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Molecular Aspects of Medicine

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https://www.readbyqxmd.com/read/28202385/long-term-consequences-of-disrupting-adenosine-signaling-during-embryonic-development
#1
REVIEW
Scott A Rivkees, Christopher C Wendler
There is growing evidence that disruption in the prenatal environment can have long-lasting effects on an individual's health in adulthood. Research on the fetal programming of adult diseases, including cardiovascular disease, focuses on epi-mutations, which alter the normal pattern of epigenetic factors such as DNA methylation, miRNA expression, or chromatin modification, rather than traditional genetic alteration. Thus, understanding how in utero chemical exposures alter epigenetics and lead to adult disease is of considerable public health concern...
February 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28159546/leishmania-infections-molecular-targets-and-diagnosis
#2
REVIEW
Mohammad Akhoundi, Tim Downing, Jan Votýpka, Katrin Kuhls, Julius Lukeš, Arnaud Cannet, Christophe Ravel, Pierre Marty, Pascal Delaunay, Mohamed Kasbari, Bruno Granouillac, Luigi Gradoni, Denis Sereno
Progress in the diagnosis of leishmaniases depends on the development of effective methods and the discovery of suitable biomarkers. We propose firstly an update classification of Leishmania species and their synonymies. We demonstrate a global map highlighting the geography of known endemic Leishmania species pathogenic to humans. We summarize a complete list of techniques currently in use and discuss their advantages and limitations. The available data highlights the benefits of molecular markers in terms of their sensitivity and specificity to quantify variation from the subgeneric level to species complexes, (sub) species within complexes, and individual populations and infection foci...
January 31, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28153453/bile-acids-and-their-receptors
#3
REVIEW
Emmanuelle Martinot, Lauriane Sèdes, Marine Baptissart, Jean-Marc Lobaccaro, Françoise Caira, Claude Beaudoin, David H Volle
Primary bile acids are synthetized from cholesterol within the liver and then transformed by the bacteria in the intestine to secondary bile acids. In addition to their involvement in digestion and fat solubilization, bile acids also act as signaling molecules. Several receptors are sensors of bile acids. Among these receptors, this review focuses on the nuclear receptor FXRα and the G-protein-coupled receptor TGR5. This review briefly presents the potential links between bile acids and cancers that are discussed in more details in the other articles of this special issue of Molecular Aspects of Medicine focused on "Bile acids, roles in integrative physiology and physiopathology"...
January 30, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28153452/adenosine-receptors-modulators-of-lipid-availability-that-are-controlled-by-lipid-levels
#4
REVIEW
Andrea Leiva, Enrique Guzmán-Gutiérrez, Susana Contreras-Duarte, Bárbara Fuenzalida, Claudette Cantin, Lorena Carvajal, Rocío Salsoso, Jaime Gutiérrez, Fabián Pardo, Luis Sobrevia
Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone, thrombosis, immune response, inflammation, and angiogenesis. This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models. Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity, leading to reduction of the circulating fatty acid levels...
January 30, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28119071/of-mice-and-humans-through-the-looking-glass-reflections-on-epigenetics-of-lipid-metabolism
#5
REVIEW
Raffaella Longo, Alessandra Ferrari, Monica Zocchi, Maurizio Crestani
Over the past decade, epigenetics has emerged as a new layer of regulation of gene expression. Several investigations demonstrated that nutrition and lifestyle regulate lipid metabolism by influencing epigenomic remodeling. Studies on animal models highlighted the role of epigenome modifiers in specific metabolic contexts and established clear links between dysregulation of epigenetic mechanisms and metabolic dysfunction. The relevance of findings in animal models has been translated to humans, as epigenome-wide association studies (EWAS) deeply investigated the relationship between lifestyle and epigenetics in human populations...
January 21, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28109856/adenosine-contribution-to-normal-renal-physiology-and-chronic-kidney-disease
#6
REVIEW
Carlos Oyarzún, Wallys Garrido, Sebastián Alarcón, Alejandro Yáñez, Luis Sobrevia, Claudia Quezada, Rody San Martín
Adenosine is a nucleoside that is particularly interesting to many scientific and clinical communities as it has important physiological and pathophysiological roles in the kidney. The distribution of adenosine receptors has only recently been elucidated; therefore it is likely that more biological roles of this nucleoside will be unveiled in the near future. Since the discovery of the involvement of adenosine in renal vasoconstriction and regulation of local renin production, further evidence has shown that adenosine signaling is also involved in the tubuloglomerular feedback mechanism, sodium reabsorption and the adaptive response to acute insults, such as ischemia...
January 18, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28104382/molecular-implications-of-adenosine-in-obesity
#7
REVIEW
Fabián Pardo, Roberto Villalobos-Labra, Delia I Chiarello, Rocío Salsoso, Fernando Toledo, Jaime Gutierrez, Andrea Leiva, Luis Sobrevia
Adenosine has broad activities in organisms due to the existence of multiple receptors, the differential adenosine concentrations necessary to activate these receptors and the presence of proteins able to synthetize, degrade or transport this nucleoside. All adenosine receptors have been reported to be involved in glucose homeostasis, inflammation, adipogenesis, insulin resistance, and thermogenesis, indicating that adenosine could participate in the process of obesity. Since adenosine seems to be associated with several effects, it is plausible that adenosine participates in the initiation and development of obesity or may function to prevent it...
January 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28093236/extracellular-atp-and-adenosine-the-yin-and-yang-in-immune-responses
#8
REVIEW
M M Faas, T Sáez, P de Vos
Extracellular adenosine 5'-triphosphate (ATP) and adenosine molecules are intimately involved in immune responses. ATP is mostly a pro-inflammatory molecule and is released during hypoxic condition and by necrotic cells, as well as by activated immune cells and endothelial cells. However, under certain conditions, for instance at low concentrations or at prolonged exposure, ATP may also have anti-inflammatory properties. Extracellular ATP can activate both P2X and P2Y purinergic receptors. Extracellular ATP can be hydrolyzed into adenosine in a two-step enzymatic process involving the ectonucleotidases CD39 (ecto-apyrase) and CD73...
January 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28089907/adenosine-and-preeclampsia
#9
REVIEW
Rocío Salsoso, Marcelo Farías, Jaime Gutiérrez, Fabián Pardo, Delia I Chiarello, Fernando Toledo, Andrea Leiva, Alfonso Mate, Carmen M Vázquez, Luis Sobrevia
Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28089906/adenosine-signaling-in-diabetes-mellitus-and-associated-cardiovascular-and-renal-complications
#10
REVIEW
Maria Peleli, Mattias Carlstrom
Diabetes mellitus is characterized by abnormal glucose and lipid metabolism, and subsequent hyperglycemia and dyslipidemia, which results from defects in pancreatic islet beta-cells insulin secretion and/or decreased insulin sensitivity in metabolically active organs (i.e. liver, skeletal muscle and adipose tissue). Accumulating evidence highlights a critical role for the adenosine system in the regulation of insulin and glucose homeostasis and the pathophysiology of type 2 diabetes (T2D). Adenosine is a key diverse extracellular signaling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors (i...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28088486/pharmacological-targeting-of-adenosine-receptor-signaling
#11
REVIEW
Maria Peleli, Bertil B Fredholm, Luis Sobrevia, Mattias Carlström
Adenosine receptor signaling plays important roles in normal physiology, but is also known to modulate the development or progression of several different diseases. The design of new, efficient, and safe pharmacological approaches to target the adenosine system may have considerable therapeutic potential, but is also associated with many challenges. This review summarizes the main challenges of adenosine receptor targeted treatment including tolerance, disease stage, cell type-specific effects, caffeine intake, adenosine level assessment and receptor distribution in vivo...
January 12, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28088487/adenosine-receptors-and-caffeine-in-retinopathy-of-prematurity
#12
REVIEW
Jiang-Fan Chen, Shuya Zhang, Rong Zhou, Zhenlang Lin, Xiaohong Cai, Jing Lin, Yuqing Huo, Xiaoling Liu
Retinopathy of prematurity (ROP) is a major cause of childhood blindness in the world and is caused by oxygen-induced damage to the developing retinal vasculature, resulting in hyperoxia-induced vaso-obliteration and subsequent delayed retinal vascularization and hypoxia-induced pathological neovascularization driven by vascular endothelial growth factor (VEGF) signaling pathway in retina. Current anti-VEGF therapy has shown some effective in a clinical trial, but is associated with the unintended effects on delayed eye growth and retinal vasculature development of preterm infants...
January 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27915051/low-but-not-high-dose-caffeine-is-a-readily-available-probe-for-adenosine-actions
#13
REVIEW
Bertil B Fredholm, Jiangning Yang, Yingqing Wang
Caffeine is very widely used and knowledge of its mode of action can be used to gain an understanding of basal physiological regulation. This review makes the point that caffeine is - in low doses - an antagonist of adenosine acting at A1, A2A and A2B receptors. We use published and unpublished data to make the point that high dose effects of caffeine are not only qualitatively different but have a different underlying mechanism. Therefore one must be careful in only using epidemiological or experimental data where rather low doses of caffeine are used to draw conclusions about the physiology and pathophysiology of adenosine...
November 30, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27890600/folate-status-and-colorectal-cancer-risk-a-2016-update
#14
REVIEW
Joel B Mason, San Yuan Tang
The consensus of epidemiologic evidence indicates that an abundant intake of foodstuffs rich in folate conveys protection against the development of colorectal cancer, and perhaps some other common cancers as well. Pre-clinical models substantiate that the relationship is a genuinely causal one. Pre-clinical models have also lent mechanistic insights into the biochemical and molecular pathways by which adequate folate exposure conveys these protective effects, and human studies are beginning to confirm the relevance of this mechanistic understanding to human cancer biology...
November 24, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27890599/adenosine-in-sperm-physiology
#15
REVIEW
Ilaria Bellezza, Alba Minelli
It has long been known that ATP and cAMP are deeply involved in sperm function whereas the role of adenosine and adenosine receptors is still far from being totally construed. The presence of adenosine in male reproductive tract and adenosine receptors on spermatozoa is strongly suggestive of a functional role of these receptors in sperm physiology and function. Spermatozoa are highly differentiated cells with fertility as the only goal. This paper, by an extensive review of the literature, outlines our current understanding of the role and effects of adenosine and adenosine receptors in spermatogenesis and in the acquisition of sperm fertilizing capacity which occurs in the femal genital tract, where the motile sperm fertilize an egg to form a zygote...
November 24, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#16
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27876557/targeting-nuclear-thymidylate-biosynthesis
#17
REVIEW
James Chon, Patrick J Stover, Martha S Field
Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA synthesis and proper cell division, and therefore has been an attractive therapeutic target. Folate analogs, known as antifolates, and nucleotide analogs that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway and are commonly used in cancer treatment. In this review, we examine the mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP synthesis inhibitors, function in cancer treatment in light of emerging evidence that dTMP synthesis occurs in the nucleus...
February 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27876556/homocysteine-and-disease-causal-associations-or-epiphenomenons
#18
REVIEW
Luciana Hannibal, Henk J Blom
Nutritional and genetic deficiencies of folate and vitamin B12 lead to elevation of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The sources and role of elevated plasma Hcy in pathology continues to be a subject of intense scientific debate. Whether a cause, mediator or marker, little is known about the molecular mechanisms and interactions of Hcy with cellular processes that lead to disease. The use of folic acid reduces the incidence of neural tube defects, but the effect of Hcy-lowering interventions with folic acid in cardiovascular disease and cognitive impairment remains controversial...
February 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27876554/interaction-between-excess-folate-and-low-vitamin-b12-status
#19
REVIEW
Ligi Paul, Jacob Selhub
Current epidemiological evidence suggests that an imbalance of high folate status and low vitamin B12 status is associated with negative health outcomes in older adults and children. Such an imbalance during pregnancy also predisposes women to diabetes and their offspring to insulin resistance and adiposity and low birthweight. In older adults, vitamin B12 status can remain low despite adequate intake due to age-related decline in vitamin B12 absorption. Pregnant women are exposed to folic acid at varying doses depending on the prenatal care prescribed in different countries...
February 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27664775/the-proton-coupled-folate-transporter-pcft-slc46a1-and-the-syndrome-of-systemic-and-cerebral-folate-deficiency-of-infancy-hereditary-folate-malabsorption
#20
REVIEW
Rongbao Zhao, Srinivas Aluri, I David Goldman
The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRα) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in "cerebral folate deficiency" (CFD), the designation for this disorder...
February 2017: Molecular Aspects of Medicine
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