{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:03Z","timestamp":1791348723587,"version":"4.3.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003705","name":"Korea Institute of Toxicology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003705","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Loperamide, a \u03bc-opioid receptor agonist that slows gastrointestinal transit, is widely used as an antidiarrheal agent and an experimental model of gastric dysmotility and functional dyspepsia (FD). However, transcriptomic alterations associated with loperamide-induced delayed gastric emptying remain poorly characterized. This study aimed to investigate gastric gene-expression profiles associated with loperamide-induced gastric dysmotility using RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male BALB\/c mice were intraperitoneally injected with loperamide after 20\u00a0h of fasting. Delayed gastric emptying was assessed in one cohort, while gastric antrum tissues from a separate cohort were collected for RNA sequencing. Differentially expressed genes (DEGs) were identified using fold change \u22651.5 and false discovery rate (FDR) &amp;lt;0.01. Gene set enrichment analysis (GSEA) and pathway-network analysis were conducted to characterize biological pathways associated with loperamide treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Loperamide significantly delayed gastric emptying, as demonstrated by increased gastric retention of phenol red. Transcriptomic analysis identified 1,356 DEGs, including 553 upregulated and 803 downregulated genes. GSEA revealed enrichment of inflammatory response-related pathways among upregulated genes, whereas synaptic transmission- and calcium signaling-related pathways were predominantly downregulated. Representative genes involved in cholinergic signaling (\n                      <jats:italic>Chrm2<\/jats:italic>\n                      and\n                      <jats:italic>Chrna9<\/jats:italic>\n                      ), glutamatergic signaling (\n                      <jats:italic>Grm7<\/jats:italic>\n                      ), and calcium-channel function (\n                      <jats:italic>Cacna1a<\/jats:italic>\n                      ) showed reduced expression, while\n                      <jats:italic>Il33<\/jats:italic>\n                      was increased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides transcriptomic insights into loperamide-induced gastric dysmotility. The findings suggest coordinated downregulation of genes associated with neuronal\/synaptic signaling together with enrichment of inflammatory response-related transcriptional pathways in the gastric antrum, providing a molecular framework for this widely used experimental model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1924065","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:48:34Z","timestamp":1791348514000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic insights into loperamide-induced gastric dysmotility: RNA-seq analysis of a mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Chunggeon","family":"Lee","sequence":"first","affiliation":[{"name":"Center for National Toxicology AI and Data, Korea Institute of Toxicology","place":["Daejeon, Republic of Korea"]},{"name":"School of Korea Institute of Toxicology, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ju","family":"Hwang","sequence":"additional","affiliation":[{"name":"Institute of Bioscience & Integrative Medicine, Daejeon University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Su","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Jeonbuk Advanced Bio Research, Korea Institute of Toxicology","place":["Jeongeup, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Toxicology Technical Research Team, Division of Jeonbuk Advanced Bio Research, Korea Institute of Toxicology","place":["Jeongeup, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Seon","family":"Kim","sequence":"additional","affiliation":[{"name":"Korean Medicine Science Research Division, Korea Institute of Oriental Medicine","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daeui","family":"Park","sequence":"additional","affiliation":[{"name":"Center for National Toxicology AI and Data, Korea Institute of Toxicology","place":["Daejeon, Republic of Korea"]},{"name":"School of Korea Institute of Toxicology, University of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Woo","family":"Song","sequence":"additional","affiliation":[{"name":"School of Korea Institute of Toxicology, University of Science and Technology","place":["Daejeon, Republic of Korea"]},{"name":"Translational Toxicology Technical Research Team, Division of Jeonbuk Advanced Bio Research, Korea Institute of Toxicology","place":["Jeongeup, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[{"name":"Institute of Bioscience & Integrative Medicine, Daejeon University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00535-022-01936-x","article-title":"Pro- and anti-inflammatory roles of interleukin (IL)-33, IL-36, and IL-38 in inflammatory bowel disease","volume":"58","author":"Andoh","year":"2023","journal-title":"J. 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