Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups. Thereafter, a total of thirty healthy adult Wistar rats (150–200 g) were randomly divided into five groups (n = 6) and treated for eight days as follows: group I (normal control), group II (doxorubicin control), group III (metformin 250 mg/kg/day), group IV (metformin 180 mg/kg/day), and group V (dapagliflozin 0.9 mg/kg/day). On the 7th day of the treatment phase, doxorubicin 20 mg/kg was administered intraperitoneal to groups II, III, IV, and V. On the 9th day (immediately after 48 h of doxorubicin administration), blood was collected from anesthetized animals for glucose, lipid profile, CK-MB & AST estimation, and ECG was recorded. Later, animals were sacrificed, and the heart was dissected for histopathological examination. We found that compared to normal control rats, CK-MB, AST, and glucose were significantly increased in doxorubicin control rats. There was a significant reversal of doxorubicin-induced hyperglycemia in the rats treated with metformin 250 mg/kg compared to doxorubicin control rats. Both metformin (180 mg/kg and 250 mg/kg) and dapagliflozin (0.9 mg/kg) significantly altered doxorubicin-induced ECG changes and reduced the levels of cardiac injury biomarkers CK-MB and AST compared to doxorubicin control rats. Metformin and dapagliflozin protected the cellular architecture of the myocardium from doxorubicin-induced myocardial injury. Current study revealed that both metformin and dapagliflozin at the FDA-recommended antidiabetic doses mitigated doxorubicin-induced acute cardiotoxicity in Wistar rats. The obtained data have opened the perspective to perform chronic studies and then to clinical studies to precisely consider metformin and dapagliflozin as potential chemoprotection in the combination of chemotherapy with doxorubicin to limit its cardiotoxicity, especially in patients with comorbid conditions like type II diabetes mellitus.

Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical data now demonstrate its ability to reduce cancer incidence, enhance immunotherapy outcomes, delay multimorbidity, and reverse biological age markers. Landmark trials such as UKPDS, CAMERA, and the ongoing TAME study illustrate its broad clinical impact on metabolic health, cardiovascular risk, and age-related disease trajectories. In oncology, trials such as MA.32 and METTEN evaluate its influence on progression-free survival and tumor response, highlighting its evolving role in cancer therapy. This review critically synthesizes the molecular underpinnings of metformin’s polypharmacology, examines results from pivotal clinical trials, and compares its effectiveness with emerging gerotherapeutics and senolytics. We explore future directions, including optimized dosing, biomarker-driven personalization, rational combination therapies, and regulatory pathways, to expand indications for aging and oncology. Metformin stands poised to play a pivotal role in precision strategies that target the shared roots of aging and cancer, offering scalable global benefits across health systems.

Cardiometabolic diseases, including hypertension, type 2 diabetes, dyslipidemia, and obesity, along with their cardiovascular complications, remain leading causes of morbidity and mortality worldwide, imposing significant public health, economic, and societal burdens. Conventional pharmacological therapies often show limited efficacy and increased adverse effects because they do not account for the body’s intrinsic circadian rhythms, which regulate organ function, drug absorption, and metabolism. Chronopharmacology, which aligns treatment timing with these biological rhythms, offers a strategy to enhance therapeutic outcomes. This review presents a comprehensive analysis of chronopharmacology principles applied to cardiometabolic disease management, integrating molecular, physiological, and clinical perspectives. It examines how core clock genes and tissue-specific circadian patterns influence drug action and absorption and summarizes evidence-based time-optimized interventions for hypertension, diabetes, dyslipidemia, obesity, and multimorbid patients. Furthermore, the review highlights emerging innovations, including artificial intelligence-guided dosing, circadian-biomarker-informed therapy selection, and wearable digital devices for real-time monitoring of biological rhythms. By synthesizing mechanistic and clinical insights, circadian-aligned treatment strategies are shown to improve drug efficacy, reduce adverse effects, and support the development of precision, rhythm-based therapeutics, offering a practical framework for personalized cardiometabolic disease care.

Myocardial protection during cardiac surgery is crucial for preventing ischemia-reperfusion injury and preserving myocardial function. Cardioplegia, a solution used to induce electromechanical cardiac arrest, is the fundamental method for myocardial protection during on-pump procedures. Del Nido cardioplegia, developed in the 1990s, has gained increasing popularity in adult cardiac surgeries over the past two decades. Del Nido cardioplegia is a crystalloid-based solution used to achieve depolarized arrest. Its mechanism of action also involves preventing intracellular calcium overload, a key driver of reperfusion injury. Numerous studies have evaluated the safety and efficacy of del Nido cardioplegia in adult cardiac surgeries, including coronary artery bypass grafting and valve procedures. Compared to standard blood cardioplegia, del Nido cardioplegia has demonstrated reduced hemodilution, transfusion requirements and shorter cardiopulmonary bypass times due to its extended arrest duration. Many studies have reported lower levels of myocardial injury biomarkers and improved myocardial functional recovery with del Nido cardioplegia. It has also been associated with reduced defibrillation requirements, which is attributable to the antiarrhythmic effects of lidocaine. While some studies have reported no significant differences in outcomes between del Nido cardioplegia and blood cardioplegia, others have favored del Nido cardioplegia in terms of myocardial protection, postoperative cardiac function, and perioperative morbidity. The choice between cardioplegia solutions remains subjective and dependent on surgeon preference and institutional practices. However, del Nido cardioplegia has emerged as an acceptable alternative to traditional cardioplegia, offering potential advantages in adult cardiac surgeries.

Background: The development of the cardiopulmonary bypass machine for extracorporeal circulation by Dr. John Gibbon marked a significant milestone in the advancement of medical technology. Subsequent enhancements in this equipment and methodologies have refined this ground-breaking invention for better cardiac surgical results. Main body of the The emergence of miniaturized extracorporeal circuits has demonstrated more promising results in various research studies. This narrative article explores the impacts of miniaturized extracorporeal circuits on different organ systems and their potential advantages over traditional bypass systems, focusing on currently commercially available devices to enhance our understanding. Short conclusion: Nevertheless, practical limitations in standard usage and acceptance have hindered its widespread implementation. Hence, this technique is still in the process of acceptance as the standard of care. The information presented in this review has been collected by accessing major databases and recent reviews, meta-analyses and clinical trials on the internet, adhering to the Revised Standards for QUality Improvement Reporting Excellence (SQUIRE 2.0) guidelines.