Inhibidores del factor prometastásico snail-1

La presente invención se refiere al uso de inhibidores del factor prometastásico snail-1 para la elaboración de un medicamento para el tratamiento de la metástasis pulmonar.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Fundació IMIMA1 Solicitud de patente con informe sobre el estado de la técnic

From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players

It is estimated that 25% of the world’s population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC.We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota

Care in puerperium during health crisis due to COVID-19

Introducción: la infección por el nuevo coronavirus COVID-19, es actualmente una emergencia de salud pública internacional y ha sido declarada pandemia por la OMS. Aún se desconocen ciertos datos sobre su etiopatogenia, surgiendo la necesidad de analizar la influencia de la enfermedad por coronavirus durante la etapa puerperal y sus consecuencias. Objetivo: sintetizar el conocimiento y las últimas recomendaciones disponibles acerca de los cuidados específicos durante el periodo del puerperio, en relación con la crisis sanitaria por COVID-19. Metodología: se llevó a cabo una búsqueda sistemática en la literatura científica para localizar los documentos de evidencia científica disponibles en las principales bases de datos referenciales: Pubmed, Biblioteca Cochrane y Science Direct. Resultados: la lactancia materna aporta numerosos beneficios al recién nacido, entre ellos, la protección frente a infecciones respiratorias como el coronavirus. Si el estado materno y neonatal lo permite, se recomienda promover la lactancia materna durante el periodo de riesgo infeccioso. La SEGO y la SETH recomiendan la administración de heparina de bajo peso molecular a dosis profilácticas para evitar la enfermedad tromboembólica. La evidencia actual indica que el riesgo de transmisión a través de la lactancia materna al recién nacido es muy poco probable. Discusión/conclusiones: la limitación principal fue la escasez de literatura científica sobre el COVID-19 en relación con el periodo puerperal. Es fundamental que cualquier puérpera con una infección por COVID-19 y su recién nacido sean valorados de manera individualizada, precozmente y evaluada por un equipo multidisciplinar para prevenir resultados adversos.Introduction: the new coronavirus COVID-19 infection is currently an international public health emergency and it has been declared a pandemic by the WHO. Certain data about its etiopathogenesis is still unknown, arising the need to analyse the influence of coronavirus disease during the puerperal stage and its consequences. Objective: to synthesize the knowledge and the latest available recommendations about specific care during puerperium period, related to the health crisis due to COVID-19. Methodology: a systematic search was carried out in the scientific literature in order to locate the scientific evidence documents available in the main reference databases: PubMed, Cochrane Library and Science Direct. Results: breastfeeding brings many benefits to newborns, including protection against respiratory infections, such as coronavirus. If maternal and neonatal status allows it, it is recommended promoting breastfeeding during the infectious risk period. Both SEGO and SETH recommend the administration of low molecular weight heparin at prophylactic doses in order to avoid thromboembolic disease. Discussion/conclusions: the main limitation was the paucity of scientific literature about COVID-19 in relation to puerperal period. It is essential that any puerperal woman with COVID-19 infection and her newborn are assessed individually, early and evaluated by a multidisciplinary team to prevent adverse outcomes

Decreased incidence of pressure ulcers in intensive care: a program goal of improving care

INTRODUCCIÓN. En sanidad, la aparición de úlceras por presión (upp), es considerado un fracaso asistencial y un gran reto al que se enfrenta el profesional de Enfermería. En cuidados intensivos, objetivamos una serie de factores que aumentan el riesgo de aparición y desarrollo de upp. Como enfermeros, tomamos conciencia de nuestro papel en la prevención y tratamiento de las upp en nuestra unidad de cuidados intensivos (UCI-1, Hospital Universitario Central de Asturias) y emprendimos medidas para disminuirlas y mejorar la calidad asistencial proporcionada. OBJETIVOS. Aumentar la calidad asistencial Disminuir las tasas de úlceras por presión MATERIAL Y MÉTODO. Estudio descriptivo, prospectivo. Muestra, N: 1265 enfermos. Realizándose seguimiento diario de enfermos a través de hoja de valoración específica. Los enfermos valorados presentaban riesgo medio- alto de padecer upp por escala Braden y riesgo bajo por dicha escala pero con condiciones particulares de riesgo objetivables. Se introducen medidas preventivas consensuadas por el equipo investigador (descritas en el trabajo de investigación). RESULTADOS. Bajada significativa de las tasas de incidencia a los cuatro meses de introducir medidas estandarizadas de prevención y mejora asistencial. CONCLUSIONES. La concienciación y unificación de criterios preventivos y de tratamiento resultó ser decisiva en la bajada significativa de la incidencia de upp y en el logro de aumento de la calidad asistencial real percibida por todo el equipo interdisciplinar.INTRODUCTION. In health, the occurrence of pressure ulcers (PU) is considered a failure of care and major challenge facing the nursing professional. In intensive care, objectify a series of factors that increase the risk of occurrence and development of PU. As nurses, we realize our role in the prevention and treatment of pressure ulcers in our intensive care unit (ICU-1, Hospital Universitario Central de Asturias) and we took measures to reduce and improve quality of care provided. OBJECTIVES. To augment quality of care To diminish rates of pressure ulcers MATERIALS AND METHODS. Prospective descriptive study. Sample, n = 1265 patients. Performing daily monitoring of patients through specific assessment sheet. The patients had rated medium-high risk of developing upp by Braden scale and low risk for this scale but with risk conditions to measure. Agreed preventive measures are introduced by the research team (described in the research). RESULTS. Llower incidence rates for four months to introduce standardized measures of prevention and improved care. CONCLUSIONS. The unification of awareness and prevention and treatment criteria proved to be instrumental in the significant decline in the incidence of PU and the achievement of increased quality of care received by all real interdisciplinary team

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer’s disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.P20-01293 from Junta de Andalucía, SpainP20-01061 from Junta de Andalucía, SpainPID2019-110960GB-I00 from the Ministry of Science and Innovation, Spai

Pseudomonas pseudoalcaligenes CECT5344, a cyanide‑degrading bacterium with by‑product (polyhydroxyalkanoates) formation capacity

Background: Cyanide is one of the most toxic chemicals produced by anthropogenic activities like mining and jewelry industries, which generate wastewater residues with high concentrations of this compound. Pseudomonas pseudoalcaligenes CECT5344 is a model microorganism to be used in detoxification of industrial wastewaters containing not only free cyanide (CN−) but also cyano-derivatives, such as cyanate, nitriles and metal-cyanide complexes. Previous in silico analyses suggested the existence of genes putatively involved in metabolism of short chain length (scl-) and medium chain length (mcl-) polyhydroxyalkanoates (PHAs) located in three different clusters in the genome of this bacterium. PHAs are polyesters considered as an alternative of petroleum-based plastics. Strategies to optimize the bioremediation process in terms of reducing the cost of the production medium are required. Results: In this work, a biological treatment of the jewelry industry cyanide-rich wastewater coupled to PHAs production as by-product has been considered. The functionality of the pha genes from P. pseudoalcaligenes CECT5344 has been demonstrated. Mutant strains defective in each proposed PHA synthases coding genes (Mpha−, deleted in putative mcl-PHA synthases; Spha−, deleted in the putative scl-PHA synthase) were generated. The accumulation and monomer composition of scl- or mcl-PHAs in wild type and mutant strains were confirmed by gas chromatographymass spectrometry (GC–MS). The production of PHAs as by-product while degrading cyanide from the jewelry industry wastewater was analyzed in batch reactor in each strain. The wild type and the mutant strains grew at similar rates when using octanoate as the carbon source and cyanide as the sole nitrogen source. When cyanide was depleted from the medium, both scl-PHAs and mcl-PHAs were detected in the wild-type strain, whereas scl-PHAs or mcl-PHAs were accumulated in Mpha− and Spha−, respectively. The scl-PHAs were identified as homopolymers of 3-hydroxybutyrate and the mcl-PHAs were composed of 3-hydroxyoctanoate and 3-hydroxyhexanoate monomers. Conclusions: These results demonstrated, as proof of concept, that talented strains such as P. pseudoalcaligenes might be applied in bioremediation of industrial residues containing cyanide, while concomitantly generate by-products like polyhydroxyalkanoates. A customized optimization of the target bioremediation process is required to gain benefits of this type of approaches

