Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy.

Despite not dividing, senescent cells acquire the ability to synthesize and secrete a plethora of bioactive molecules, a feature known as the senescence-associated secretory phenotype (SASP). In addition, senescent cells often upregulate autophagy, a catalytic process that improves cell viability in stress-challenged cells. Notably, this "senescence-related autophagy" can provide free amino acids for the activation of mTORC1 and the synthesis of SASP components. However, little is known about the functional status of mTORC1 in models of senescence induced by CDK4/6 inhibitors (e.g., Palbociclib), or the effects that the inhibition of mTORC1 or the combined inhibition of mTORC1 and autophagy have on senescence and the SASP. Herein, we examined the effects of mTORC1 inhibition, with or without concomitant autophagy inhibition, on Palbociclib-driven senescent AGS and MCF-7 cells. We also assessed the pro-tumorigenic effects of conditioned media from Palbociclib-driven senescent cells with the inhibition of mTORC1, or with the combined inhibition of mTORC1 and autophagy. We found that Palbociclib-driven senescent cells display a partially reduced activity of mTORC1 accompanied by increased levels of autophagy. Interestingly, further mTORC1 inhibition exacerbated the senescent phenotype, a phenomenon that was reversed upon autophagy inhibition. Finally, the SASP varied upon inhibiting mTORC1, or upon the combined inhibition of mTORC1 and autophagy, generating diverse responses in cell proliferation, invasion, and migration of non-senescent tumorigenic cells. Overall, variations in the SASP of Palbociclib-driven senescent cells with the concomitant inhibition of mTORC1 seem to depend on autophagy.

Efecto de extractos de frutas y hortalizas en la incorporación de glucosa en células musculares in vitro / Effect of fruit and vegetable extracts on the incorporation of glucose in muscle cells "in vitro"

Skeletal muscle appears to play a central role in the development of insulin resistance (IR) and consequently the metabolic syndrome due to high-fat diets, obesity, and aging. Recent evidence suggests that some bioactive compounds present in natural products can affect blood glucose, possibly due to interactions between the compounds and glucose transporters. As an objective, to evaluate the effect of the extract of the green bean (PV, Phaseolus vulgaris) and apple of small fruit of thinning (Malus domestica, MAF and MIT extracts) on the incorporation of glucose in C2C12 muscle cells. For this, the cytotoxic effect of the extracts on the cells was determined by detecting formazan. Subsequently, glucose incorporation was determined using a fluorescent glucose analog in cells treated with the extracts. Finally, the effect of the extracts on IL-6 and TNFα production was evaluated by ELISA. Results: PV and MAF decreased 50% of viability at 1000µg / mL while MIT only decreased 10% at that concentration. PV had no significant effect on glucose incorporation and the MAF and MIT extract extracts significantly increased glucose incorporation at 100 µg / mL (13500 and 18000 URF respectively). PV increases the secretion of IL-6 and TNF-α, MAF and MIT only increase the expression of IL-6. Conclusion: These results make it possible to establish natural extracts derived from thinning small fruit apple can be used as a possible treatment for pathologies with high blood glucose levels.

mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership.

Cellular senescence is a form of proliferative arrest triggered in response to a wide variety of stimuli and characterized by unique changes in cell morphology and function. Although unable to divide, senescent cells remain metabolically active and acquire the ability to produce and secrete bioactive molecules, some of which have recognized pro-inflammatory and/or pro-tumorigenic actions. As expected, this "senescence-associated secretory phenotype (SASP)" accounts for most of the non-cell-autonomous effects of senescent cells, which can be beneficial or detrimental for tissue homeostasis, depending on the context. It is now evident that many features linked to cellular senescence, including the SASP, reflect complex changes in the activities of mTOR and other metabolic pathways. Indeed, the available evidence indicates that mTOR-dependent signaling is required for the maintenance or implementation of different aspects of cellular senescence. Thus, depending on the cell type and biological context, inhibiting mTOR in cells undergoing senescence can reverse senescence, induce quiescence or cell death, or exacerbate some features of senescent cells while inhibiting others. Interestingly, autophagy-a highly regulated catabolic process-is also commonly upregulated in senescent cells. As mTOR activation leads to repression of autophagy in non-senescent cells (mTOR as an upstream regulator of autophagy), the upregulation of autophagy observed in senescent cells must take place in an mTOR-independent manner. Notably, there is evidence that autophagy provides free amino acids that feed the mTOR complex 1 (mTORC1), which in turn is required to initiate the synthesis of SASP components. Therefore, mTOR activation can follow the induction of autophagy in senescent cells (mTOR as a downstream effector of autophagy). These functional connections suggest the existence of autophagy regulatory pathways in senescent cells that differ from those activated in non-senescence contexts. We envision that untangling these functional connections will be key for the generation of combinatorial anti-cancer therapies involving pro-senescence drugs, mTOR inhibitors, and/or autophagy inhibitors.

