Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection

Journal of Molecular and Cellular Cardiology Plus, Год журнала: 2024, Номер 9, С. 100085 - 100085

Опубликована: Июль 17, 2024

Dynamin-related protein 1 (Drp1) is a mitochondrial fission and viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported novel Drp1 inhibitor (DRP1i1), delivered using cardiac-targeted nanoparticle drug delivery system, as more effective approach achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) the encapsulation efficiency 99.3 ± 0.1 %. In vivo, following injury mice, NanoDRP1i1 significantly reduced infarct size serine-616 phosphorylation of Drp1, restored cardiomyocyte to that sham group. Imaging by mass spectrometry revealed higher accumulation heart tissue when NanoDRP1i1. human cardiac organoids subjected simulated injury, treatment at reperfusion cell death, contractile dysfunction, superoxide levels. Following treatment, organoid proteomics further confirmed reprogramming dysfunction markers enrichment network, cytoskeletal metabolic regulation networks compared These proteins included known cardioprotective regulators identified vivo murine studies promising tool compound study Drp1-mediated exhibits therapeutic potential cardioprotection, especially nanoparticles.

Язык: Английский

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Single–cell transcriptional and epigenetic mapping reveals cellular and molecular mechanisms driving non-ischemic cardiac fibrosis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 13, 2024

ABSTRACT Cardiac fibrosis is a major cause of cardiac dysfunction. Recently, single-cell genomic approaches have revealed in unprecedented resolution the orchestrated cellular responses driving fibrosis. Yet, fibrosis-causing phenotypes that emerge heart following non-ischemic stress, and transcriptional circuits govern cell identity drive fibrosis, are not well understood. Applying paired multiomic approach, we reveal key circuits, mouse human hearts, which associated with development insults, independent disease model, species or biological sex. Strikingly, find regulatory events reversible at epigenomic level, further pointing to factors regulating resolution. The regulators identified this study represent promising targets ameliorate context chronic stressors such as aging hypertension.

Язык: Английский

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Proteomics Studies on Extracellular Vesicles Derived from Glioblastoma: Where Do We Stand?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9778 - 9778

Опубликована: Сен. 10, 2024

Like most tumors, glioblastoma multiforme (GBM), the deadliest brain tumor in human adulthood, releases extracellular vesicles (EVs). Their content, reflecting that of origin, can be donated to nearby and distant cells which, by acquiring it, become more aggressive. Therefore, study EV-transported molecules has very important. Particular attention been paid EV proteins uncover new GBM biomarkers potential druggable targets. Proteomic studies have mainly performed “bottom-up” mass spectrometry (MS) analysis EVs isolated different procedures from conditioned media cultured biological fluids patients. Although a great number dysregulated identified, translation these findings into clinics remains elusive, probably due multiple factors, including lack standardized for isolation/characterization their proteome. Thus, it is time change research strategies adopting, addition harmonized selection techniques, MS methods aimed at identifying selected tumoral protein mutations and/or isoforms post-translational modifications, which deeply influence behavior. Hopefully, data integrated with those other “omics” disciplines will lead discovery pathways novel therapies.

Язык: Английский

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