Coffee consumption increases the antioxidant capacity of plasma and has no effect on the lipid profile or vascular function in healthy adults in a randomized controlled trial

ABSTRACT: Coffee, a source of antioxidants, has controversial effects on cardiovascular health. Objective: We evaluated the bioavailability of chlorogenic acids (CGAs) in 2 coffees and the effects of their consumption on the plasma antioxidant capacity (AC), the serum lipid profile, and the vascular function in healthy adults. Methods: Thirty-eight men and 37 women with a mean 6 SD age of 38.5 6 9 y and body mass index of 24.1 6 2.6 kg/m2 were randomly assigned to 3 groups: a control group that did not consume coffee or a placebo and 2 groups that consumed 400 mL coffee/d for 8 wk containing a medium (MCCGA; 420 mg) or high (HCCGA; 780 mg) CGA content. Both were low in diterpenes (0.83 mg/d) and caffeine (193 mg/d). Plasma caffeic and ferulic acid concentrations were measured by GC, and the plasma AC was evaluated with use of the ferric-reducing antioxidant power method. The serum lipid profile, nitric oxide (NO) plasma metabolites, vascular endothelial function (flow-mediated dilation; FMD), and blood pressure (BP) were evaluated.Results: After coffee consumption (1 h and 8 wk), caffeic and ferulic acid concentrations increased in the coffee-drinking groups, although the values of the 2 groups were significantly different (P < 0.001); caffeic and ferulic acid concentrations were undetectable in the control group. At 1 h after consumption, the plasma AC in the control group was significantly lower than the baseline value (22%) and significantly increased in the MCCGA (6%) and HCCGA (5%) groups (P < 0.05). After 8 wk, no significant differences in the lipid, FMD, BP, or NO plasma metabolite values were observed between the groups. Conclusions: Both coffees, which contained CGAs and were low in diterpenes and caffeine, provided bioavailable CGAs and had a positive acute effect on the plasma AC in healthy adults and no effect on blood lipids or vascular function. The group that did not drink coffee showed no improvement in serum lipid profile, FMD, BP, or NO plasma metabolites. This trial was registered at registroclinico.sld.cu as RPCEC00000168

Multi‑omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma

PPM's lab is funded by the Ministry of Economy of Spain (SAF2015-67919-R), Junta de Andalucia (P20-00688, PI-0135-2020, PIGE-0213-2020, PIGE-04402019, PI-0245-2017), University of Granada (B-CTS-480-UGR20), International Association for the Study of Lung Cancer (IASLC), and Spanish Association for Cancer Research (LAB-AECC-2018). PP is supported by a PhD "La Caixa Foundation"LCF/BQ/DE15/10360019 Fellowship. AA is supported by an FPU17/00067 fellowship. IFC was supported by a PhD FPI-fellowship (BES-2013-064596). DJG was supported by a "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier"predoctoral fellowship. MSBC and CC's work is supported by the project DPI2017-84439-R Ministry of Economy of Spain and FEDER and by the fellowship "Beca de Iniciacion a la Investigacion del Plan Propio de Investigacion 2019" by University of Granada. MSBC is supported by an FPU19/00576 predoctoral fellowship. CNIO Proteomics Unit is a member of Proteored PRB3 and is supported by grant PT17/0019, of the PE I + D + i 2013-2016, funded by ISCIII and ERDF.SWI/SNF complexes are major targets of mutations in cancer. Here, we combined multiple “-omics” methods to assess SWI/SNF composition and aberrations in LUAD. Mutations in lung SWI/SNF subunits were highly recurrent in our LUAD cohort (41.4%), and over 70% of the mutations were predicted to have functional impact. Furthermore, SWI/ SNF expression in LUAD suffered an overall repression that could not be explained exclusively by genetic alterations. Finally, SWI/SNF mutations were associated with poorer overall survival in TCGA-LUAD. We propose SWI/SNF-mutant LUAD as a separate clinical subgroup with practical implications.Spanish Government SAF2015-67919-R DPI2017-84439-RJunta de Andalucia P20-00688 PI-0135-2020 PIGE-0213-2020 PIGE-0440-2019 PI-0245-2017University of Granada B-CTS-480-UGR20International Association for the Study of Lung Cancer (IASLC)Spanish Association for Cancer Research LAB-AECC-2018La Caixa Foundation LCF/BQ/DE15/10360019PhD FPI-fellowship BES-2013-064596"Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowshipEuropean Commissionfellowship "Beca de Iniciacion a la Investigacion del Plan Propio de Investigacion 2019" by University of Granada Instituto de Salud Carlos III PT17/0019European Commission PT17/0019 FPU17/00067 FPU19/0057

