomics identified a concomitant decrease in its metabolite, IPA, alongside disruptions in the tricarboxylic acid cycle and glycolysis. IPA supplementation alleviated ATO\u2010induced intestinal inflammation and behavioural deficits. Mechanistically, IPA inhibited ATO\u2010induced BRD4 degradation and the associated reduction in H4 acetylation, thereby restoring the expression of the metabolic enzyme PFKM and the synaptic protein PSD95.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IPA mitigates ATO\u2010induced intestinal injury and glycolytic dysfunction via the \u2018BRD4\u2010H4ac\u2010PFKM\u2019 axis, providing novel insights for preventing and treating ATO\u2010induced neurotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70632","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:16:38Z","timestamp":1788329798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota\u2010derived indole\u20103\u2010propionic acid attenuates Arsenic trioxide\u2010induced cognitive impairment by inhibiting ubiquitination and degradation of BRD4"],"prefix":"10.1111","author":[{"given":"Kai","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Pharmacy First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy First Affiliated Hospital of Harbin Medical University  Harbin 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