{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:41:01Z","timestamp":1784310061587,"version":"3.55.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002386","name":"Cairo University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002386","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1\u03b2) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg\/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 \u00d7 10<jats:sup>6<\/jats:sup> cell\/rat) into rat tail vein; DM-Anak received Anak 0.5 \u03bcg\/kg\/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2\u2013related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNF\u03b1), IL1\u03b2, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNF\u03b1\/IL1\u03b2\/caspase1 and Nrf2\/IL10 pathways.<\/jats:p>","DOI":"10.1007\/s00210-024-03152-1","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T08:02:09Z","timestamp":1716364929000},"page":"8023-8041","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interleukin 1\u03b2 receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy"],"prefix":"10.1007","volume":"397","author":[{"given":"Lamiaa Mohamed","family":"Mahmoud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya Aly Ashraf Abdel","family":"Mageed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackline Moawad","family":"Saadallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira Farouk","family":"Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liala Ahmed","family":"Rashed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hania Ibrahim","family":"Ammar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"issue":"5","key":"3152_CR1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.4239\/wjd.v5.i5.697","volume":"5","author":"NK Agrawal","year":"2014","unstructured":"Agrawal NK, Kant S (2014) Targeting inflammation in diabetes: newer therapeutic options. World J Diabetes 5(5):697","journal-title":"World J Diabetes"},{"issue":"2","key":"3152_CR2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/path.3960","volume":"227","author":"A Amin","year":"2012","unstructured":"Amin A, Choi SK, Galan M et al (2012) Chronic inhibition of endoplasmic reticulum stress and inflammation prevents ischaemia-induced vascular pathology in type II diabetic mice. J Pathol 227(2):165\u2013174","journal-title":"J Pathol"},{"issue":"1","key":"3152_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-015-0142-x","volume":"6","author":"HI Ammar","year":"2015","unstructured":"Ammar HI, Sequiera GL, Nashed MB et al (2015) Comparison of adipose tissue-and bone marrow-derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats. Stem Cell Res Ther 6(1):1\u201314","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"3152_CR4","doi-asserted-by":"publisher","first-page":"H1290","DOI":"10.1152\/ajpheart.00317.2020","volume":"320","author":"HI Ammar","year":"2021","unstructured":"Ammar HI, Shams Eldeen AM, Shoukry HS et al (2021) Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol-Heart Circ Physiol 320(4):H1290\u2013H1302","journal-title":"Am J Physiol-Heart Circ Physiol"},{"key":"3152_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s13577-014-0095-x","volume":"27","author":"B Amorin","year":"2014","unstructured":"Amorin B, Alegretti AP, Valim V et al (2014) Mesenchymal stem cell therapy and acute graft-versus-host disease: a review. Human Cell 27:137\u2013150","journal-title":"Human Cell"},{"issue":"2","key":"3152_CR6","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1002\/jcp.26009","volume":"233","author":"HC Chandramoorthy","year":"2018","unstructured":"Chandramoorthy HC, Bin-Jaliah I, Karari H et al (2018) MSCs ameliorates DPN induced cellular pathology via [Ca2+] i homeostasis and scavenging the pro-inflammatory cytokines. J Cell Physiol 233(2):1330\u20131341","journal-title":"J Cell Physiol"},{"issue":"1","key":"3152_CR7","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1038\/s41598-018-20703-8","volume":"8","author":"C Chandramouli","year":"2018","unstructured":"Chandramouli C, Reichelt ME, Curl CL et al (2018) Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia. Sci Rep 8(1):2346","journal-title":"Sci Rep"},{"issue":"1","key":"3152_CR8","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1161\/CIRCRESAHA.111.243196","volume":"110","author":"M Coggins","year":"2012","unstructured":"Coggins M, Rosenzweig A (2012) The fire within: cardiac inflammatory signaling in health and disease. Circ Res. 110(1):116\u201325","journal-title":"Circ Res."},{"issue":"2","key":"3152_CR9","doi-asserted-by":"publisher","first-page":"240","DOI":"10.3390\/cells11020240","volume":"11","author":"JS da Silva","year":"2022","unstructured":"da Silva JS, Gon\u00e7alves RGJ, Vasques JF et al (2022) Mesenchymal stem cell therapy in diabetic cardiomyopathy. Cells. 11(2):240","journal-title":"Cells."},{"key":"3152_CR10","doi-asserted-by":"publisher","first-page":"631463","DOI":"10.3389\/fendo.2021.631463","volume":"12","author":"E De Klerk","year":"2021","unstructured":"De Klerk E, Hebrok M (2021) Stem cell-based clinical trials for diabetes mellitus. Front Endocrinol 12:631463","journal-title":"Front Endocrinol"},{"key":"3152_CR11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fphys.2020.00124","volume":"11","author":"MJ De Blasio","year":"2020","unstructured":"De Blasio MJ, Huynh N, Deo M et al (2020) Defining the progression of diabetic cardiomyopathy in a mouse model of type 1 diabetes. Front Physiol 11:124","journal-title":"Front Physiol"},{"issue":"33","key":"3152_CR12","doi-asserted-by":"publisher","first-page":"13998","DOI":"10.1073\/pnas.0810087106","volume":"106","author":"JA Ehses","year":"2009","unstructured":"Ehses JA, Lacraz G, Giroix MH et al (2009) IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Nat Acad Sci 106(33):13998\u201314003","journal-title":"Proc Nat Acad Sci"},{"issue":"4","key":"3152_CR13","first-page":"2023","volume":"6","author":"P Fanlo Mateo","year":"2023","unstructured":"Fanlo Mateo P, Gracia-Tello BD, Fonseca Aizpuru E et al (2023) Efficacy and safety of anakinra plus standard of care for patients with severe Covid-19: a randomized phase 2\/3 clinical trial. JAMA Netw Open. 6(4):2023","journal-title":"JAMA Netw Open."},{"issue":"3","key":"3152_CR14","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/ni.1703","volume":"10","author":"L Franchi","year":"2009","unstructured":"Franchi L, Eigenbrod T, Mu\u00f1oz-Planillo R et al (2009) The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 10(3):241\u2013247","journal-title":"Nat Immunol"},{"key":"3152_CR15","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.biopha.2017.08.098","volume":"95","author":"S Gheibi","year":"2017","unstructured":"Gheibi S, Kashfi K, Ghasemi A (2017) A practical guide for induction of type-2 diabetes in rat: incorporating a high-fat diet and streptozotocin. Biomed Pharmacother 95:605\u2013613","journal-title":"Biomed Pharmacother"},{"issue":"11","key":"3152_CR16","doi-asserted-by":"publisher","first-page":"5973","DOI":"10.3390\/ijms22115973","volume":"22","author":"P Grubi\u0107 Rotkvi\u0107","year":"2021","unstructured":"Grubi\u0107 Rotkvi\u0107 P, Planini\u0107 Z, Liberati Pr\u0161o AM et al (2021) The mystery of diabetic cardiomyopathy: from early concepts and underlying mechanisms to novel therapeutic possibilities. Int J Mol Sci 22(11):5973","journal-title":"Int J Mol Sci"},{"issue":"2","key":"3152_CR17","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/biof.1587","volume":"46","author":"CR Harrell","year":"2020","unstructured":"Harrell CR, Markovic BS, Fellabaum C et al (2020) The role of Interleukin 1 receptor antagonist in mesenchymal stem cell-based tissue repair and regeneration. Biofactors 