Gestational diabesity and foetoplacental vascular dysfunction.

Gestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D-glucose and other nutrients, thereby negatively affecting the foetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre-pregnancy normal weight, viz. classic GDM. However, women with GDM and prepregnancy obesity (gestational diabesity, GDty) or overweight (GDMow) show a different metabolic status than women with classic GDM. GDty and GDMow are associated with altered l-arginine/nitric oxide and insulin/adenosine axis signalling in the human foetoplacental microvascular and macrovascular endothelium. These alterations differ from those observed in classic GDM. Here, we have reviewed the consequences of GDty and GDMow in the modulation of foetoplacental endothelial cell function, highlighting studies describing the modulation of intracellular pH homeostasis and the potential implications of NO generation and adenosine signalling in GDty-associated foetal vascular insulin resistance. Moreover, with an increase in the rate of obesity in women of childbearing age worldwide, the prevalence of GDty is expected to increase in the next decades. Therefore, we emphasize that women with GDty and GDMow should be characterized with a different metabolic state from that of women with classic GDM to develop a more specific therapeutic approach for protecting the mother and foetus.

La Tomasa reduce parámetros metabólicos e inflamatorios asociados a síndrome metabólico en un modelo murino / Tomasa reduces metabolic and inflammatory parameters associated with metabolic syndrome in a murine model

In our country, cardiovascular diseases (CVD) are the main cause of death. Unhealthy eating habits and sedentary lifestyles, among other factors, have contributed to increase the risk for CDV in the population. An alternative to the commonly used pharmacological therapies is the use of validated natural products that can be incorporated in the development of functional foods or supplements. In particular, the tomato has been shown to have a protective role in CVD; its high content of antioxidants, particularly lycopene, provides it with extensively documented beneficial properties. Tomasa, a by-product of the agroindustry, maintains some of the beneficial characteristics of its fruit of origin. Mice fed with a high-fat (hypercaloric) diet increase their body weight and visceral adipose mass, and also display an increase in metabolic and inflammatory parameters. Our results allow us to conclude that the consumption of Tomasa in mice fed a hypercaloric diet reduces the blood levels of cholesterol, glycaemia and pro-inflammatory cytokines. These results support the rationale of using of this by-product in the generation of functional ingredients with proven beneficial effects.

Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro.

Aging is one of the main risk factors for the development of chronic diseases, with both the vascular endothelium and platelets becoming functionally altered. Cellular senescence is a form of permanent cell cycle arrest initially described in primary cells propagated in vitro, although it can also be induced by anticancer drugs and other stressful stimuli. Attesting for the complexity of the senescent phenotype, senescent cells synthesize and secrete a wide variety of bioactive molecules. This "senescence-associated secretory phenotype" (SASP) endows senescent cells with the ability to modify the tissue microenvironment in ways that may be relevant to the development of various physiological and pathological processes. So far, however, the direct role of factors secreted by senescent endothelial cells on platelet function remains unknown. In the present work, we explore the effects of SASP factors derived from senescent endothelial cells on platelet function. To this end, we took advantage of a model in which immortalized endothelial cells (HMEC-1) were induced to senesce following exposure to doxorubicin, a chemotherapeutic drug widely used in the clinic. Our results indicate that (1) low concentrations of doxorubicin induce senescence in HMEC-1 cells; (2) senescent HMEC-1 cells upregulate the expression of selected components of the SASP and (3) the media conditioned by senescent endothelial cells are capable of inducing platelet activation and aggregation. These results suggest that factors secreted by senescent endothelial cells in vivo could have a relevant role in the platelet activation observed in the elderly or in patients undergoing therapeutic stress.

SASP-Dependent Interactions between Senescent Cells and Platelets Modulate Migration and Invasion of Cancer Cells.

Alterations in platelet aggregation are common in aging individuals and in the context of age-related pathologies such as cancer. So far, however, the effects of senescent cells on platelets have not been explored. In addition to serving as a barrier to tumor progression, cellular senescence can contribute to remodeling tissue microenvironments through the capacity of senescent cells to synthesize and secrete a plethora of bioactive factors, a feature referred to as the senescence-associated secretory phenotype (SASP). As senescent cells accumulate in aging tissues, sites of tissue injury, or in response to drugs, SASP factors may contribute to increase platelet activity and, through this mechanism, generate a microenvironment that facilitates cancer progression. Using in vitro models of drug-induced senescence, in which cellular senescence was induced following exposure of mammary epithelial cells (MCF-10A and MCF-7) and gastric cancer cells (AGS) to the CDK4/6 inhibitor Palbociclib, we show that senescent mammary and gastric cells display unique expression profiles of selected SASP factors, most of them being downregulated at the RNA level in senescent AGS cells. In addition, we observed cell-type specific differences in the levels of secreted factors, including IL-1ß, in media conditioned by senescent cells. Interestingly, only media conditioned by senescent MCF-10A and MCF-7 cells were able to enhance platelet aggregation, although all three types of senescent cells were able to attract platelets in vitro. Nevertheless, the effects of factors secreted by senescent cells and platelets on the migration and invasion of non-senescent cells are complex. Overall, platelets have prominent effects on migration, while factors secreted by senescent cells tend to promote invasion. These differential responses likely reflect differences in the specific arrays of secreted senescence-associated factors, specific factors released by platelets upon activation, and the susceptibility of target cells to respond to these agents.

Niveles Plasmáticos de Citoquinas Proinflamatorias en Cáncer de Próstata / Serum levels of proinflammatory cytokines in prostate cancer

INTRODUCTION: Prostate cancer has become an important public health problem affecting millions of men worldwide every year. Like other malignant tumors, prostate cancer shows evidence of a strong inflammatory component that is dependent on the release of pro-inflammatory cytokines, which might play a major role in the development and progression of the tumor, helping in its early stage, progression and aggressiveness. AIMS: The goal of this study was to determine the relationships between the serum levels of pro-inflammatory cytokines and the different stages of prostate cancer. To this end, sera from patients enrolled by The Laboratory of Metabolic Diseases and Cancer of the Faculty of Pharmacy and Biochemistry at the University Juan Agustín Maza in Argentina, were analyzed through ELISA and their pro-inflammatory cytokines (IL-6, TNF-α and MCP-1) quantified. Patients were first classified into three groups (Control, at Risk, and Cancer subjects) and anthropometric, biochemical and histological parameters of prostate were then determined for all groups. RESULTS AND CONCLUSIONS: Despite displaying elevated serum concentrations of IL-6 and TNF-α in the Cancer and the Risk groups compared to the Control group, the differences did not reach significance. However, there was a positive correlation between these cytokines only in the Risk and Cancer groups, showing a general inflammatory behavior in these patients. The results obtained provide general data about the behavior of pro-inflammatory cytokines in prostate cancer. However, they do not demonstrate a direct correlation between serum levels and neoplastic progression. Nevertheless, these findings do not rule out a possible relationship between prostate cancer and serum levels of pro-inflammatory cytokines.

Phaseolus vulgaris Exerts an Inhibitory Effect on Platelet Aggregation through AKT Dependent Way.

The Phaseolus vulgaris (common bean), a worldwide vegetable of high consumption, can act as a nutritional supplement in the diet of oversized individuals to reduce weight. Studies have demonstrated the existence of molecules capable of inhibiting the breakdown of carbohydrates via inhibition of both α-amylases and glycosidases. Here, we describe a novel property of the Phaseolus vulgaris: inhibition of thrombotic cardiovascular events. Using assays to test platelet aggregation and secretion, and flow cytometry against the surface expression of P-Selectin. We show that bean extracts significantly reduced adenosine 5'-diphosphate and arachidonic acid induced-platelet aggregation. The mechanism underlying such effect appears to be mediated by AKT, since AKT hypo-phosphorylation decreases the "inside out" activation of platelets. In sum, our results support the hypothesis that common beans are nutritional ingredients that help reduce the risk of cardiovascular diseases associated with platelet hyper-reactivity.

