{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T11:29:34Z","timestamp":1770895774672,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":327,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> This study investigates the impact of a high\u2010sugar environment on H9C2 cardiomyocytes and explores the protective effects of carvedilol in the context of diabetic cardiomyopathy (Dia\u2010CM). Transcriptomic analysis identified 21,655 differentially expressed genes associated with Dia\u2010CM, demonstrating significant separation among samples.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> H9C2 cardiomyocytes were cultured in a high\u2010sugar environment to simulate Dia\u2010CM conditions. Cell viability, cytokine levels, and protein expression were assessed using CCK\u20108 assays, ELISA, and Western blot techniques. Intervention experiments with NLRP3, caspase\u20101, and ROS inhibitors were conducted to evaluate their protective effects. The therapeutic potential of carvedilol was assessed by examining its impact on cell viability, cytokine levels, and key biomarkers. An in\u2010depth analysis of carvedilol\u2019s regulatory effects on ROS and key proteins in H9C2 cells was also conducted.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In vitro, a high\u2010sugar environment significantly reduced H9C2 cell survival, increased ROS levels, activated inflammatory responses, and upregulated NLRP3, caspase\u20101, and GSDMD\u2010N proteins. Inhibitors of NLRP3, caspase\u20101, and ROS ameliorated these effects. Carvedilol treatment improved cell activity, reduced inflammatory cytokine levels, suppressed ROS production, and downregulated NLRP3, pro\u2010caspase\u20101, GSDMD\u2010N, and p\u2010NF\u2010<jats:italic>\u03ba<\/jats:italic>B proteins. Moderate\u2010dose carvedilol exhibited optimal intervention effects.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> A high\u2010sugar environment induces cardiomyocyte damage through ROS production and NLRP3 inflammasome activation. Inhibitors of NLRP3, caspase\u20101, and ROS provide effective protection. Carvedilol significantly mitigates the detrimental effects of a high\u2010sugar environment on H9C2 cardiomyocytes, potentially through inhibiting the NLRP3\u2010ASC inflammasome and caspase\u20101\/GSDMD\u2010dependent signaling pathway\u2010mediated pyroptosis. These findings offer insights into Dia\u2010CM mechanisms and highlight carvedilol as a promising therapeutic intervention.<\/jats:p>","DOI":"10.1155\/2024\/9378405","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T23:03:49Z","timestamp":1732403029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diabetic Cardiomyopathy Uncovered: Transcriptomics, NLRP3, and Carvedilol Mechanisms"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9944-3544","authenticated-orcid":false,"given":"Alimujiang","family":"Abudoureyimu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9744-1230","authenticated-orcid":false,"given":"Alimu","family":"Aihaiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1447-2465","authenticated-orcid":false,"given":"Nuliman","family":"Abudoujilili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8084-248X","authenticated-orcid":false,"given":"Mayila","family":"Tuergong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8017-0532","authenticated-orcid":false,"given":"Guzainuer","family":"Adili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4883-192X","authenticated-orcid":false,"given":"Maihebubaimu","family":"Maimaiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3534-8373","authenticated-orcid":false,"given":"Dilinuer","family":"Mohetaer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3004-9237","authenticated-orcid":false,"given":"Yimamumaimaiti","family":"Maiamaitishawuti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00542-2"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2080413"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.791643"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7921363"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/db19-1009"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3218275"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2062988"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9265016"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3163629"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.020768"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2022.09.019"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.29680"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6659282"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17071054"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.812362"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01751-2"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105697"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.747803"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113506"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00519"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02509-22"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091317"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2012627"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.882198"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.946766"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.598353"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413361"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14233"},{"key":"e_1_2_13_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.637021"},{"key":"e_1_2_13_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.709077"},{"key":"e_1_2_13_31_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2345658"},{"key":"e_1_2_13_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073710"},{"key":"e_1_2_13_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.014"},{"key":"e_1_2_13_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101523"},{"key":"e_1_2_13_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.667644"},{"key":"e_1_2_13_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01920"},{"key":"e_1_2_13_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.608183"},{"key":"e_1_2_13_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189952"},{"key":"e_1_2_13_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2033381"},{"key":"e_1_2_13_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8040328"},{"key":"e_1_2_13_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184003"},{"key":"e_1_2_13_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02598-5"},{"key":"e_1_2_13_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1170-1"},{"key":"e_1_2_13_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413634"},{"key":"e_1_2_13_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-022-00752-w"},{"key":"e_1_2_13_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0669-6"},{"key":"e_1_2_13_47_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103307"},{"key":"e_1_2_13_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104771"},{"key":"e_1_2_13_49_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9205908"},{"key":"e_1_2_13_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2023.113858"},{"key":"e_1_2_13_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112978"}],"container-title":["Journal of Diabetes Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2024\/9378405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T17:02:06Z","timestamp":1735837326000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2024\/9378405"}},"subtitle":[],"editor":[{"given":"Carla","family":"Iacobini","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1155\/2024\/9378405"],"URL":"https:\/\/doi.org\/10.1155\/2024\/9378405","archive":["Portico"],"relation":{},"ISSN":["2314-6745","2314-6753"],"issn-type":[{"value":"2314-6745","type":"print"},{"value":"2314-6753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"9378405"}}