BCL7A is silenced by hypermethylation to promote acute myeloid leukemia

The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s40364‑ 023‑ 00472‑x. Additional file 1: Supplementary Figure 1. Diagram displaying CpG‑ methylation status around the BCL7A TSS. Genomic DNA from the NB4 cell line was subjected to bisulfite conversion and used for subsequent TA‑ cloning. Supplementary Figure 2. Schematic representation of the differ‑ ent lentiviral plasmids used in the experimental procedures. The specific region of the long isoform of BCL7A is colored in blue. Supplementary Figure 3. Western blot including the Decitabine (DAC) treatment over the NB4 cell line shown in Fig. 2c. Supplementary Figure 4. Protein‑protein interactions between BCL7A and SMARCA4 as determined by Mashtalir et al (2020). Supplementary Figure 5. DepMap AML cell lines collection data showing BCL7A Methylation Fraction (1kb upstream TSS) vs BCL7Aex‑ pression level. NB4 and M07e are marked. Supplementary Figure 6. Competition cell growth effect of BCL7A expression restoration on in vitro proliferation. Supplementary Table 1. Additional file 2: Supplementary Table 2. Differential expression analysis resultsP.P.M.’s laboratory is funded by Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía and FEDER (P20‑00688), Aula de Investigación sobre la Leucemia infantil: Heroes contra la Leucemia, the Ministry of Science and Innovation of Spain (grant PID2021‑126111OB‑I00), Junta de Andalucía (grants PIGE‑0440–2019, PI‑0135–2020), the University of Granada (grants B‑CTS‑126‑UGR18, B‑CTS‑480‑UGR20, and E‑CTS‑304‑UGR20), and the Spanish Association for Cancer Research (LABORATORY‑AECC‑2018). J.R.P‑M, A.A, and M.S.B‑C were supported by fellowships FPU18/03709, FPU17/00067, and FPU19/00576 respectively funded by the Spanish Ministry of Science, Innovation and UniversitiesBackground Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most fre‑ quently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leuke‑ mogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here, we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose role in acute myeloid malignancies is currently unknown. Methods Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the correlation between BCL7A expression and promoter hypermethylation. Methylation‑specific PCR, bisulfite sequenc‑ ing, and 5‑aza‑2’‑deoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth was compared between BCL7A‑expressing and non‑expressing mouse xenografts using in vivo fluorescence imaging. Results BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGA‑LAML (N = 160), TARGET‑AML (N = 188), and Glass et al. (2017) (N = 111). The AML‑derived cell line NB4 silenced the BCL7A expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor sup‑ pressor role in AML. Conclusions BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expres‑ sion exerts tumor suppressor activity in AML cell lines and xenograft models.Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía and FEDER (P20‑00688)Ministry of Science and Innovation of Spain (grant PID2021‑126111OB‑I00)Junta de Andalucía (grants PIGE‑0440–2019, PI‑0135–2020)University of Granada (B‑CTS‑126‑UGR18, B‑CTS‑480‑UGR20, E‑CTS‑304‑UGR20)Spanish Association for Cancer Research (LABORATORY‑AECC‑2018)Spanish Ministry of Science, Innovation and Universities FPU18/03709, FPU17/00067, FPU19/0057