Our analysis showed that the structure and dynamics of the regenerated extracellular matrix was very similar to that of the native bone, suggesting that biomineralization was significantly enhanced by the choice of the most appropriate implant material.
In the questf or new antibiotics, two novel engineered cationic antimicrobialpeptides (eCAPs)h ave been rationallyd esigned. WLBU2 and D8 (all 8v alines are the denantiomer)e fficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxict oe ukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structurea nd pore evidence. We suggest that protein secondary structure is not ac riticald eterminant of bactericidal activity,b ut that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydro-carbonr egion may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model,b oth locate deep into its hydrocarbonr egion where they are primedf or self-promoted uptake into the periplasm.T he partially a-helicals econdarys tructure of WLBU2 in ar ed blood cell (RBC) membrane model containing 50 % cholesterol, could play ar ole in destabilizingt his RBC membrane modelc ausing pore formationt hat is not observed with the D8 randomc oil, which correlates with RBC hemolysis causedb yWLBU2 but not by D8.[a] Prof. Figure 4. CD results of WLBU2i na queouss olution, pH 7and with lipidmembrane models. A) WLBU2 in G(À)I M( black trace) and WLBU2 in water (red trace), B) secondary structure results of WLBU2 in G(À)I Mmodel with decreasing WLBU2:lipid molar ratio in 15 mm PBS, (C) Secondary structure results of 10 mm WLBU2 in 15 mm PBS in six model membranes at 10:1 lipid:peptide molar ratio. R 2 indicates the goodnesso ft he fit to the Brahms and Brahmsd ata set. [49] All CD experiments were carried out at 37 8C. The errors on the percentages are 3-5 %.
CXCL14, chemokine (C-X-C motif) ligand 14, is a novel highly conserved chemokine with unique features. Despite exhibiting the typical chemokine fold, it has a very short N-terminus of just two amino acid residues responsible for chemokine receptor activation. CXCL14 actively participates in homeostatic immune surveillance of skin and mucosae, is linked to metabolic disorders and fibrotic lung diseases and possesses strong anti-angiogenic properties in early tumor development. In this work, we investigated the interaction of CXCL14 with various glycosaminoglycans (GAGs) by nuclear magnetic resonance spectroscopy, microscale thermophoresis, analytical heparin (HE) affinity chromatography and in silico approaches to understand the molecular basis of GAG-binding. We observed different GAG-binding modes specific for the GAG type used in the study. In particular, the CXCL14 epitope for HE suggests a binding pose distinguishable from the ones of the other GAGs investigated (hyaluronic acid, chondroitin sulfate-A/C, −D, dermatan sulfate). This observation is also supported by computational methods that included molecular docking, molecular dynamics and free energy calculations. Based on our results, we suggest that distinct GAG sulfation patterns confer specificity beyond simple electrostatic interactions usually considered to represent the driving forces in protein–GAG interactions. The CXCL14–GAG system represents a promising approach to investigate the specificity of GAG–protein interactions, which represents an important topic for developing the rational approaches to novel strategies in regenerative medicine.
Mucin glycoproteins are key components of native mucus which serves as an initial barrier in the human body against microbial attack. Mucins are able to prevent bacterial adhesion and can trap viruses. However, the weak mechanical properties of mucin solutions have so far prevented their application in a physiological environment. Here, methylcellulose biopolymers are used as mechanical adjuvants to overcome this limitation and generate a thermoresponsive mucin/methylcellulose hybrid system. The hybrid material developed combines the selective permeability properties brought about by mucins with the thermal autogelation properties of methylcellulose. As a consequence, triggered by contact with body‐warm surfaces, the hybrid material rapidly forms a gel at physiological conditions, and this external temperature stimulus can also be harnessed to stimulate drug release from incorporated thermosensitive liposomes. Finally, the hybrid gel selectively retards the release of embedded molecules which can be used to further control and prolong drug release from the material.
SXL with riboflavin and blue light intensities below a defined damage threshold can induce a long lasting growth inhibitory effect on young rabbit eyes. Therefore, SXL might be a realistic approach to inhibit eye elongation in highly myopic eyes.
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