The Potential Role of Senescence As a Modulator of Platelets and Tumorigenesis.

In addition to thrombus formation, alterations in platelet function are frequently observed in cancer patients. Importantly, both thrombus and tumor formation are influenced by age, although the mechanisms through which physiological aging modulates these processes remain poorly understood. In this context, the potential effects of senescent cells on platelet function represent pathophysiological mechanisms that deserve further exploration. Cellular senescence has traditionally been viewed as a barrier to tumorigenesis. However, far from being passive bystanders, senescent cells are metabolically active and able to secrete a variety of soluble and insoluble factors. This feature, known as the senescence-associated secretory phenotype (SASP), may provide senescent cells with the capacity to modify the tissue environment and, paradoxically, promote proliferation and neoplastic transformation of neighboring cells. In fact, the SASP-dependent ability of senescent cells to enhance tumorigenesis has been confirmed in cellular systems involving epithelial cells and fibroblasts, leaving open the question as to whether similar interactions can be extended to other cellular contexts. In this review, we discuss the diverse functions of platelets in tumorigenesis and suggest the possibility that senescent cells might also influence tumorigenesis through their ability to modulate the functional status of platelets through the SASP.

Ingesta de tomate reduce niveles de colesterol en ratas Wistar / Tomato intake lowers cholesterol levels in rats

Cardiovascular diseases are closely associated with lifestyle risk factors, some of them modifiable. Animal studies and clinical observations have suggested a relationship between serum total cholesterol and atherosclerosis. Studies have shown that levels of triglycerides and cholesterol were modified by the consumption of fresh tomato juice. The aim of this study was to investigate the effect of daily consumption of tomato mash on cholesterol and other biochemical parameters in Wistar rats. To carry out this research two groups of rats (n = 6 each one), were formed, one of which was supplemented with a mash diet tomato and the other was used for control. After 15 days of testing, the rats were sacrificed and plasma collected was used for biochemical determination of total cholesterol, triglycerides, glucose, glutamicoxaloacetic transaminase and glutamic pyruvic transaminase. The cholesterol level decreased in the study group (33,7+/-2,78 mg/dL) with respect to that of control group (58,6+/-10,6 mg/dL). This study showed an ipocholesterolemic effect of the tomato in rats. Future studies could examine this activity in dyslipidemic subjects.

Gene expression of adipose tissue, endothelial cells and platelets in subjects with metabolic syndrome (Review).

Metabolic syndrome is a combination of medical disorders including hypertension, dyslipidemia, hyperglycemia, insulin resistance and increased waist circumference, and is associated with a higher risk of cardiovascular disease. An increase in adipose tissue mass is associated with the augmented secretion of certain adipokines, such as interleukin-6, tumor necrosis factor-α and resistin, which cause endothelial dysfunction (an increase in vasoconstrictor molecules and in the expression of adhesion molecules as well as a decrease of vasodilator molecules, amongst other features) and hemostasis alterations that also favor a prothrombotic state (increased fibrinogen and plasminogen activator inhibitor-1 concentrations and platelet activation/aggregation). This interaction between adipose tissue, endothelial cells and platelets is associated with an increase or decrease in the expression of several transcription factors (peroxisome proliferator-activated receptors, CCAAT-enhancer-binding proteins, carbohydrate responsive element-binding proteins and sterol regulatory element-binding proteins) that play a crucial role in the regulation of distinct metabolic pathways related to the metabolic syndrome. In the present review, we present the primary changes in adipose tissue, endothelial cells and platelets in subjects with metabolic syndrome and their possible target sites at the gene expression level.

