{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:48:23Z","timestamp":1788432503792,"version":"build-2803163510"},"reference-count":70,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":339,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>No study is currently available regarding the establishment and utilization of a thermal stress (TS)-induced damage model in animal intestinal organoids (IO). To study the efficacy and possible molecular mechanisms of zinc (Zn) proteinate with moderate chelation strength (Zn-Prot M) in alleviating TS-induced intestinal damage, two experiments were conducted by establishing and using the TS-induced damage model of broiler jejunal organoids (JO). In Exp. 1, the effect of TS on the integrity and barrier function of JOs over time was investigated using a 2 [culture temperatures, 40\u00b0C (normal temperature, NT) and 44\u00b0C (high temperature, HT)] \u00d7 6 (incubation time points, 0, 3, 6, 9, 12, and 15\u2009h) factorial design, and the data were analyzed by single degree of freedom contrast and two-way ANOVA. In Exp. 2, the efficacies of Zn-Prot M and Zn sulfate (ZnS) in reducing the effect of TS were compared via 2 (Zn sources, ZnS and Zn-Prot M) \u00d7 2 (added Zn levels, 50 and 100\u2009\u03bcmol\/L) factorial design with control groups under HT (HT-C) and NT (NT-C), and the data were analyzed by T-test, single degree of freedom contrast and two-way ANOVA. The results showed that in Exp. 1, the integrity and barrier function of JOs were substantially damaged after 12\u2009h of TS, as evidenced by the increased diamine oxidase (DAO) content by 17% and lactate dehydrogenase (LDH) activity by 84% (P\u2009&amp;lt;\u20090.05) and the observed fluorescein isothiocyanate-dextran (FITC-D) entrance into the JOs. In Exp. 2, TS increased (P\u2009&amp;lt;\u20090.05) DAO contents by 95% and LDH activities by 105% in the culture media, and mRNA or phosphorylated protein expression levels of C-jun N-terminal kinase (JNK) by 27% or 117%, and FITC-D accumulation was observed in the JOs. TS decreased (P\u2009&amp;lt;\u20090.05) the budding percentage of JOs by 35% and proportions of proliferating cell nuclear antigen (PCNA) by 56% and 5-ethynyl-2'-deoxyuridine (EdU) positive cells by 58%. Additionally, TS decreased (P\u2009&amp;lt;\u20090.05) mRNA and protein or phosphorylated protein expression levels of G protein-coupled receptor 39 (GPR39), phospholipase C beta 1 (PLC\u03b21), phosphatidylinositol 3-kinase (PI3K), serine threonine kinase (AKT), extracellular regulated protein kinase (ERK), and p38 mitogen activated protein kinase (p38 MAPK) by 37\u201372%. Meanwhile, supplementation of Zn, particularly 50\u2009\u03bcmol\/L of Zn as Zn-Prot M, reversed (P\u2009&amp;lt;\u20090.05) all the above changes by 21\u2013132%. In conclusion, supplemental Zn, particularly 50\u2009\u03bcmol\/L of Zn as Zn-Prot M, could effectively alleviate the TS-induced damage to the integrity and barrier function of broiler JOs possibly by promoting cell proliferation via GPR39\/PLC\u03b21-mediated PI3K\/AKT and MAPK signaling pathways. To our knowledge, this is the first study to establish and utilize the TS-induced damage model in animal IOs to explore the protective efficacy of a nutrient and possible mechanisms.<\/jats:p>","DOI":"10.1093\/jas\/skaf423","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:41:04Z","timestamp":1764942064000},"source":"Crossref","is-referenced-by-count":8,"title":["Zinc proteinate alleviates thermal stress-induced damage to broiler jejunal organoid integrity and barrier function possibly by promoting cell proliferation via GPR39\/PLC\u03b21-mediated PI3K\/AKT and MAPK signaling pathways"],"prefix":"10.1093","volume":"103","author":[{"given":"Weizhen","family":"Song","sequence":"first","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Hu","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Animal Science, North Carolina State University , Raleigh, NC, 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Ching","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Animal Science, North Carolina State University , Raleigh, NC, 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Odle","sequence":"additional","affiliation":[{"name":"Department of Animal Science, North Carolina State University , Raleigh, NC, 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles Todd","family":"See","sequence":"additional","affiliation":[{"name":"Department of Animal Science, North Carolina State University , Raleigh, NC, 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Hu","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengchen","family":"Wang","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiudong","family":"Liao","sequence":"additional","affiliation":[{"name":"Mineral Nutrition Research Division, State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences , Beijing 100193,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mineral Nutrition Research Division, State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences , Beijing 100193,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xugang","family":"Luo","sequence":"additional","affiliation":[{"name":"Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University , Yangzhou 225000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"issue":"11","key":"2025122410322781800_skaf423-B1","doi-asserted-by":"publisher","first-page":"4599","DOI":"10.1093\/jas\/sky345","article-title":"The effect of recovery from heat stress on circulating bioenergetics and inflammatory biomarkers","volume":"96","author":"Abuajamieh","year":"2018","journal-title":"J. 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