Person: Pajares Villandiego, María Josefa
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Pajares Villandiego
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María Josefa
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Ciencias de la Salud
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0000-0002-9427-7937
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811611
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Publication Open Access Antidiabetic effects of Pediococcus acidilactici pA1c on HFD-induced mice(MDPI, 2022) Cabello Olmo, Miriam; Oneca Agurruza, María; Pajares Villandiego, María Josefa; Jiménez, Maddalen; Ayo, Josune; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 0011-1365-2020-000086Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.Publication Open Access Epigenetic regulation of microRNAs in cancer: shortening the distance from bench to bedside(MDPI, 2021) Pajares Villandiego, María Josefa; Alemany Cosme, Ester; Goñi Irigoyen, Saioa; Bandrés Elizalde, Eva; Palanca Ballester, Cora; Sandoval, Juan; Ciencias de la Salud; Osasun ZientziakCancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.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 Methods for analysis of specific DNA methylation status(Elevier, 2021) Pajares Villandiego, María Josefa; Palanca Ballester, Cora; Urtasun Alonso, Raquel; Alemany Cosme, Ester; Lahoz, Agustín; Sandoval, Juan; Ciencias de la Salud; Osasun ZientziakMethylation of CpG dinucleotides plays a crucial role in the regulation of gene expression and therefore in the development of different pathologies. Aberrant methylation has been associated to the majority of the diseases, including cancer, neurodegenerative, cardiovascular and autoimmune disorders. Analysis of DNA methylation patterns is crucial to understand the underlying molecular mechanism of these diseases. Moreover, DNA methylation patterns could be used as biomarker for clinical management, such as diagnosis, prognosis and treatment response. Nowadays, a variety of high throughput methods for DNA methylation have been developed to analyze the methylation status of a high number of CpGs at once or even the whole genome. However, identification of specific methylation patterns at specific loci is essential for validation and also as a tool for diagnosis. In this review, we describe the most commonly used approaches to evaluate specific DNA methylation. There are three main groups of techniques that allow the identification of specific regions that are differentially methylated: bisulfite conversion-based methods, restriction enzyme-based approaches, and affinity enrichment-based assays. In the first group, specific restriction enzymes recognize and cleave unmethylated DNA, leaving methylated sequences intact. Bisulfite conversion methods are the most popular approach to distinguish methylated and unmethylated DNA. Unmethylated cytosines are deaminated to uracil by sodium bisulfite treatment, while the methyl cytosines remain unconverted. In the last group, proteins with methylation binding domains or antibodies against methyl cytosines are used to recognize methylated DNA. In this review, we provide the theoretical basis and the framework of each technique as well as the analysis of their strength and the weaknesses.Publication Open Access Lactiplantibacillus plantarum DSM20174 attenuates the progression of non-alcoholic fatty liver disease by modulating gut microbiota, improving metabolic risk factors, and attenuating adipose inflammation(MDPI, 2022) Riezu Boj, José I.; Barajas Vélez, Miguel Ángel; Pérez Sánchez, Tania; Pajares Villandiego, María Josefa; Araña Ciordia, Miriam; Milagro Yoldi, F. I.; Urtasun Alonso, Raquel; Ciencias de la Salud; Osasun ZientziakNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, reaching epidemic proportions worldwide. Targeting the gut–adipose tissue–liver axis by modulating the gut microbiota can be a promising therapeutic approach in NAFLD. Lactiplantibacillus plantarum, a potent lactic-acid-producing bacterium, has been shown to attenuate NAFLD. However, to our knowledge, the possible effect of the Lactiplantibacillus plantarum strain DSM20174 (L.p. DSM20174) on the gut–adipose tissue axis, diminishing inflammatory mediators as fuel for NAFLD progression, is still unknown. Using a NAFLD mouse model fed a high-fat, high-fructose (HFHF) diet for 10 weeks, we show that L.p DSM20174 supplementation of HFHF mice prevented weight gain, improved glucose and lipid homeostasis, and reduced white adipose inflammation and NAFLD progression. Furthermore, 16S rRNA gene sequencing of the faecal microbiota suggested that treatment of HFHF-fed mice with L.p DSM20174 changed