Previously, we have demonstrated that Gly m 4, one of the major soybean allergens, could pass through the Caco-2 epithelial barrier and have proposed a mechanism of sensitization. However, it is not known yet whether Gly m 4 can reach the intestine in its intact form after digestion in stomach. In the present work, we studied an influence of various factors including lipids (fatty acids and lysolipids) on digestibility of Gly m 4. Using fluorescent and CD spectroscopies, we showed that Gly m 4 interacted with oleic acid and LPPG (lyso-palmitoyl phosphatidylglycerol), but its binding affinity greatly decreased under acidic conditions, probably due to the protein denaturation. The mimicking of gastric digestion revealed that Gly m 4 digestibility could be significantly reduced with the change of pH value and pepsin-to-allergen ratio, as well as by the presence of LPPG. We suggested that the protective effect of LPPG was unlikely associated with the allergen binding, but rather connected to the pepsin inhibition due to the lipid interaction with its catalytic site. As a result, we assumed that, under certain conditions, the intact Gly m 4 might be able to reach the human intestine and thereby could be responsible for allergic sensitization.
An increase in the frequency of mycoses and spreading of multidrug-resistant fungal pathogens necessitates the search for new antifungal agents. Earlier, we isolated the novel defensin from lentil Lens culinaris seeds, designated as Lc-def, which inhibited the growth of phytopathogenic fungi. Here, we studied an antifungal activity of Lc-def against human pathogenic Candida species, structural stability of the defensin, and its immunomodulatory effects that may help to prevent fungal infection. We showed that Lc-def caused 50% growth inhibition of clinical isolates of Candida albicans, C. krusei, and C. glabrata at concentrations of 25–50 μM, but was not toxic to different human cells. The lentil defensin was resistant to proteolysis by C. albicans and was not cleaved during simulated gastroduodenal digestion. By using the multiplex xMAP assay, we showed for the first time for plant defensins that Lc-def increased the production of such essential for immunity to candidiasis pro-inflammatory cytokines as IL-12 and IL-17 at the concentration of 2 μM. Thus, we hypothesized that the lentil Lc-def and plant defensins in general may be effective in suppressing of mucocutaneous candidiasis due to their antifungal activity, high structural stability, and ability to activate a protective immune response.
Background
Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients.
Methods
37 patients with IE were enrolled into the study. Coagulation was assessed using standard coagulation assays (activated partial thromboplastin time (APTT), prothrombin, fibrinogen, D-dimer concentrations) and integral assays (thromboelastography (TEG) and thrombodynamics (TD)). Platelet functional activity was estimated by flow cytometry. Single nuclear polymorphisms of coagulation system genes were studied.
Results
Fibrinogen concentration and fibrinogen-dependent parameters of TEG and TD were increased in patients indicating systemic inflammation. In majority of patients clot growth rate in thrombodynamics was significantly shifted towards hypercoagulation in consistency with D-dimers elevation. However, in some patients prothrombin, thromboelastography and thrombodynamics were shifted towards hypocoagulation. Resting platelets were characterized by glycoprotein IIb-IIIa activation and degranulation. In patients with fatal IE, we observed a significant decrease in fibrinogen and thrombodynamics. In patients with embolism, we observed a significant decrease in the TEG R parameter. No association of embolism or mortality with genetic polymorphisms was found in our cohort.
Conclusions
Our findings suggest that coagulation in patients with infective endocarditis is characterized by general hypercoagulability and platelet pre-activation. Some patients, however, have hypocoagulant coagulation profile, which presumably can indicate progressing of hypercoagulation into consumption coagulopathy.
In this work, cationic meso-arylsubstituted porphyrin and its Zn(II) complex were synthesized. The compounds were characterized by multinuclear NMR spectroscopy, electronic spectroscopy and ESI-mass spectrometry. The photodynamic activity of the porphyrins was studied in relation to S. aureus bacteria and their biofilms. Application of polymeric micelles of Pluronic F-127 as nanosized delivery vehicles supports high antimicrobial photodynamic activity of the synthesized porphyrins. The influence of the central metal atom on the dark and light-induced toxicity of the synthesized compounds was revealed.
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