Current Molecular Medicine 

About: Current Molecular Medicine is an academic journal published by Bentham Science Publishers. The journal publishes majorly in the area(s): Medicine & Cancer. It has an ISSN identifier of 1566-5240. Over the lifetime, 1812 publications have been published receiving 73777 citations.

Functions of S100 Proteins

Abstract: The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.

Fundamental concepts of the angiogenic process.

Abstract: The process of angiogenesis encompasses the growth and regression of capillary blood vessels. Angiogenesis is finely regulated at the molecular and genetic levels, not unlike other physiologic processes such as coagulation, glucose metabolism, and blood pressure. During the development of the field of angiogenesis research over the past three decades, fundamental concepts have been introduced along the way in an attempt where possible, to unify new data from a variety of different laboratories. I have assembled here the major concepts which underlie the angiogenic process as we currently understand it. Many of these are now taken for granted, but this was not always the case, and I have tried to show how they were developed. My goal is to provide a conceptual framework for those basic scientists or clinicians who may enter this rapidly expanding field. Each concept discussed here is accompanied by a few key references as a guide to the pertinent literature.

Stress Induction of GRP78/BiP and Its Role in Cancer

Abstract: GRP78, also referred to as BiP, is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors. Further, due to its anti-apoptotic property, stress induction of GRP78 represents an important pro-survival component of the unfolded protein response. GRP78 is induced in a wide variety of cancer cells and cancer biopsy tissues. Recent progress, utilizing overexpression and siRNA approaches, establishes that GRP78 contributes to tumor growth and confers drug resistance to cancer cells. The discovery of GRP78 expression on the cell surface of cancer cells further leads to the development of new therapeutic approaches targeted against cancer, in particular, hypoxic tumors where GRP78 is highly induced. Progress has also been made in understanding how Grp78 is induced by ER stress. The identification of the transcription factors interacting with the ER stress response element leads to the discovery of multiple pathways whereby mammalian cells can sense ER stress and trigger the transcription of Grp78. In addition, advances have been made in understanding how Grp78 expression is regulated in the context of chromatin modification. This review summarizes the transcriptional regulation of Grp78, the molecular basis for the cytoprotective function of GRP78 and its role in cancer progression, drug resistance and potential future cancer therapy.

Immunosuppressive properties of mesenchymal stem cells: advances and applications.

Abstract: Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohn’s disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory.

The Retinal Pigment Epithelium in Health and Disease

Abstract: Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal cells that are strategically situated behind the photoreceptor (PR) cells. The inconspicuousness of this monolayer contrasts sharply with its importance [1]. The relationship between the RPE and PR cells is crucial to sight; this is evident from basic and clinical studies demonstrating that primary dysfunctioning of the RPE can result in visual cell death and blindness. RPE cells carry out many functions including the conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition. The magnitude of the demands imposed on this single layer of cells in order to execute these tasks, will become apparent to the reader of this review as will the number of clinical disorders that take origin from these cells.