Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle.

The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer.

HMGB1 decreases CCR-2 expression and migration of M2 macrophages under hypoxia.

Objective: The hypoxic milieu at tumor microenvironment is able to drive the behavior of infiltrating tumor cells. Considering that hypoxia-mediated HMGB1 release is known to promote tumor growth, as well to enhance the pro-tumoral profile of M2 macrophages by a RAGE-dependent mechanism, it is tempting to evaluate the potential contribution of HMGB1 under hypoxia to restrain M2 macrophages mobility.

Methods: CCR-2 expression was evaluated in M2 polarized macrophages by western blotting and immunocytochemistry.

Skewed Signaling through the Receptor for Advanced Glycation End-Products Alters the Proinflammatory Profile of Tumor-Associated Macrophages.

Tumors are complex tissues composed of variable amounts of both non-cellular components (matrix proteins) and a multitude of stromal cell types, which are under an active cross-talk with tumor cells. Tumor-associated macrophages (TAMs) are the major leukocyte population among the tumor-infiltrating immune cells. Once they are infiltrated into tumor stroma they undergo a polarized activation, where the M1 and M2 phenotypes represent the two extreme of the polarization heterogeneity spectrum.

Lysyl oxidase isoforms in gastric cancer.

Gastric cancer (GC) is the fifth most frequent cancer in the world and shows the highest incidence in Latin America and Asia. An increasing amount of evidence demonstrates that lysyl oxidase isoforms, a group of extracellular matrix crosslinking enzymes, should be considered as potential biomarkers and therapeutic targets in GC. In this review, we focus on the expression levels of lysyl oxidase isoforms, its functions and the clinical implications in GC.

Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism.

Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors.

HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism.

The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells.

Differential expression of two-pore domain potassium channels in rat cerebellar granule neurons.

Two pore domain potassium (K2P) channels are mostly present in the central nervous system (CNS) where they play important roles in modulating neuronal excitability. K2P channels give rise to background K(+) currents (IKSO) a key component in setting and maintaining the resting membrane potential in excitable cells. Here, we studied the expression and relative abundances of K2P channels in cerebellar granule neurons (CGNs), combining molecular biology, electrophysiology and immunologic techniques.

Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.

Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro.

Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases.

Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well.

The receptor for advanced glycation end-products: a complex signaling scenario for a promiscuous receptor.

Firstly described in 1992, the receptor for advanced glycation end-products has attracted increasing attention due to its diverse ligand repertoire and involvement in several pathophysiological processes associated with inflammation such as in diabetes, cancer, autoimmune diseases and neurodegenerative diseases. This receptor in addition to its binding capacity for advanced glycation end-products also recognizes some molecules classified as both, pathogen- and damage-associated molecular patterns and thus triggering the transcription of genes encoding inflammatory mediators. Some of these ligands are common for both, the receptor of advanced glycation end-products and members of the Toll-like receptor family, generating shared signaling cascades.

Interference with endothelial cell function by JG-03-14, an agent that binds to the colchicine site on microtubules.

JG-03-14, a novel tetrasubstituted pyrrole with microtubule-depolymerizing and anti-proliferative activities, was tested for its effect on endothelial cell (EC) functions in vitro. JG-03-14 was a potent inhibitor of EC vessel-like tube formation on extracellular matrix (IC(50) of 40nM) and caused the involution of established vessels, potential anti-angiogenic and vascular-disrupting activities, respectively. These actions were not due to the inhibition of EC proliferation or to the induction of apoptosis by JG-03-14.

Adenovirus RIDalphabeta complex inhibits lipopolysaccharide signaling without altering TLR4 cell surface expression.

The transmembrane heterotrimer complex 10.4K/14.5K, also known as RID (for "receptor internalization and degradation"), is encoded by the adenovirus E3 region, and it down-regulates the cell surface expression of several unrelated receptors.

Inhibition of chemokine expression by adenovirus early region three (E3) genes.

Adenoviruses (Ad) have a variety of immunoregulatory genes, many of which are clustered in a 3.5-kb segment of DNA known as early region 3 (E3). Ad E3 codes for proteins that downregulate surface expression of class I major histocompatibility antigens and also inhibit tumor necrosis factor alpha (TNF-alpha)- and Fas-induced cytolysis.