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Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.

This study aims to develop bacterial cellulose with enhanced flame retardancy and flexibility. The bacterial cellulose was phosphorylated with phytic acid to improve its flame retardancy. Urea and xylitol were used as plasticizers, and their effects in improving the flexibility of bacterial cellulose were compared and evaluated. The optimal conditions for producing phosphorylated bacterial cellulose were found to be as follows: phytic acid:xylitol molar ratio of 1:10, phytic acid concentration of 10% (o.w.f.), and shaking at 30°C for 30 min at 90 rpm in a shaking water bath. A thermogravimetric analysis revealed that phosphorylated bacterial cellulose exhibited enhanced thermal properties compared with the original bacterial cellulose. Fourier transform infrared spectroscopy and X-ray diffraction confirmed that the chemical and crystalline structures of bacterial cellulose remained unchanged after phosphorylation. Mechanical properties such as the tensile strength, flexibility, and dimensional stability of the as-produced phosphorylated bacterial cellulose improved by using xylitol. In particular, the tensile strength and flexibility of the phosphorylated bacterial cellulose increased 5.7 and 2-fold, respectively, compared with those of the original bacterial cellulose. Therefore, this study demonstrated that the flame retardancy and flexibility of bacterial cellulose can be improved by using eco-friendly materials such as phytic acid and xylitol. The as-produced phosphorylated bacterial cellulose can be proposed as a fabric material with sufficient mechanical properties. [ABSTRACT FROM AUTHOR]

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin‐based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3‐palmitate (EV‐P), an ester lipidic prodrug for entecavir (EV), was employed. The EV‐P‐loaded TS was prepared by ultra‐sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 μm), crystallinity (melting point of 160–165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS‐injected site, drug aggregates of up to 500 μm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS‐injected site, with >4 weeks remaining of the oily vehicle in micro‐computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long‐acting delivery, with improved local tolerability. [ABSTRACT FROM AUTHOR]