Modifications of histones in parasites as drug targets.

Post-translational modifications of histones and histone modifying enzymes play important roles in gene regulations and other physiological processes in parasites. Inhibitors of such modifying enzymes could be useful as novel therapeutics against parasitic diseases or as chemical probes for investigation of epigenetics. Development of parasitic histone modulators has got rapid expansion in the last few years. A number of highly potent and selective compounds have been reported, together with extensive preclinical studies of their biological activity. Some of these compounds have been widely used in humans targeting cancer and are found non-toxic. This review summarizes the antiparasitic activities of histone and histone modifying enzymes inhibitors evaluated in last few years. As the current chemotherapy against parasites is still not satisfactory, therefore, such compounds represents good starting points for the discovery of effective antiparasitic drugs.

Proteomic Analysis of Exosome-Like Vesicles Isolated From Saliva of the Tick Haemaphysalis longicornis.

Extracellular vesicles (EVs), are considered as vehicles of cellular communication. Parasites usually release EVs in their excretory-secretory products to modulate host environment. However, little is known about the secretion of EVs by ticks. In this study, we show for the first time that the tick Haemaphysalis longicornis secretes EVs in saliva that resembles exosomes. EVs were purified from pilocarpine induced saliva of partially engorged H. longicornis ticks. Electron microscopy analysis revealed the presence of exosome-like vesicles with a size of 100 nm. Proteomic analysis by LC-MS/MS identified a total of 356 proteins in tick-derived EVs. Proteome data of tick-derived EVs was validated by Western blot analysis. Immunodetection of Hsp70 and GAPDH proteins indicated that the proteomics data of tick-derived EVs were highly reliable. Bioinformatics analysis (Gene Ontology) indicated association of certain biological and molecular functions with proteins which may be helpful during tick development. Likewise, KEGG database revealed involvement of vesicular proteins in proton transport, detoxification, ECM-receptor interaction, ribosome, RNA transport, ABC transporters, and oxidative phosphorylation. The results of this study provide evidence that EVs are being secreted in tick saliva and suggest that tick saliva-derived EVs could play important roles in host-parasite relationships. Moreover, EVs could be a useful tool in development of vaccines or therapeutics against ticks.