Niemann Pick diseases types A (NPDA) and C (NPDC) are lysosomal storage disorders (LSDs) leading to cognitive impairment, neurodegeneration, and early death. NPDA and NPDC have different genetic ...origins, being caused by mutations in the acid sphingomyelinase (ASM) or the cholesterol transport protein NPC1, respectively. However, they share a common pathological hallmark in the accumulation of lipids in the endolysosomal compartment. Here, we tested the hypothesis that polyphenols reduce lipid overload in NPD cells by enhancing the secretion of extracellular vesicles (ECVs). We show that among the polyphenols tested, the ellagic acid metabolites, urolithin A and B, were the safest and most efficient in increasing ECV secretion. They reduced levels of accumulating lipids and lysosomal size and permeabilization in cultured bone marrow-derived macrophages and neurons from ASMko and NPC1 mutant mice, which mimic NPDA and NPDC, respectively. Moreover, oral treatment with ellagic acid reduced lipid levels, ameliorated lysosomal alterations, and diminished microglia activation in the brain of NPD mice. These results support the therapeutic value of ECV secretion and polyphenols for NPDs, which may also help treat other LSDs characterized by intracellular lipid overload.
•Brain ECV contain increased amounts of intracellular accumulating lipids in mouse models for Niemann Pick diseases (NPDs)•Polyphenols enhance ECV secretion in cellular models for NPDs•Urolithins A/B enhance ECV secretion and reduce lipid storage and lysosomal anomalies in cellular models for NPDs•Oral treatment with ellagic acid ameliorates brain pathology in mouse models for NPDs
Metastasis development represents an important threat for melanoma patients, even when diagnosed at early stages and upon removal of the primary tumor. In this scenario, determination of prognostic ...biomarkers would be of great interest. Serum contains information about the general status of the organism and therefore represents a valuable source for biomarkers. Thus, we aimed to define serological biomarkers that could be used along with clinical and histopathological features of the disease to predict metastatic events on the early‐stage population of patients. We previously demonstrated that in stage II melanoma patients, serum levels of dermcidin (DCD) were associated with metastatic progression. Based on the relevance of the immune response on the cancer progression and the recent association of DCD with local and systemic immune response against cancer cells, serum DCD was analyzed in a new cohort of patients along with interleukin 4 (IL‐4), IL‐6, IL‐10, IL‐17A, interferon γ (IFN‐γ), transforming growth factor‐β (TGF‐ β), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF). We initially recruited 448 melanoma patients, 323 of whom were diagnosed as stages I‐II according to AJCC. Levels of selected cytokines were determined by ELISA and Luminex, and obtained data were analyzed employing machine learning and Kaplan–Meier techniques to define an algorithm capable of accurately classifying early‐stage melanoma patients with a high and low risk of developing metastasis. The results show that in early‐stage melanoma patients, serum levels of the cytokines IL‐4, GM‐CSF, and DCD together with the Breslow thickness are those that best predict melanoma metastasis. Moreover, resulting algorithm represents a new tool to discriminate subjects with good prognosis from those with high risk for a future metastasis.
Melanoma displays a remarkable capacity for dissemination even when detected at early stages. We developed a decision rule that considers Breslow thickness of the removed malignant lesion and IL‐4, GM‐CSF, and DCD serum levels in order to foresee the risk for future metastasis development of those stage I‐II patients. This algorithm may represent a tool to design more personalized follow‐up strategies.
Aznar Vallejo Eduardo, Corbella Díaz Dolores, Pico Graña Berta et al. Le livre nommé Le Canarien. Textes français de la conquête des Canaries au XVe siècle. Texte édité et annoté. Paris : Éditions du ...Centre National de la Recherche Scientifique, 2008. 294 p. (Sources d'histoire médiévale, 38)
Graphene oxide is a derivate of graphene obtained by oxidation of graphite and other carbonaceous materials. The more accepted structure consists in carbonyl and carboxyl groups located at the edge ...of the graphene network and hydroxyl and epoxy groups attached to the basal plane. The percentage of O-groups depends on the synthesis route and the material used as carbon source. In addition, highly oxidized fragments, called oxidative debris, OD, are produced during the oxidation process. These fragments are adsorbed onto the graphene oxide network and can be removed by alkaline washing. The purified material has lower O/C ratio than graphene oxide and its properties are also quite different. Due to its structure, graphene oxide can be adsorbed at the air-water interface of the aqueous solution by diffusion, Gibbs monolayers, or by spreading on a clean water subphase resulting in a Langmuir film. This review is intended to provide information on the importance of controlling the chemical composition, structure, size, and oxidative debris, on the manufacture of graphene oxide films. To this end the review shows the influence of the synthesis route and the starting material on the structure of graphene oxide and analyzes several examples of the behavior and properties of films prepared with different types of graphene oxides. The great variability of behaviors of graphene oxide films caused by the different structure of this material provides a great opportunity to fine-tune the properties of films according to the needs of different applications.
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•Effect of the synthesis routes on the structure of graphene oxide.•Surface activity of graphene oxide dispersions.•Influence of the chemical composition on the Langmuir films of graphene oxides.•Effect of oxidative debris on the structure of graphene oxide films.
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