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https://www.readbyqxmd.com/read/29317679/primed-primary-metabolism-in-systemic-leaves-a-functional-systems-analysis
#1
Jens Schwachtje, Axel Fischer, Alexander Erban, Joachim Kopka
Plants evolved mechanisms to counteract bacterial infection by preparing yet uninfected systemic tissues for an enhanced defense response, so-called systemic acquired resistance or priming responses. Primed leaves express a wide range of genes that enhance the defense response once an infection takes place. While hormone-driven defense signalling and defensive metabolites have been well studied, less focus has been set on the reorganization of primary metabolism in systemic leaves. Since primary metabolism plays an essential role during defense to provide energy and chemical building blocks, we investigated changes in primary metabolism at RNA and metabolite levels in systemic leaves of Arabidopsis thaliana plants that were locally infected with Pseudomonas syringae...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315239/mangiferin-accelerates-glycolysis-and-enhances-mitochondrial-bioenergetics
#2
Zhongbo Liu, Pasha Apontes, Ekaterina V Fomenko, Nan Chi, Victor L Schuster, Irwin J Kurland, Jeffrey E Pessin, Yuling Chi
One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF) that improved glucose utilization in high fat diet (HFD)-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29302811/gene-expression-analysis-in-peripheral-blood-cells-of-patients-with-hereditary-leiomyomatosis-and-renal-cell-cancer-syndrome-hlrcc-identification-of-nrf2-pathway-activation
#3
Carolina Arenas Valencia, Liliana Lopez Kleine, Andres M Pinzon Velasco, Andrea Y Cardona Barreto, Clara E Arteaga Diaz
Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare disease that is inherited in an autosomal dominant manner. Affected patients may develop from cutaneous and uterine leiomyomas to type 2 papillary renal cell carcinoma (Schmidt and Linehan, Int J Nephrol Renovasc Dis 7:253-260, 2014). HLRCC is caused by germline mutations in the FH gene, which produces the fumarate hydratase protein that participates in the tricarboxylic acid cycle during the conversion of fumarate to malate. In FH-deficient cells, high concentrations of fumarate lead to a series of intricate events, which seem to be responsible for the malignant transformation (Yang et al...
January 4, 2018: Familial Cancer
https://www.readbyqxmd.com/read/29291387/a-pilot-study-of-the-metabolomic-profiles-of-saliva-from-female-orthodontic-patients-with-external-apical-root-resorption
#4
Jinling Zhou, Huimin Hu, Renhuan Huang
BACKGROUND: Orthodontically induced external apical root resorption (OIEARR) is one of the most severe complications of orthodontic treatment, which is hard to diagnose at early stage by merely radiographic examination. This study aimed to identify salivary metabolic products using unbiased metabolic profiling in order to discover biomarkers that may indicate OIEARR. MATERIALS AND METHODS: Unstimulated saliva samples were analyzed from 19 healthy orthodontic patients with EARR (n=8) and non-EARR (n=11)...
December 29, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29284039/from-in-vivo-to-in-vitro-major-metabolic-alterations-take-place-in-hepatocytes-during-and-following-isolation
#5
Shamir Cassim, Valérie-Ann Raymond, Pascal Lapierre, Marc Bilodeau
The liver plays a key role in maintaining physiological homeostasis and hepatocytes are largely responsible for this. The use of isolated primary hepatocytes has become an essential tool for the study of nutrient physiology, xenobiotic metabolism and several liver pathologies. Since hepatocytes are removed from their normal environment, the isolation procedure and in vitro culture of primary hepatocytes is partially known to induce undesired metabolic changes. We aimed to perform a thorough metabolic profiling of primary cells before, during and after isolation using state-of-the-art techniques...
2017: PloS One
https://www.readbyqxmd.com/read/29278724/perturbation-of-muscle-metabolism-in-patients-with-muscular-dystrophy-in-early-or-acute-phase-of-disease-in-vitro-high-resolution-nmr-spectroscopy-based-analysis
#6
Niraj Kumar Srivastava, Ramakant Yadav, Somnath Mukherjee, Neeraj Sinha
BACKGROUND: Muscular dystrophy is an inherited muscle disease, characterized by progressive muscle wasting and weakness of variable distribution and severity. METHODS: In vitro, high-resolution proton nuclear magnetic resonance (NMR) spectroscopy based analysis was performed on perchloric acid (PCA) extract of muscle specimens of patients suffering from various types of muscular dystrophies to identify alteration in hydrophilic low-molecular weight substances (aqueous metabolites) as compared to muscle of control subjects as well as in between the types of muscular dystrophy...
