{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:10:32Z","timestamp":1764601832359,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["22K17655","19K16564","20K21659","23K10481","21K06926","21K11223","22K11423","23K16547"],"award-info":[{"award-number":["22K17655","19K16564","20K21659","23K10481","21K06926","21K11223","22K11423","23K16547"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor \u03baB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system.<\/jats:p>","DOI":"10.3390\/ijms25094735","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T08:18:27Z","timestamp":1714119507000},"page":"4735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1"],"prefix":"10.3390","volume":"25","author":[{"given":"Kei","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Fujiwara-Tani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Nukaga","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isao","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Kishi","sequence":"additional","affiliation":[{"name":"Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyomu","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-8825","authenticated-orcid":false,"given":"Hiroki","family":"Kuniyasu","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/annonc\/mdu086","article-title":"Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model\u2014A study based on data from an international multicentre project (EPCRC-CSA)","volume":"25","author":"Blum","year":"2014","journal-title":"Ann. 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