ABSTRACT
We present a rare case of delayed coronary artery obstruction following a transcatheter aortic valve replacement (TAVR). Interestingly, the patient did not meet the criteria for traditionally recognized risk factors for delayed coronary obstruction. This case piques interest as to whether the severity of calcification on aortic valve leaflets plays any role in coronary obstruction post transcatheter aortic valve replacement. There is no consensus as to the optimal approach to investigation and revascularization in patients with delayed coronary obstruction. We report a case with successful emergent revascularization of the left main coronary artery following transcatheter aortic valve replacement.
ABSTRACT
Silencing genes in insects by introducing double-stranded RNA (dsRNA) in the diet holds promise as a new pest management method. It has been demonstrated that nanoparticles (NPs) can potentiate dsRNA silencing effects by promoting cellular internalization and protecting dsRNA against early degradation. However, many mysteries of how NPs and dsRNA are internalized by gut epithelial cells and, subsequently, transported across the midgut epithelium remain to be unraveled. The sole purpose of the current study is to investigate the role of endocytosis and transcytosis in the transport of branched amphipathic peptide nanocapsules (BAPCs) associated with dsRNA through midgut epithelium cells. Spodoptera frugiperda midguts and the epithelial cell line Sf9, derived from S. frugiperda, were used to study transcytosis and endocytosis, respectively. Results suggest that clathrin-mediated endocytosis and macropinocytosis are largely responsible for cellular uptake, and once within the midgut, transcytosis is involved in shuttling BAPCs-dsRNA from the lumen to the hemolymph. In addition, BAPCs were not found to be toxic to Sf9 cells or generate damaging reactive species once internalized.
ABSTRACT
Understanding cellular uptake mechanisms of nanoparticles with therapeutic potential has become critical in the field of drug delivery. Elucidation of cellular entry routes can aid in the dissection of the complex intracellular trafficking and potentially allow for the manipulation of nanoparticle fate after cellular delivery (i.e., avoid lysosomal degradation). Branched amphiphilic peptide capsules (BAPCs) are peptide nanoparticles that have been and are being explored as delivery systems for nucleic acids and other therapeutic molecules in vitro and in vivo. In the present study, we determined the cellular uptake routes of BAPCs with and without a magnetic nanobead core (BAPc-MNBs) in two cell lines: macrophages and intestinal epithelial cells. We also studied the influence of size and growth media composition in this cellular process. Substituting the water-filled core with magnetic nanobeads might provide the peptide bilayer nanocapsules with added functionalities, facilitating their use in bio/immunoassays, magnetic field guided drug delivery, and magnetofection among others. Results suggest that BAPc-MNBs are internalized into the cytosol using more than one endocytic pathway. Flow cytometry and analysis of reactive oxygen and nitrogen species (ROS/RNS) demonstrated that cell viability was minimally impacted by BAPc-MNBs. Cellular uptake pathways of peptide vesicles remain poorly understood, particularly with respect to endocytosis and intracellular trafficking. Outcomes from these studies provide a fundamental understanding of the cellular uptake of this peptide-based delivery system which will allow for strengthening of their delivery capabilities and expanding their applications both in vitro and in vivo.
