A new classification of cardio-oncology syndromes

Abstract Increasing evidence suggests a multifaceted relationship exists between cancer and cardiovascular disease (CVD). Here, we introduce a 5-tier classification system to categorize cardio-oncology syndromes (COS) that represent the aspects of the relationship between cancer and CVD. COS Type I is characterized by mechanisms whereby the abrupt onset or progression of cancer can lead to cardiovascular dysfunction. COS Type II includes the mechanisms by which cancer therapies can result in acute or chronic CVD. COS Type III is characterized by the pro-oncogenic environment created by the release of cardiokines and high oxidative stress in patients with cardiovascular dysfunction. COS Type IV is comprised of CVD therapies and diagnostic procedures which have been associated with promoting or unmasking cancer. COS Type V is characterized by factors causing systemic and genetic predisposition to both CVD and cancer. The development of this framework may allow for an increased facilitation of cancer care while optimizing cardiovascular health through focused treatment targeting the COS type

Inducing Stem Cell Myogenesis Using NanoScript

Transcription factors (TFs) are multidomain proteins that play a critical role in orchestrating stem cell differentiation, but several limitations hinder the full potential of TF-based gene regulation. Here we report a unique strategy to emulate TFs and differentiate stem cells in a nonviral approach using an artificial, nanoparticle-based transcription factor called NanoScript. The NanoScript platform consists of a gold nanoparticle functionalized with small molecules that mimic the various domains of TFs. As a result, NanoScript mimics the function and structure of TF proteins. Specifically, NanoScript was designed to regulate muscle cell differentiation by targeting myogenic regulatory factors (MRFs), which play an important role in inducing myogenesis. This NanoScript-MRF is stable in physiological environments, localizes within the nucleus, induces differentiation of adipose-derived mesenchymal stem cells into mature muscle cells in 7 days, and is naturally excreted from induced muscle cells. As such, NanoScript represents a safe and powerful tool for applications requiring gene manipulation

The 2020 ACC/AHA Guidelines for Management of Patients With Valvular Heart Disease: Highlights and Perioperative Implications

Valvular heart disease contributes to a large burden of morbidity and mortality in the United States. During the last decade there has been a paradigm shift in the management of valve disease, primarily driven by the emergence of novel transcatheter technologies. In this article, the latest update of the American College of Cardiology/American Heart Association valve heart disease guidelines is reviewed

Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

<p>Abstract</p> <p>Background</p> <p>Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata.</p> <p>Results</p> <p>Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI) nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells.</p> <p>Conclusions</p> <p>PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations.</p

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation

Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs. NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles. We demonstrate that NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by over 15-fold. Moreover, NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner. Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential for various stem cell applications

Integrating Epigenetic Modulators into NanoScript for Enhanced Chondrogenesis of Stem Cells

<i>N</i>-(4-Chloro-3-(trifluoro­methyl)­phenyl)-2-ethoxy­benzamide (CTB) is a small molecule that functions by altering the chromatin architecture to modulate gene expression. We report a new CTB derivative with increased solubility and demonstrate CTB’s functionality by conjugating it on the recently established NanoScript platform to enhance gene expression and induce stem cell differentiation. NanoScript is a nanoparticle-based artificial transcription factor that emulates the structure and function of transcription factor proteins (TFs) to effectively regulate endogenous gene expression. Modifying NanoScript with CTB will more closely replicate the TF structure and enhance CTB functionality and gene expression. To this end, we first conjugated CTB onto NanoScript and initiated a time-dependent increase in histone acetyl­transferase activity. Next, because CTB is known to trigger the pathway involved in regulating <i>Sox9</i>, a master regulator of chondrogenic differentiation, we modifed a <i>Sox9</i>-specific NanoScript with CTB to enhance chondrogenic gene activity and differentiation. Because NanoScript is a tunable and robust platform, it has potential for various gene-regulating applications, such as stem cell differentiation