Del espiritu de las leyes

Pie de imp. del vol. III: Madrid, en la Imprenta de doña Rosa Sanz.Retrato de Montesquieu en p. II del vol. I: "Aº Guerrero dibº", "Esteban Boix grabó

Hydroxytyrosyl punicate: A first overview of a novel phenolipid with antiproliferative and antitrypanosomal activity

Polyunsaturated fatty acids and phenolic compounds are two families of natural products that have been widely investigated for their health benefits. The aim of this study was to prepare the novel phenolipid hydroxytyrosyl punicate (HT-PA) and evaluate its antiproliferative and antiparasitic properties. HT-PA was synthesized from hydroxytyrosol (HT) and punicic acid (PA) in a two-step chemical synthesis. HT-PA had an EC50 of 8.93 µM against non–small cell lung carcinoma A549 cells and was more active than HT or PA. It achieved a selectivity index of 11.20 for tumor cell line A549 over non-tumor cell line MCR-5. HT-PA displayed 80-fold and 60-fold greater activity against Trypanosoma brucei parasites (EC50 of 0.95 µM) compared with HT and PA, respectively, and > 100-fold selectivity for T. brucei over healthy MRC-5 cells

Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial

[EN]Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235

Nuclear translocation of glutaminase GLS2 in human cancer cells associates with proliferation arrest and differentiation

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase

Proyecto AMBERIA (CGL2014-52163): avance de resultados

Bienal de la Real Sociedad de Historia Natural (22º. 2017. Coimbra)En la XXI Bienal de la Real Sociedad Española de Historia Natural celebrada en Burgos en el año 2015, se expuso una presentación del proyecto AMBERIA: “El ámbar de Iberia: un excepcional registro de los bosques cretácicos en los albores de los ecosistemas terrestres modernos”, subvencionado por el MINECO, que acababa de ser concedido. El objetivo de ese trabajo fue exponer las líneas maestras de las investigaciones que se iban a realizar en un tema tan apasionante como son las resinas fósiles con inclusiones biológicas del Cretácico Inferior (Albiense superior, alrededor de 105 Ma). Ahora el objetivo del presente trabajo es dar a conocer algunos de los resultados más interesantes que hemos obtenido durante el desarrollo de este proyecto.Departamento de Biología, Universidad Autónoma de Madrid, EspañaMuseo Geominero, Instituto Geológico y Minero de España, EspañaDepartamento de Zoología y Antropología Física, Universidad Complutense de Madrid, EspañaDepartament de Dinàmica de la Terra i de l’Oceà and Institut de Recerca de la Biodiversitat, Universitat de Barcelona, EspañaMuseo de Prehistoria y Arqueología de Cantabria, EspañaMuseum of Comparative Zoology, Harvard University, Estados UnidosDepartament Ciències Agràries i del Medi Natural, Universitat Jaume I, EspañaUniversidad Nebrija, EspañaInstitut de Ciència i Tecnologia ambientals, Universitat Autònoma de Barcelona, EspañaPeer reviewe

Occupational exposure to pesticides and endometrial cancer in the Screenwide case-control study

Background: Endometrial cancer is the most common gynaecological tumour in developed countries and disease burden is expected to increase over the years. Identifying modifiable risk factors may help developing strategies to reduce the expected increasing incidence of these neoplasms. Objective: This study evaluates the association between occupational exposure to pesticides and endometrial cancer using data from a recent case-control study in Spain. Methods: The analyses included data from 174 consecutive incident endometrial cancer cases and 216 hospital controls frequency-matched by age. Data were collected through structured epidemiological questionnaires and exposure to pesticides was assessed using a Spanish job-exposure matrix (MatEmESp). Results: Overall, 12% of controls and 18% of cases were occupationally exposed to pesticides. We observed a positive association between occupational exposure to pesticides and endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88 compared to non-exposed). In general, exposures that occurred farther in the past were significantly associated with endometrial cancer. Exposure to insecticides, fungicides and herbicides were positively associated with endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88, OR = 4.40; 95% CI = 1.65-13.33, and OR = 5.25; 95% CI = 1.84-17.67, respectively). The agricultural, poultry and livestock activities scenario was associated with endometrial cancer (OR = 4.16; 95% CI = 1.59-12.32), while the cleaning exposure scenario was not (OR = 1.22; 95% CI = 0.55-2.67). Conclusions: Assessment of occupational exposure to pesticides assessed using a Spanish job-exposure matrix revealed a positive association with endometrial cancer. The elucidation of the role of pesticide compounds on endometrial cancer should shed a light on the aetiology of this tumour

La arquitectura y el urbanismo del Campus de la Universidad de Alicante como recurso a[tra]ctivo

Es evidente que uno de los principales recursos con los que cuenta la Universidad de Alicante es su Campus, no solo el de San Vicente del Raspeig sino también y además la constelación de Sedes Universitarias y Estaciones Científicas que lo componen. La calidad de sus edificios, todos ellos dignísimos para el fin al que sirven y algunos sencillamente magníficas obras de arquitectura, tanto las de nueva planta como las históricas que albergan las Sedes; la ordenación ejemplar de sus espacios libres donde la vegetación es, por derecho propio, protagonista indiscutible de un proyecto paisajístico modélico; o las esculturas, placas y homenajes y donaciones, embajadas y mecenazgos que salpican el espacio público dotándolo de identidad y cualificándolo, componen un conjunto notable poseedor de un enorme atractivo para la vida de la comunidad universitaria, para sus visitantes y para sus posibles futuros habitantes (nuevos estudiantes, PDI y PAS). El presente proyecto tiene como objetivo poner en valor todo ese patrimonio mediante su conocimiento y difusión a través de diversos canales que pretenden llegar al mayor público posible desde el rigor de la investigación y el atractivo de la presentación de sus resultados

Infequus: plataforma de enfermedades infecciosas equinas

Desarrollo de la herramienta de formación online Infequus, que ofrecerá a los alumnos y profesionales información actualizada sobre el diagnóstico y control de las enfermedades infecciosas en la especie equina

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients

[Background] Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5′ CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. [Methods] Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). [Results] Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. [Conclusion] Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient’s resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.The study was funded, in part, by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004–00889)

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation