Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 224 - 236
Published: Aug. 6, 2024
Language: Английский
Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111070 - 111070
Published: Feb. 1, 2024
Language: Английский
Citations
9
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: Aug. 2, 2024
Abstract Background Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), medicinal plant with antioxidant activity. Results We isolated MC-ELNs using ultracentrifugation and characterized them canonical mammalian extracellular vesicles features. In vivo studies proved ameliorated enhanced cardiac function myocardial structure. vitro assays revealed promoted cell survival, diminished reactive oxygen species, protected mitochondrial integrity DOX-treated H9c2 cells. found treatment decreased protein level p62 through ubiquitin-dependent degradation pathway NRVM However, suppressed DOX-induced ubiquitination degradation, recovered bound Keap1 promoting Nrf2 nuclear translocation expressions downstream gene HO-1. Furthermore, both knockdown inhibition p62-Keap1 interaction abrogated cardioprotective effect MC-ELNs. Conclusions Our findings demonstrated beneficials via increasing stability, shedding light on preventive approaches
Language: Английский
Citations
9
Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321
Published: Aug. 19, 2024
Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.
Language: Английский
Citations
9
Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 4089 - 4116
Published: Sept. 1, 2024
With the continuous refinement of therapeutic measures, survival rate tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring mechanism and prevention strategy therapy-related toxicity (CTR-CVT) remains one research hotspots in field Cardio-Oncology recent years. Cardiotoxicity anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias vascular toxicity, mechanistically endothelial dysfunction, ferroptosis, mitochondrial dysfunction oxidative stress. To address cardiotoxicity induced different drugs, various measures put place, such as reducing accumulation shifting with less cardiotoxicity, using cardioprotective early detection. Due very limited treatments available ameliorate drugs-induced a few innovations are being shifted from animal studies human studies. Examples include transplantation. Mitochondrial transplantation proven be effective vivo vitro experiments. Several demonstrated that intercellular transfer can doxorubicin(DOX)-induced laying foundation for innovative therapies cardiotoxicity. In this review, we will discuss current status terms pathogenesis treatment, focus on transplantation, hope review bring some inspiration you.
Language: Английский
Citations
9
Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)
Published: Jan. 1, 2025
ABSTRACT Cardiomyopathies, a diverse group of diseases affecting the heart muscle, continue to pose significant clinical challenges due their complex aetiologies and limited treatment options targeting underlying genetic molecular dysregulations. Emerging evidence indicates that Metrnl, myokine, adipokine cardiokine, plays role in pathogenesis various cardiomyopathies. Therefore, objective this review is examine mechanism Metrnl cardiomyopathies, with expectation providing new insights for these diseases.
Language: Английский
Citations
1
Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)
Published: Jan. 1, 2025
ABSTRACT The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which primarily attributed interaction with iron in mitochondria, leading lipid peroxidation and myocardial ferroptosis. This study aimed investigate the role gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, ferroptosis were assessed vivo. cardioprotective effects mechanisms ILA explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) bulk RNA‐seq, further validated Nrf2 knockout mice. findings revealed that DOX treatment disrupted microbiota, significantly reducing levels tryptophan metabolite ILA. In DIC models, supplementation markedly improved cardiac reduced collagen deposition, mitigated atrophy. snRNA‐seq analyses indicated played a crucial Experimental data demonstrated decreased both mice DOX‐treated H9C2 cells, evidenced by restoration GPX4 SLC7A11 reduction ACSL4. Mechanistically, functions as ligand for aryl hydrocarbon receptor (AhR), upregulation expression. protective against abolished silencing AhR. Moreover, beneficial on eliminated Nrf2‐deficient conclusion, exerts therapeutic inhibiting through activation AhR/Nrf2 signalling pathway. Identifying microbial could offer viable strategies DIC.
Language: Английский
Citations
1
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 27, 2025
Doxorubicin (DOX) is a prevalent chemotherapeutic drug for treating several malignancies. However, the mechanisms of DOX induced cardiac toxicity not fully understood. Previous studies have demonstrated that autophagy activation essential in DOX-induced toxicity. Nevertheless, on role protein 5 (ATG5) remain limited. Therefore, this study aimed to investigate ATG5 Mice were intravenously administered (5 mg/kg) 4 weeks establish model. Heart function was determined using echocardiography, and tissue assessed expression, mRNA levels, fibrosis, immunofluorescent staining. treatment upregulated autophagy-related gene expression but inhibited autophagic flux vitro vivo. DOX-treated mice exhibited decreased heart cardiomyocyte size increased oxidative stress, apoptosis. These effects partially alleviated by rAAV9 expressing shRNA-ATG5 deteriorated rAAV9-ATG5. We genetic knockdown or inhibition chemical inhibitors GATA4 which reduced overexpression activator vivo, suggesting ATG5-mediated promoted degradation. Moreover, enforced re-expression significantly counteracted toxic hearts. In conclusion, our manipulating regulate degradation may be promising approach
Language: Английский
Citations
1
Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 686, P. 1074 - 1088
Published: Feb. 6, 2025
Language: Английский
Citations
1
Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156624 - 156624
Published: March 6, 2025
Doxorubicin (Dox)-induced cardiomyopathy (DIC) is characterized by severe myocardial damage that can progress to dilated and potentially lead heart failure. No effective prevention or treatment strategies are available for DIC. Sauchinone, a diastereomeric lignan isolated from Saururus chinensis, known its notable anti-inflammatory effects. However, paucity of research on sauchinone in relation disease exists, particularly regarding role DIC, which remains unclear. This study aimed assess the therapeutic potential alleviating cardiac injury elucidate molecular mechanism Male C57BL/6J mice were used construct chronic acute DIC models vivo. The administered intragastrically concurrently with first injection Dox evaluate effect H9c2, rat cardiomyocyte cell line, was treated various concentrations conjunction protective effects vitro. Supplementation exogenous mitigated Dox-induced atrophy, fibrosis, ventricular remodeling, while preserving function. Sauchinone reduced abnormal apoptosis both vitro Additionally, restored mitochondrial function decreased reactive oxygen species levels, may be attributed activation nuclear factor erythroid 2-related 2 (NRF2) signaling, thereby attenuating oxidative damage. Furthermore, significantly inhibited NOD-like receptor thermal protein domain associated 3 (NLRP3) inflammasome infiltration inflammatory factors, stress inhibiting progression NLRP3 agonist nigericin abolished progression, antagonist MCC950 further enhanced beneficial vivo key novel finding present use sauchinone, effectively limits Specifically, not only alleviates but also delays Mechanistically, inactivation NRF2-mediated antioxidant pathways have been identified as two critical signaling regulated plays vital blocking holds promise approach cardiomyopathy.
Language: Английский
Citations
1
Toxicology, Journal Year: 2023, Volume and Issue: 494, P. 153597 - 153597
Published: July 25, 2023
Language: Английский
Citations
19