Mejora de una explotación agrícola de 100ha mediante la transformación del método convencional al de la agricultura regenerativa en TM de Bigas i Riells

Upgrading project for a conventional farm to a regenerative agriculture.Projecte de millora d'una explotació agrícola convencional a una agricultura regenerativa.Proyecto de mejora de una explotación agrícola convencional a una agricultura regenerativa.Objectius de Desenvolupament Sostenible::13 - Acció per al ClimaObjectius de Desenvolupament Sostenible::15 - Vida d'Ecosistemes Terrestre

Novel methylselenoesters induce programed cell death via entosis in pancreatic cancer cells

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds

Novel methylselenoesters as antiproliferative agents

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.The authors express their gratitude to the Plan de Investigación de la Universidad de Navarra, PIUNA (Ref 2014-26), “la Caixa” and “CAN” Foundations for financial support for the project. The research leading to these results has also received funding from “la Caixa” Banking Foundation and from the Asociación de Amigos de la Universidad de Navarra, to whom Nuria Díaz-Argelich wishes to expresses her gratitude

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents

In this work, an innovative series of methylselenoesters as methylselenol precursors has been designed, synthesized and evaluated. The chemical characteristics of the carbonyl-selenium bond allow a nucleophilic attack that can render methylselenol, a key molecule in selenium biological activity. The scaffolds were chosen among carboaromatic and heteroaromatic rings with reported antitumoral activity to improve the action of methylselenol and to provide enough chemical variety to modulate the strength of the carbonyl-selenium bond, therefore hindering or facilitating a nucleophilic attack, i.e., by water. The release rate of methylselenol was determined, as well as the cytotoxic activity of the compounds against a panel of cancer cell lines. The leader compounds were further investigated to determine their mechanism of action as entosis inducers, which had not been previously described. In addition, other selenium compounds were evaluated. Methylseleninic acid and selenite were tested in a leukemic cell line to explore their genome-wide epigenetic effect. Furthermore, these compounds were also evaluated as immune regulators in the context of ovarian cancer

Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 &lt; 10 &micro;M at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector &beta;1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds

Design, synthesis and biological evaluation of novel methyl selenoesters as antiproliferative and cytotoxic agents

In this work, an innovative series of methylselenoesters as methylselenol precursors has been designed, synthesized and evaluated. The chemical characteristics of the carbonyl-selenium bond allow a nucleophilic attack that can render methylselenol, a key molecule in selenium biological activity. The scaffolds were chosen among carboaromatic and heteroaromatic rings with reported antitumoral activity to improve the action of methylselenol and to provide enough chemical variety to modulate the strength of the carbonyl-selenium bond, therefore hindering or facilitating a nucleophilic attack, i.e., by water. The release rate of methylselenol was determined, as well as the cytotoxic activity of the compounds against a panel of cancer cell lines. The leader compounds were further investigated to determine their mechanism of action as entosis inducers, which had not been previously described. In addition, other selenium compounds were evaluated. Methylseleninic acid and selenite were tested in a leukemic cell line to explore their genome-wide epigenetic effect. Furthermore, these compounds were also evaluated as immune regulators in the context of ovarian cancer

Novel methylselenoesters induce programed cell death via entosis in pancreatic cancer cells

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds