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Molecular Aspects of Medicine

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https://read.qxmd.com/read/30710596/mendelian-randomisation-a-powerful-and-inexpensive-method-for-identifying-and-excluding-non-genetic-risk-factors-for-colorectal-cancer
#1
REVIEW
Alex J Cornish, Ian P M Tomlinson, Richard S Houlston
Colorectal cancer (CRC) is the third most common cancer in economically developed countries and a major cause of cancer-related mortality. The importance of lifestyle and diet as major determinants of CRC risk is suggested by differences in CRC incidence between countries and in migration studies. Previous observational epidemiological studies have identified associations between modifiable environmental risk factors and CRC, but these studies can be susceptible to reverse causation and confounding, and their results can therefore conflict...
January 30, 2019: Molecular Aspects of Medicine
https://read.qxmd.com/read/30664911/involvement-of-a-2b-adenosine-receptors-as-anti-inflammatory-in-gestational-diabesity
#2
REVIEW
Carolina Cabalín, Roberto Villalobos-Labra, Fernando Toledo, Luis Sobrevia
Pregnant women that are obese may develop gestational diabetes mellitus (GDM) configuring a new metabolic condition referred to as gestational diabesity. The metabolic alterations seen in gestational diabesity include a combination of an exacerbated pro-inflammatory state and fetoplacental endothelial dysfunction. Also, gestational diabesity associates with supra-physiological extracellular concentration of adenosine in the foetoplacental blood. Since adenosine plays a central role in the inflammatory response in GDM and obesity, it is likely that this nucleoside will play a similar role in gestational diabesity...
January 18, 2019: Molecular Aspects of Medicine
https://read.qxmd.com/read/30610887/impaired-signalling-pathways-mediated-by-extracellular-vesicles-in-diabesity
#3
REVIEW
Tamara Sáez, Fernando Toledo, Luis Sobrevia
Diabesity, obesity, and type 2 diabetes mellitus (T2DM) are the most prevalent diseases nowadays and associate with high risk of cardiovascular complications. The impaired signalling pathways associated with the metabolism of D-glucose, lipids, and insulin have been studied for many years aiming to understand the cellular mechanisms of these diseases. Extracellular vesicles (EVs), including exosomes and microvesicles, carry different microRNAs or proteins as cargoes, acting as a mechanism of cell-to-cell communication to modulate different cell functions altering the metabolic regulatory pathways...
January 14, 2019: Molecular Aspects of Medicine
https://read.qxmd.com/read/30513311/diabesity-associated-oxidative-and-inflammatory-stress-signalling-in-the-early-human-placenta
#4
REVIEW
Denise Hoch, Martin Gauster, Sylvie Hauguel-de Mouzon, Gernot Desoye
Early pregnancy is characterized by a series of complex and tightly regulated events to ultimately establish implantation and early placental development. One of the key events is the opening of the decidual spiral arteries into the intervillous space. It leads to a rise in oxygen tension in the intervillous space and the placenta and will induce transcriptional and translational changes of oxygen-sensitive molecules including antioxidants. Diabetes and/or obesity ('diabesity') are associated with changes in the maternal environment, which can affect any of the distinct developmental processes ensuing modifications of onset or magnitude of oxygen tension changes...
December 15, 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30513310/diabesity-and-mood-disorders-multiple-links-through-the-microbiota-gut-brain-axis
#5
REVIEW
Aitak Farzi, Ahmed M Hassan, Geraldine Zenz, Peter Holzer
The global prevalence of diabesity is on the rise, and the clinical, social and economic health burden arising from this epidemic is aggravated by a significant co-morbidity of diabesity with neuropsychiatric disease, particularly depression. Importantly, not only is the prevalence of mood disorders elevated in patients with type 2 diabetes, depressed patients are also more prone to develop diabetes. This reciprocal relationship calls for a molecular and systemic analysis of diabesity-brain interactions to guide preventive and therapeutic strategies...
December 7, 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30472165/endoplasmic-reticulum-stress-and-development-of-insulin-resistance-in-adipose-skeletal-liver-and-foetoplacental-tissue-in-diabesity
#6
REVIEW
Roberto Villalobos-Labra, Mario Subiabre, Fernando Toledo, Fabián Pardo, Luis Sobrevia
Diabesity is an abnormal metabolic condition shown by patients with obesity that develop type 2 diabetes mellitus. Patients with diabesity present with insulin resistance, reduced vascular response to insulin, and vascular endothelial dysfunction. Along with the several well-described mechanisms of insulin resistance, a state of endoplasmic reticulum (ER) stress, where the primary human targets are the adipose tissue, liver, skeletal muscle, and the foetoplacental vasculature, is apparent. ER stress characterises by the activation of the unfolded protein response via three canonical ER stress sensors, i...
November 27, 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30755310/pathophysiology-of-organ-and-tissue-fibrosis
#7
EDITORIAL
Maurizio Parola, Massimo Pinzani
No abstract text is available yet for this article.
February 2019: Molecular Aspects of Medicine
https://read.qxmd.com/read/30290200/endocannabinoids-exercise-pain-and-a-path-to-health-with-aging
#8
REVIEW
Bruce A Watkins
Physical activity is an important lifestyle factor for growth, development, and sustained health throughout life. In recent years, the benefits of physical activity have drawn more attention to its physiological effects on the body, including well-being. The endocannabinoid system (ECS) has emerged as a focal point to ascertain the mechanisms for how exercise benefits the body and how it reduces or controls pain. The ECS, its ligands [the endocannabinoids (eCB)], receptors (CB1 and CB2), enzymes for the synthesis and degradation of eCB, and the polyunsaturated fatty acids (PUFA) that serve as substrates, comprise a powerful biological organization of multiple controls that affects mood, inflammation, pain, and other neurological aspects of the central nervous system and peripheral nervous system...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30244005/docosanoids-and-elovanoids-from-omega-3-fatty-acids-are-pro-homeostatic-modulators-of-inflammatory-responses-cell-damage-and-neuroprotection
#9
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30102930/omega-3-fatty-acids-and-leukocyte-endothelium-adhesion-novel-anti-atherosclerotic-actions
#10
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29627343/omega-3-fatty-acids-membrane-remodeling-and-cancer-prevention
#11
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29572110/biological-activities-of-non-enzymatic-oxygenated-metabolites-of-polyunsaturated-fatty-acids-neo-pufas-derived-from-epa-and-dha-new-anti-arrhythmic-compounds
#12
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29572109/n-docosahexaenoylethanolamine-a-neurotrophic-and-neuroprotective-metabolite-of-docosahexaenoic-acid
#13
REVIEW
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 reduces the deleterious effects of ethanol on neurogenic differentiation of neural stem cells (NSCs)...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29544992/omega-3-fatty-acids-and-non-alcoholic-fatty-liver-disease-evidence-of-efficacy-and-mechanism-of-action
#14
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29329795/omega-3-fatty-acids-and-adipose-tissue-biology
#15
REVIEW
Ondrej Kuda, Martin Rossmeisl, Jan Kopecky
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL)...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29325757/the-role-of-fatty-acids-and-their-endocannabinoid-like-derivatives-in-the-molecular-regulation-of-appetite
#16
REVIEW
Renger F Witkamp
Intake, absorption and synthesis of fatty acids, including those produced by the intestinal microbiota are tightly monitored via specific receptors and, indirectly through their conversion into a variety of signalling molecules. The resulting information is integrated and translated to different physiological processes, including the regulation of appetite and satiation. Direct chemosensing of fatty acids takes place via interaction with free fatty acid (FFA) and other receptors. These are present in the oronasal cavity and along the entire gastrointestinal tract, in various other tissues, and, for some receptors also in brain...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/29305120/brain-docosahexaenoic-acid-uptake-and-metabolism
#17
REVIEW
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...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/28887275/ffa4-gpr120-as-a-fatty-acid-sensor-involved-in-appetite-control-insulin-sensitivity-and-inflammation-regulation
#18
REVIEW
Dong-Soon Im
Unsaturated long-chain fatty acids have been suggested to be beneficial in the context of cardiovascular disorders based in epidemiologic studies conducted in Greenland and Mediterranean. DHA and EPA are omega-3 polyunsaturated fatty acids that are plentiful in fish oil, and oleic acid is an omega-9 monounsaturated fatty acid, rich in olive oil. Dietary intake of these unsaturated long-chain fatty acids have been associated with insulin sensitivity and weight loss, which contrasts with the impairment of insulin sensitivity and weight gain associated with high intakes of saturated long-chain fatty acids...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/28802833/new-pro-resolving-n-3-mediators-bridge-resolution-of-infectious-inflammation-to-tissue-regeneration
#19
REVIEW
Charles N Serhan, Nan Chiang, Jesmond Dalli
While protective, the acute inflammatory response when uncontrolled can lead to further tissue damage and chronic inflammation that is now widely recognized to play important roles in many commonly occurring diseases, such as cardiovascular disease, neurodegenerative diseases, metabolic syndrome, and many other diseases of significant public health concern. The ideal response to initial challenges of the host is complete resolution of the acute inflammatory response, which is now recognized to be a biosynthetically active process governed by specialized pro-resolving mediators (SPM)...
December 2018: Molecular Aspects of Medicine
https://read.qxmd.com/read/30391234/diabesity-and-antidiabetic-drugs
#20
REVIEW
Joseph M Pappachan, Cornelius J Fernandez, Elias C Chacko
The prevalence of "diabesity" - diabetes related to obesity - has increased tremendously over the past few decades because of the global obesity epidemic. Although bariatric surgery is the best treatment option for patients with diabesity, a majority of patients are managed only with antidiabetic drugs for various reasons. Diabetes control with antidiabetic agents may affect diabesity outcomes positively or negatively because of their effects on body weight and other metabolic parameters. For this reason, rational use of anti-diabetic medications is imperative to optimise long-term management of diabesity...
November 15, 2018: Molecular Aspects of Medicine
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