{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:47:11Z","timestamp":1761648431793,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Important Weak Subject Construction Project of Shanghai Pudong New Area Health Commission","award":["PWZbr2022-12"],"award-info":[{"award-number":["PWZbr2022-12"]}]},{"name":"Shanghai Post-doctoral Excellence Program","award":["2022561"],"award-info":[{"award-number":["2022561"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M732652"],"award-info":[{"award-number":["2023M732652"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Cultivation Program of Shanghai East Hospital","award":["DFPY2022007"],"award-info":[{"award-number":["DFPY2022007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Background: Acute cholecystitis (AC) is characterized by gallbladder inflammation and is commonly accompanied by disordered gallbladder motility. Although laparoscopic cholecystectomy is the standard treatment, it carries procedure-related risks. Low-intensity pulsed ultrasound (LIPUS), a safe and noninvasive modality widely applied for muscle repair, may offer therapeutic benefits for AC-associated motility dysfunction. Methods: In vivo, LIPUS (0.5 W\/cm2) was applied for 15 min daily to acute cholecystitis guinea pigs over three consecutive days, starting 24 h after reversing common bile duct ligation (CBDL) surgery. In vitro, LIPUS (0.5 W\/cm2) was delivered for 5 min to isolated gallbladder muscle strips and for 30 s to isolated interstitial cells of Cajal (ICCs). Gallbladder function and histology were assessed in vitro and in vivo using immunofluorescence, Western blotting, calcium imaging, muscle strip contractility testing, and related molecular methods. Results: LIPUS increased intracellular Ca2+ by activating the Ano1 channel in ICCs, thereby enhancing gallbladder smooth muscle contractility. At 72 h, the LIPUS 72 h (+) group showed a 71.3% increase in gallbladder muscle tone (p = 0.0001) and a 40.7% reduction in inflammation scores (p = 0.0001) compared with the LIPUS 72 h (\u2212) group. Conclusions: LIPUS alleviates gallbladder contractile dysfunction in acute cholecystitis by acting on ICCs through mechanisms involving the promotion of ICC recovery and a reduction in inflammation.<\/jats:p>","DOI":"10.3390\/bioengineering12111164","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LIPUS Enhances Gallbladder Motility via ANO1 in Acute Cholecystitis Guinea Pigs"],"prefix":"10.3390","volume":"12","author":[{"given":"Liping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhai","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-7942","authenticated-orcid":false,"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4624-3134","authenticated-orcid":false,"given":"Fan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"},{"name":"Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1001\/jama.2022.2969","article-title":"Acute Cholecystitis","volume":"327","author":"Walter","year":"2022","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1001\/jama.2022.7768","article-title":"A Review of Acute Cholecystitis","volume":"328","author":"Abdulrahman","year":"2022","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"G467","DOI":"10.1152\/ajpgi.00415.2007","article-title":"Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle","volume":"294","author":"Balemba","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1002\/jcp.27197","article-title":"Neutrophils injure gallbladder interstitial Cajal-like cells in a guinea pig model of acute cholecystitis","volume":"234","author":"Lin","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_5","first-page":"435","article-title":"Neutrophil depletion reduces interstitial cajal-like cell injury and alleviates inflammation-induced motor dysfunction in guinea-pig gallbladder during acute cholecystitis","volume":"25","author":"Zhang","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1113\/jphysiol.2014.277152","article-title":"Ano1, a Ca2+-activated Cl\u2212 channel, coordinates contractility in mouse intestine by Ca2+ transient coordination between interstitial cells of Cajal","volume":"592","author":"Singh","year":"2014","journal-title":"J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1113\/expphysiol.2011.058248","article-title":"Anoctamins and gastrointestinal smooth muscle excitability","volume":"97","author":"Sanders","year":"2012","journal-title":"Exp. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4887","DOI":"10.1113\/jphysiol.2009.176198","article-title":"Expression of anoctamin 1\/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles","volume":"587","author":"Hwang","year":"2009","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"G228","DOI":"10.1152\/ajpgi.00363.2016","article-title":"Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine","volume":"312","author":"Malysz","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jhbp.516","article-title":"Tokyo guidelines 2018: Flowchart for the management of acute cholecystitis","volume":"25","author":"Okamoto","year":"2017","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5319","DOI":"10.1007\/s00464-016-4882-1","article-title":"Surgical management of empyematous cholecystitis: A register study of over 12,000 cases from a regional quality control database in Germany","volume":"30","author":"Ambe","year":"2016","journal-title":"Surg. Endosc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1177\/02692155221097035","article-title":"Effects of low-intensity pulsed ultrasound on knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials","volume":"36","author":"Chen","year":"2022","journal-title":"Clin. Rehabil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2413930","DOI":"10.1002\/advs.202413930","article-title":"LIPUS promotes calcium oscillation and enhances calcium dependent autophagy of chondrocytes to alleviate osteoarthritis","volume":"12","author":"Guan","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15823","DOI":"10.1002\/jcb.28853","article-title":"Low-intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K\/AKt signaling pathways","volume":"120","author":"Xie","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/978-3-319-22536-4_21","article-title":"Stimulation of bone repair with ultrasound","volume":"Volume 880","author":"Escoffre","year":"2016","journal-title":"Therapeutic Ultrasound. Advances in Experimental Medicine and Biology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.3892\/mmr.2020.11575","article-title":"Role of MAPK\/JNK signaling pathway on the regulation of biological behaviors of MC3T3-E1 osteoblasts under titanium ion exposure","volume":"22","author":"Zhu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1007\/s10439-014-1081-x","article-title":"Low-intensity pulsed ultrasound activates integrin-mediated mechanotransduction pathway in synovial cells","volume":"42","author":"Sato","year":"2014","journal-title":"Ann. Biomed. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1093\/pm\/pnaa090","article-title":"The regenerative potential of therapeutic ultrasound on neural tissue: A pragmatic review","volume":"21","author":"Haffey","year":"2020","journal-title":"Pain Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s13287-022-02887-z","article-title":"Advances in the application of low-intensity pulsed ultrasound to mesenchymal stem cells","volume":"13","author":"Xia","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19476035221093060","DOI":"10.1177\/19476035221093060","article-title":"Low-intensity pulsed ultrasound enhances the efficacy of bone marrow\u2013derived MSCS in osteoarthritis cartilage repair by regulating autophagy-mediated exosome release","volume":"13","author":"Xia","year":"2022","journal-title":"Cartilage"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s11255-016-1298-8","article-title":"Ultrasound induces contraction of the bladder smooth muscle","volume":"48","author":"Ren","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106739","DOI":"10.1016\/j.ultras.2022.106739","article-title":"Ca2+ signaling-mediated low-intensity pulsed ultrasound-induced proliferation and activation of motor neuron cells","volume":"124","author":"Truong","year":"2022","journal-title":"Ultrasonics"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Qin, H.C., Du, L., Luo, Z.W., He, Z., Wang, Q., Chen, S.Y., and Zhu, Y.L. (2022). The therapeutic effects of low-intensity pulsed ultrasound in musculoskeletal soft tissue injuries: Focusing on the molecular mechanism. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1080430"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.21037\/qims-20-680","article-title":"Review on experimental study and clinical application of low- intensity pulsed ultrasound in inflammation","volume":"11","author":"Xu","year":"2021","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_25","first-page":"G485","article-title":"Selective lesioning of interstitial cells of Cajal by methylene blue and light leads to loss of slow waves","volume":"266","author":"Liu","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jhbp.912","article-title":"Pathophysiology and pathology of acute cholecystitis: A secondary publication of the Japanese version from 1992","volume":"29","author":"Adachi","year":"2021","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1159\/000489987","article-title":"Acute cholecystitis reduces interstitial cells of cajal in porcine gallbladder through decreased mRNA synthesis","volume":"47","author":"Huang","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.biopha.2017.11.108","article-title":"Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells","volume":"96","author":"Franca","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bone.2013.09.018","article-title":"Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation","volume":"58","author":"Nakao","year":"2014","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1093\/cercor\/bhaa062","article-title":"Ultrasound stimulation suppresses LPS-Induced proinflammatory responses by regulating NF-\u03baB and CREB activation in microglial cells","volume":"30","author":"Chang","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_31","first-page":"179","article-title":"Effects of low-intensity pulsed ultrasound on contraction of rats bladder smooth muscle in vitro","volume":"32","author":"Ren","year":"2016","journal-title":"Chin. J. Med. Imaging Technol."},{"key":"ref_32","first-page":"81","article-title":"Interstitial cells of Cajal and telocytes in the urinary system: Facts and distribution","volume":"56","author":"Wolnicki","year":"2016","journal-title":"Folia Med. Cracov"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1113\/jphysiol.2006.116624","article-title":"Structure and organization of interstitial cells of Cajal in the gastrointestinal tract","volume":"576","author":"Komuro","year":"2006","journal-title":"J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s10495-024-01950-9","article-title":"LIPUS regulates the progression of knee osteoarthritis in mice through primary cilia-mediated TRPV4 channels","volume":"29","author":"Wu","year":"2024","journal-title":"Apoptosis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70304","DOI":"10.1096\/fj.202401142RR","article-title":"Mechanosensitive Ca2+ channel TRPV1 activated by low-intensity pulsed ultrasound ameliorates acute kidney injury through Notch1-Akt-eNOS signaling","volume":"39","author":"Huangfu","year":"2025","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s12264-024-01186-2","article-title":"L-Type calcium channel modulates low-intensity pulsed ultrasound-induced excitation in cultured hippocampal neurons","volume":"40","author":"Fan","year":"2024","journal-title":"Neurosci. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.bioeng.6.040803.140126","article-title":"Mechanical bioeffects of ultrasound","volume":"6","author":"Dalecki","year":"2004","journal-title":"Annu. Rev. Biomed. Eng."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/11\/1164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:39:59Z","timestamp":1761647999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/11\/1164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["bioengineering12111164"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering12111164","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]}}}