46(2):263\u2013275","journal-title":"Biofactors"},{"key":"3152_CR18","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.3389\/fimmu.2019.01004","volume":"10","author":"DG Helou","year":"2019","unstructured":"Helou DG, Martin SF, Pallardy M et al (2019) Nrf2 involvement in chemical-induced skin innate immunity. Front Immunol 10:1004","journal-title":"Front Immunol"},{"key":"3152_CR19","doi-asserted-by":"publisher","first-page":"e000267","DOI":"10.1161\/JAHA.113.000267","volume":"2","author":"Y Higashikuni","year":"2013","unstructured":"Higashikuni Y, Tanaka K, Kato M et al (2013) Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1b upregulation via nuclear factor kBac tivation. J Am Heart Assoc. 2:e000267","journal-title":"J Am Heart Assoc."},{"issue":"23","key":"3152_CR20","doi-asserted-by":"publisher","first-page":"10023","DOI":"10.3390\/ijms231710023","volume":"2022","author":"Y Huang","year":"2022","unstructured":"Huang Y, Wu Q, Tam PKH (2022) Immunomodulatory mechanisms of mesenchymal stem cells and their potential clinical applications. Int J Mol Sci 2022(23):10023","journal-title":"Int J Mol Sci"},{"key":"3152_CR21","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1161\/CIRCULATIONAHA.107.731877","volume":"117","author":"I Ikonomidis","year":"2008","unstructured":"Ikonomidis I, Lekakis JP, Nikolaou M et al (2008) Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation 117:2662\u20132669","journal-title":"Circulation"},{"issue":"6","key":"3152_CR22","doi-asserted-by":"crossref","first-page":"925","DOI":"10.3181\/00379727-231-2310907","volume":"231","author":"S Jesmin","year":"2006","unstructured":"Jesmin S, Zaedi S, Maeda S et al (2006) Effects of a selective endothelin a receptor antagonist on the expressions of iNOS and eNOS in the heart of early streptozotocin-induced diabetic rats. Exp Biol Med 231(6):925\u2013931","journal-title":"Exp Biol Med"},{"issue":"4","key":"3152_CR23","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","volume":"122","author":"G Jia","year":"2018","unstructured":"Jia G, Hill MA, Sowers JR (2018) Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 122(4):624\u2013638","journal-title":"Circ Res"},{"issue":"1","key":"3152_CR24","doi-asserted-by":"publisher","first-page":"4754","DOI":"10.1038\/s41598-022-08398-4","volume":"12","author":"QH Jin","year":"2022","unstructured":"Jin QH, Kim HK, Na JY et al (2022) Anti-inflammatory effects of mesenchymal stem cell-conditioned media inhibited macrophages activation in vitro. Sci Rep 12(1):4754","journal-title":"Sci Rep"},{"issue":"45","key":"3152_CR25","doi-asserted-by":"publisher","first-page":"146","DOI":"10.4093\/dmj.2020.0282","volume":"2021","author":"Jin Joo Park","year":"2021","unstructured":"Jin Joo Park (2021) Epidemiology, pathophysiology, diagnosis and treatment of heart failure in diabetes. Diabetes Metab J 2021(45):146\u2013157","journal-title":"Diabetes Metab J"},{"key":"3152_CR26","doi-asserted-by":"publisher","first-page":"694864","DOI":"10.3389\/fphys.2021.694864","volume":"12","author":"N Kaur","year":"2021","unstructured":"Kaur N, Guan Y, Raja R et al (2021) Mechanisms and therapeutic prospects of diabetic cardiomyopathy through the inflammatory response. Front Physiol. 12:694864","journal-title":"Front Physiol."},{"issue":"21","key":"3152_CR27","doi-asserted-by":"publisher","first-page":"13016","DOI":"10.3390\/ijms232113016","volume":"23","author":"SS Kuppa","year":"2022","unstructured":"Kuppa SS, Kim HK, Kang JY et al (2022) Role of mesenchymal stem cells and their paracrine mediators in macrophage polarization: an approach to reduce inflammation in osteoarthritis. Int J Mol Sci 23(21):13016","journal-title":"Int J Mol Sci"},{"issue":"9","key":"3152_CR28","doi-asserted-by":"publisher","first-page":"e6963","DOI":"10.1371\/journal.pone.0006963","volume":"4","author":"G Lacraz","year":"2009","unstructured":"Lacraz G, Giroix MH, Kassis N et al (2009) Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat. PloS one 4(9):e6963","journal-title":"PloS one"},{"issue":"15","key":"3152_CR29","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1056\/NEJMoa065213","volume":"356","author":"CM Larsen","year":"2007","unstructured":"Larsen CM, Faulenbach M, Vaag A et al (2007) Interleukin-1\u2013receptor antagonist in type 2 diabetes mellitus. New England J Med 356(15):1517\u20131526","journal-title":"New England J Med"},{"key":"3152_CR30","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1371\/journal.pmed.0010045","volume":"1","author":"M Lehrke","year":"2004","unstructured":"Lehrke M, Reilly MP, Millington SC et al (2004) An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 1:e45","journal-title":"PLoS Med."},{"issue":"1","key":"3152_CR31","first-page":"42","volume":"6","author":"H Liu","year":"2021","unstructured":"Liu H, Zhao Y, Xie A et al (2021) Interleukin-1\u03b2, oxidative stress, and abnormal calcium handling mediate diabetic arrhythmic risk. Basic Trans Sci 6(1):42\u201352","journal-title":"Basic Trans Sci"},{"issue":"1","key":"3152_CR32","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s40261-022-01231-w","volume":"43","author":"X Liu","year":"2023","unstructured":"Liu X, Shi J, Wang D et al (2023) Therapeutic polypeptides and peptidomimetics: powerful tools for COVID-19 treatment. Clin Drug Invest 43(1):13\u201322","journal-title":"Clin Drug Invest"},{"issue":"8","key":"3152_CR33","doi-asserted-by":"publisher","first-page":"e0237305","DOI":"10.1371\/journal.pone.0237305","volume":"15","author":"GS Marchini","year":"2020","unstructured":"Marchini GS, Cestari IN, Salemi VM et al (2020) Early changes in myocyte contractility and cardiac function in streptozotocin-induced type 1 diabetes in rats. PLoS One 15(8):e0237305","journal-title":"PLoS One"},{"issue":"4","key":"3152_CR34","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1089\/rej.2017.2002","volume":"20","author":"AR Mendelsohn","year":"2017","unstructured":"Mendelsohn AR, Larrick JW (2017) Inflammation, stem cells, and the aging hypothalamus. Rejuv Res 20(4):346\u2013349","journal-title":"Rejuv Res"},{"issue":"2022","key":"3152_CR35","doi-asserted-by":"publisher","first-page":"174998","DOI":"10.1016\/j.ejphar.2022.174998","volume":"925","author":"R Mikkelsen Rasmus","year":"2022","unstructured":"Mikkelsen Rasmus R, Hundahl Malthe P, Torp Christopher K et al (2022) Immunomodulatory and immunosuppressive therapies in cardiovascular disease and type 2 diabetes mellitus: a bedside-to-bench approach. Eur J Pharmacol 925(2022):174998","journal-title":"Eur J Pharmacol"},{"issue":"5","key":"3152_CR36","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.3390\/ijms23052850","volume":"23","author":"M Mousaei Ghasroldasht","year":"2022","unstructured":"Mousaei Ghasroldasht M, Seok J, Park HS et al (2022) Stem cell therapy: from idea to clinical practice. Int J Mol Sci 23(5):2850","journal-title":"Int J Mol Sci"},{"issue":"1","key":"3152_CR37","doi-asserted-by":"publisher","first-page":"e0170971","DOI":"10.1371\/journal.pone.0170971","volume":"12","author":"SIR Okoduwa","year":"2017","unstructured":"Okoduwa SIR, Umar IA, James DB et al (2017) Appropriate insulin level in selecting fortified diet-fed, streptozotocin-treated rat model of type 2 diabetes for anti-diabetic studies. PLoS One 12(1):e0170971","journal-title":"PLoS One"},{"issue":"5","key":"3152_CR38","doi-asserted-by":"publisher","first-page":"177","DOI":"10.4239\/wjd.v4.i5.177","volume":"4","author":"JM Pappachan","year":"2013","unstructured":"Pappachan JM, Varughese GI, Sriraman R et al (2013) Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World J Diabetes 4(5):177","journal-title":"World J Diabetes"},{"issue":"2","key":"3152_CR39","doi-asserted-by":"publisher","first-page":"146","DOI":"10.4093\/dmj.2020.0282","volume":"45","author":"JJ Park","year":"2021","unstructured":"Park JJ (2021) Epidemiology, pathophysiology, diagnosis and treatment of heart failure in diabetes. Diabetes Metab J 45(2):146\u2013157","journal-title":"Diabetes Metab J"},{"key":"3152_CR40","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3389\/fphar.2017.00363","volume":"8","author":"C Peir\u00f3","year":"2017","unstructured":"Peir\u00f3 C, Lorenzo \u00d3, Carraro R et al (2017) IL-1\u03b2 inhibition in cardiovascular complications associated to diabetes mellitus. Front Pharmacol 8:363. https:\/\/doi.org\/10.3389\/fphar.2017.00363","journal-title":"Front Pharmacol"},{"issue":"1","key":"3152_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-018-1039-2","volume":"9","author":"D Philipp","year":"2018","unstructured":"Philipp D, Suhr L, Wahlers T et al (2018) Preconditioning of bone marrow-derived mesenchymal stem cells highly strengthens their potential to promote IL-6-dependent M2b polarization. Stem Cell Res Ther 9(1):1\u201317","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"3152_CR42","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1016","volume":"7","author":"RJ Pickering","year":"2018","unstructured":"Pickering RJ, Rosado CJ, Sharma A et al (2018) Recent novel approaches to limit oxidative stress and inflammation in diabetic complications. Clin Trans immunol 7(4):e1016","journal-title":"Clin Trans immunol"},{"issue":"Suppl. 2","key":"3152_CR43","doi-asserted-by":"publisher","first-page":"S244","DOI":"10.2337\/dcS15-3015","volume":"39","author":"RM Pollack","year":"2016","unstructured":"Pollack RM, Donath MY, LeRoith D et al (2016) Antiinflammatory agents in the treatment of diabetes and its vascular complications. Diabetes Care 39(Suppl. 2):S244\u2013S252","journal-title":"Diabetes Care"},{"key":"3152_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-017-0531-4","volume":"8","author":"E Redondo-Castro","year":"2017","unstructured":"Redondo-Castro E, Cunningham C, Miller J et al (2017) Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro. Stem Cell Res Ther 8:1\u201311","journal-title":"Stem Cell Res Ther"},{"key":"3152_CR45","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s10557-008-6154-3","volume":"23","author":"FN Salloum","year":"2009","unstructured":"Salloum FN, Chau V, Varma A et al (2009) Anakinra in experimental acute myocardial infarction\u2014does dosage or duration of treatment matter? Cardiovasc Drugs Ther 23:129\u2013135","journal-title":"Cardiovasc Drugs Ther"},{"key":"3152_CR46","doi-asserted-by":"publisher","first-page":"3924858","DOI":"10.1155\/2016\/3924858","volume":"2016","author":"A Saparov","year":"2016","unstructured":"Saparov A, Ogay V, Nurgozhin T et al (2016) Preconditioning of human mesenchymal stem cells to enhance their regulation of the immune response. Stem Cells Int 2016:3924858","journal-title":"Stem Cells Int"},{"issue":"7","key":"3152_CR47","doi-asserted-by":"publisher","first-page":"10942","DOI":"10.1002\/jcp.27947","volume":"234","author":"AM Shams Eldeen","year":"2019","unstructured":"Shams Eldeen AM, Ashour H, Shoukry HS et al (2019) Combined treatment with systemic resveratrol and resveratrol preconditioned mesenchymal stem cells, maximizes antifibrotic action in diabetic cardiomyopathy. J Cell Physiol 234(7):10942\u201310963","journal-title":"J Cell Physiol"},{"key":"3152_CR48","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1007\/s11626-011-9424-5","volume":"47","author":"Z Shao-Fang","year":"2011","unstructured":"Shao-Fang Z, Hong-Tian Z, Zhi-Nian Z et al (2011) PKH26 as a fluorescent label for live human umbilical mesenchymal stem cells. In Vitro Cell Devel Biology-Animal 47:516\u2013520","journal-title":"In Vitro Cell Devel Biology-Animal"},{"issue":"24","key":"3152_CR49","doi-asserted-by":"publisher","first-page":"13228","DOI":"10.3390\/ijms222413228","volume":"22","author":"Y Sun","year":"2021","unstructured":"Sun