258 research outputs found

    March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity.

    Get PDF
    In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs

    TNF Superfamily: A Growing Saga of Kidney Injury Modulators

    Get PDF
    Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF) and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK-) dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored

    Increasing Students’ Interest With Low-Cost CellBots

    Get PDF
    This paper introduces the use of a flexible and affordable\ud educational robot specifically developed for the practical experimentation\ud inherent to technological disciplines. The robot has\ud been designed to be reconfigurable and extendible, serving as an\ud experimental platform across several undergraduate courses. As\ud most students have a mobile cell phone, this was used as the main\ud control computer for the so-called CellBot, thus avoiding any need\ud to deal with the details of microcontrollers or other embedded computing\ud devices. Assessment results are also presented, based on a\ud pre- and post-survey of student opinion administered to 204 science\ud and engineering students from several universities. Among\ud the conclusions are that 83% of the students prefer to use these\ud low-cost robots as tools to improve their learning of the theory in\ud several disciplines, and 71% of the students stated that they prefer\ud to have their own robot to experiment with, instead of using a didactic\ud kit loaned to them by the universityCNP

    Design of innovative clothing for pressure injury prevention: end-user evaluation in a mixed-methods study

    Get PDF
    The global relevance of pressure injury (PI) prevention technologies arise from their impact on the quality of life of people with limited mobility and the costs associated with treating these preventable injuries. The purpose of this mixed methods study is to evaluate the design of a prototype integrating Smart Health Textiles for PI prevention based on feedback from specialist nurses who care for individuals who are prone to or have PIs. This is a mixed methods study. A structured questionnaire was conducted as part of an evaluation of a prototype garment for the prevention of PIs. This questionnaire was applied during the evaluation of the prototype and afterwards focus group discussions were held with experts. Descriptive statistics techniques were used to analyze the data and thematic and integrated content analysis was conducted through concomitant triangulation. Nineteen nurses took part, aged 30 to 39 years (52.6%) and with 12.31 ± 8.96 years of experience. Participants showed that the prototype required more manipulation and physical effort, which interfered its usefulness, in addition to presenting difficulties with the openings and the material of the closure system, which interfered with the ease of use and learning. Overall satisfaction with the product was moderate, with some areas for improvement found, such as satisfaction, recommendations to colleagues, and pleasantness of use. It is concluded that areas for improvement have been found in all dimensions, including in the design of openings and the choice of materials. These findings supply significant insights for improving clothing to meet the needs of healthcare professionals and patients.The 4NoPressure project was co-financed by the Operational Program for Competitiveness and Internationalization (COMPETE 2020) under the PORTUGAL 2020 Partnership Agreement, with support from the European Regional Development Fund (ERDF), reference number POCI-01-0247- FEDER-039869

    Magnetic nanosystem for cancer therapy using oncocalyxone A, an antitomour secondary metabolite isolated from a Brazilian plant

    Get PDF
    none14siThis paper describes the investigation and development of a novel magnetic drug delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic Brazilian plant. It has a series of pharmacological properties: antioxidant, cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was associated with magnetite nanoparticles in order to obtain magnetic properties. The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and Magnetization curves. The MO-20 presented a size of about 30 nm and globular morphology. In addition, drug releasing experiments were performed, where it was observed the presence of the anomalous transport. The results found in this work showed the potential of onco A for future applications of the MO-20 as a new magnetic drug release nanosystem for cancer treatment.openBarreto, Antônio C.H.; Santiago, Vivian R.; Freire, Rafael M.; Mazzetto, Selma E.; Denardin, Juliano C.; Mele, Giuseppe; Cavalcante, Igor M.; Ribeiro, Maria E.N.P.; Ricardo, Nágila M.P.S.; Gonçalves, Tamara; Carbone, Luigi; Lemos, Telma L.G.; Pessoa, Otília D.L.; Fechine, Pierre B.A.*Barreto, Antônio C. H.; Santiago, Vivian R.; Freire, Rafael M.; Mazzetto, Selma E.; Denardin, Juliano C.; Mele, Giuseppe; Cavalcante, Igor M.; Ribeiro, Maria E. N. P.; Ricardo, Nágila M. P. S.; Gonçalves, Tamara; Carbone, Luigi; Lemos, Telma L. G.; Pessoa, Otília D. L.; Fechine, Pierre B. A

    High-resolution genetic map and QTL analysis of growth-related traits of Hevea brasiliensis cultivated under suboptimal temperature and humidity conditions

    Get PDF
    Rubber tree (Hevea brasiliensis) cultivation is the main source of natural rubber worldwide and has been extended to areas with suboptimal climates and lengthy drought periods; this transition affects growth and latex production. High-density genetic maps with reliable markers support precise mapping of quantitative trait loci (QTL), which can help reveal the complex genome of the species, provide tools to enhance molecular breeding, and shorten the breeding cycle. In this study, QTL mapping of the stem diameter, tree height, and number of whorls was performed for a full-sibling population derived from a GT1 and RRIM701 cross. A total of 225 simple sequence repeats (SSRs) and 186 single-nucleotide polymorphism (SNP) markers were used to construct a base map with 18 linkage groups and to anchor 671 SNPs from genotyping by sequencing (GBS) to produce a very dense linkage map with small intervals between loci. The final map was composed of 1,079 markers, spanned 3,779.7 cM with an average marker density of 3.5 cM, and showed collinearity between markers from previous studies. Significant variation in phenotypic characteristics was found over a 59-month evaluation period with a total of 38 QTLs being identified through a composite interval mapping method. Linkage group 4 showed the greatest number of QTLs (7), with phenotypic explained values varying from 7.67 to 14.07%. Additionally, we estimated segregation patterns, dominance, and additive effects for each QTL. A total of 53 significant effects for stem diameter were observed, and these effects were mostly related to additivity in the GT1 clone. Associating accurate genome assemblies and genetic maps represents a promising strategy for identifying the genetic basis of phenotypic traits in rubber trees. Then, further research can benefit from the QTLs identified herein, providing a better understanding of the key determinant genes associated with growth of Hevea brasiliensis under limiting water conditions
    corecore