47 research outputs found
A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments
PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm,
a hydrodynamic diameter of 120 nm and a zeta potential of â20 mV were prepared
and investigated with regard to their biological activity. This review
summarizes the physicochemical properties (dissolution, protein adsorption,
dispersability) of these nanoparticles and the cellular consequences of the
exposure of a broad range of biological test systems to this defined type of
silver nanoparticles. Silver nanoparticles dissolve in water in the presence
of oxygen. In addition, in biological media (i.e., in the presence of
proteins) the surface of silver nanoparticles is rapidly coated by a protein
corona that influences their physicochemical and biological properties
including cellular uptake. Silver nanoparticles are taken up by cell-type
specific endocytosis pathways as demonstrated for hMSC, primary T-cells,
primary monocytes, and astrocytes. A visualization of particles inside cells
is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM
analysis. By staining organelles, their localization inside the cell can be
additionally determined. While primary brain astrocytes are shown to be fairly
tolerant toward silver nanoparticles, silver nanoparticles induce the
formation of DNA double-strand-breaks (DSB) and lead to chromosomal
aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell
lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo
induced a moderate pulmonary toxicity, however, only at rather high
concentrations. The same was found in precision-cut lung slices of rats in
which silver nanoparticles remained mainly at the tissue surface. In a human
3D triple-cell culture model consisting of three cell types (alveolar
epithelial cells, macrophages, and dendritic cells), adverse effects were also
only found at high silver concentrations. The silver ions that are released
from silver nanoparticles may be harmful to skin with disrupted barrier (e.g.,
wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the
data obtained on the effects of this well-defined type of silver nanoparticles
on various biological systems clearly demonstrate that cell-type specific
properties as well as experimental conditions determine the biocompatibility
of and the cellular responses to an exposure with silver nanoparticles
Aqueous alteration processes in Jezero crater, Marsâimplications for organic geochemistry
The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments
Cytomegalovirus-specific CD8+ T-cells are associated with a reduced incidence of early relapse after allogeneic stem cell transplantation.
Leukemia relapse is the main cause for mortality after allogeneic stem cell transplantation (allo-SCT). Donor-derived allo-immune responses eliminate the residual host hematopoiesis and protect against relapse. Cytomegalovirus (CMV) reactivation (CMV-R) after allo-SCT may trigger anti-leukemic effects. The impact of CMV-specific CD8+ T-cells (CMV-CTLs) on the outcome after allo-SCT is currently unknown. Here, we studied the relationship between CMV-CTLs, overall T-cell reconstitution and relapse incidence in 103 patients with acute leukemia (n = 91) or myelodysplastic syndrome (n = 12) following CMV-seropositive recipient/donor (R+/D+) allo-SCT. Patients were subdivided based on the presence or absence of CMV-CTLs at 3 months after allo-SCT. Presence of CMV-CTLs was associated with preceding CMV-R and a fast T-cell reconstitution. Univariate analysis showed a significantly lower 1-, 2- and 5-year cumulative incidence of relapse (CIR) in patients with CMV-CTLs compared to those without CMV-CTLs. Multivariable regression analysis of the outcome performed with other relevant parameters chosen from univariate analysis revealed that presence of CMV-CTLs and chronic graft-versus-host disease (cGvHD) were the only independent factors associated with a low CIR. Onset of relapse was significantly later in patients with CMV-CTLs (median 489 days) than in in those without (median 152 days, p = 0.041) during a five-year follow-up. Presence of CMV-CTLs was associated with a lower incidence of early relapses (1 and 2-years), while cGvHD lead to a lower incidence of late relapses (2 to 5-years). In conclusion, our data show that CMV-CTLs indicate a functional immune-reconstitution protective against early relapse
Sorodiscordùncia na atenção às pessoas com HIV/AIDS: implicaçÔes para o enfermeiro Serodiscordance in care for people with HIV/AIDS: implications for nurses
