Nanoparticles (microvesicles – MVs) are found in peripheral blood. They bud from cell membranes. During the isolation process additional MVs are released from blood cells, so optimization and reduction of additional MVs are pivotal if MVs are used as a diagnostic marker for certain diseases. We showed that a size and a concentration of MVs are dependent on temperature during the isolation, where higher concentrations of smaller MVs were observed at lower temperatures. On the basis of pictures of deformed blood cells found in the isolates indicate we can speculate how fragmentation of blood cells may take place. The results show that the contents of isolates reflect the properties of blood cells and their interaction with the surrounding solution, which differ in different diseasesand may therefore present a relevant clinical parameter.
COBISS.SI-ID: 29065433
HIV-1 represents an elusive target for therapeutic compounds due to its high rate of mutation. Targeting structural patterns instead of a constantly changing specific 3D structure may represent an approach that is less sensitive to viral mutations. The V3 loop of gp120 of HIV-1, which is responsible for binding of viral gp120 to CCR5 or CXCR4 coreceptors, has already been identified as an effective target for the inhibition of viral entry. The peptide derived from the V3 loop of gp120 specifically interacts with the lipid A moiety of LPS, as does the full gp120 protein. NMR analysis of V3 in complex with LPS shows formation of an amphipathic turn, similar to the interaction between antimicrobial peptides and LPS. LPS inhibited binding of gp120 to the surface of target T cells. Nonendotoxic LPS antagonists inhibited viral infection, demonstrating the possibility for the development of an inhibitor of HIV-1 attachment to T cells based on the recognition of a conserved structural pattern.
COBISS.SI-ID: 4677402
TLR4 is involved in activation of innate immune response. Despite numerous studies, the role of separate domains of TLR4 in the regulation of receptor activation is poorly understood. Replacement of the TLR4 ectodomain with LPS-binding proteins MD-2 or CD14 resulted in a robust ligand-independent constitutive activation. This demonstratesan intrinsic dimerization propensity of the transmembrane and cytoplasmic domains of TLR4 and reveals a previously unknown function of the ectodomain in inhibiting spontaneous receptor dimerization. This is important for the sensitivity of TLR4 to activation by different agonists.
COBISS.SI-ID: 4652570