https://escholarship.org/content/qt1759w1fj/qt1759w1fj.pdf?t=quohjd

Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo

Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.

/pdf/extracellular-vesicles-in-cardiovascular-diseases-11zbf7exdy.pdf

Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers.

The results of this work demonstrate exosomes as a novel physiological mechanism by which induced vascular progenitor cells exert their angiogenic effect. Moreover, angiogenic cargo of proteins and...

Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model

Heart failure (HF) after myocardial infarction (MI) due to blockage of coronary arteries is a major public health issue. MI results in massive loss of cardiac muscle due to ischemia. Unfortunately, the adult mammalian myocardium presents a low regenerative potential, leading to two main responses to injury: fibrotic scar formation and hypertrophic remodeling. To date, complete heart transplantation remains the only clinical option to restore heart function. In the last two decades, tissue engineering has emerged as a promising approach to promote cardiac regeneration. Tissue engineering aims to target processes associated with MI, including cardiomyogenesis, modulation of extracellular matrix (ECM) remodeling, and fibrosis. Tissue engineering dogmas suggest the utilization and combination of two key components: bioactive molecules and biomaterials. This chapter will present current therapeutic applications of biomaterials in cardiac regeneration and the challenges still faced ahead. The following biomaterial-based approaches will be discussed: Nano-carriers for cardiac regeneration-inducing biomolecules; corresponding matrices for their controlled release; injectable hydrogels for cell delivery and cardiac patches. The concept of combining cardiac patches with controlled release matrices will be introduced, presenting a promising strategy to promote endogenous cardiac regeneration.

/pdf/inducing-endogenous-cardiac-regeneration-can-biomaterials-gz0faf8zqh.pdf

Inducing Endogenous Cardiac Regeneration: Can Biomaterials Connect the Dots?

Cardiovascular diseases (CVDs) are an important cause of death and disease worldwide. Because injured cardiac tissue cannot be repaired itself, it is urgent to develop other alternate therapies. Stem cells can be differentiated into cardiomyocytes, endothelial cells, and vascular smooth muscle cells for the treatment of CVDs. Therefore, cell therapy has recently been considered a viable treatment option that can significantly improve cardiac function. Nonetheless, implanted stem cells rarely survive in the recipient heart, suggesting that the benefits of stem cell therapy may involve other mechanisms. Exosomes derived from stem cells have a myocardial protection function after myocardial injury, and may be a promising and effective therapy for CVDs. Here, we discuss the application and mechanism of exosomes derived from stem cells in the diagnosis and treatment of CVDs and provide evidence for the application of exosomes in CVDs. Graphical Abstract.

Exosomes: Cell-Free Therapy for Cardiovascular Diseases.

High‐risk neuroblastoma (HR‐NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5‐year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR‐NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR‐NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box‐binding protein‐associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR‐NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN‐amplified, high‐risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN‐amplified NB cells compared with MYCN‐non‐amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN‐amplified NB. RNA‐seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell‐cycle regulator, cell‐cycle‐dependent kinase 1 (CDK1), resulting in cell‐cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN‐amplified HR‐NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR‐NB patients by blocking cell‐cycle progression and the proliferation of tumor cells.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.15815

TAF1D promotes proliferation by transcriptionally activating G2/M phase‐related genes in MYCN ‐amplified neuroblastoma

Characterization of an Enterovirus species E isolated from naturally infected bovine in China.

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TAF1D promotes proliferation by transcriptionally activating G2/M phase‐related genes in MYCN ‐amplified neuroblastoma

Characterization of an Enterovirus species E isolated from naturally infected bovine in China.