Fractions of aqueous and methanolic extracts from tomato (Solanum lycopersicum L.) present platelet antiaggregant activity.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Its prevention emphasizes three aspects: not smoking, physical activity and a healthy diet. Recently, we screened the antithrombotic activity of a selected group of fruits and vegetables. Among them, tomato showed an important effect. The aim of this study was to evaluate and characterize the platelet antiaggregatory activity of tomato (Solanum lycopersicum L.). For this, we obtained aqueous and methanolic tomato extracts and evaluated the effect of pH (2 and 10) and temperature (22, 60 and 100°C) on this activity. Furthermore, in order to isolate the antiaggregant principle, we separated tomato extracts into several fractions (A-D) by size exclusion chromatography. In addition, we evaluated the platelet antiaggregating activity ex vivo in Wistar rats. Aqueous and methanolic extracts of tomato treated at 22, 60 and 100°C and pH 2 and 10 still inhibited platelet aggregation (in vitro). Moreover, it was noted that one of the fractions (fraction C), from both aqueous and methanolic extracts, presented the highest activity (∼70% inhibition of platelet aggregation) and concentration dependently inhibited platelet aggregation significantly compared with control (P < 0.05). These fractions did not contain lycopene but presented two peaks of absorption, at 210 and 261 nm, compatible with the presence of nucleosides. In rats treated with tomato macerates, a mild platelet antiaggregating effect ex vivo was observed. Further studies are required to identify the molecules with platelet antiaggregating activity and antiplatelet mechanisms of action.

Expresión de ICAM-1 en el endotelio de arterias humanas mediante inmunohistoquímica / ICAM-1 Expression in endothelium of human arteries by immunohistochemistry

Las enfermedades cardiovasculares son la principal causa de muerte a nivel mundial. Entre ellas tienen gran relevancia las de tipo isquémicas, en donde el desarrollo de placas ateroscleróticas es el proceso fisiopatológico central. El estudio de la aterosclerosis es fundamental para comprender como se inicia este proceso patológico y los factores que influyen en su desarrollo. Distintas metodologías de laboratorio, entre otras la inmunohistoquímica, permiten reconocer las células y moléculas que participan en el proceso ateromatoso y que van interactuando según la progresión de la lesión. Un marcador de disfunción endotelial es la mayor expresión de la molécula de adhesión intercelular ICAM-1. En este trabajo se realizó la estandarización de inmunohistoquímica para la molécula de adhesión ICAM-1, y se estudió su expresión en arterias humanas sanas y con placa ateromatosa. En las muestras de arterias humanas con patología aterosclerótica, la expresión de ICAM-1 se observó aumentada, pero fue de difícil reconocimiento. Esto principalmente porque el tejido empleado como control en la estandarización fue una amígdala con hiperplasia y proceso inflamatorio que aumenta notablemente la expresión de ICAM-1. La implementación del método de inmunohistoquímica para ICAM-1 en arterias humanas permitirá conocer estados de disfunción endotelial y el desarrollo futuro del diseño e implementación de métodos de diagnóstico en aquellos procesos ateroclerótico en estado incipiente.

Cardiovascular diseases (CVD) are the leading cause of death in the world. Among them the ischemic type are of great importance, where the development of atherosclerotic plaques is the central pathophysiological process. The study of atherosclerosis is critical to understand how this disease process begins and factors influencing its development. Various laboratory methods, including immunohistochemistry, allow the recognition of cells and molecules involved in the atheromatous process that are interacting according to the progression of the lesion. A marker of endothelial dysfunction is the increased expression of intercellular adhesion molecule ICAM-1. In this paper, an immunohistochemistry method was standardized for the adhesion molecule ICAM-1, and its expression was studied in healthy human arteries with atheromatous plaque. In samples of human arteries with atherosclerotic disease, the expression of ICAM-1 was observed to be increased, but was hardly recognizable. This mainly because the tissue used as a control for standardization was a tonsil with an inflammatory process and hyperplasia, which significantly increases the expression of ICAM-1. The implementation of the immunohistochemistry method for ICAM-1 in human arteries will reveal endothelial dysfunction states that will enable a future design and implementation of methods of diagnosis in atherosclerotic processes in the early stages.

High levels of hsCRP are associated with carbohydrate metabolism disorder.