Objetivo: analisar a produção cientĂfica sobre a prĂĄtica sexual em casais sorodiscordantes e destacar as implicaçÔes para a prĂĄtica do enfermeiro. MĂ©todo: trata-se de uma revisĂŁo integrativa realizada nas bases de dados da Biblioteca Virtual em SaĂșde, Lilacs, SciELO, PubMED, CINAHL, sendo selecionados 12 artigos que atenderam aos critĂ©rios de inclusĂŁo, publicados de 2009 a 2014. Resultados: a maioria dos artigos foram publicados por enfermeiros em 2011 e 2013 nas revistas Caderno de SaĂșde PĂșblica, Temas em Psicologia e Revista da Escola de Enfermagem USP; sendo prevalente o descritor, casamento. As publicaçÔes foram agrupadas em duas categorias temĂĄticas: PrĂĄticas sexuais apĂłs o diagnĂłstico do HIV; e SorodiscordĂąncia na vida afetivo-sexual de portadores do HIV/AIDS: implicaçÔes para o enfermeiro. ConclusĂ”es: açÔes de enfermagem pautadas na orientação sexual contribuam para melhorar a qualidade de vida dos sorodiscordantes
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Characterization of High-Avidity Cytomegalovirus-Specific T Cells with Differential Tetramer Binding Coappearing after Allogeneic Stem Cell Transplantation
Abstract
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tetlow CTLs) and high tetramer binding (CMV tethigh CTLs) in 53/115 CMV IgG+ patients stem cell transplanted from CMV IgG+ donors. However, the relevance of these coappearing differentially tetramer binding (âdualâ) CMV-CTLs was unclear. In this study, we investigated the kinetics, properties, and clinical impact of coappearing CMV tetlow and tethigh CTLs after allogeneic SCT. Patients with dual CMV-CTLs had more CMV tethigh than tetlow CTLs. Chimerism analysis of isolated CMV tetlow and tethigh CTLs revealed their exclusive donor origin. CMV tetlow and tethigh CTLs had an identical effector memory CD45RAâCCR7â and CD45RA+CCR7â T cell distribution, equal differentiation, senescence, and exhaustion marker expression and were negative for regulatory CD8+ T cell markers. Isolated CMV tetlow and tethigh CTLs were equally sensitive to CMV peptides in IFN-Îł release and cytotoxicity assays. However, CMV tethigh CTLs proliferated more in response to low CMV peptide concentrations than tetlow CTLs. TCR repertoire analysis revealed that CMV tetlow and tethigh CTLs use different TCRs. Finally, dual CMV-CTLs were not associated with CMV antigenemia. In conclusion, these data show for the first time, to our knowledge, that both CMV tetlow and tethigh CTLs are functional effector T cells differing by proliferation, numbers in peripheral blood, and probably by their precursors without increasing the CMV reactivation risk after allogeneic SCT.</jats:p
miR-625-3p upregulation in CD8+ T cells after stimulation.
<p>(A-B) CD8+ T cells were isolated from PBMCs of 3 healthy donors by MACS negative selection and stimulated with CD2/CD3/CD28 beads, PHA + IL-2, PHA alone, IL-2 or IL-7 + IL-15. BrdU uptake (A) and miR-625-3p expression (B) were measured 5 days after stimulation. (C-D) Established HLA-A2 restricted CMV and HA-1 specific CD8+ T-cell clones were stimulated with CD14+ monocytes loaded with CMV pp65 NLV or HA-1 peptide, respectively, in the presence of IL-2. BrdU uptake (C) and miR-625-3p expression (D) were measured 5 days after stimulation. Y-axis: (A, C) Relative uptake of BrdU was calculated as [absorbance of sampleâabsorbance of unstimulated control] / absorbance of unstimulated control; Statistical analysis for BrdU uptake was calculated by (A) one way ANOVA followed by Dunnettâs multiple comparison test for overall CD8+ T cells and (C) Unpaired t-test for antigen-specific cells. **indicates p<0.01, *** indicates p<0.001. (B, D) relative fold change in miR-625-3p expression was calculated by 2<sup>-ÎÎct</sup> method using RNU48 and U6 snRNA as reference genes. Fold change above dotted line indicates significant fold change value >2. Data are representative of three independent experiments. All measurements were performed in duplicates.</p
miR-625-3p expression in CD8+ T cells in relation to proliferation.
<p>(A-F) CD8+ T cells isolated from PBMCs of 4 healthy donors were stimulated with PHA and 80 IU/ml IL-2 was repeatedly added every second day (A-C) or only on day 2 (D-F). BrdU uptake (A, D), miR-625-3p expression (B, E) and viable cell counts determined by trypan blue staining (C, F) were measured on different days until day 20 (A-C) or 17 (D-F) after stimulation. (G, H) CD8+ T cells isolated from PBMCs of 3 healthy donors were stimulated with CD2/CD3/CD28 beads in the presence or absence of rapamycin (RapaB). BrdU uptake (G) and miR-625-3p expression (H) were measured on day 5 after stimulation. X axis: (A-F) days post SCT. Y-axis: (A,D,G) Relative uptake of BrdU was calculated as [absorbance of sampleâabsorbance of unstimulated control] / absorbance of unstimulated control. (B,E,H) Relative fold change in miR-625-3p expression was calculated by 2<sup>-ÎÎct</sup> method using RNU48 and U6 snRNA as reference genes. All measurements were performed in duplicates. Fold change above dotted line indicates significant fold change value >2. Statistical comparisons were performed by paired t-test; *indicates p<0.05.</p