Lampreys, the jawless vertebrates, contain three Pax6 genes with distinct expression in eye, brain and pancreas

10.1038/s41598-019-56085-8Scientific Reports911955

Bidirectional link between upper and lower airways in patients with allergic rhinitis

Abstract Objective Exhaled nitric oxide has been proposed as a noninvasive marker of eosinophilic airway inflammation in lower airways. The aim of the study was to investigate the impact of atopy, pollen exposure, and pharmacological treatment on NO production in lower airways of patients with allergic rhinitis. Subjects and methods Measurements of exhaled NO were performed in 79 non-asthmatic subjects with seasonal allergic rhinitis outside and in pollen season, before and after pharmacological treatment, and in 54 healthy controls. Results Patients with allergic rhinitis had significantly higher levels of exhaled NO (18.3 ± 11.0 ppb) than healthy controls (13.0 ± 7.2 ppb) measured outside the pollen season (P = 0.0024). Increased exhaled NO levels were also found in patients with allergic rhinitis in the pollen season (27.0 ± 20.0 ppb) compared with the levels outside pollen season (P = 0.0001), before pharmacological treatment. In rhinitic patients treated by nasal corticosteroids and antihistamines in the pollen season, the levels of exhaled NO were significantly lower (17.0 ± 16.4 ppb; P = 0.045) than those before treatment. No difference was found in NO levels in rhinitic patients outside and in pollen season after pharmacological treatment. Conclusions This study has shown the presence of eosinophilic airway inflammation in the lower airways in allergic rhinitis patients. A significant increase of exhaled NO after pollen exposure in rhinitic patients underlies the impact of inflammation on the upper respiratory tract. A bidirectional link between upper and lower airways is confirmed by a decrease in exhaled NO in the pollen season, almost to the starting levels, after application of topic corticosteroids and antihistamines.</p

Structure-activity relationship of acridine derivatives to amyloid aggregation of lysozyme

Background: Amyloid-related diseases (such as Alzheimer's disease or diabetes type II) are associated with self-assembly of protein into amyloid aggregates. Methods: Spectroscopic and atomic force microscopy were used to determine the ability of acridines to affect amyloid aggregation of lysozyme. Results: We have studied the effect of acridine derivatives on the amyloid aggregation of lysozyme to investigate the acridine structure-activity relationship. The activity of the effective planar acridines was characterized by the half-maximum depolymerization concentration DC(50) and half-maximal inhibition concentration IC(50). For the most effective acridine derivatives we examined their interaction with DNA and their effect on cell viability in order to investigate their eventual influence on cells. We thus identified planar acridine derivatives with intensive anti-amyloid activity (IC(50) and DC(50) values in micromolar range), low cytotoxicity and weak ability to interfere with the processes in the cell. Conclusions: Our findings indicate that both the planarity and the tautomerism of the 9-aminoacridine core together with the reactive nucleophilic thiosemicarbazide substitution play an important role in the anti-amyloid activities of studied derivatives. General significance: The present findings favor the application of the selected active planar acridines in the treatment of amyloid-related diseases

Presence of Magnetic Fluids Leads to the Inhibition of Insulin Amyloid Aggregation

Insulin amyloid aggregation caused serious problems in the treatment of diabetes by insulin injection or by insulin pumps. In vitro formation of insulin amyloid fibrils was investigated in presence of several types of magnetic fluids. Interaction of magnetic fluids with insulin amyloid aggregates led to decrease of insulin fibrillization. The inhibiting activities are affected by coating layer of studied magnetic fluids as well as by their physical properties (diameter, concentration of magnetic particles). The highest inhibiting efficiencies were detected for sterically stabilized magnetic fluids in saline solution (75%) and for magnetic fluids modified by dextran (80%)

In Vitro and In Vivo Evaluation of a Water-in-Oil Microemulsion System for Enhanced Peptide Intestinal Delivery

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration