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Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
Naeim Ehtesham, Fariborz Khorvash, Majid Kheirollahi
MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs)...
October 17, 2016: Journal of Molecular Neuroscience: MN
Qian Wang, Renato Polimanti, Henry R Kranzler, Lindsay A Farrer, Hongyu Zhao, Joel Gelernter
Schizophrenia (SZ) and HIV infection are serious disorders with a complex phenotypic relationship. Observational studies have described their comorbidity; their genetic correlation is not well studied. We performed extensive analysis in search of common genetic factors for SZ and HIV, and their relationship with risky sexual behavior (RSB). Summary statistics from genome-wide association studies of HIV infection and schizophrenia were obtained and 2379 European Americans were genotyped and assessed for RSB score...
October 17, 2016: Human Genetics
Miroslav Zeman, Marek Vecka, František Perlík, Barbora Staňková, Robert Hromádka, Eva Tvrzická, Jakub Širc, Jakub Hrib, Aleš Žák
Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein[a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL. In addition to its pronounced hypolipidemic action, niacin exerts many other, non-hypolipidemic effects (e.g., antioxidative, anti-inflammatory, antithrombotic), which favorably influence the development and progression of atherosclerosis...
December 1, 2016: Acta Pharmaceutica
Domenico Maurizio Toraldo, Michele De Benedetto, Luana Conte, Francesco De Nuccio
Obstructive sleep apnea (OSA) is characterized by repetitive interruptions of breathing, causing a Chronic Intermittent Hypoxia (CIH) that can be a key step in the development and progression of cardiovascular diseases. Nowadays, in fact, there is scientific evidence showing the close relationship between OSA and atherosclerosis, even in those patients who do not show co-morbidities such as hypertension, diabetes, high levels of low-density lipoprotein (LDL), cigarette smoking and obesity, which normally are able to activate the endothelium...
October 7, 2016: Current Vascular Pharmacology
Chen Zhang, Cassandra L Miller, Rakshya Gorkhali, Juan Zou, Kenneth Huang, Edward M Brown, Jenny J Yang
Ca(2+)-sensing receptors (CaSRs) play a central role in regulating extracellular calcium concentration ([Ca(2+)]o) homeostasis and many (patho)physiological processes in multiple organs. This regulation is orchestrated by a cooperative response to extracellular stimuli such as small changes in Ca(2+), Mg(2+), amino acids, and other ligands. In addition, CaSR is a pleiotropic receptor regulating several intracellular signaling pathways, including calcium mobilization and intracellular calcium oscillation. Nearly 200 mutations and polymorphisms have been found in CaSR in relation to a variety of human disorders associated with abnormal Ca(2+) homeostasis...
2016: Frontiers in Physiology
Felix Kliewe, Jacqueline Kumme, Mathias Grigat, Stefan Hintze, Hans-Joachim Schüller
Structural genes of phospholipid biosynthesis in the yeast S. cerevisiae are transcribed when precursor molecules inositol and choline (IC) are limiting. Gene expression is stimulated by the heterodimeric activator Ino2/Ino4 which binds to ICRE (inositol/choline-responsive element) promoter sequences. Activation is prevented by repressor Opi1, counteracting Ino2 when high concentrations of IC are available. Here we show that ICRE-dependent gene activation is not only repressed by an excess of IC but also under conditions of phosphate starvation...
October 15, 2016: Yeast
Ana Cecilia Gomes Silva, Daniela Volcan Almeida, Bruna Felix Nornberg, Jessica Ribeiro Pereira, Diego Martins Pires, Carine Dahl Corcini, Antonio Sergio Varela Junior, Luis Fernando Marins
Growth hormone (GH) transgenesis presents a high potential application in aquaculture. However, excess GH may have serious consequences due to pleiotropic actions. In order to study these effects in zebrafish (Danio rerio), two transgenic lines were developed. The first expresses GH ubiquitously and constitutively (F0104 line), while the second expresses the GH receptor in a muscle-specific manner (Myo-GHR line). Results from the F0104 line showed accelerated growth but increased reproductive difficulties, while Myo-GHR did not show the expected increase in muscle mass...
October 14, 2016: Transgenic Research
Torsten Will, Henrike Schmidtberg, Marisa Skaljac, Andreas Vilcinskas
Heat shock protein 83 (HSP83) is homologous to the chaperone HSP90. It has pleiotropic functions in Drosophila melanogaster, including the control of longevity and fecundity, and facilitates morphological evolution by buffering cryptic deleterious mutations in wild populations. In the pea aphid Acyrthosiphon pisum, HSP83 expression is moderately induced by bacterial infection but upregulated more strongly in response to heat stress and fungal infection. Stress-inducible heat shock proteins are of considerable evolutionary and ecological importance because they are known to buffer environmental variation and to influence fitness under non-optimal conditions...
October 14, 2016: Development Genes and Evolution
Hector R Martínez, César E Escamilla-Ocañas, Juan Miguel Tenorio-Pedraza, David Gómez-Almaguer, Jose Carlos Jaime-Perez, Leticia A Olguín-Ramírez, Sergio Salazar-Marioni, María Teresa González-Garza
INTRODUCTION: Increased cytokine expression is a prominent finding in amyotrophic lateral sclerosis (ALS). Due to their interdependence and pleiotropism, interpretation of CSF concentrations of a single cytokine is challenging. We describe a cytokine analysis in ALS patients using a pathway-based statistical method to identify changes in the whole cytokine network. METHODS: We analyzed 19 cytokines in CSF of ALS patients and controls. An equality of concentration matrices was conducted that allowed us to evaluate disturbances in the relationship of cytokines between controls and ALS patients with less and more than 12months of disease length...
October 11, 2016: Cytokine
Chiara Santulli, Claudia Brizi, Matteo Micucci, Ambra Del Genio, Assunta De Cristofaro, Federica Bracco, Giuseppina Lucia Pepe, Ilaria Di Perna, Roberta Budriesi, Alberto Chiarini, Maria Frosini
Ischemic brain injury is one of the most important causes of death worldwide. The use of one-drug-multi-target agents based on natural compounds is a promising therapeutic option for cerebral ischemia due to their pleiotropic properties. This study assessed the neuroprotective properties of Castanea sativa Mill. bark extract (ENC) in human astrocytoma U-373 MG cells subjected to oxygen-glucose deprivation and reperfusion and rat cortical slices subjected to ischemia-like conditions or treated with glutamate or hydrogen peroxide...
October 14, 2016: Journal of Cellular Biochemistry
Shahram Ala, Mina Alvandipour, Majid Saeedi, Maliheh Hamidian, Afshin Shiva, Nasrin Rahmani, Fatemeh Faramarzi
BACKGROUND: Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor widely used in treatment of hypercholesterolemia and prevention of coronary heart disease and has various pleiotropic effects. In this study, the efficacy of atorvastatin emulgel (2 %) in reducing postoperative pain at rest, pain during defecation and analgesic requirement after open hemorrhoidectomy was investigated. METHODS: A total of 66 patients with third- and fourth-degree hemorrhoids undergoing open hemorrhoidectomy were included in this prospective, double-blind, randomized controlled trial...
October 13, 2016: World Journal of Surgery
Maurizio Sabbatini, Michela Bosetti, Alessia Borrone, Liah Moalem, Antonio Taveggia, Giovanni Verna, Mario Cannas
Apoptosis and inflammatory processes may be at the basis of reducing graft survival. Erythropoietin is a tissue-protective hormone with pleiotropic potential, and it interferes with the activities of pro-inflammatory cytokines and stimulates healing following injury, preventing destruction of tissue surrounding the injury site. It may represent a useful tool to increase the autograft integration. Through the use of multipanel kit cytokine analysis we have detected the cytokines secreted by human tissue adipose mass seeded in culture following withdrawal by Coleman's modified technique in three groups: control, after lipopolysaccharides stimulation and after erythropoietin stimulation...
January 2016: Journal of Tissue Engineering
Tony Karlsborn, A K M Firoj Mahmud, Hasan Tükenmez, Anders S Byström
INTRODUCTION: The Elongator complex, comprising six subunits (Elp1p-Elp6p), is required for formation of 5-carbamoylmethyl (ncm(5)) and 5-methoxycarbonylmethyl (mcm(5)) side chains on wobble uridines in 11 out of 42 tRNA species in Saccharomyces cerevisiae. Loss of these side chains reduces the efficiency of tRNA decoding during translation, resulting in pleiotropic phenotypes. Overexpression of hypomodified [Formula: see text], which in wild-type strains are modified with mcm(5)s(2)U, partially suppress phenotypes of an elp3Δ strain...