AIM: To determine risk parameters associated with high values of high sensitive C-reactive protein (hsCRP) in subjects with different glucose fasting levels. METHODS: Anthropometric parameters, arterial pressure, glycemia, lipid profile, uric acid, and hsCRP were studied in a population of 513 individuals between 40 and 65 years. RESULTS: In total, 349 (68.0%) were normoglycemic (NG); 113 (22.0%) had impaired fasting glucose (IFG); and 51 (9.9%) were diabetic subjects. A multivariate linear regression analysis showed that the natural logarithm of hsCRP was associated significantly with glycemia levels (P = 0.009), uric acid (P = 0.001), diastolic blood pressure (P = 0.011), smoking habit (P = 0.021), BMI (P<0.001), and sex (P<0.001). One-third of the NG subjects had high hsCRP levels. A multiple logistic regression analysis showed that sex and BMI were variables related to high levels of hsCRP in subjects with IFG and NG. In NG subjects, uric acid levels were associated with risk of presenting high hsCRP levels and were higher in women than men. In NG women, ROC curves analysis identified a uric acid level of 3.9 mg/dl as a cut-off point to predict a high value of hsCRP. Those individuals with uric acid values higher than 3.9 mg/dl and normal glycemia had 3.5-fold more risk of having hsCRP levels over 3.0 mg/l. CONCLUSIONS: We sustain that high levels of hsCRP are associated with disturbance in carbohydrate metabolism. In addition, we believe that in low cardiovascular risk population, such as NG women, uric acid levels above 3.9 mg/dl might represent a signal of possible pro-inflammatory state and cardiovascular risk.

El consumo de futas y hortalizas ayuda a prevenir el daño endotelial / Consumption of fruits and vegetables in the prevention of endothelial damage

The endothelium helps to maintain the normal structure and homeostasis of the vasculature. However, chronic exposure to cardiovascular (CV) risk factors causes endothelial dysfunction, a phenomenon that is characterized by inflammation, reduced bioavailability of nitric oxide (NO) and a prothrombotic state. Epidemiological studies have shown that regular consumption of fruits and vegetables reduces CV risk, which has caused interest in knowing the bioactive compounds and the mechanisms involved. Among the components that protect the endothelium are antioxidants (vitamin C, vitamin E and poly phenols) and polyunsaturated fatty acids. Vitamin C and E promote vasodilatation protecting NO by blocking the reactive oxygen species (ROS). Poly phenols improve endothelial function primarily by increasing levels of NO, and inhibition of angiogenesis and platelet activation. Diets rich in poly-unsaturated fatty acids have shown beneficial effects by reducing the gene expression of cyclooxygenase-2 and the expression of cell adhesion molecules. This review mainly highlights the current understanding of endothelial dysfunction and the protective effect of endothelial cells by bioactive components of fruits and vegetables.

El endotelio normal ayuda a mantener la estructura y la hemostasia vascular. Sin embargo, la exposición crónica a factores de riesgo cardiovascular (CV) produce disfunción endotelial, fenómeno que se caracteriza por inflamación, disminución en la biodisponibilidad de óxido nítrico (NO) y un estado protrombótico. Estudios epidemiológicos han demostrado que el consumo regular de frutas y hortalizas disminuye el riesgo CV, lo que ha causado interés en conocer los compuestos bioactivos y los mecanismos involucrados. Entre los componentes que protegen el endotelio se encuentran las moléculas antioxidantes (vitamina C, vitamina E y polifenoles) y ácidos grasos poliinsaturados. Las vitaminas C y E favorecen la vasodilatación protegiendo el NO al bloquear las especies reactivas del oxigeno (ROS). Los polifenoles mejoran la función endotelial principalmente por el aumento de los niveles de NO, y la inhibición de la angiogénesis y de la activación plaquetaria. Dietas ricas en ácidos grasos poliinsaturados han mostrado efectos beneficiosos, mediante la reducción de la expresión géni-ca de la ciclooxigenasa-2 y de la expresión de moléculas de adhesión celular. Esta revisión principalmente señala los conocimientos actuales de la disfunción endotelial y el efecto protector de las células endoteliales por componentes bioactivos de frutas y hortalizas.

