Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.     

Co-volume method for Riemannian mean curvature flow in subjective surfaces multiscale segmentation

We introduce semi-implicit complementary volume numerical scheme for solving the level setformulation of Riemannian mean curvature flow problem arising in image segmentation, edge detection, missing boundary completion and subjective contour extraction. The scheme is robust and efficient since it is linear, and it is stable in L_∞ and weighted W ^1,1 sense without any restriction on a time step. The computational results related to medical image segmentation with partly missing boundaries and subjective contours extraction are presented.     

A hybrid multilevel-active set method for large box-constrained linear discrete ill-posed problems

Many questions in science and engineering give rise to linear ill-posed problems, whose solution is known to satisfy box constraints, such as nonnegativity. The solution of discretized versions of these problems is highly sensitive to perturbations in the data, discretization errors, and round-off errors introduced during the computations. It is therefore often beneficial to impose known constraints during the solution process. This paper describes a two-phase algorithm for the solution of large-scale box-constrained linear discrete ill-posed problems. The first phase applies a cascadic multilevel method and imposes the constraints on each level by orthogonal projection. The second phase improves the computed approximate solution on the finest level by an active set method. The latter allows several indices of the active set to be updated simultaneously. This reduces the computational effort significantly, when compared to standard active set methods that update one index at a time. Applications to image restoration are presented.     

Mark Maybury (Author), Intelligent Multimedia Information Retrieval

User Modeling and User-Adapted Interaction -     

Un problema di approssimazione connesso con la sintesi di filtri digitali non ricorsivi

In this paper we present a synthesis algorithm for non-recursive digital filters. By the well-known «frequency sampling method», the approximation problem can be related to a convex optimization problem. Finally, we exhibit a synthesis procedure based on the classical simplex algorithm.     

4-Hydroxynonenal and cholesterol oxidation products in atherosclerosis

4-Hydroxynonenal (HNE) is by far the most investigated aldehydic end-product of oxidative breakdown of membrane n-6 polyunsaturated fatty acids. Its potential involvement in the pathogenesis of atherosclerosis has been corroborated by its consistent detection in both oxidized LDL and fibrotic plaque in humans. HNE has been shown to activate both macrophage and smooth muscle cells, i.e. the two key cell types in chronic inflammatory processes characterized by excessive fibrogenesis. By signalling to the nucleus, the aldehyde may up-regulate in these cells both expression and synthesis of monocyte chemotactic protein 1 (MCP-1) and transforming growth factor beta1 (TGFbeta1). Oxysterols, namely 27 carbon atoms oxidation products of cholesterol, are found in relatively high amount in LDL from hypercholesterolemic individuals and are consistently detectable in foam cells and necrotic core of human atherosclerotic lesion. As for HNE, the challenge of cells of the macrophage lineage with a mixture of oxysterols like that detectable in hypercholesterolemic individuals led to a marked overexpression of TGFbeta1 and MCP-1. Both HNE and oxysterols then appear to be candidates for a primary role in the progression of the atherosclerotic process.     

Genetic bases of the nutritional approach to migraine

ABSTRACT

Migraine is a common multifactorial and polygenic neurological disabling disorder characterized by a genetic background and associated to environmental, hormonal and food stimulations. A large series of evidence suggest a strong correlation between nutrition and migraine and indicates several commonly foods, food additives and beverages that may be involved in the mechanisms triggering the headache attack in migraine-susceptible persons. There are foods and drinks, or ingredients of the same, that can trigger the migraine crisis as well as some foods play a protective function depending on the specific genetic sensitivity of the subject. The recent biotechnological advances have enhanced the identification of some genetic factors involved in onset diseases and the identification of sequence variants of genes responsible for the individual sensitivity to migraine trigger-foods. Therefore many studies are aimed at the analysis of polymorphisms of genes coding for the enzymes involved in the metabolism of food factors in order to clarify the different ways in which people respond to foods based on their genetic constitution.

This review discusses the latest knowledge and scientific evidence of the role of gene variants and nutrients, food additives and nutraceuticals interactions in migraine.