In vivo Kinetic Biodistribution of Nano‐Sized Outer Membrane Vesicles Derived from Bacteria

Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter‐species, and inter‐kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)—bacterial extracellular vesicles—with immune‐modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF‐α and IL‐6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM‐1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post‐injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo.     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Properties and applications of β‐glycosidase from Bacteroides thetaiotaomicron that specifically hydrolyses isoflavone glycosides

To modify the glycan part of glycosides, the gene encoding β‐glycosidase was cloned from Bacteroides thetaiotaomicron VPI‐5482. The cloned gene, bt_1780, was expressed in Escherichia coli MC1061 and the expressed enzyme was purified using Ni‐NTA affinity chromatography. The purified enzyme, BTBG, showed optimal activity at 50 °C and pH 5.5. Interestingly, this enzyme did not have any hydrolysing activity on ordinary β‐linkage–containing substrates such as xylobiose, lactose and cello‐oligosaccharide, but specifically hydrolysed isoflavone glycosides such as daidzin, genistin and glycitin. Compared to a commercial beta glucosidase, BTBG selectively hydrolysed isoflavone glycosides in soybean extract mixture solution. These results suggest that BTBG may be a specialized enzyme for the hydrolysis of glycosides and that the substrate specificity of BTBG is applicable for the bioconversion of isoflavone glycosides in the food industry.