December 23, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29274283/mechanistic-and-structural-insight-into-promiscuity-based-metabolism-of-cardiac-drug-digoxin-by-gut-microbial-enzyme
#7
Kundan Kumar, Shubham K Jaiswal, Gaurao V Dhoke, Gopal N Srivastava, Ashok K Sharma, Vineet K Sharma
The recent advances in microbiome studies have revealed the role of gut microbiota in altering the pharmacological properties of oral drugs, which contributes to patient-response variation and undesired effect of the drug molecule. These studies are essential to guide us for achieving the desired efficacy and pharmacological activity of the existing drug molecule or for discovering novel and more effective therapeutics. However, one of the main limitations is the lack of atomistic details on the binding and metabolism of these drug molecules by gut-microbial enzymes...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29251788/nucleic-acid-polymer-rep-2139-and-nucleos-t-ide-analogues-act-synergistically-against-chronic-hepadnaviral-infection-in-vivo
#8
Jonathan Quinet, Catherine Jamard, Madeleine Burtin, Matthieu Lemasson, Sylviane Guerret, Camille Sureau, Andrew Vaillant, Lucyna Cova
Nucleic acid polymer (NAP) REP 2139 treatment was shown to block the release of viral surface antigen in DHBV-infected ducks and in patients with chronic HBV or HBV/HDV infection. In this preclinical study, a novel combination therapy consisting of REP 2139 with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was evaluated in vivo in the chronic DHBV infection model. DHBV-infected duck groups were treated as follows: normal saline (control); REP 2139-Ca; TDF; REP 2139-Ca + TDF; REP 2139-Ca + TDF + ETV...
December 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29248653/hyperpolarized-1-4-13c2-fumarate-enables-magnetic-resonance-based-imaging-of-myocardial-necrosis
#9
Jack J Miller, Angus Z Lau, Per Mose Nielsen, Giles McMullen-Klein, Andrew J Lewis, Nichlas Riise Jespersen, Vicky Ball, Ferdia A Gallagher, Carolyn A Carr, Christoffer Laustsen, Hans Erik Bøtker, Damian J Tyler, Marie A Schroeder
OBJECTIVES: The aim of this study was to determine if hyperpolarized [1,4-13C2]malate imaging could measure cardiomyocyte necrosis after myocardial infarction (MI). BACKGROUND: MI is defined by an acute burst of cellular necrosis and the subsequent cascade of structural and functional adaptations. Quantifying necrosis in the clinic after MI remains challenging. Magnetic resonance-based detection of the conversion of hyperpolarized [1,4-13C2]fumarate to [1,4-13C2]malate, enabled by disrupted cell membrane integrity, has measured cellular necrosis in vivo in other tissue types...
December 8, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29242126/significance-of-elevated-prohibitin-1-levels-in-multiple-sclerosis-patients-lymphocytes-towards-the-assessment-of-subclinical-disease-activity-and-its-role-in-the-central-nervous-system-pathology-of-disease
#10
Madathiparambil Kumaran Satheesh Kumar, Sreepriya Nair, Ullas Mony, Sugavanan Kalingavarman, Ramaswamynathan Venkat, Thanghalazhi Balakrishnan Sivanarayanan, Ayalur Kodakara Kochugovindan Unni, Ramiah Rajeshkannan, Anandakumar Anandakuttan, Sureshkumar Radhakrishnan, Krishnakumar N Menon
Multiple Sclerosis (MS) is an autoimmune-neurodegenerative disorder managed therapeutically by modulating lymphocytes activity which has potential in disease management. Prohibitin 1(PHB) that controls the reactive oxygen species (ROS) and present on the activated lymphocytes have significance in the therapy of MS as esters of fumaric acid that regulates ROS is in phase II/III clinical trials. Thus, we evaluated the expression levels of PHB1 in experimental autoimmune encephalomyelitis (EAE), the animal model of MS and on MS patient's lymphocytes...
December 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29236231/dimethyl-fumarate-a-review-in-moderate-to-severe-plaque-psoriasis
#11
Hannah A Blair
Fumaric acid esters (FAEs) have been used in the treatment of psoriasis in some European countries for over 20 years, and are recommended in the European guidelines for the management of moderate to severe plaque psoriasis. Dimethyl fumarate (Skilarence®; hereafter referred to as DMF) is an orally administered FAE indicated for the treatment of moderate to severe plaque psoriasis in adults in need of systemic medicinal therapy; unlike other available FAEs, it is not formulated in combination with monoethyl fumarate salts...
December 13, 2017: Drugs
https://www.readbyqxmd.com/read/29226743/molecular-docking-and-molecular-dynamics-simulations-of-fumarate-hydratase-and-its-mutant-h235n-complexed-with-pyromellitic-acid-and-citrate
#12
S Subasri, Santosh Kumar Chaudhary, K Sekar, Manish Kesherwani, D Velmurugan
Fumarase catalyzes the reversible, stereospecific hydration/dehydration of fumarate to L-malate during the Kreb's cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0...
December 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29223716/alkaline-degradation-of-lyophilized-dmsa-prior-to-labeling-with-99mtc-identification-and-development-of-the-degradation-pathway-by-hplc-and-ms
#13
Erika V Almeida, Samuel L De Brito
INTRODUCTION: Complexes of technetium-99m (99mTc) with meso-dimercaptosuccinic acid (DMSA) have been widely used as diagnostic agents in nuclear medicine. The degradation products (DP) of DMSA formed under different forced conditions have been identified through HPLC-DAD and LC-MSn studies. In this study, the DMSA kit was subjected to forced degradation under hydrolysis conditions as prescribed by the International Conference on Harmonization (ICH) guideline Q1A. METHODS: Chromatographic separation was accomplished on a reverse phase Shim-Pack VP-ODS (150 mm × 4...
November 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#14
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29216582/cellular-and-mitochondrial-determination-of-low-molecular-mass-organic-acids-by-lc-ms-ms
#15
Jessica Fiori, Elisa Amadesi, Flaminia Fanelli, Concetta Valentina Tropeano, Michela Rugolo, Roberto Gotti
A selective and sensitive method for the determination of low molecular mass organic acids (LMMOAs) in cell and mitochondrial extracts is presented. The analytical method consists in the separation by reversed phase liquid chromatography and detection with tandem mass spectrometry (LC-MS/MS) of the LMMOAs like malic, succinic, formic and citric acids. These acids are among the cellular intermediates of the tricarboxylic acid cycle (TCA), thus their quantitation can provide essential information about the catabolic and anabolic processes occurring in cells under physiological and pathological conditions...
November 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29209134/metabolically-based-liver-damage-pathophysiology-in-patients-with-urea-cycle-disorders-a-new-hypothesis
#16
Ivan Ivanovski, Miloš Ješić, Ana Ivanovski, Livia Garavelli, Petar Ivanovski
The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs...
November 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29208641/alternative-oxidase-isoforms-are-differentially-activated-by-tricarboxylic-acid-cycle-intermediates
#17
Jennifer Selinski, Andreas Hartmann, Gabriele Deckers-Hebestreit, David A Day, James Whelan, Renate Scheibe
The cyanide-insensitive alternative oxidase (AOX) is a non-proton-pumping ubiquinol oxidase that catalyzes the reduction of oxygen to water and is post-translationally regulated by redox mechanisms and 2-oxo acids. Arabidopsis thaliana possesses five AOX isoforms (AOX1A-D and AOX2). AOX1D expression is increased in aox1a knock-out mutants from A. thaliana (especially after restriction of the cytochrome c pathway), but cannot compensate for the lack of AOX1A, suggesting a difference in regulation of these isoforms...
December 5, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29207610/integration-of-micrornaome-proteomics-and-metabolomics-to-analyze-arsenic-induced-malignant-cell-transformation
#18
Youyou Zhou, Yanfu Wang, Juan Su, Zheng Wu, Chao Wang, Weiming Zhong, Xiaomei Liu, Linhui Cui, Xiaoyu Zhou, Yufang Ma, Yi Xin, Jianglin Zhang, Lisha Wu, Xing Hu, Xiang Chen, Cong Peng, MingYang Gao
Long-term exposure to arsenic has been linked to tumorigenesis in different organs and tissues, such as skin; however, the detailed mechanism remains unclear. In this present study, we integrated "omics" including microRNAome, proteomics and metabolomics to investigate the potential molecular mechanisms. Compared with non-malignant human keratinocytes (HaCaT), twenty-six miRNAs were significantly altered in arsenic-induced transformed cells. Among these miRNAs, the differential expression of six miRNAs was confirmed using Q-RT-PCR, representing potential oxidative stress genes...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205274/production-of-cellulosic-organic-acids-via-synthetic-fungal-consortia
#19
Scott A Scholz, Ian Graves, Jeremy J Minty, Xiaoxia Nina Lin
Consolidated bioprocessing is a potential breakthrough technology for reducing costs of biochemical production from lignocellulosic biomass. Production of cellulase enzymes, saccharification of lignocellulose and conversion of the resulting sugars into a chemical of interest occur simultaneously within a single bioreactor. In this study, synthetic fungal consortia composed of the cellulolytic fungus Trichoderma reesei and the production specialist Rhizopus delemar demonstrated conversion of microcrystalline cellulose (MCC) and alkaline pre-treated corn stover to fumaric acid in a fully consolidated manner without addition of cellulase enzymes or expensive supplements such as yeast extract...
December 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29198140/development-of-stabilized-tenofovir-disoproxil-tablet-degradation-profile-stabilization-and-bioequivalence-in-beagle-dogs
#20
Ga-Hui Oh, Joo-Eun Kim, Young-Joon Park
The purpose of this study was to develop a hydrolysis-resistant optimized oral formulation of tenofovir disoproxil (TD) using a stabilizer. To develop a stabilized TD tablet bioequivalent to the commercial TD fumarate (TDF, Viread®) tablet, TD free base was prepared and its degradation profile and stability were investigated. The TD tablet showed antiviral activity, but its absorption was limited in the intestinal tract because of premature degradation. The drug subjected to severe conditions for the stress test was catalyzed under neutral, basic, oxidative, and thermolytic conditions, whereas it was comparatively stable under acidic, photolytic, and humid states...
December 4, 2017: Drug Development and Industrial Pharmacy
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