2016: Metabolomics: Official Journal of the Metabolomic Society
Denada Dibra, Abhisek Mitra, Melissa Newman, Xueqing Xia, Camille Keenan, Jeffry J Cutrera, J Michael Mathis, Xiao-Jing Wang, Jeffrey Myers, Shulin Li
Establishment of a permissive pre-malignant niche in concert with mutant stem are key triggers to initiate skin carcinogenesis. An understudied area of research is finding upstream regulators of both these triggers. IL27, a pleiotropic cytokine with both pro- and anti-inflammatory properties, was found to be a key regulator of both. Two step skin carcinogenesis model and K15-KRASG12D mouse model were used to understand the role of IL27 in skin tumors. CD11b-/- mice and small-molecule of ETAR signaling (ZD4054) inhibitor were used in vivo to understand mechanistically how IL27 promotes skin carcinogenesis...
October 12, 2016: Oncotarget
Qinghong Wang, Jianguo Liu
IL-27 is a pleiotropic cytokine that has diverse immune regulatory activities under both physiological and pathological conditions. IL-27 enhances the functions of Th1 and CD8(+) T cells, promotes the development of Tfh and Tr1, and suppresses the functions of Th2, Treg, Th9, and Th17 cells. IL-27 is also involved in regulation of immune responses of B cells, NK, DCs, and macrophages. IL-27 production is strictly regulated at both transcriptional and posttranscriptional levels. Given its broad effects on immune regulation, IL-27 has been implicated in the pathogeneses of autoimmune and infectious diseases as well as cancers...
2016: Advances in Experimental Medicine and Biology
Helen Ross-Adams, Stephen Ball, Kate Lawrenson, Silvia Halim, Roslin Russell, Claire Wells, Siri H Strand, Torben F Ørntoft, Melissa Larson, Sebastian Armasu, Charles E Massie, Mohammad Asim, Martin M Mortensen, Michael Borre, Kathryn Woodfine, Anne Y Warren, Alastair D Lamb, Jonathan Kay, Hayley Whitaker, Antonio Ramos-Montoya, Adele Murrell, Karina D Sørensen, Brooke L Fridley, Ellen L Goode, Simon A Gayther, John Masters, David E Neal, Ian G Mills
Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues...
October 9, 2016: Oncotarget
Li Li, Yan Ma, Shuang Liu, Jin Zhang, Xin-Yan Xu
Human papillomavirus (HPV)-specific CD8(+) T cells are present in HPV-infected cervical cancer patients and have demonstrated potent antitumor properties. However, these cells cannot control tumor progression in most patients. To investigate the underlying mechanisms involved in suppressing or promoting CD8(+) T cell functions, we focused on interleukin 10 (IL-10), a pleiotropic cytokine with controversial roles in antitumor immunity. We found that compared to healthy controls, circulating CD8(+) T cells in HPV 16-infected cervical cancer patients expressed significantly higher levels of IL-10...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Nathan D Schwalm, Guy E Townsend, Eduardo A Groisman
: The utilization of simple sugars is widespread across all domains of life. In contrast, the breakdown of complex carbohydrates is restricted to a subset of organisms. A regulatory paradigm for integration of complex polysaccharide breakdown with simple sugar utilization was established in the mammalian gut symbiont Bacteroides thetaiotaomicron, whereby sensing of monomeric fructose regulates catabolism of both fructose and polymeric fructans. We now report that a different regulatory paradigm governs utilization of monomeric arabinose and the arabinose polymer arabinan...
October 11, 2016: MBio
Hui Zhao, Wei Wang, Jie Zhang, Tuo Liang, Guang-Pu Fan, Zhi-Wei Wang, Pei-De Zhang, Xu Wang, Jing Zhang
BACKGROUND: Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis. METHOD: Eight-week-old cTnTR(141W) transgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression...
2016: American Journal of Translational Research
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