Actividad antioxidante, hipolipemiante y antiplaquetaria del tomate ( Solanum lycopersicum L. ) y el efecto de su procesamiento y almacenaje / Antioxidant activity, lipid lowering and antiplatelet of tomato(Solanum lycopersicum L. ) and its effect of processing and storage

Cardiovascular diseases (CVD) are the main cause of mortality worldwide. To prevent CVD it is recommended to quit smoking, the practice of physical activity and the consumption of healthy food. In this context, numerous studies have shown the importance of frequent consumption of fruits and vegetables (at least5 a day). It has been described an inverse relationship between vegetables consumption and the risk of developing CVD, which is mainly explained by its antioxidant activity, and in some cases lipid-lowering and platelet effects. In this sense, the increase in regular consumption of tomato (Solanum lycopersicum L.) and related products, can improve the some cardiovascular parameters. The current lifestyle favors the consumption of processed foods, a situation that may affect the stability of tomato components and their physicochemical properties. This review addresses the antioxidant activities, lipid-lowering and antiaggregant properties of tomato, as well as the effect of processing and storage. Additionally, a summary of some patents associated with beneficial effects on health. As bibliographic source www.pubmed.org was mainly used, the terms used in the search were and platelet, tomato, and platelet, antioxidant, among others, then search the full texts of items of common interest.

Las enfermedades cardiovasculares (ECV) son la principal causa de muerte en el mundo. En su prevención tiene mucha importancia el no fumar, realizar actividad física y consumir alimentos saludables. En este contexto, numerosos estudios han demostrado la importancia del consumo frecuente de frutas y hortalizas (al menos 5 porciones al día). Se ha descrito una relación inversa entre su ingesta y el riesgo de desarrollar ECV, lo que se explica principalmente por su actividad antioxidante, hipolipemiante y en algunos casos antiplaquetaria. En ese sentido aumentar el consumo actual de tomate (Solanum lycopersicum L.) y productos del tomate, puede mejorar algunos parámetros cardiovasculares. El actual estilo de vida induce a las personas a consumir alimentos procesados, lo que podría afectar la estabilidad de sus componentes y sus propiedades fisicoquímicas. Esta revisión aborda la actividad antioxidante, hipolipemiante y antiagregante plaquetaria del tomate, como también el efecto que tiene el procesamiento y almacenaje sobre dichas actividades. Adicionalmente se resumen algunas patentes asociadas a efectos beneficiosos en la salud. Como fuentes bibliográficas se utilizó principalmente www.pubmed.org; los términos utilizados en la búsqueda fueron: antiplatelet, tomato, platelet, antioxidant, entre otros; luego se buscaron los textos completos de los artículos que interesaban.

El consumo de manzanas contribuye a prevenir el desarrollo de enfermedades cardiovasculares y cáncer: antecedentes epidemiológicos y mecanismos de acción / Apple consumption helps to prevent cardiovascular diseases and cancer: epidemiology and mode of action

Consumption of fruit and vegetables has the potential to reduce non-transmissible diseases (NTD), such as cardiovascular diseases (CVD) and cancer, which are major public health concerns. Chile is a major apple producer and exporter in the world. Its production is concentrated in the sixth (O'Higgins) and seventh (Maule) regions of Central Chile. Phenolics and flavonoids are responsible for apple's high antioxidant activity. Many epidemiologic studies have shown that a diet rich in apples can reduce cardiovascular events (myocardial infarct and stroke) and some type of cancers. The mechanisms involved are not well understood. Nevertheless, antioxidants are key-players. Some of their in-vitro activities are inhibition of low-density lipoprotein (LDL) oxidation, cholesterol levels reduction, endothelium protection, reduction of neoplastic cells proliferation and apoptosis activation. Consequently, daily apple consumption campaigns in the country should be implemented, as well as funding research focused on molecular mechanisms involved in its antioxidant activity.