the diversity and altered specific bacterial taxa at the levels of family, genus, and species in the gut microbiota. In conclusion, the beneficial effects of L.p DSM20174 in preventing fatty liver progression may be related to modulations in the composition and potential function of gut microbiota associated with lower metabolic risk factors and a reduced M1-like/M2-like ratio of macrophages and proinflammatory cytokine expression in white adipose tissue and liver.Publication Open Access Pediococcus acidilactici pA1c® improves the beneficial effects of metformin treatment in type 2 diabetes by controlling glycaemia and modulating intestinal microbiota(MDPI, 2023) Cabello Olmo, Miriam; Oneca Agurruza, María; Urtasun Alonso, Raquel; Pajares Villandiego, María Josefa; Goñi Irigoyen, Saioa; Riezu Boj, José I.; Milagro Yoldi, F. I.; Ayo, Josune; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun ZientziakType 2 diabetes (T2D) is a complex metabolic disease, which involves maintained hyperglycemia, mainly due to the development of an insulin resistance process. Metformin administration is the most prescribed treatment for diabetic patients. In a previously published study, we demonstrated that Pediococcus acidilactici pA1c® (pA1c) protects from insulin resistance and body weight gain in HFD-induced diabetic mice. The present work aimed to evaluate the possible beneficial impact of a 16-week administration of pA1c, metformin, or the combination of pA1c and metformin in a T2D HFD-induced mice model. We found that the simultaneous administration of both products attenuated hyperglycemia, increased high-intensity insulin-positive areas in the pancreas and HOMA-β, decreased HOMA-IR and also provided more beneficial effects than metformin treatment (regarding HOMA-IR, serum C-peptide level, liver steatosis or hepatic Fasn expression), and pA1c treatment (regarding body weight or hepatic G6pase expression). The three treatments had a significant impact on fecal microbiota and led to differential composition of commensal bacterial populations. In conclusion, our findings suggest that P. acidilactici pA1c® administration improved metformin beneficial effects as a T2D treatment, and it would be a valuable therapeutic strategy to treat T2D.Publication Open Access Whole exome sequencing characterization of individuals presenting extreme phenotypes of high and low risk of developing tobacco-induced lung adenocarcinoma(AME Publishing, 2021) Patiño García, Ana; Guruceaga, Elizabeth; Segura, Víctor; Sánchez Bayona, Rodrigo; Andueza, María Pilar; Tamayo Uria, Ibon; Serrano, Guillermo; Fusco, Juan Pablo; Pajares Villandiego, María Josefa; Gúrpide, Alfonso; Ocón, Marimar; Sanmamed, Miguel F.; Rodríguez Ruiz, María; Melero, Ignacio; Lozano, María Dolores; Andrea, Carlos de; Pita, Guillermo; González Neira, Anna; González, Alvaro; Zulueta, Javier J.; Montuenga, Luis M.; Pío, Rubén; Pérez Gracia, José Luis; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako GobernuaBackground: tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop lung cancer at advanced ages while others develop it at young ages. Here, we assess for the first time the genetic background of these clinically relevant extreme phenotypes using whole exome sequencing (WES). Methods: we performed WES of germline DNA from heavy smokers who either developed lung adenocarcinoma at an early age ( extreme cases, n=50) or did not present lung adenocarcinoma or other tumors at an advanced age (extreme controls, n=50). We selected non-synonymous variants located in exonic regions and consensus splice sites of the genes that showed significantly different allelic frequencies between both cohorts. We validated our results in all the additional extreme cases (i.e., heavy smokers who developed lung adenocarcinoma at an early age) available from The Cancer Genome Atlas (TCGA). Results: the mean age for the extreme cases and controls was respectively 49.7 and 77.5 years. Mean tobacco consumption was 43.6 and 56.8 pack-years. We identified 619 significantly different variants between both cohorts, and we validated 108 of these in extreme cases selected from TCGA. Nine validated variants, located in relevant cancer related genes, such as PARP4, HLA-A or NQO1, among others, achieved statistical significance in the False Discovery Rate test. The most significant validated variant (P=4.48x10(-5)) was located in the tumor-suppressor gene ALPK2. Conclusions: we describe genetic variants associated with extreme phenotypes of high and low risk for the development of tobacco-induced lung adenocarcinoma. Our results and our strategy may help to identify high-risk subjects and to develop new therapeutic strategies.