Colchicine for the primary prevention of cardiovascular events.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the clinical benefit and harms of colchicine as primary prevention of cardiovascular outcomes in the general population.pre-print346 K

New therapeutic uses for old drugs. Are we making the right choices?

In recent years, several important research groups and pharmaceutical companies have opened new projects related to reformulation and patent of the use of old drugs. Further efforts are underway to modify old chemical structures to increase safety, bioavailability and reduce unwanted adverse effects

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology

Importancia de la respuesta inmune celular adaptativa en la infección por SARS-CoV-2

La infección por el virus SARS-CoV-2 afecta la respuesta inmune innata y adaptativa del hospedador. Si la respuesta inmune innata es exacerbada, se produce la tormenta de citocinas afectando la respuesta inmune adaptativa que redunda en una disfunción del sistema inmune. El reconocimiento y eliminación viral más eficiente es por medio de los anticuerpos neutralizantes y la memoria celular adaptativa contra el virus. La memoria celular de linfocitos citotóxicos, de células NK y NKT es trascendental en la eliminación del virus y las células infectadas por éste. A la par, la memoria de células Th1 y B son críticas para la producción de anticuerpos. Sin embargo, la presencia de anticuerpos no define la respuesta celular de memoria efectiva contra el virus. Las vacunas usadas en la actualidad generan una buena respuesta CD4+ y B de memoria, pero no todas generan CD8+ de memoria. Al disminuir la respuesta de memoria CD8+ la posibilidad de manifestaciones clínicas incrementa. En pacientes con comorbilidades o deficiencias en la respuesta de interferón, su memoria CD8+ es menor y por ello son más propensos a desarrollar cuadros clínicos más complejos. Se concluye que el papel de la memoria inmunológica CD8+ es clave para la eliminación del virus SARS-CoV-2

Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs

Cellular senescence is defined as irreversible cell cycle arrest caused by various processes that render viable cells non-functional, hampering normal tissue homeostasis. It has many endogenous and exogenous inducers, and is closely connected with age, age-related pathologies, DNA damage, degenerative disorders, tumor suppression and activation, wound healing, and tissue repair. However, the literature is replete with contradictory findings concerning its triggering mechanisms, specific biomarkers, and detection protocols. This may be partly due to the wide range of cellular and in vivo animal or human models of accelerated aging that have been used to study senescence and test senolytic drugs. This review summarizes recent findings concerning senescence, presents some widely used cellular and animal senescence models, and briefly describes the best-known senolytic agents

