{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:14:42Z","timestamp":1789035282845,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":252,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Radiation\u2010induced heart disease (RIHD) severely compromises the long\u2010term survival of cancer patients. Although ferroptosis has been implicated as a key contributor to RIHD pathogenesis, the underlying regulatory mechanisms remain incompletely defined. Prompted by clinical observations of elevated serum iron concentrations following thoracic radiotherapy, this study investigated iron\u2010metabolic alterations during RIHD progression and evaluated the cardioprotective efficacy of salidroside in mitigating ferroptosis through restoration of iron homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a retrospective cohort of 98 patients undergoing thoracic radiotherapy, clinical data were collected, and serum iron concentrations were measured before and after treatment. To elucidate the underlying mechanisms, an RIHD mouse model was established using single\u2010dose precordial irradiation at 20\u2009Gy, followed by salidroside administration. Cardiac function, mitochondrial integrity, and ferroptosis\u2010related markers were systematically assessed. Mechanistic targets were identified using bulk and single\u2010cell RNA sequencing and subsequently validated by molecular docking and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical analysis revealed significantly elevated serum iron concentrations after radiotherapy (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Consistent with this clinical phenotype, irradiated mice exhibited cardiac dysfunction, mitochondrial damage, and disrupted iron metabolism. Multiomics analyses identified the transferrin receptor 1 (TFRC) as a potentially critical regulator of these pathological processes. Salidroside treatment significantly ameliorated cardiac injury and attenuated ferroptosis\u2010related alterations. KEGG pathway analysis further demonstrated enrichment of TFRC in the HIF\u20101 signaling pathway, and salidroside reduced HIF\u20101\n                      <jats:italic>\u03b1<\/jats:italic>\n                      expression, suggesting attenuation of irradiation\u2010associated hypoxic\u2010stress signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thoracic radiotherapy may promote RIHD pathogenesis by inducing disrupted iron homeostasis, thereby contributing to cardiomyocyte ferroptosis and mitochondrial injury. Salidroside effectively ameliorates myocardial damage by attenuating iron overload and ferroptosis. Collectively, these findings highlight the translational potential of salidroside as a promising adjunctive cardioprotective agent for patients undergoing thoracic radiotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/cdr\/5141802","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:57:37Z","timestamp":1789034257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Investigation of Salidroside Modulates Iron Overload to Mitigate Radiation\u2010Induced Heart Disease"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6230-276X","authenticated-orcid":false,"given":"Jiaming","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyao","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoquan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209825"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/pcmedi\/pbz025"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.03.026"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.48095\/ccko202410"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.028"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2023.109407"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004967"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02800-1"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3505"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2010.05.009"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.050773"},{"key":"e_1_2_11_12_2","article-title":"Studying Ferroptosis and Iron Metabolism Pre- and Post-Radiotherapy Treatment in Breast Cancer Patients","volume":"35","author":"El-Benhawy S. 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