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EN
Recent research on the action of vanadium compounds shows its important effect on adipogenesis processes and adipocyte function. On the basis of previous screening tests in cellular models, the novel vanadium complex (N′-[(E)-(5-bromo-2-oxophenyl)methylidene]4-methoxybenzohydrazide)oxido(1,10-phenanthroline)vanadium(IV) was selected for this study. This complex exhibits potent inhibition of tyrosine phosphatases, and differences in the degree of inhibition were observed particularly for phosphatases. A significant increase in intracellular lipid accumulation and proliferative effect on 3T3-L1 preadipocytes confirmed the ability of this complex to enhance adipogenesis. The insulinomimetic activity of the tested complex was also demonstrated in fully differentiated 3T3-L1 adipocytes, in which glucose utilization was potentiated. The obtained results support the hypothesis that vanadium complexes show promising possibilities for use as new therapeutic strategies for the treatment of type 2 diabetes.
EN
In this study, 110 newly synthesized vanadium complexes from different structural groups were screened in three cell-based models representing the main target tissues for anti-diabetic drugs. In glucose utilization in C2C12 myocyte experiments, 93% of vanadium complexes were shown to have equal or greater activity than bis(maltolato)oxovanadium(IV) (BMOV), the methyl analog of bis(ethylmaltolato)oxovanadium(IV) (BEOV) which has been tested in clinical trials. Moreover, 49% and 50% of these complexes were shown to have equal or greater activity than BMOV in lipid accumulation in 3T3-L1 adipocytes and insulin secretion in RINm5F beta cell experiments, respectively. These results were the basis for the selection of compounds for the subsequent steps in the characterization of anti-diabetic properties. This study provides strong support for the application of screening cell-based assays with a phenotypic approach for the discovery of novel anti-diabetic drugs from the vanadium complex class. This is especially desirable due to the multiple and not fully defined mechanisms of action vanadium compounds.
EN
The work presents materials characteristics of fibrous polysaccharide substrates (calcium alginate, CA) modified with short peptides. Three types of synthesized peptides (hexapeptides) were composed of: cysteine (C) and tryptophan (W) named - (WWC)2or cysteine (C) and tyrosine (Y) named (YYC)2 or phenyloalanine (F) named 6F. The peptides size distribution (DLS method) showed that they agglomerated in an alcohol medium. These results were used to select a modification method of the fibrous substrates i.e. the peptides were deposited on the fibrous alginate substrate by the electrospraying technique. Using this method three kinds of polysaccharide- peptides systems were obtained i.e.: CA/(WWC)2, CA/(YYC)2CA/6F. As a reference material, the pure calcium alginate fibrous substrate was used. The results of modification with short peptides were evaluated via scanning electron microscopy (SEM): small aggregates were observed (40-100 nm) on the surface of fibers, and the fibers size remained the same after modification (11-12 μm). The size of aggregates depended on the kind of short peptide; the smaller (40 nm) aggregates were observed when the peptide had only aromatic chain (6F), the bigger (<100 nm) ones were observed when the peptide had heterocyclic rings in the chain (WWC and YYC). All materials were contacted with osteoblast-like cells (MG-63) to test biocompatibility (cells viability after 3 and 7 days) and the results proved showed higher viability in the polysaccharide-peptide system which increased with the time of observation. The durability of polysaccharide-peptide systems was tested using the enzymatic assay: collagenase confirmed the stability of materials. The progress of degradation rate was observed using infrared spectroscopy (FTIR-ATR) - the ratio on bands with C-O and C-OH increased after degradation under in vitro conditions.Results of the investigations on the fibrous substrates have confirmed that the system is a good model of an extracellular matrix (ECM) due to its chemical composition and microstructure which both have biomimetic characteristics. Thus, it may be used as a filling of bone defects supporting the regeneration of the damaged tissue. Additionally, it may also serve as the model research system of ECM.
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