Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders

Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4⁺ and CD8⁺ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.     

Response of Corn Seedlings (Zea mays L.) to Different Concentrations of Nitrogen in Absence and Presence of Silicon

Silicon - Corn plants are highly demanding of nitrogen and the application of silicon has been studied because it minimizes stress from different natures, and for the better utilization of some...     

A shock-fitting technique for 2D unstructured grids

A new floating shock-fitting technique featuring the explicit computation of shocks by means of the Rankine-Hugoniot relations has been implemented on two-dimensional unstructured grids. This paper illustrates the algorithmic features of this original technique and the results obtained in the computation of the hypersonic flow past a circular cylinder and a steady Mach reflection.     

Iron determination by FAAS in fish feed and feces after ultrasound-assisted extraction

This paper proposes a method to determine iron in samples of fish feed and feces using ultrasound in the extraction of the analyte and in subsequent quantification by flame atomic absorption spectrometry. Using HCl 0.10 mol L⁻¹ as the extraction solution, the optimal conditions of extraction were found to be: granulometry of the sample <60 μm; a sonication time of five cycles of 10 s and sonication power of 136 W. The method was applied in studies of the availability of iron in four food sources used in the diet of Nile Tilapia. The results obtained with the proposed extraction method allowed us to calculate the coefficients of apparent digestibility of iron in the food sources, which was not possible when using results obtained from samples mineralized by acid digestion.     

Film-loaded SAW waveguides for integrated acousto-optical polarization converters

We report on a detailed theoretical and experimental investigation of film-loaded surface acoustic wave (SAW) waveguides in lithium niobate (LiNbO3) for integrated acousto-optical (AO) polarization converters. The numerical analysis is based on both a scalar and a full-vectorial model. Dispersion plots and figures of merit for several structures are given, which lead to design parameters for optimized polarization converters. It is pointed out that very attractive structures are metal/dielectric/LiNbO3 strip waveguides and dielectric/LiNbO3 slot waveguides, in which metal is either gold (Au) or aluminum (Al), and the dielectric film is an optical transparent material such as silicon oxide (SiO2), magnesium oxide (MgO), or aluminium oxide (Al2O3). Polarization converters with the designed acoustical waveguides have been realized and characterized by optical conversion and laser probing measurements.     

POESIA: An ontological workflow approach for composing Web services in agriculture

This paper describes the POESIA approach to systematic composition of Web services. This pragmatic approach is strongly centered in the use of domain-specific multidimensional ontologies. Inspired by applications needs and founded on ontologies, workflows, and activity models, POESIA provides well-defined operations (aggregation, specialization, and instantiation) to support the composition of Web services. POESIA complements current proposals for Web services definition and composition by providing a higher degree of abstraction with verifiable consistency properties. We illustrate the POESIA approach using a concrete application scenario in agroenvironmental planning.Received: 15 December 2002, Accepted: 16 April 2003, Published online: 30 September 2003Edited by: V. AtluriRenato Fileto: fileto@ic.unicamp.br     

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc^−/−) and their wild type (Hdc^+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc^−/− and Hdc^+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc^+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.     

Photochemical grafting of acrylated azo dyes onto polymeric surfaces,IV. Grafting of 4-(N-ethyl-N-2-acryloxyethyl)amino-4′-nitro-azobenzene onto cellulose

Photochemically induced grafting and graft-polymerization of 4-(N-ethyl-N-2-acryloxyethyl)amino-4′-nitro-azobenzene I , brought into contact in the solid state with cellulose by evaporation of solvent from monomer solutions, has been investigated kinetically at 30°C. Two constant rate periods were observed. The first one was interpreted on the basis of a self-sensitized grafting mechanism of monomeric or oligomeric species of I , photochemically initiated by hydrogen abstraction from the cellulose surface. The second one was explained as a self-sensitized photochemically induced graft-polymerization of I on the first grafted layer. Some particular features, such as concurrent photodegradation of the first grafted layer at low surface coverage, are discussed in the light of the proposed mechanism.     

Monitoring ligand modulation of protein-protein interactions by mass spectrometry: estrogen receptor alpha-SRC1

Many drugs and chemicals exert their biological effect by modulating protein-protein interactions. In vitro approaches to characterize these mechanisms are often based on indirect measurements (e.g., fluorescence). Here, we used mass spectrometry (MS) to directly monitor the effect of small-molecule ligands on the binding of a coactivator peptide (SRC1) by the human estrogen receptor alpha ligand binding domain (hERalpha LBD). Nanoelectrospray mass spectrometry (nanoESI-MS) and high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with chemical cross-linking were employed to follow these processes. The chemical cross-linking protocol used prior to high-mass MALDI analysis allows detection of intact noncovalent complexes. The binding of intact hERalpha LBD homodimer with two coactivator peptides was detected with nanoESI-MS and high-mass MALDI-MS only in the presence of an agonist ligand. Furthermore, high-mass MALDI-MS revealed an increase of the homodimer abundance after incubating the receptor with a ligand, independent of the ligand character (i.e., agonist, antagonist). The binding characteristics of the compounds tested by MS correlate very well with their biological activity reported by cell-based assays. High-mass MALDI appears to be an efficient and simple tool for directly monitoring ligand regulation mechanisms involved in protein-protein interactions. Furthermore, the combination of both MS methods allows identifying and characterizing endocrine-disrupting compounds or new drug compounds in an efficient way.     

Time Resolved Infrared Spectroscopic Analysis of Aerosol Formed by Photo-Oxidation of 1,3,5-Trimethylbenzene and α-Pinene

Secondary organic aerosol generated from the photo-oxidation of 1,3,5-trimethylbenzene and α-pinene in a smog chamber was investigated. Fourier Transform Infrared Spectroscopy (FT-IR) was used to monitor the time dependent change of five different functional groups in the aerosol (carboxylic acids, alcohols, organonitrates, ketones/aldehydes═carbonyls, and aliphatic carbon) sampled with an impactor on zinc-selenide discs. Based on model compounds for oxidation products of 1,3,5-trimethylbenzene and α-pinene, calibration factors for the different functional groups were calculated, and relative molar fractions of the functional groups were estimated from the analysis of the FT-IR spectra of the smog chamber samples. We show chemical evolutions of secondary organic aerosol on a time scale of up to 20 h. Time series with up to eight measurements per experiment show a strong increase in the relative amounts of carboxylic acid groups and a moderate increase of alcohol and carbonyl groups, whereas the relative amounts of organonitrates and the aliphatic carbon decrease. These findings support the assumption that the chemical composition of the aerosol continues to change for a long time after the particle formation has considerably slowed down. According to these observed changes with time, average, sum formulas of the molecules in the secondary organic aerosol are suggested.