LAS ESTATINAS AFECTAN LA VIABILIDAD DE LÍNEAS CELULARES DE LEUCEMIA Y LINFOMA HUMANAS IN VITRO

Se ha propuesto que las estatinas inducen apoptosis sobre células tumorales. Para probar dicha hipótesis, seanalizó el efecto de las estatinas atorvastatina, fluvastatina, lovastatina, mevastatina, pravastatina y simvastatina en el rangode concentraciones de 1 pM hasta 100 μM, sobre la viabilidad de las líneas celulares humanas Jurkat E6.1, Jurkat D1.1(Linfoma T) , Daudi (Linfoma B), U937 (leucemia monocítica) y HL-60 (leucemia promielomonocítica) in vitro en cultivos de48 horas, analizados por la técnica de hidrolización del compuesto bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difenilltetrazolio(MTT). Lovastatina y mevastatina son los más potentes inductores de muerte celular independientemente del tipo celular (Ic50 entre 12 y 50 μM). Para las otras estatinas se observan diferencias en el Ic50 según la línea celular atorvastatina (38,1y 48,6 μM Jurkats, 55,3 μM Daudi y 100 μM para las otras líneas), pravastatina (25 μM HL-60, 55,6 y 60,7 μM Jurkats y >100 μM Daudi y U937), simvastatina (25,1 μM Jurkat D1.1, 50,2 μM Jurkat E6.1, 45,2 μM Daudi y 51,3 μM HL-60, y > 100μM U937) y para fluvastatina en todos los casos > 100 μM. La disminución de la viabilidad celular se revierte completamentecuando las células son incubadas con 10 μM mevalonato. Se concluye que la lovastatina y mevastatina son las más potentesinductoras de muerte seguida por atorvastatina, pravastatina y simvastatina cuyo efecto depende del tipo de línea celular y lafluvastatina no tiene efectos importantes en la viabilidad de las líneas celulares estudiadas.ABSTRACT: Statins have been proposed to induce apoptosis of tumor cells. In order to test this hypothesis, the effect ofatorvastatin, fluvastatin, lovastatin, mevastatin, pravastatin, simvastatin on cell viability was assessed by in vitro culture for48 hr, at concentrations ranging from 1 pM to 100 μM on human cell lines Jurkat E6.1, Jurkat D1.1 (T cell lymphoma), Daudi(B cell lymphoma), U937 (monocitic leukemia) and HL-60 (pro mielomonocitic leukemia) and analyzed the oxidation of(3-(4.5-Dimethylthiazol-2-yl)-2.5- diphenyltetrazolium bromide (MTT). Lovastatin and mevastatin are the most potent inductors ofcell death independently of the cell type (Ic 50 between 12 and 50 μM). Differences in the Ic50 are observed depending on thecell line: atorvastatina (38.1 and 48.6 μM Jurkats, 55.3 μM Daudi y 100 μM for the others lines), pravastatin (25 μM HL-60,55.6 y 60.7 μM Jurkats and > 100 μM Daudi and U937), simvastatin (25.1 μM Jurkat D1.1, 50.2 μM Jurkat E6.1, 45.2 μMDaudi and 51,3 μM HL-60, and > 100 μM U937) and for fluvastatin > 100 μM in all cases. The decrease in cell viability isreverted completely when the cells were incubated with 10 μM mevalonate. It is concluded that lovastatin and mevastatin arethe most potent inductors of cell death followed by atorvastatin, pravastatin and simvastatin whose effect depends upon thecell type and fluvastatin does not have any important effects on cell viability on the cell lines studied

Overview of Memory NK Cells in Viral Infections: Possible Role in SARS-CoV-2 Infection

NK cells have usually been defined as cells of the innate immune system, although they are also involved in adaptative responses. These cells belong to the innate lymphocyte cells (ILC) family. They remove unwanted cells, tumoral cells and pathogens. NK cells are essential for viral infection clearance and are involved in tolerogenic responses depending on the dynamic balance of the repertoire of activating and inhibitory receptors. NK plasticity is crucial for tissue function and vigilant immune responses. They directly eliminate virus-infected cells by recognising viral protein antigens using a non-MHC dependent mechanism, recognising viral glycan structures and antigens by NCR family receptors, inducing apoptosis by Fas-Fas ligand interaction, and killing cells by antibody-dependent cell cytotoxicity via the FcγIII receptor. Activating receptors are responsible for the clearance of virally infected cells, while inhibitory KIR receptor activation impairs NK responses and facilitates virus escape. Effective NK memory cells have been described and characterised by a low NKG2A and high NKG2C or NKG2D expression. NK cells have also been used in cell therapy. In SARS-CoV-2 infection, several contradicting reports about the role of NK cells have been published. A careful analysis of the current data and possible implications will be discussed

Overview of Memory NK Cells in Viral Infections: Possible Role in SARS-CoV-2 Infection

NK cells have usually been defined as cells of the innate immune system, although they are also involved in adaptative responses. These cells belong to the innate lymphocyte cells (ILC) family. They remove unwanted cells, tumoral cells and pathogens. NK cells are essential for viral infection clearance and are involved in tolerogenic responses depending on the dynamic balance of the repertoire of activating and inhibitory receptors. NK plasticity is crucial for tissue function and vigilant immune responses. They directly eliminate virus-infected cells by recognising viral protein antigens using a non-MHC dependent mechanism, recognising viral glycan structures and antigens by NCR family receptors, inducing apoptosis by Fas-Fas ligand interaction, and killing cells by antibody-dependent cell cytotoxicity via the FcγIII receptor. Activating receptors are responsible for the clearance of virally infected cells, while inhibitory KIR receptor activation impairs NK responses and facilitates virus escape. Effective NK memory cells have been described and characterised by a low NKG2A and high NKG2C or NKG2D expression. NK cells have also been used in cell therapy. In SARS-CoV-2 infection, several contradicting reports about the role of NK cells have been published. A careful analysis of the current data and possible implications will be discussed