Héctor Figueroa

Fueling inflammation at tumor microenvironment: the role of multiligand/rage axis

The receptor for advanced glycation end products (RAGE), firstly described in 1992, is a single-transmembrane and multiligand member of the immunoglobulin protein family. RAGE engagement produces activation of multiple intracellular signaling mechanisms involved in several inflammation-associated clinical entities, such as diabetes, cancer, renal and heart failures, as well as neurodegenerative diseases. Although RAGE expression has been extensively reported in many cancer types, it is now emerging as a relevant element that can continuously fuel an inflammatory milieu at the tumor microenvironment, thus changing our perception of its contribution to cancer biology. In this review, we will discuss the role of multiligand/RAGE axis, particularly at the multicellular cross talk established in the inflammatory tumor microenvironment. A better understanding of its contribution may provide new targets for tumor management and risk assessment.

Effects of Preweaning Sensorimotor Stimulation on Behavioral and Neuronal Development in Motor and Visual Cortex of the Rat

The present study investigates the effects of early sensorimotor stimulation on behavioral and neuronal cytodifferentiation in motor and visual cortex of lactating rats. Seventy-two male and female Sprague-Dawley albino rats were systematically submitted to environmental stimulation during the early postnatal period (postnatal days 5-21). On postnatal day 22, four behavioral tests were performed (open field, narrow path crossing, hind limb support and ascending on a rope). In order to evaluate dynamic neuronal changes induced by sensorimotor enrichment, brains were stained through the Golgi-Cox-Sholl method. Morphometric studies were carried out in pyramidal neurons located in motor and visual cortical layers II and III, by measuring their basal dendritic length and branching. Further, wide cortical field studies were performed with the aim of evaluating the degree of development reached by clusters of pyramidal cells. The results indicate that sensorimotor stimulation carried out during the suckling period produced a significant increase in neuronal cytodifferentiation as observed in single cell studies. However, collective neuronal evaluations yielded less significant results. Consistently, rats exposed to enriched environments showed a better performance in behavioral adaptive responses.

Advanced Glycation and ROS: A Link between Diabetes and Heart Failure

Despite many advances achieved to date, heart failure (HF) remains a leading cause of morbidity and mortality. There is a widely-accepted consensus that HF and diabetes are strongly linked by at least 3 mechanisms: associated comorbidities, coronary atherosclerosis or a specific diabetic cardiomiopathy. For the last 2 mechanisms, advanced glycation end-products may contribute to trigger key processes relevant to HF by affecting cardiac function through cross-linking or receptor engagement. This review focuses on the main effects of advanced glycation end-products on cardiomyocytes and endothelial cell function. Some pharmacological approaches are also discussed.

Diabetes and cancer: Looking at the multiligand/RAGE axis

The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years. Although the association is not fully understood, current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms, including hyperinsulinemia, hyperglycemia and chronic inflammation. In this context, the receptor for advanced glycation end-products (RAGE) has emerged as a focal point in its contribution to malignant transformation and tumor growth. We highlight how RAGE, once activated, as it manifests itself in conditions such as diabetes or hyperglycemia, is able to continuously bring about an inflammatory milieu, thus supporting the contribution of chronic inflammation to the development of malignancies.

Facing up the ROS labyrinth--Where to go?

Evidence indicates that oxidative stress refers to a condition where cells are subjected to excessive levels of reactive oxygen species (ROS). Overall vascular function is dependent upon a fine balance between oxidant and antioxidant mechanisms which is required, at least in part, for proper functioning of the endothelium. Considerable experimental and clinical data indicate that the intracellular oxidant milieu is also involved in several redox-sensitive cellular signaling pathways, such as ion transport systems, protein phosphorylation, and gene expression and thus also plays important roles as modulator of vascular cell function, such as cell growth, apoptosis, migration, angiogenesis and cell adhesion. Overproduction of ROS under pathophysiologic conditions is integral in the development of vascular disease. This fact stimulated an intensive search of new pharmacological approaches to improve vascular hemeostasis and, particularly those intended to decrease oxidative stress or augment the antioxidant defense mechanisms.

