Background: In the field of plastic surgery, capsular contracture after silicone breast implant surgery is a major clinical problem. This experimental study confirms that the synthetic tryptophan metabolite N-(3',4'-dimethoxycinnamonyl) anthranilic acid (Tranilast) reduces capsule formation and prevents capsular contracture.
Methods: Eighteen New Zealand white rabbits were divided into 2 groups.
The modulation of a cell signaling process using a molecular binder followed by an analysis of the cellular response is crucial for understanding its role in the cellular function and developing pharmaceuticals. Herein, we present the modulation of the ERK2-mediated signaling pathway through the cytosolic delivery of a native regulatory protein for ERK2, that is, PEA-15 (phosphoprotein enriched in astrocytes, 15 kDa), and its engineered variants using a bacterial toxin-based delivery system. Based on biochemical and structural analyses, PEA-15 variants with different phosphorylation sites and a high affinity for ERK2 were designed.
View Article and Find Full Text PDFWith the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform.
View Article and Find Full Text PDFAge-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules.
View Article and Find Full Text PDFThe intracellular delivery of proteins with high efficiency in a receptor-specific manner is of great significance in molecular medicine and biotechnology, but remains a challenge. Herein, we present the development of a highly efficient and receptor-specific delivery platform for protein cargos by combining the receptor binding domain of Escherichia coli Shiga-like toxin and the translocation domain of Pseudomonas aeruginosa exotoxin A. We demonstrated the utility and efficiency of the delivery platform by showing a cytosolic delivery of diverse proteins both in vitro and in vivo in a receptor-specific manner.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2015
The cell-specific cytosolic delivery of functional macromolecules with high efficiency is of great significance in molecular medicine and biotechnology. Herein, we present a Shiga-like toxin II-based high-efficiency and receptor-specific intracellular delivery system. We designed and constructed the Shiga-like toxin-based carrier (STC) to comprise the targeting and translocation domains, and used it for delivering a protein cargo.
View Article and Find Full Text PDFGlycoprotein Ibα (GpIbα), a family of LRR (leucine-rich repeat) proteins, is a membrane protein on the platelet, and plays an important role in atherothrombotic events. The complex formation of GpIbα with the von Willebrand Factor (vWF) has been revealed to lead to acute coronary syndrome (ACS) or stroke. A considerable attention has been paid to understand the biological functions of GpIbα and its regulation.
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