Las enfermedades no transmisibles (ENT), especialmente las cardiovasculares (ECV) y el cáncer, representan un grave problema de salud pública. Es conocido que el consumo de frutas y hortalizas disminuye el riesgo de sufrir dichas enfermedades. El manzano (Malus domestica Borkh.) se cultiva en Chile en una amplia zona geográfica, concentrándose principalmente en las regiones sexta y séptima. La actividad antioxidante de la manzana se debe principalmente a su contenido en fenoles y flavonoides. Varios estudios epidemiológicos han mostrado que el consumo de manzanas puede prevenir el desarrollo de ECV (infarto agudo de miocardio y enfermedad cerebro vascular) y ciertos tipos de cáncer. Los mecanismos por los cuales se producen dichos efectos, no están totalmente aclarados, sin embargo la participación de los antioxidantes es fundamental. Entre los principales hallazgos se han descrito, en relación a ECV: inhibición de la oxidación de low-density lipoprotein (LDL), disminución de colesterol total y protección de endotelio; y en relación a cáncer: disminución de la proliferación de células neoplásicas y activación de la apoptosis de las mismas. Debido al incuestionable efecto protector para la salud humana que presenta la ingesta de manzana, se deben impulsar estrategias que apunten a incentivar su consumo diario en el país. Asimismo, se deben seguir estudiando los principios activos y los mecanismos moleculares.

Polimorfismo 4G/5G del inhibidor del activador de plasminógeno tipo 1 en síndrome metabólico / Plasminogen activator inhibitor-1 polymorphisms in metabolic syndrome

El inhibidor del activador de plasminógeno tipo 1 (PAl-1, Plasminogen Activator Inhibitor 1) es el inhibidor primario de la fibrinólisis. Se ha descrito que un aumento o disminución puede asociarse a riesgo de trombosis y hemorragia, respectivamente. De los nueve polimorfismos que se han descrito en su gen, el denominado 4G15G ha sido el más estudiado. Se ha visto que personas con el genotipo 4G/4G presentan mayor concentración plasmática do PAl-1. En individuos con Síndrome Metabólico (SM) se ha observado mayor concentración do PAl-1. El propósito de este estudio fue conocer el genotipo 4G/5G en individuos con SM (n: 82) respecto a un grupo control (n: 75). Para ello se utilizo el método PCR alelo especifica. La frecuencia genotípica obtenida en los sujetos con SM fue de 23 por ciento, 43 por ciento y 34 por ciento para los genotipos 4G/4G, 4G/5G y 5G/5G, respectivamente. En los sujetos sin SM so observo una prevalencia de 11 por ciento, 56 por ciento, 33 por ciento para los genotipos 4G/4G, 4G/5G y 5G/5G, respectivamente. Las diferencias entre los distintos genotipos y la condición de ser o no SM no fueron significativas (p= 0,083), posiblemente porque nuestra población en estudio fue pequeña. Por otra parte, no hubo relación entre el genotipo y la concentración plasmática de PAl-1; es posible que esta última este influenciada por distintos factores, además del polimorfismo 4G/5G. La frecuencia genotípica obtenida en este estudio fue similar a la encontrada en sujetos latinos y diferentes a las de afroamericanos e italianos, posiblemente el genotipo pudiera estar influenciado por la raza.

Polimorfismos de los genes cytochrome P450 y VKORC1 afectan la terapia anticoagulante oral / Polymorphisms of cytochrome P450 genes and VKORC1 affect the oral anticoagulant therapy

Los llamados factores vitaminas k dependientes (FII, FVII, FIXy FX), requieren ser carboxilados por la enzima gamma carboxilasa de los hepatocitos para ser funcionales. Esta enzima utiliza como cofactor vitamina K reducida, condición que se logra por acción de la enzima epóxido reductasa. Los anticoagulantes orales (ACO) son antagonistas de la vitamina K, quedando esta última en forma oxidada, no pudiendo actuar como cofactor. La variabilidad interindividual del tratamiento anticoagulante (TAC) se explica por factores ambientales, desconocidos y genéticos. Entre estos últimos los polimorfismos genéticos del cytochrome P450 (CYP2C9) y de la vitamina K epóxido reductasa (VKOR), los cuales se han relacionado con la variación en las dosis de ACO en distintas poblaciones del mundo. En dicho contexto se muestran resultados preliminares de un polimorfismo de CYP2C9 obtenidos en el Programa de Investigación de Factores de Riesgo de Enfermedades Cardiovasculares (PIFRECV). Además se describen brevemente otros polimorfismos que podrían influir sobre la variabilidad en la respuesta al TAC.