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Molecular Aspects of Medicine

Natividad R Fuentes, Eunjoo Kim, Yang-Yi Fan, Robert S Chapkin
Proteins are often credited as the macromolecule responsible for performing critical cellular functions, however lipids have recently garnered more attention as our understanding of their role in cell function and human health becomes more apparent. Although cellular membranes are the lipid environment in which many proteins function, it is now apparent that protein and lipid assemblies can be organized to form distinct micro- or nanodomains that facilitate signaling events. Indeed, it is now appreciated that cellular function is partly regulated by the specific spatiotemporal lipid composition of the membrane, down to the nanosecond and nanometer scale...
April 5, 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...
March 26, 2018: Molecular Aspects of Medicine
Eleonora Scorletti, Christopher D Byrne
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism...
March 22, 2018: Molecular Aspects of Medicine
Jean-Marie Galano, Jérôme Roy, Thierry Durand, Jetty Chung-Yung Lee, Jean-Yves Le Guennec, Camille Oger, Marie Demion
ω3 Polyunsaturated fatty acids (ω3 PUFAs) have several biological properties including anti-arrhythmic effects. However, there are some evidences that it is not solely ω3 PUFAs per se that are biologically active but the non-enzymatic oxygenated metabolites of polyunsaturated fatty acids (NEO-PUFAs) like isoprostanes and neuroprostanes. Recent question arises how these molecules take part in physiological homeostasis, show biological bioactivities and anti-inflammatory properties. Furthermore, they are involved in the circulations of childbirth, by inducing the closure of the ductus arteriosus...
March 20, 2018: Molecular Aspects of Medicine
Hee-Yong Kim, Arthur A Spector
N-Docosahexaenoylethanolamine (synaptamide) is an endocannabinoid-like metabolite endogenously synthesized from docosahexaenoic acid (DHA, 22:6n-3), the major omega-3 polyunsaturated fatty acid present in the brain. Although its biosynthetic mechanism has yet to be established, there is a closely linked relationship between the levels of synaptamide and its precursor DHA in the brain. Synaptamide at nanomolar concentrations promotes neurogenesis, neurite outgrowth and synaptogenesis in developing neurons. Synaptamide also attenuates the lipopolysaccharide-induced neuroinflammatory response and reduce the deleterious effects of ethanol on neurogenic differentiation of neural stem cells (NSCs)...
March 20, 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...
March 17, 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...
March 5, 2018: Molecular Aspects of Medicine
Javier I Ottaviani, Christian Heiss, Jeremy P E Spencer, Malte Kelm, Hagen Schroeter
The last 8 years have seen significant developments in our understanding of dietary flavanols and procyanidins in the context of human health and nutrition. During the same time, recognition of the importance of nutrition in primary disease prevention and health maintenance has increased. In addition, the concept of dietary bioactives (food constituents that although not essential to human life and procreation, may nevertheless play an important role in disease risk reduction, primary disease prevention, and healthy aging) has been created and developed...
February 23, 2018: Molecular Aspects of Medicine
Cecilia Lässer, Su Chul Jang, Jan Lötvall
Extracellular vesicles (EVs), such as exosomes and microvesicles, have over the last 10-15 years been recognized to convey key messages in the molecular communication between cells. Indeed, EVs have the capacity to shuttle proteins, lipids, and nucleotides such as RNA between cells, leading to an array of functional changes in the recipient cells. Importantly, the EV secretome changes significantly in diseased cells and under conditions of cellular stress. More recently, it has become evident that the EV secretome is exceptionally diverse, with many different types of EVs being released by a single cell type, and these EVs can be described in terms of differences in density, molecular cargos, and morphology...
April 2018: Molecular Aspects of Medicine
Pradip B Devhare, Ratna B Ray
Extracellular vesicles (EVs) are membrane derived nanometer-sized vesicles. EVs are released by normal, diseased, and transformed cells in vitro and in vivo, and carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. Transferring biological information via EVs to neighboring cells and inter-cellular communication not only maintain physiological functions, but also involve in the pathogenesis of several diseases, including cancer. The aim of this review is to discuss the emerging role of EVs in viral hepatitis, non-alcoholic or alcoholic liver disease and liver cancers...
April 2018: Molecular Aspects of Medicine
Cameron Murphy, Joseph Withrow, Monte Hunter, Yutao Liu, Yao Liang Tang, Sadanand Fulzele, Mark W Hamrick
Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population...
April 2018: Molecular Aspects of Medicine
Cesar G Fraga, Patricia I Oteiza, Monica Galleano
Polyphenols are bioactives claimed to be responsible for some of the health benefits provided by fruit and vegetables. It is currently accepted that the bioactivities of polyphenols can be mostly ascribed to their interactions with proteins and lipids. Such interactions can affect cell oxidant production and cell signaling, and explain in part the ability of polyphenols to promote health. EC can modulate redox sensitive signaling by: i) defining the extent of oxidant levels that can modify cell signaling, function, and fate, e...
February 10, 2018: Molecular Aspects of Medicine
R J Scott Lacombe, Raphaël Chouinard-Watkins, Richard P Bazinet
Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources...
February 8, 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...
February 6, 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...
February 6, 2018: Molecular Aspects of Medicine
Jinmiao Chen, Laurent Rénia, Florent Ginhoux
Advances in single-cell RNA-sequencing have helped reveal the previously underappreciated level of cellular heterogeneity present during cellular differentiation. A static snapshot of single-cell transcriptomes provides a good representation of the various stages of differentiation as differentiation is rarely synchronized between cells. Data from numerous single-cell analyses has suggested that cellular differentiation and development can be conceptualized as continuous processes. Consequently, computational algorithms have been developed to infer lineage relationships between cell types and construct developmental trajectories along which cells are re-ordered such that similarity between successive cell pairs is maximized...
February 2018: Molecular Aspects of Medicine
Claudia Bevilacqua, Bertrand Ducos
Laser microdissection (LM) has become widely democratized over the last fifteen years. Instruments have evolved to offer more powerful and efficient lasers as well as new options for sample collection and preparation. Technological evolutions have also focused on the post-microdissection analysis capabilities, opening up investigations in all disciplines of experimental and clinical biology, thanks to the advent of new high-throughput methods of genome analysis, including RNAseq and proteomics, now globally known as microgenomics, i...
February 2018: Molecular Aspects of Medicine
Yu Fen Samantha Seah, Hongxing Hu, Christoph A Merten
Single-cell technology has a major impact on the field of immunology. It enables the kinetics and logic of immune signaling and immune cell migration to be elucidated, facilitates antibody screening and allows massively parallelized analysis of B- and T-cell repertoires. Impressive progress has been made over the last decade, strongly boosted by microfluidic approaches. In this review, we summarize the most powerful microfluidic systems based on continuous flow, nanowells, valves and droplets and we analyze their benefits for phenotypic characterization, drug discovery and next generation sequencing experiments...
February 2018: Molecular Aspects of Medicine
Lu Wen, Fuchou Tang
Epigenetic regulation plays crucial roles in the development and disease processes. Since different cell types with distinct epigenetic characteristics are always intermingled together in the tissues or organs, the single cell analysis provides a universal resolution for dissecting their intrinsic complexities. In this review, we discuss recent advances of developing single cell epigenome sequencing techniques for profiling DNA modifications (5mC, 5hmC, 5fC and 5caC), chromatin accessibility, histone modifications, protein-DNA interactions and three-dimensional genome architecture (Hi-C) in an individual mammalian cell...
February 2018: Molecular Aspects of Medicine
Benjamin J Povinelli, Alba Rodriguez-Meira, Adam J Mead
The hematopoietic system is well established as a paradigm for the study of cellular hierarchies, their disruption in disease and therapeutic use in regenerative medicine. Traditional approaches to study hematopoiesis involve purification of cell populations based on a small number of surface markers. However, such population-based analysis obscures underlying heterogeneity contained within any phenotypically defined cell population. This heterogeneity can only be resolved through single cell analysis. Recent advances in single cell techniques allow analysis of the genome, transcriptome, epigenome and proteome in single cells at an unprecedented scale...
February 2018: Molecular Aspects of Medicine
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