Y, Ding S (2021) NLRP3 inflammasome in diabetic cardiomyopathy and exercise intervention. Int J Mol Sci 22(24):13228","journal-title":"Int J Mol Sci"},{"issue":"9","key":"3152_CR50","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41569-020-0339-2","volume":"17","author":"Y Tan","year":"2020","unstructured":"Tan Y, Zhang Z, Zheng C et al (2020) Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol 17(9):585\u2013607","journal-title":"Nat Rev Cardiol"},{"key":"3152_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12933-014-0158-z","volume":"13","author":"S Vallejo","year":"2014","unstructured":"Vallejo S, Palacios E, Romacho T et al (2014) The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats. Cardiovasc Diabetol 13:1\u201313","journal-title":"Cardiovasc Diabetol"},{"issue":"8","key":"3152_CR52","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1002\/stem.3022","volume":"37","author":"S Vander Beken","year":"2019","unstructured":"Vander Beken S, Vries JC, Meier-Schiesser B et al (2019) Newly defined ATP-binding cassette subfamily B member 5 positive dermal mesenchymal stem cells promote healing of chronic iron-overload wounds via secretion of interleukin-1 receptor antagonist. Stem Cells 37(8):1057\u20131074","journal-title":"Stem Cells"},{"issue":"4","key":"3152_CR53","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3109\/08916930903305641","volume":"43","author":"V Volarevic","year":"2010","unstructured":"Volarevic V, Al-Qahtani A, Arsenijevic N et al (2010) Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis. Autoimmunity 43(4):255\u2013263","journal-title":"Autoimmunity"},{"key":"3152_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.851941","volume":"13","author":"M Wang","year":"2022","unstructured":"Wang M, Li Y, Li S et al (2022) Endothelial dysfunction and diabetic cardiomyopathy. Front Endocrinol 13:851941","journal-title":"Front Endocrinol"},{"issue":"1","key":"3152_CR55","doi-asserted-by":"publisher","first-page":"e762","DOI":"10.1002\/iid3.762","volume":"11","author":"P Wang","year":"2023","unstructured":"Wang P, Qian H, Xiao M et al (2023) Role of signal transduction pathways in IL-1\u03b2-induced apoptosis: pathological and therapeutic aspects. Immun Inflamm Disease 11(1):e762","journal-title":"Immun Inflamm Disease"},{"issue":"12","key":"3152_CR56","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.3390\/ijms19123805","volume":"19","author":"Q Xue","year":"2018","unstructured":"Xue Q, Yan Y, Zhang R et al (2018) Regulation of iNOS on immune cells and its role in diseases. Int J Mol Sci 19(12):3805","journal-title":"Int J Mol Sci"},{"issue":"1","key":"3152_CR57","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41392-021-00507-5","volume":"6","author":"P Yu","year":"2021","unstructured":"Yu P, Zhang X, Liu N et al (2021) Pyroptosis: mechanisms and diseases. Signal Transduct Targeted Ther 6(1):128","journal-title":"Signal Transduct Targeted Ther"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-024-03152-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-024-03152-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-024-03152-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T13:08:29Z","timestamp":1727960909000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-024-03152-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,22]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["3152"],"URL":"https:\/\/doi.org\/10.1007\/s00210-024-03152-1","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,22]]},"assertion":[{"value":"19 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Institutional Animal Care and Use Committee of Cairo University approved the current research in accordance with ARRIVE guidelines and EU Directive 2010\/63\/EU guidelines for animals. The approval number is ID: CU III F 28 20.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}