Although cancer-therapy-related cardiac dysfunction (CTRCD) is a critical issue in clinical practice, there is a glaring lack of evidence regarding cardiotoxicity management. To determine an effective and suitable dosage of treatment using angiotensin receptor–neprilysin inhibitors (ARNI) with sodium–glucose cotransporter 2 inhibitors (SGLT2i), we adopted a clinically relevant rodent model with doxorubicin, which would mimic cardiac dysfunction in CTRCD patients. After the oral administration of drugs (vehicle, SGLT2i, ARNI, Low-ARNI/SGLT2i, ARNI/SGLT2i), several physiologic parameters, including hemodynamic change, cardiac function, and histopathology, were evaluated. Bulk RNA-sequencing was performed to obtain insights into the molecular basis of a mouse heart response to Low-ARNI/SGLT2i treatment. For the first time, we report that the addition of low-dose ARNI with SGLT2i resulted in greater benefits than ARNI, SGLT2i alone or ARNI/SGLT2i combination in survival rate, cardiac function, hemodynamic change, and kidney function against doxorubicin-induced cardiotoxicity through peroxisome proliferator-activated receptor signaling pathway. Low-dose ARNI with SGLT2i combination treatment would be practically beneficial for improving cardiac functions against doxorubicin-induced heart failure with minimal adverse effects. Our findings suggest the Low-ARNI/SGLT2i combination as a feasible novel strategy in managing CTRCD patients.

Background: Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM.Methods: The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM.Results: Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy.Conclusion: DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.

In mammals, the early embryo travels down the oviduct to the uterus and prepares for implantation. The unique features of preimplantation development include compaction followed by blastocyst formation. This first cell lineage specification involves various proteins including cell polarity regulators, kinases, and transcription factors. In this study, a novel gene named predicted gene 11545 ( Gm11545 ) expressed predominantly in mouse early embryos was identified and characterized at the transcript, protein, cellular, and functional levels. The Gm11545 protein localized to both cytoplasmic and membrane regions of preimplantation embryos. Remarkably, knockdown of Gm11545 led to arrest of mouse embryos at the morula stage and consequent impairment of blastocyst formation. Expression patterns of the key transcription factors critical for early lineage specification, octamer‐binding transcription factor 4 and caudal type homeobox 2, were affected by Gm11545 depletion. Based on the collective findings, we propose that the novel protein identified in this study, Gm11545, is implicated in cell proliferation and cell lineage specification critical for blastocyst formation.—Kim, J., Kim, J., Jeong, J., Hong, S. H., Kim, D., Choi, S., Choi, I., Oh, J. S., Cho, C. Identification of a novel embryo‐prevalent gene, Gm11545 , involved in preimplantation embryogenesis in mice. FASEB J. 33, 11326–11337 (2019). www.fasebj.org

Background/Introduction: Obstructive sleep apnoea (OSA) is a well-established risk factor for the development and exacerbation of cardiac arrhythmias. Continuous positive airway pressure therapy is recommended as the primary non-invasive treatment for OSA. However, suboptimal patient compliance remains a common challenge. Purpose: This study explores the benefits of surgery in reducing the occurrence of arrhythmias associated with OSA. The study aims to investigate the impact of surgery in managing OSA-associated arrhythmias. Methods: Data from the Korean Health Insurance, from January 2009 to December 2020, were retrospectively compiled and analysed to investigate the clinical outcomes of 359,851 individuals with OSA. Propensity score matching (PSM) at a 1:4 ratio was employed to compare patients who underwent surgery with those who did not. A final cohort of 117,665 participants (85.4% men, aged 60 years old or younger: 94.2%) was established, with 23,533 having undergone surgery for OSA and 94,132 receiving non-surgical management. Over a five-year follow-up period, the occurrence rates of atrial fibrillation (AF), premature beats (premature atrial contractions or premature ventricular contractions), ventricular arrhythmias, sudden cardiac arrest, atrioventricular block, and sinus node dysfunction were evaluated. Results: Across the six types of arrhythmias, the cohort that underwent surgery for OSA consistently exhibited a lower incidence of arrhythmias than the non-surgical cohort. In the PSM analysis, a statistically significant reduction in the incidence of AF, premature beats, and sudden cardiac arrest was observed in groups of patients who underwent surgery for OSA. Among those who developed AF, the group that underwent surgery for OSA had a fivefold higher incidence than the non-surgical group (hazard ratio [HR] 5.384, 95% confidence interval [CI] 3.459-8.381). The incidence of premature beats was more than four times higher in the non-surgical group (HR 4.284, 95% CI 2.96-6.177, p<0.0001), and sudden arrest was more than 24x higher in the non-surgical group (HR 24.089, 95% CI 3.348-173.312). Conclusion: This study suggests a potential causative relationship between OSA and arrhythmias. Additionally, surgical intervention for OSA may be considered an effective strategy for preventing arrhythmias in young patients. Further clinical research is warranted to validate and refine these observations.Figure 1Figure 2

Kim SW, et al. Int J Arrhythm. 2026 ;27:e6. https://doi.org/10.18501/ija.2026.27.e6