Dpto. Ciencias - Zientziak Saila [desde mayo 2018 / 2018ko maiatzetik]
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Browsing Dpto. Ciencias - Zientziak Saila [desde mayo 2018 / 2018ko maiatzetik] by Department/Institute "Ciencias de la Salud"
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Publication Open Access Altered cortical palmitoylation induces widespread molecular disturbances in Parkinson's disease(MDPI, 2022) Cervilla-Martínez Juan F.; Rodríguez-Gotor Juan J.; Wypijewski, Krzysztof J.; Fontán-Lozano Ángela; Wang, Tao; Santamaría Martínez, Enrique; Fuller, William; Mejías, Rebeca; Ciencias de la Salud; Osasun ZientziakThe relationship between Parkinson’s disease (PD), the second-most common neurodegenerative disease after Alzheimer’s disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the differential palmitoyl proteome (palmitome) in the cerebral cortex of PD patients compared to controls (n = 4 per group). Data-mining of the cortical palmitome from PD patients and controls allowed us to: (i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls; (ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes; and (iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we partially characterized the altered palmitome in the cortex of PD patients, which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study suggests that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.Publication Open Access APP for working on executive function(Octaedro, 2024) Bausela Herreras, Esperanza; Ciencias de la Salud; Osasun Zientziak; Institute for Advanced Social Research - ICOMMUNITASThis app aims to enhance the executive functions of children. It is expected to contribute and have a positive impact on the development of instrumental skills, thereby facilitating access to the curriculum. The ultimate goal of any intervention designed to address executive function difficulties should be to increase the child's capacity for self-regulation (cognitive, behavioral, and emotional).Publication Open Access A combination of apple vinegar drink with Bacillus coagulans ameliorates high fat diet-induced body weight gain, insulin resistance and hepatic steatosis(MDPI, 2020) Urtasun Alonso, Raquel; Araña Ciordia, Miriam; Pajares Villandiego, María Josefa; Oneca Agurruza, María; Torre Hernández, Paloma; Barajas Vélez, Miguel Ángel; Encío Martínez, Ignacio; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako GobernuaObesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.Publication Open Access EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2(Nature Publishing Group, 2010-09-14) Gómez-Benito, María; Conchillo, Ana; García, M. A.; Vázquez Urio, Iria; Maicas, Miren; Vicente, Carmen; Cristobal, I.; Marcotegui, Nerea; García-Ortí, L.; Bandrés Elizalde, Eva; Calasanz, María José ; Alonso, M. M.; Odero, María D.; Ciencias; Zientziak; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako GobernuaBakground: the EVI1(ecotropic virus integration site 1) gene codes for a zinc-finger transcription factor, whose transcriptional activation leads to a particularly aggressive form of acute myeloid leukaemia (AML). Although, EVI1 interactions with key proteins in hematopoiesis have been previously described, the precise role of this transcription factor in promoting leukaemic transformation is not completely understood. Recent works have identified specific microRNA (miRNA) signatures in different AML subgroups. However, there is no analysis of miRNAs profiles associated with EVI1 overexpression in humans. Methods: we performed QT-RT-PCR to assess the expression of 250 miRNAs in cell lines with or without EVI1 overexpression and in patient samples. We used ChIP assays to evaluated the possible binding of EVI1 binding to the putative miRNA promoter. Proliferation of the different cell lines transfected with the anti- or pre-miRs was quantified by MTT. Results: our data showed that EVI1 expression was significantly correlated with the expression of miR-1-2 and miR-133-a-1 in established cell lines and in patient samples. ChIP assays confirmed that EVI1 binds directly to the promoter of these two miRNAs. However, only miR-1-2 was involved in abnormal proliferation in EVI1 expressing cell lines. Conclusions: our data showed that EVI1 controls proliferation in AML through modulation of miR-1-2. This study contributes to further understand the transcriptional networks involving transcription factors and miRNAs in AML.Publication Open Access A fermented food product containing lactic acid bacteria protects ZDF rats from the development of type 2 diabetes(MDPI, 2019) Cabello Olmo, Miriam; Oneca Agurruza, María; Torre Hernández, Paloma; Sainz, Neira; Moreno Aliaga, María J.; Guruceaga, Elizabeth; Díaz, Jesús Vicente; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako GobernuaType 2 diabetes (T2D) is a complex metabolic disease, which involves a maintained hyperglycemia due to the development of an insulin resistance process. Among multiple risk factors, host intestinal microbiota has received increasing attention in T2D etiology and progression. In the present study, we have explored the effect of long-term supplementation with a non-dairy fermented food product (FFP) in Zucker Diabetic and Fatty (ZDF) rats T2D model. The supplementation with FFP induced an improvement in glucose homeostasis according to the results obtained from fasting blood glucose levels, glucose tolerance test, and pancreatic function. Importantly, a significantly reduced intestinal glucose absorption was found in the FFP-treated rats. Supplemented animals also showed a greater survival suggesting a better health status as a result of the FFP intake. Some dissimilarities have been observed in the gut microbiota population between control and FFP-treated rats, and interestingly a tendency for better cardiometabolic markers values was appreciated in this group. However, no significant differences were observed in body weight, body composition, or food intake between groups. These findings suggest that FFP induced gut microbiota modifications in ZDF rats that improved glucose metabolism and protected from T2D development.Publication Open Access The regulators of peroxisomal acyl-carnitine shuttle CROT and CRAT promote metastasis in melanoma(Elsevier, 2023) Lasheras Otero, Irene; Feliu, Iker; Maíllo Ruiz de Infante, Alberto; Moreno, Haritz; Redondo Muñoz, Marta; Aldaz Donamaría, Paula; Bocanegra Gondán, Ana Isabel; Olías Arjona, Ana; Lecanda, Fernando; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Larráyoz, Ignacio M.; Gómez-Cabrero, David; Wellbrock, Claudia; Vicent, Silvestre; Arozarena Martinicorena, Imanol; Ciencias; Zientziak; Ciencias de la Salud; Osasun ZientziakCirculating tumor cells are the key link between a primary tumor and distant metastases, but once in the bloodstream, loss of adhesion induces cell death. To identify the mechanisms relevant for melanoma circulating tumor cell survival, we performed RNA sequencing and discovered that detached melanoma cells and isolated melanoma circulating tumor cells rewire lipid metabolism by upregulating fatty acid (FA) transport and FA betaoxidation‒related genes. In patients with melanoma, high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with reduced progression-free and overall survival. Among the highest expressed regulators in melanoma circulating tumor cells were the carnitine transferases carnitine O-octanoyltransferase and carnitine acetyltransferase, which control the shuttle of peroxisome-derived medium-chain FAs toward mitochondria to fuel mitochondrial FA beta-oxidation. Knockdown of carnitine O-octanoyltransferase or carnitine acetyltransferase and short-term treatment with peroxisomal or mitochondrial FA beta-oxidation inhibitors thioridazine or ranolazine suppressed melanoma metastasis in mice. Carnitine O-octanoyltransferase and carnitine acetyltransferase depletion could be rescued by medium-chain FA supplementation, indicating that the peroxisomal supply of FAs is crucial for the survival of nonadherent melanoma cells. Our study identifies targeting the FA-based cross-talk between peroxisomes and mitochondria as a potential therapeutic opportunity to challenge melanoma progression. Moreover, the discovery of the antimetastatic activity of the Food and Drug Administration‒approved drug ranolazine carries translational potential.