Purkinje Cell Impairment Induced by Early Movement Restriction

In the present work the effects of movement restriction imposed during the early postweaning period on both Purkinje cell dendritic development and exploratory behavior were analyzed. Male and female Sprague-Dawley albino rats were reared either in isolated-restricted or social-standard environments from postnatal day 18 to 30. On the 31st postnatal day, all rats were behaviorally evaluated by the open-field test and then sacrificed under deep ether anesthesia. Vermian cerebellar sections were later stained with the Golgi-Cox-Sholl method and the Purkinje cell dendritic morphology was quantified under light microscopy. The results indicate that early somatomotor restriction severely impairs both exploratory behavior and Purkinje cell dendritic growth.

Cell line cross-contamination in biomedical research: a call to prevent unawareness

AbstractDuring the 1950s, cross-contamination of cell lines emerged as a problem with serious consequences on the quality of biomedical research. Unfortunately, this situation has worsened over years. In this context, some actions should be urgently undertaken to avoid the generation of misleading data due to the increasingly and sometimes neglected use of cross-contaminated cell lines. Unawareness about this problem may then turn many scientists into victims or even perpetrators of this unwanted situation. Collaborative actions involving researchers, cell banks, journals, and funding agencies are needed to save the scientific reputation as well as many public or private resources that are used to produce misleading data.

Evidence of involvement of the receptor for advanced glycation end-products (RAGE) in the adhesion of Helicobacter pylori to gastric epithelial cells.

The adherence of Helicobacter pylori to gastric epithelial cells is required for prolonged persistence in the stomach and for induction of injury. Here, we first reported a new role of the receptor for advanced glycation end-products (RAGE) on the adherence of H. pylori to gastric epithelial cells, assessed by different methods and binding to immobilized RAGE. RAGE-targeted knock-down in MKN74 cell line markedly reduced not only the adhesion of H. pylori, but also the levels of IL-8 transcripts and protein released in response to infection. These data suggest that RAGE may represent a new factor on the pathogenesis of H. pylori infection.

High prevalence of virulence-associated genotypes in Helicobacter pylori clinical isolates in the Region del Maule, Chile.

Abstract The prevalence of Helicobacter pylori infection and the gastric cancer mortality rate in Chile are remarkably high. This study identified some virulence-associated genes in 78 H. pylori clinical isolates from dyspeptic patients from the Region del Maule, which is the region with the higher gastric cancer mortality rate in the country. The cagA, vacA and babA2 genes were detected in 94.9%, 100% and 97.4%, respectively. Two or more EPIYA C motifs were presented in 48.6% of cagA-positive strains, and this was associated with more severe histopathological findings in the gastric mucosa.

Effects of preweaning environmental stimulation on neuronal and behavioral impairment produced by undernutrition.

The present study investigates the effects of sensorimotor stimulation on the basal dendrogenesis of superficial cerebrocortical neurons and the accomplishment in the associated exploratory behavior in rats simultaneously exposed to nutritional deprivation. Sprague-Dawley albino rats were submitted to nutritional-environmental influences from birth to the 21st postnatal day. Exploratory behavior was assessed by the evaluation of locomotor activity in the open-field apparatus. In order to evaluate changes in neuronal morphology induced by nutritional-environmental variables, brains were stained according to the Golgi-Cox-Sholl procedure. Dendritic development was assessed under camera lucida by measuring basal dendritic branching of layer II and III pyramidal neurons, located in the dorsomedial region of the visual cortex of the rat. Morphometrical analysis revealed that both basal dendritic length and branching were significantly reduced by undernutrition. In contrast, environmental stimulation during the suckling period compensated for the neuronal impairment produced by protein-calorie deprivation. An improvement was also observed in exploratory behavior although to a lesser degree, as shown by the open field test data. In conclusion, the present results indicate that sensorimotor stimulation applied during the period of fastest rate of cortical cytodifferentiation compensates for neuronal and behavioral impairment produced by undernutrition.