ABSTRACT
Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Gastric Mucosa/chemistry , Helicobacter pylori , Precancerous Conditions/chemistry , Receptors, Immunologic/analysis , Stomach Neoplasms/chemistry , Biomarkers/analysis , Biopsy , Cyclin D1/analysis , Gastric Mucosa/microbiology , /analysis , Helicobacter Infections/metabolism , Immunohistochemistry , Mucin-1/analysis , beta Catenin/analysisABSTRACT
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.