Unlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia‐ exposed human cardiomyocytes through comprehensive multi‐level analysis

European Journal of Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Aims Hyperglycaemic conditions increase cardiac stress, a common phenomenon associated with inflammation, aging, and metabolic imbalance. Sodium–glucose cotransporter 2 inhibitors, class of anti‐diabetic drugs, showed to improve cardiovascular functions although their mechanism action has not yet been fully established. This study investigated the effects empagliflozin on cardiomyocytes following high glucose exposure, specifically focusing inflammatory responses. Methods results A three‐part strategy was formulated: (i) meta‐analysis selected randomized clinical trials carried out assess anti‐inflammatory in diabetic patients; (ii) impact human cardiomyocyte AC16 cells exposed normal (5 mM) (33 concentrations for 7 days explored by evaluating gene expression protein levels pivotal markers endoplasmic reticulum damage, calcium modulation; (iii) silico data from bioinformatic analyses were exploited construct an interaction map delineating potential tissue. Empagliflozin reversed high‐glucose mediated alterations at transcriptional level, decreasing inflammatory, metabolic, aging signatures. Specifically, vitro experiments cardiomyocytes, meta‐analyses biomarkers peripheral blood samples, sequencing pathological heart tissues, all support that exerts both systemically directly tissue, cardiomyocytes. Conclusion Our provides insights based robust mechanistic optimizing failure management highlights intricate interplay between diabetes, health.

Language: Английский

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Biguanides antithetically regulate tumor properties by the dose-dependent mitochondrial reprogramming-driven c-Src pathway

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101941 - 101941

Published: Feb. 1, 2025

Highlights•Biguanides activate or suppress TNBC progression in a dose-dependent manner•Biguanides regulate c-Src by the antithetical regulation of AMPK-FAO•Combination dasatinib with metformin suppresses and metastasisSummaryThe biguanide attenuates mitochondrial oxidation is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation fatty acid β-oxidation (FAO) subgroup patients breast cancer (BC) after Considering that FAO can Src kinase aggressive triple-negative BC (TNBC), we postulate low-dose biguanide-driven AMPK-ACC-FAO signaling may pathway TNBC. The low bioavailability xenografts mimics metformin's vitro effect. Pharmacological genetic inhibition significantly enhances anti-tumor properties biguanides. Lower doses biguanides induce higher signaling. Dasatinib synergistically inhibit patient-derived xenograft growth, but not high-fat diet-fed mice. This combination also metastatic progression. A inhibitors provides synergy to target suffering limited treatment options.Graphical abstract

Language: Английский

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Sodium-dependent glucose transporter 2 inhibitors improve heart function in patients with type 2 diabetes and heart failure

World Journal of Cardiology, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 21, 2025

This article discusses the study by Grubić Rotkvić et al on mechanisms of action sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type diabetes mellitus (T2DM) and heart failure (HF). T2DM HF are highly comorbid, a significantly increased prevalence T2DM. SGLT2i exhibit potential reducing hospitalization rates for cardiovascular mortality through multiple mechanisms, including improving blood glucose control, promoting urinary sodium excretion, sympathetic nervous system activity, lowering both preload afterload heart, alleviating inflammation oxidative stress, enhancing endothelial function, myocardial energy metabolism, stabilizing cardiac ion homeostasis. Further research clinical practice will help optimize use patients.

Language: Английский

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The comprehensive effects of high-sensitivity C-reactive protein and triglyceride glucose index on cardiometabolic multimorbidity

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

The triglyceride-glucose index (TyG index) is one of the surrogate markers insulin resistance, and high-sensitivity C-reactive protein (hsCRP) reflects systemic inflammation. Existing studies suggest that resistance or inflammation may be indicative cardiometabolic disease, but few existing have combined TyG levels before assessing multimorbidity. Our study data came from China Health Retirement Longitudinal Study (CHARLS). Participants in this were followed for 9 years, we used these to conduct a long-term analysis assess effects hsCRP on multimorbidity Chinese adults over 45 years age. To effect middle-aged as well elderly Chinese. (CHARLS), which included total 4,483 participants who did not cardiovascular metabolic diseases at baseline, was CHARLS 2011, last survey 2020. A five considered study: diabetes, hypertension, hyperlipidemia, heart disease stroke. person defined having when he/she had two more same time. (median cut-off) (1mg/L each divided into groups four (Group L-L: index=median L-H: hsCRP>=1mg/L; H-H: hsCRP>=1mg/L). Multiple regression equations fitted analyse influence increases risk CMM events independently hsCRP, does reverse. When elevated also elevated, condition significantly danger High can enhance people, joint use assessment better way achieve primary prevention people.

Language: Английский

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Effect of dapagliflozin on malignant ventricular arrhythmias in elderly after acute myocardial infarction: a propensity score-matched cohort study

European Journal of Clinical Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Engineered Prussian Blue‐Curcumin Nanozyme with RONS Scavenging Properties for Augmented Reversible Treatment of Cardiac Hypertrophy

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Pathological cardiac hypertrophy, often triggered by the excessive production and accumulation of reactive oxygen nitrogen species (RONS), may ultimately lead to heart failure. The treatment myocardial hypertrophy involves antioxidant stress therapy. In this study, coordinating curcumin with ferric ions during synthesis Prussian blue nanoparticles, a blue‐curcumin (PB‐Cur) nanozyme is successfully engineered exceptional (RONS) elimination capabilities. Following PVP modification, PB‐Cur exhibited favorable biocompatibility stability in aqueous solutions. Furthermore, shows remarkable reversible efficacy against both vitro vivo models. After one week treatment, group transverse aortic constriction (TAC)‐induced models displayed notable decrease fibrosis. Echocardiographic findings also revealed substantial improvement function among TAC mice following administration. Mechanistically, through (ROS) elimination, effectively downregulated oxidative stress‐related pathways, including MAPK PI3K‐Akt, which hold promise for treating diseases.

Language: Английский

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Empagliflozin attenuates hypoxia-induced heart failure of zebrafish embryos via influencing MMP13 expression

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117453 - 117453

Published: Sept. 26, 2024

Language: Английский

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