{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T15:00:19Z","timestamp":1780844419390,"version":"3.54.1"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stress urinary incontinence (SUI) is primarily caused by structural and functional damage to the external urethral sphincter (EUS). In previous studies, metformin, a known AMP\u2010activated protein kinase (AMPK) activator, has shown repair effects after skeletal muscle injury. This study explored its therapeutic effect and molecular mechanisms in SUI associated with EUS injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SUI model was established by double vaginal dilation. Rats were assigned to sham, vehicle\u2010treated, or metformin\u2010treated (200\u2009mg\/kg\/day, oral) groups. Urodynamic testing was performed after 7 and 14\u2009days. Subsequently, EUS tissues were isolated for histological (hematoxylin and eosin [H&amp;E], Masson's), apoptotic (TUNEL), ultrastructural (transmission electron microscopy [TEM]), and molecular analyses. Finally, C2C12 myotubes cells were treated with varying concentrations of metformin to evaluate the expression of phosphorylated AMPK (p\u2010AMPK) and MYH1\/2, which are markers of skeletal muscle fiber type and regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Abdominal leak point pressure (ALPP) and bladder leak point pressure (BLPP) decreased after double vaginal dilation, suggesting that SUI was established. After treatment for 7 and 14\u2009days, respectively, metformin significantly increased ALPP and BLPP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) without affecting maximum bladder capacity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). Masson's staining and TEM revealed that metformin improved disorganized EUS architecture. Further, Western blot analysis demonstrated that metformin increased the expression of MYH1\/2 and p\u2010AMPK in\u00a0vivo and in\u00a0vitro. Meanwhile TUNEL assay showed that metformin treatment reduced apoptotic cells in the EUS from SUI rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results indicate that metformin enhances EUS repair to improve SUI via activating the AMPK signaling pathway. These findings provide new insights into therapeutic strategies for SUI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70171","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:17:16Z","timestamp":1773807436000},"page":"796-808","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin enhances external urethral sphincter integrity and restores continence via\n                    <scp>AMPK<\/scp>\n                    activation in a rat model of stress urinary incontinence"],"prefix":"10.1002","volume":"9","author":[{"given":"Yuting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine Third Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation 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