{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:01:52Z","timestamp":1778151712997,"version":"3.51.4"},"reference-count":89,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    is an opportunistic protozoan, with many species of cross\u2010human infectivity. It causes life\u2010threatening diarrhoea in children and CD4\u2010defective patients. Despite its limited efficacy, nitazoxanide remains the primary anti\u2010cryptosporidial drug.\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infects the intestinal brush border (intracellular\u2013extracytoplasmic) and down\u2010regulates pyroptosis to prevent expulsion. Romidepsin is a natural histone deacetylase inhibitor that triggers pyroptosis. Romidepsin's effect on cryptosporidiosis was assessed in immunocompromised mice via gasdermin\u2010D (GSDM\u2010D) immunohistochemical expression, IFN\u2010\u03b3, IL\u20101\u03b2 and IL\u201018 blood levels by ELISA, and via parasite scanning by modified Ziehl\u2013Neelsen staining and scanning electron microscopy (SEM). Oocyst deformity and local cytokines were also assessed in ex vivo ileal explants. Following intraperitoneal injection of romidepsin, oocyst shedding significantly reduced at the 9th, 12th and 15th d.p.i. compared with infected\u2010control and drug\u2010control (nitazoxanide\u2010treated) mice. H&amp;E staining of intestinal sections from romidepsin\u2010treated mice showed significantly low intestinal scoring with marked reduction in epithelial hyperplasia, villous blunting and cellular infiltrate. SEM revealed marked oocyst blebbing and paucity (in vivo and ex vivo) after romidepsin compared with nitazoxanide. Regarding pyroptosis, romidepsin triggered significantly higher intestinal GSDM\u2010D expression in vivo, and higher serum\/culture IFN\u2010\u03b3, IL\u20101\u03b2 and IL\u201018 levels in romidepsin\u2010treated mice than in the control groups. Collectively, in cryptosporidiosis, romidepsin succeeded in enhancing pyroptosis in the oocysts and infected epithelium, reducing infection and shifting the brush border towards normalisation.\n                  <\/jats:p>","DOI":"10.1111\/pim.13032","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T11:38:35Z","timestamp":1710761915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pyroptosis Tuning in Intestinal Cryptosporidiosis via the Natural Histone\n                    <scp>Deacetylase<\/scp>\n                    Inhibitor Romidepsin"],"prefix":"10.1111","volume":"46","author":[{"given":"Noha E.","family":"Shalaby","sequence":"first","affiliation":[{"name":"Medical Parasitology Department, Faculty of Medicine Tanta University  Tanta Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeinab 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