8-oxoguanine DNA glycosylase 1 upregulation as a risk factor for obesity and colorectal cancer

DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)—a DNA repair enzyme—may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.Partial funding for open access charge: Universidad de Málag

Oligodendrocyte metabolism throughout its differentiation: immunocytochemistry study and its impact in remyelination

Introduction: Oligodendrocytes (OL) role in demyelinating pathologies such as multiple sclerosis and other neurodegenerative diseases is only recently being subject of extensive research. While the genetic and molecular aspects have been thoroughly studied, their metabolism was overshadowed. In order to develop new therapies to promote remyelination of already damaged axons, we need to accurately describe how OL metabolism affects axon myelination and trophic support (1). The objective of this study is to obtain cytological evidence of the extent of both glycolytic metabolism and oxidative phosphorylation by immunocytochemistry throughout the development of OL. Methods: Oligodendroglia cells from post-natal mice cortices were obtained and cultured. A wide assortment of differentiation-stage-specific cell surface antigens, a glycolytic and an oxidative phosphorylation marker were combined in several immunofluorescences to study both metabolic pathways in each step of differentiation. Results: After analysing them under confocal microscopy and imaging software, we observed a constant upregulation of glycolytic metabolism throughout differentiation, while oxidative phosphorylation seemed to increase with differentiation to then decrease when oligodendrocytes achieved their final maturation stage. Conclusions: Therefore, oxidative phosphorylation may be crucial in the differentiation of precursors and glycolysis would thus be the preferred metabolic pathway for fully matured OL. [1] Rosko L. et al. Neuroscientist. 2019;25(4):334–43.Supported by UMA and IBIMA and funding from two ongoing projects: - ‘Modulation of oligodendrocyte metabolism via blood vessel remodelling as target to promote remyelination’ (funding by NEURATRIS). - ‘Blood vessel remodelling modulates remyelination by oligodendrocyte metabolic reprogramming’ (funding by Arsep Foundation). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Gastrointestinal Stromal Tumor (GIST) and its relationship with germline mutations

We present the case of a 38-year-old man with a history of abdominal paraganglioma 10 years ago, who consulted for hematemesis and asthenia of 5 days' evolution. An upper gastrointestinal endoscopy was performed where a raised submucosal lesion, about 2 cm, with ulceration on its surface, was observed at the corporal-antral junction. The CT scan revealed nodular thickening of the gastric wall at the level of the lesser curvature. After the resolution of his hematemesis, it was decided to intervene on the patient, performing a partial gastrectomyUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Gastrointestinal cancer: Relationship between histology and microbiota

Este trabajo fue presentado como comunicación tipo póster en el citado congreso.Objectives: Review of the published literature concerning the relationship between microbiome and gastrointestinal cancer. Methods: Present work is focused on systematic research in the most prominent biomedical databases finds relevant works in Pubmed and the library’s catalog of the University of Málaga (Jábega) of published journals in the last 5 years. Results: In this work, the mechanisms used by the microbiome to damage gastrointestinal epithelial cells and cause cancer are explained. Some of them are the dysbiosis, destruction of the mucosal barrier, chronic inflammation, damage caused by metabolites produced in the digestion and the direct attack of certain toxins to the cell’s DNA. These mechanisms adjust the immune response, by activation or inhibition using different cytokines. There is also a deeper look into several microorganisms and how they cause gastrointestinal cancer using toxins or virulence factors to activate them. Conclusions: The evidence found so far about the microbiota and gastrointestinal cancer is enough to assume the relationship between them, although there is much left to research. With these findings, it can be expected that in a near future certain microorganisms could be used for screening purposes, due to their increase in early stages of the tumor genesis and also, in a preventive way to try to eradicate them, even avoid cancer. Studies on the microbiota are hardly beginning, and results appear to be promising.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial

Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting onequarter of the world"s adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk. Methods and results: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of 1.9 mm Hg [95% confidence interval (CI): 3.4; 0.6] and 2.6 mm Hg (CI: 4.2; 1.0), respectively, and reduced diastolic BP of 1.5 mm Hg (CI: 2.3; 0.6) and 1.9 mm Hg (CI: 2.8; 1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR Z 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR Z 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group. Conclusions: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe

Evaluación del perfil competencial del estudiantado UCM por nivel de iniciativa emprendedora y género. Validación del Modelo Entrecomp de competencias emprendedoras

Examinar la relación entre las competencias emprendedoras propuestas por el Marco Europeo de Competencias Emprendedoras (Entrecomp) y el nivel de intención emprendedora. Se consideran las siguientes variables: sexo, estudios que realiza, si compagina trabajo y estudio, y Universidad en la que estudia

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Her2-Positive and Microsatellite Instability Status in Gastric Cancer-Clinicopathological Implications.

Gastric cancer (GC) is one of the leading causes of cancer-related death. The combination of new molecular classifications with clinicopathological data could contribute to the individualization of patients and to the development of new therapeutic strategies. We examined the various associations in two molecular types of GC: HER2-positive (human epidermal growth factor receptor 2) and microsatellite instability (MSI), assessing their influence on treatment and prognosis. A retrospective study of 142 GC patients was performed with molecular characterization through HER2 overexpression and DNA repair protein expression for MSI. The percentage of HER2-positive tumors was 13.4%, predominantly in men. Correlations were found with intestinal type, metastases, advanced stages and chemotherapy. Almost 75% of HER2-positive patients died. MSI occurred in 16.2%, associated with advanced age, female sex, distal location and intestinal type. These patients had few metastases and low stages. The percentage of deaths was higher among MSI patients who received perioperative chemotherapy. The determination of HER2 and MSI status in GC is important for their association with specific clinicopathological features and for their prognostic and predictive value