{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:56:24Z","timestamp":1774522584412,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Insomnia is a prevalent sleep disorder that severely impairs physical and mental health. Clinical research has shown that Tuina, a form of therapeutic massage, can improve sleep quality and restore normal sleep patterns, yet the underlying biological mechanism remains unclear. This study aimed to determine whether Tuina improves sleep-related behaviors by modulating the Piezo1\u2013calcium signaling pathway through mechanical stimulation of the nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A rat model of sleep disturbances was induced using PCPA. Rats received daily Tuina on the dorsal regions corresponding to the Governor Vessel and Bladder meridians. sleep-related behavioral parameters, cognitive function, hippocampal neurotransmitters, and expression of Piezo1 and downstream proteins (CaM, CaN) were assessed. The Piezo1 agonist Yoda1 was used to verify mechanistic involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tuina treatment significantly improved sleep-related behavioral parameters and cognitive performance in PCPA-treated rats. At the molecular level, PCPA-induced sleep disruption led to Piezo1 upregulation, intracellular calcium overload, and subsequent overactivation of the CaM\/CaN signaling pathway. These alterations were accompanied by neurotransmitter imbalance and hippocampal neuronal damage. Tuina intervention effectively suppressed Piezo1 expression, normalized calcium homeostasis, and inhibited downstream CaM\/CaN activation, thereby restoring neurotransmitter levels and preserving neuronal integrity. Critically, the therapeutic benefits of Tuina were largely reversed by co-administration of the Piezo1 agonist Yoda1, supporting the involvement of Piezo1-mediated calcium signaling in its mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tuina\u2019s therapeutic effect involves suppression of Piezo1-dependent calcium signaling, contributing to normalization of hippocampal function and neurotransmitter balance. This provides mechanistic evidence that Tuina\u2019s mechanical stimulation modulates sleep-related behavioral endpoints via central mechanosensitive ion channels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1777810","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T09:55:19Z","timestamp":1774518919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuina ameliorates sleep disturbances in PCPA-treated rats through Piezo1-mediated calcium signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaqi","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Central Laboratory, Ruijin Hospital, Luwan Branch, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Liang","sequence":"additional","affiliation":[{"name":"TCM of Department, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Tuina, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinying","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00018-025-05854-y","article-title":"Altered venous flow drives endothelial to mesenchymal transition in varicose veins by suppressing PIEZO1-KLF2 signaling","volume":"82","author":"Ahalya","year":"2025","journal-title":"Cell Mol. 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