21 resultados para Skin melanoma


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A precise determination of the neutron skin thickness of a heavy nucleus sets a basic constraint on the nuclear symmetry energy (the neutron skin thickness is the difference of the neutron and proton rms radii of the nucleus). The parity radius experiment (PREX) may achieve it by electroweak parity-violating electron scattering (PVES) on 208Pb. We investigate PVES in nuclear mean field approach to allow the accurate extraction of the neutron skin thickness of 208Pb from the parity-violating asymmetry probed in the experiment. We demonstrate a high linear correlation between the parity-violating asymmetry and the neutron skin thickness in successful mean field forces as the best means to constrain the neutron skin of 208Pb from PREX, without assumptions on the neutron density shape. Continuation of the experiment with higher precision in the parity-violating asymmetry is motivated since the present method can support it to constrain the density slope of the nuclear symmetry energy to new accuracy.

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Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.

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Peripheral nerve injury is typically associated with long-term disturbances in sensory localization, despite nerve repair and regeneration. Here, we investigate the extent of correct reinnervation by back-labeling neuronal soma with fluorescent tracers applied in the target area before and after sciatic nerve injury and repair in the rat. The subpopulations of sensory or motor neurons that had regenerated their axons to either the tibial branch or the skin of the third hindlimb digit were calculated from the number of cell bodies labeled by the first and/or second tracer. Compared to the normal control side, 81% of the sensory and 66% of the motor tibial nerve cells regenerated their axons back to this nerve, while 22% of the afferent cells from the third digit reinnervated this digit. Corresponding percentages based on quantification of the surviving population on the experimental side showed 91%, 87%, and 56%, respectively. The results show that nerve injury followed by nerve repair by epineurial suture results in a high but variable amount of topographically correct regeneration, and that proportionally more neurons regenerate into the correct proximal nerve branch than into the correct innervation territory in the skin

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Peer-reviewed

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We analyze the influence of the single-particle structure on the neutron density distribution and the neutron skin in Ca, Ni, Zr, Sn, and Pb isotopes. The nucleon density distributions are calculated in the Hartree-Fock+BCS approach with the SLy4 Skyrme force. A close correlation is found between the quantum numbers of the valence neutrons and the changes in the position and the diffuseness of the nuclear surface, which in turn affect the neutron skin thickness. Neutrons in the valence orbitals with low principal quantum number and high angular momentum mainly displace the position of the neutron surface outwards, while neutrons with high principal quantum number and low angular momentum basically increase the diffuseness of the neutron surface. The impact of the valence shell neutrons on the tail of the neutron density distribution is discussed.

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Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene.