Background: Most cystic echinococcosis cases in Southern Brazil are caused by Echinococcus granulosus and Echinococcus ortleppi. Proteomic studies of helminths have increased our knowledge about the molecular survival strategies that are used by parasites. Here, we surveyed the protein content of the hydatid fluid compartment in E. granulosus and E. ortleppi pulmonary bovine cysts to better describe and compare their molecular arsenal at the host-parasite interface. Methods: Hydatid fluid samples from three isolates of each species were analyzed using mass spectrometry-based proteomics (LC-MS/MS). In silico functional analyses of the identified proteins were performed to examine parasite survival strategies. Results: The identified hydatid fluid protein profiles showed a predominance of parasite proteins compared to host proteins that infiltrate the cysts. We identified 280 parasitic proteins from E. granulosus and 251 from E. ortleppi, including 52 parasitic proteins that were common to all hydatid fluid samples. The in silico functional analysis revealed important molecular functions and processes that are active in pulmonary cystic echinococcosis, such as adhesion, extracellular structures organization, development regulation, signaling transduction, and enzyme activity. Conclusions: The protein profiles described here provide evidence of important mechanisms related to basic cellular processes and functions that act at the host-parasite interface in cystic echinococcosis. The molecular tools used by E. granulosus and E. ortleppi for survival within the host are potential targets for new therapeutic approaches to treat cystic echinococcosis and other larval cestodiases. Graphical

Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle. Cells treated with RA showed increased levels of p21 and its encoding gene, CDKN1A. RA reduced mRNA and protein levels of SRY-box transcription factor 2 (SOX2) as well as mRNA levels of beta III Tubulin (TUBB3), whereas the levels of CD99 increased. Exposure to RA reduced the capability of SK-ES-1 to form tumorspheres with high expression of SOX2 and Nestin. Gene expression of CD99 and CDKN1A was reduced in ES tumors compared to non-tumoral tissue, whereas transcript levels of SOX2 were significantly higher in tumors. For NES and TUBB3, differences between tumors and control tissue did not reach statistical significance. Low expression of CD99 and NES, and high expression of SOX2, were significantly associated with a poorer patient prognosis indicated by shorter overall survival (OS). Our results indicate that RA may display rather complex modulatory effects on multiple target genes associated with the maintenance of stem cell’s features versus their differentiation, cell cycle regulation, and patient prognosis in ES.

The vast majority of cystic echinococcosis cases in Southern Brazil are caused by Echinococcus granulosus and Echinococcus ortleppi . Comparative proteomic studies of helminths have increased the knowledge about the molecular survival strategies adopted by parasites. Here, we surveyed the protein contents of the hydatid fluid compartment of E. granulosus and E. ortleppi pulmonary bovine cysts, in an attempt to compare their molecular arsenal in this host-parasite interface. Hydatid fluid samples from three isolates of each species were analyzed by trypsin digestion and mass spectrometry. We identified 280 proteins in E. granulosus and 251 proteins in E. ortleppi , highlighting a core of 52 proteins common to all samples of hydatid fluid. The in silico functional analysis revealed important molecular functions and processes active in pulmonary cystic echinococcosis. Some were more evident in one species, such as apoptosis in E. ortleppi , and cysteine protease activity in E. granulosus , while many molecular activities have been found in fluids of both species, such as proteolysis, development signaling and extracellular structures organization. The similar molecular tools employed by E. granulosus and E. ortleppi for their survival within the host are potential targets for new therapeutic approaches to deal with cystic echinococcosis and other larval cestodiases.