Lauritsenoh8092

Pyridoxal phosphate (PLP)-dependent α-oxoamine synthases are generally believed to be responsible for offloading and elongating polyketides or catalyzing the condensation of amino acids and acyl-CoA thioester substrates, such as serine into sphingolipids and cysteate into sulfonolipids. Previously, we discovered vitroprocines, which are tyrosine- and phenylalanine-polyketide derivatives, as potential new antibiotics from the genus Vibrio. Using bioinformatics analysis, we identified putative genes of PLP-dependent enzyme from marine Vibrio sp. QWI-06, implying a capability to produce amino-polyketide derivatives. One of these genes was cloned, and the recombinant protein, termed Vibrio sp. QWI-06 α-oxoamine synthases-1 (VsAOS1), was overexpressed for structural and biochemical characterization. The crystal structure of the dimeric VsAOS1 was determined at 1.8-Å resolution in the presence of L-glycine. The electron density map indicated a glycine molecule occupying the pyridoxal binding site in one monomer, suggesting a snapshot of the initiation process upon the loading of amino acid substrate. In mass spectrometry analysis, VsAOS1 strictly acted to condense L-glycine with C12 or C16 acyl-CoA, including unsaturated acyl analog. Furthermore, a single residue replacement of VsAOS1 (G243S) allowed the enzyme to generate sphingoid derivative when L-serine and lauroyl-CoA were used as substrates. Our data elucidate the mechanism of substrate binding and selectivity by the VsAOS1 and provide a thorough understanding of the molecular basis for the amino acid preference of AOS members.Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5β1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.Silicone-based fillers have been applied in several branches of medicine, such as soft tissue augmentation, because of their stability and durability. However, the inherently hydrophobic surfaces of silicone occasionally cause excessive deposition of the fibrous matrix in vivo, leading to severe fibrosis. In this study, we evaluated the use of a zwitterionic copolymer to offer a facile surface treatment method for silicone-based fillers and performed a preclinical trial of the formulation as-prepared. The copolymer has amphiphilic moieties, which act as macromolecular surfactants that can functionalize and stabilize the silicone particles during fabrication. The effectiveness and safety of the particle filler were evaluated histologically by scoring the peri-implant tissues into previously defined categories. Our results suggest that zwitterion-coated silicone fillers can inhibit protein adsorption, and thus, help attenuate foreign body reactions in a rat model. This demonstrates their potential for wide application in different fields within the discipline of medicine.The mechanical response of lipid membranes to nanoscale deformations is of fundamental importance for understanding how these interfaces behave in multiple biological processes; in particular, the nanoscale mechanics of non-lamellar membranes represents a largely unexplored research field. Among these mesophases, inverse bicontinuous cubic phase QII membranes have been found to spontaneously occur in stressed or virally infected cells and to play a role in fundamental processes, such as cell fusion and food digestion. find more We herein report on the fabrication of thin ( ̴150 nm) supported QII cubic phase lipid films (SQIIFs) and on their characterization via multiple techniques including Small Angle X-Ray Scattering (SAXS), Ellipsometry and Atomic Force Microscopy (AFM). Moreover, we present the first nanomechanical characterization of a cubic phase lipid membrane, through AFM-based Force Spectroscopy (AFM-FS). Our analysis reveals that the mechanical response of these architectures is strictly related to their topology and structure. The observed properties are strikingly similar to those of macroscopic 3D printed cubic structures when subjected to compression tests in material science; suggesting that this behaviour depends on the 3D organisation, rather than on the length-scale of the architecture. We also show for the first time that AFM-FS can be used for characterizing the structure of non-lamellar mesophases, obtaining lattice parameters in agreement with SAXS data. In contrast to classical rheological studies, which can only probe bulk cubic phase solutions, our AFM-FS analysis allows probing the response of cubic membranes to deformations occurring at length and force scales similar to those found in biological interactions.The article is dedicated to the comprehensive biocompatibility investigation of synthesised graphene oxide (GO) enriched with oxygen-containing functional groups (⁓85%). GO was synthesised through a modified Hummers and Offeman's method and characterised using 13C NMR, Raman, and IR spectroscopy, XRD, HRTEM, along with size dimensions and ζ-potentials in aqueous dispersions. Biocompatibility study included tests on haemocompatibility (haemolysis, platelet aggregation, binding to human serum albumin and its esterase activity), antioxidant activity (2,2-diphenyl-1-picrylhydrazyl reaction, NO-radical uptake, Radachlorin photobleaching, photo-induced haemolysis), genotoxicity using DNA comet assay, as well as metabolic activity and proliferation of HEK293 cells.Aquatic collagens, as the alternative sources of mammalian collagen, have received increasing attention due to its low-cost, low-antigenicity, biocompatibility, and biodegradability. Pepsin-soluble collagens were extracted from the skins of Oreochromis mossambicus (Om-PSC) and Gadus macrocephalus (Gm-PSC), and their structural properties and bioactivities were probed to reveal their potential applications in biomedical material for tissue engineering. The results of Fourier transforms-infrared spectroscopy (FT-IR), circular dichroism (CD), X-ray diffraction (XRD), ultraviolet (UV) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that Om-PSC and Gm-PSC had similar and intact triple helical structures. The amino acid composition and peptide profiles revealed Om-PSC and Gm-PSC were identified as type I collagen with the typical repetitive sequence of (Gly-X-Y) n. However, the denaturation temperature (Td) was determined to be 29.7 ℃ of Om-PSC, much higher than that of Gm-PSC (17.3 ℃). Toxicological experiments demonstrated Om-PSC and Gm-PSC both had good biocompatibility and cytocompatibility, which met the requirements of medical materials. Fluorescence imaging and cell cycle distribution revealed Om-PSC and Gm-PSC could promote the proliferation of fibroblast and osteoblast cells. Therefore, Om-PSC and Gm-PSC showed the advantages in medical materials.Inspired by the ordered porous nanostructure of bone, biomimetic functionalization porous biomaterial could be considered as promising substitutes for bone regeneration. To realize the relevant biomimetic porous structure, polyvinyl alcohol (PVA)-based biomimetic cuttlebone aerogel scaffold which simultaneously contained modified carbon nanotubes (MCNTs) and hydroxyapatite (HAP) was first prepared using a one-step rapid freeze-drying method. By adjusting the MCNTs contents, both the surface hydrophilicity and the mechanical properties of the scaffold could be improved concurrently. Besides, the PVA/MCNTs/HAP enhanced the adhesion, differentiation and gene expression of osteogenic markers performances of MC3T3-E1 cells. Furthermore, the aerogel scaffolds were implanted into the calvarial defect model of SD IGS Rat to evaluate osteogenic performance in vivo. The Micro-CT characterization and bone content theoretical analysis after 8 weeks together indicated that the PVA/MCNTs/HAP aerogel scaffolds could accelerate bone regeneration without the contribution of endogenous cytokines. The unique biomimetic porous structure, superior mechanical properties and excellent bone regeneration capacity of PVA/MCNTs/HAP aerogel scaffolds made them potential materials for bone regeneration.The association of cationic carriers with different anionic mucoadhesive biopolymers has been widely explored as an alternative to improve their delivery routes and specific targeting. This work presents a complete analysis of the association between chondroitin sulfate (CS) and cationic liposomes (CLs)/lipoplex (CL-pDNA). In this study, plasmid DNA (pDNA) was used as a genetic cargo for association with carriers. Firstly, we measured the stoichiometry of pseudo complexes and evaluated their colloidal properties, structural and morphological characteristics. Optimized CL-pDNA lipoplexes (positive z-potential) and CL-CS / CL-pDNA-CS (negative z-potential with CS mass ratio of 9% (w/w)) were further studied in detail. Small-angle X-ray scattering analysis and cryo-transmission electron microscopy micrographs revealed that the electrostatic interaction between CS and CL / CL-pDNA easily reorganized the lipid bilayers resulting in nanoscale uni/multilamellar vesicles. A high CS mass ratio (9% (w/w)) led to the reassembly of liposomal structure, wherein the pDNA was easily exchanged for CS chains, forming more than 50% of dense multilamellar vesicles. This data evidenced that the association between CS and CLs is not a conventional coating process since it generates complex and hybrid structures. We believe that these obtained colloidal data may be used in the future to investigate polymer-tailored nanocarriers and their production process. In brief, the colloidal study of hybrid structures may open interesting perspectives for developing novel carriers for drug and gene delivery applications.

Diabetes affects the lives of patients and their close relatives. Considering the proven benefit of patient education programs, DiaLife was elaborated as the first German education program addressing the needs of relatives. The objective of this study was to investigate its efficacy.

The evaluation was implemented in the form of a cRCT with longitudinal design and waiting list condition.In total, 179 relatives were recruited. Participants' diabetes-related knowledge was defined as the primary outcome. Diabetes-related strains, family interaction and other psychosocial factors were determined as secondary outcomes.

A generalized estimating equation model showed a persistent increase of diabetes-related knowledge in the intervention group compared to the control group regardless of the type of diabetes. Concerning secondary outcomes, mixed linear models showed an improvement for relatives of people with type 2 diabetes who participated in the DiaLife program.

This study provides evidence of DiaLife's efficacy regarding a persistent increase of diabetes-related knowledge and a positive effect on psychosocial outcomes in relatives of people with type 2 but not in type 1 diabetes.