[Abstract unavailable

Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.

Ulvans (from Ulva lactuca) constitute a dietary fiber structurally similar to the mammalian glycosaminoglycans but with unexplored biological or cytotoxic activities. From native low-viscosity preparations containing 33.5 molar % and 18.4 molar % of sulfate residues and uronic acid residues, respectively, we derived desulfated, reduced and desulfated-reduced polysaccharides with respectively 5.2, 2.9, and 4.5-4.9 molar % of sulfate residues and uronic acid residues. The effects of these preparations were examined on the adhesion, proliferation and differentiation of normal or tumoral colonic epithelial cells cultured in conventional (0.3-0.8 x 10(6) cells/ml) or rotating bioreactor (3-8 x 10(6) cells/ml) culture conditions. In conventional culture conditions, ulvan modified the adhesion phase and the proliferation of normal colonic cells and undifferentiated HT-29 cells according to their molecular weights and to the relative molar proportion of sulfate residues. From the native polysaccharides, we have screened sulfated ulvans (MW < 5,000) which inhibited the Caco-2 cell proliferation/differentiation program by inducing a low cell reactivity to Ulex europeaus-1 lectins in defined (p < 0.001) or serum-supplemented media (p < 0.01) but were inactive on normal colonocytes. In conclusion, this dietary fiber could be a source of oligosaccharides with a bioactivity, a cytotoxicity or a cytostaticity targeted to normal or cancerous epithelial cells.

Background and AimsHuman breast milk is an extremely dynamic fluid containing many biologically-active components which change throughout the feeding period and throughout the day. We designed a miRNA assay on minimized amounts of raw milk obtained from mothers of preterm infants. We investigated changes in miRNA expression within month 2 of lactation and then over the course of 24 hours.Materials and MethodsAnalyses were performed on pooled breast milk, made by combining samples collected at different clock times from the same mother donor, along with time series collected over 24 hours from four unsynchronized mothers. Whole milk, lipids or skim milk fractions were processed and analyzed by qPCR. We measured hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-146-5p, and hsa-let-7a, d and g (all -5p). Stability of miRNA endogenous controls was evaluated using RefFinder, a web tool integrating geNorm, Normfinder, BestKeeper and the comparative ΔΔCt method.ResultsMiR-21 and miR-16 were stably expressed in whole milk collected within month 2 of lactation from four mothers. Analysis of lipids and skim milk revealed that miR-146b and let-7d were better references in both fractions. Time series (5H-23H) allowed the identification of a set of three endogenous reference genes (hsa-let-7d, hsa-let-7g and miR-146b) to normalize raw quantification cycle (Cq) data. We identified a daily oscillation of miR-16-5p.PerspectivesOur assay allows exploring miRNA levels of breast milk from mother with preterm baby collected in time series over 48–72 hours.