{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:04:17Z","timestamp":1789589057498,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic cardiomyopathy (DCM) is a progressive heart disorder associated with diabetes mellitus, leading to structural and functional cardiac abnormalities. The mechanisms responsible include renin\u2010angiotensin\u2010aldosterone (RAAS) activation, inflammation, apoptosis, and metabolic disturbances. Despite well\u2010established epidemiological links, treatments for DCM are elusive. This study evaluated the efficacy of a novel combination of recombinant Klotho (KL) and the angiotensin receptor blocker telmisartan (TEL) in treating DCM, as well as investigating potential mechanisms involved. DCM was induced with a single dose of streptozotocin (55\u2009mg\/kg,\n                    <jats:italic>i.p<\/jats:italic>\n                    .), followed by a 4\u2010week induction period. For treatment, rats were assigned to five groups: Normal control (NC), Diabetic control (DC), DC\u2009+\u2009KL (0.01\u2009mg\/kg,\n                    <jats:italic>S.C<\/jats:italic>\n                    .), DC\u2009+\u2009TEL (10\u2009mg\/kg,\n                    <jats:italic>p.o<\/jats:italic>\n                    .), and KL\u2009+\u2009TEL combination. Plasma biochemistry assessed cardiac damage (LDH, CK\u2010MB) and stress markers (ANP, BNP). Electrocardiogram (ECG) measured heart parameters, including heart rate (HR), QTc, JT interval, RR interval, and T\n                    <jats:sub>peak<\/jats:sub>\n                    \u2013T\n                    <jats:sub>end<\/jats:sub>\n                    intervals. Histological analysis (H&amp;E, Masson's trichrome, and Picrosirius red) was performed to assess myocardial structure and fibrosis. Lastly, immunohistochemistry analysis was performed to check the expression of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), pSMAD 2\/3, matrix metalloproteinase 9 (MMP9), and PRKN. KL and TEL combination treatment significantly reduced cardiac damage markers, reduced ECG abnormalities, including QT\n                    <jats:sub>c<\/jats:sub>\n                    , improved HR while suppressing pro\u2010fibrotic signaling, enhancing mitophagy, and decreasing fibroblast proliferation. The involvement of pathways involving TGF\u2010\u03b21, pSMAD\u20102\/3, MMP9, and pFOXO3a conferred protection to the heart in experimental in\u2010vivo settings. These findings suggest that the combination of KL and TEL effectively mitigates key pathological features of DCM, highlighting its potential as a targeted treatment strategy.\n                  <\/jats:p>","DOI":"10.1002\/cbin.70078","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:33:54Z","timestamp":1757421234000},"page":"1669-1681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Combination of Exogenous Klotho Combined With Telmisartan Ameliorated Diabetic Cardiomyopathy via an Antifibrotic Mechanism"],"prefix":"10.1002","volume":"49","author":[{"given":"Mansi Vinodkumar","family":"Trivedi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani Pilani Campus India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant R.","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani Pilani Campus India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4627-5504","authenticated-orcid":false,"given":"Anil Bhanudas","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani Pilani Campus India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.121771"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1997.0435"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154277"},{"issue":"10","key":"e_1_2_13_5_1","first-page":"1048","article-title":"Fosinopril and Valsartan Intervention in Gene Expression of Klotho, MMP\u20109, TIMP\u20101, and PAI\u20101 in the Kidney of Spontaneously Hypertensive Rats","volume":"35","author":"Cheng X.","year":"2010","journal-title":"Journal of Central South University. 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