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Molecular Aspects of Medicine

Nicolas G Bazan
The functional significance of the selective enrichment of the omega-3 essential fatty acid docosahexaenoic acid (DHA; 22C and 6 double bonds) in cellular membrane phospholipids of the nervous system is being clarified by defining its specific roles on membrane protein function and by the uncovering of the bioactive mediators, docosanoids and elovanoids (ELVs). Here, we describe the preferential uptake and DHA metabolism in photoreceptors and brain as well as the significance of the Adiponectin receptor 1 in DHA retention and photoreceptor cell (PRC) survival...
September 20, 2018: Molecular Aspects of Medicine
Maurizio Parola, Massimo Pinzani
The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as sustained activation of liver fibrogenesis and wound healing response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular and tissue process responsible for driving the excess accumulation of extracellular matrix (ECM) components (i.e., liver fibrosis) sustained by an eterogeneous population of hepatic myofibroblasts (MFs)...
September 10, 2018: Molecular Aspects of Medicine
Diptiman Chanda, Eva Otoupalova, Samuel R Smith, Thomas Volckaert, Stijn P De Langhe, Victor J Thannickal
Idiopathic pulmonary fibrosis (IPF) is a progressive and terminal lung disease with no known cure. IPF is a disease of aging, with median age of diagnosis over 65 years. Median survival is between 3 and 5 years after diagnosis. IPF is characterized primarily by excessive deposition of extracellular matrix (ECM) proteins by activated lung fibroblasts and myofibroblasts, resulting in reduced gas exchange and impaired pulmonary function. Growing evidence supports the concept of a pro-fibrotic environment orchestrated by underlying factors such as genetic predisposition, chronic injury and aging, oxidative stress, and impaired regenerative responses may account for disease development and persistence...
August 22, 2018: Molecular Aspects of Medicine
Mohammad Askandar Iqbal, Shweta Arora, Gopinath Prakasam, George A Calin, Mansoor Ali Syed
Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene expression via post-transcriptional regulation of mRNA...
August 17, 2018: Molecular Aspects of Medicine
Ella J Baker, M Hayati Yusof, Parveen Yaqoob, Elizabeth A Miles, Philip C Calder
Endothelial cells (ECs) play a role in the optimal function of blood vessels. When endothelial function becomes dysregulated, the risk of developing atherosclerosis increases. Specifically, upregulation of adhesion molecule expression on ECs promotes the movement of leukocytes, particularly monocytes, into the vessel wall. Here, monocytes differentiate into macrophages and may become foam cells, contributing to the initiation and progression of an atherosclerotic plaque. The ability of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) to influence the expression of adhesion molecules by ECs and to modulate leukocyte-endothelial adhesion has been studied in cell culture using various types of ECs, in animal feeding studies and in human trials; the latter have tended to evaluate soluble forms of adhesion molecules that circulate in the bloodstream...
August 13, 2018: Molecular Aspects of Medicine
Nikolaos G Frangogiannis
Cardiac fibrosis is a common pathophysiologic companion of most myocardial diseases, and is associated with systolic and diastolic dysfunction, arrhythmogenesis, and adverse outcome. Because the adult mammalian heart has negligible regenerative capacity, death of a large number of cardiomyocytes results in reparative fibrosis, a process that is critical for preservation of the structural integrity of the infarcted ventricle. On the other hand, pathophysiologic stimuli, such as pressure overload, volume overload, metabolic dysfunction, and aging may cause interstitial and perivascular fibrosis in the absence of infarction...
August 2, 2018: Molecular Aspects of Medicine
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October 2018: Molecular Aspects of Medicine
Friederike Cuello, Ilka Wittig, Kristina Lorenz, Philip Eaton
Oxidants are produced endogenously and can react with and thereby post-translationally modify target proteins. They have been implicated in the redox regulation of signal transduction pathways conferring protection, but also in mediating oxidative stress and causing damage. The difference is that in scenarios of injury the amount of oxidants generated is higher and/or the duration of oxidant exposure sustained. In the cardiovascular system, oxidants are important for blood pressure homeostasis, for unperturbed cardiac function and also contribute to the observed protection during ischemic preconditioning...
October 2018: Molecular Aspects of Medicine
Albert van der Vliet, Yvonne M W Janssen-Heininger, Vikas Anathy
The lung is a delicate organ with a large surface area that is continuously exposed to the external environment, and is therefore highly vulnerable to exogenous sources of oxidative stress. In addition, each of its approximately 40 cell types can also generate reactive oxygen species (ROS), as byproducts of cellular metabolism and in a more regulated manner by NOX enzymes with functions in host defense, immune regulation, and cell proliferation or differentiation. To effectively regulate the biological actions of exogenous and endogenous ROS, various enzymatic and non-enzymatic antioxidant defense systems are present in all lung cell types to provide adequate protection against their injurious effects and to allow for appropriate ROS-mediated biological signaling...
October 2018: Molecular Aspects of Medicine
Nicolas Stankovic-Valentin, Frauke Melchior
Reversible post-translational modifications (PTMs) ensure rapid signal transmission from sensors to effectors. Reversible modification of proteins by the small proteins Ubiquitin and SUMO are involved in virtually all cellular processes and can modify thousands of proteins. Ubiquitination or SUMOylation is the reversible attachment of these modifiers to lysine residues of a target via isopeptide bond formation. These modifications require ATP and an enzymatic cascade composed of three classes of proteins: E1 activating enzymes, E2 conjugating enzymes and E3 ligases...
October 2018: Molecular Aspects of Medicine
Julius Grosche, Juliane Meißner, Johannes A Eble
Fibrosis is characterized by excess deposition of extracellular matrix (ECM). However, the ECM changes during fibrosis not only quantitatively but also qualitatively. Thus, the composition is altered as the expression of various ECM proteins changes. Moreover, also posttranslational modifications, secretion, deposition and crosslinkage as well as the proteolytic degradation of ECM components run differently during fibrosis. As several of these processes involve redox reactions and some of them are even redox-regulated, reactive oxygen species (ROS) influence fibrotic diseases...
October 2018: Molecular Aspects of Medicine
Cristhiaan D Ochoa, Ru Feng Wu, Lance S Terada
The endoplasmic reticulum (ER) produces the vast majority of all proteins secreted into the extracellular space, including hormones and cytokines, as well as cell surface receptors and other proteins which interact with the environment. Accordingly, this organelle controls essentially all vital links to a cell's external milieu, responding to systemic metabolic, inflammatory, endocrine, and mechanical stimuli. The central role the ER plays in meeting protein synthetic and quality control requirements in the face of such demands is matched by an extensive and versatile ER stress response signaling network...
October 2018: Molecular Aspects of Medicine
Valeska Helfinger, Katrin Schröder
Cancer is the leading cause of death worldwide after cardiovascular diseases. This has been the case for the last few decades despite there being an increase in the number of cancer treatments. One reason for the apparent lack of drug effectiveness might be, at least in part, due to unspecificity for tumors; which often leads to substantial side effects. One way to improve the treatment of cancer is to increase the specificity of the treatment in accordance with the concept of individualized medicine. This will help to prevent further progression of an existing cancer or even to reduce the tumor burden...
October 2018: Molecular Aspects of Medicine
Andreas Weigert, Andreas von Knethen, Dominik Fuhrmann, Nathalie Dehne, Bernhard Brüne
Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype...
October 2018: Molecular Aspects of Medicine
Erika Folestad, Anne Kunath, Dick Wågsäter
Members of the platelet-derived growth factor (PDGF) family are well known to be involved in different pathological conditions. The cellular and molecular mechanisms induced by the PDGF signaling have been well studied. Nevertheless, there is much more to discover about their functions and some important questions to be answered. This review summarizes the known roles of two of the PDGFs, PDGF-C and PDGF-D, in vascular diseases. There are clear implications for these growth factors in several vascular diseases, such as atherosclerosis and stroke...
August 2018: Molecular Aspects of Medicine
Susmita Sil, Palsamy Periyasamy, Annadurai Thangaraj, Ernest T Chivero, Shilpa Buch
Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are expressed in several cell types including the brain cells such as neuronal progenitors, neurons, astrocytes, and oligodendrocytes. Emerging evidence shows that PDGF-mediated signaling regulates diverse functions in the central nervous system (CNS) such as neurogenesis, cell survival, synaptogenesis, modulation of ligand-gated ion channels, and development of specific types of neurons. Interestingly, PDGF/PDFGR signaling can elicit paradoxical roles in the CNS, depending on the cell type and the activation stimuli and is implicated in the pathogenesis of various neurodegenerative diseases...
August 2018: Molecular Aspects of Medicine
Barbara Mara Klinkhammer, Jürgen Floege, Peter Boor
Fibrosis is part of a tissue repair response to injury, defined as increased deposition of extracellular matrix. In some instances, fibrosis is beneficial; however, in the majority of diseases fibrosis is detrimental. Virtually all chronic progressive diseases are associated with fibrosis, representing a huge number of patients worldwide. Fibrosis occurs in all organs and tissues, becomes irreversible with time and further drives loss of tissue function. Various cells types initiate and perpetuate pathological fibrosis by paracrine activation of the principal cellular executors of fibrosis, i...
August 2018: Molecular Aspects of Medicine
Natalia Papadopoulos, Johan Lennartsson
Platelet-derived growth factors (PDGF) promotes cell proliferation, survival and migration, primarily of cells of mesenchymal origin. Dysfunction of PDGF signaling has been observed in a wide array of pathological conditions, such as cancer, fibrosis, neurological conditions and atherosclerosis. Reported abnormalities of the PDGF pathway include overexpression or amplification of PDGF receptors (PDGFRs), gain of function point mutations or activating chromosomal translocations. Current development of therapeutic drugs often aims at producing compounds that specifically target interaction between PDGFs and their receptors by specific DNA aptamers and ligand traps, or downregulate PDGFRs with blocking antibodies, or inhibit tyrosine kinase activity of PDGFRs with small molecules...
August 2018: Molecular Aspects of Medicine
Anil Kumar, Xuri Li
PDGFs and their receptors are critical regulators of numerous tissues and organs, including the eye. Extensive studies have shown that PDGFs and their receptors play critical roles in many ocular neovascular diseases, such as neovascular age-related macular degeneration, retinopathy of prematurity, and proliferative vitreoretinopathy. In addition, PDGFs and PDGFRs are also important players in ocular diseases involving the degeneration of retinal neuronal and vascular cells, such as glaucoma and retinitis pigmentosa...
August 2018: Molecular Aspects of Medicine
Weisi Lu, Xuri Li
Vascular stem/progenitor cells (VSCs) include endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and mesenchymal stem cells. VSCs can produce functional and mature vascular cells required to build blood vessels. VSCs therefore play critical roles in vascular repair and regeneration, particularly, in various retinal vasculopathies, in which vascular defects are a devastating pathology. The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are important regulators of numerous physiological events and diseases, and they play key roles in regulating the formation and function of blood vessels...
August 2018: Molecular Aspects of Medicine
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