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dichloroacetate

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https://www.readbyqxmd.com/read/29275483/enhanced-photocatalytic-activity-using-go-tio2-catalyst-for-the-removal-of-dca-solutions
#1
Paula Ribao, Maria J Rivero, Inmaculada Ortiz
This work aimed to optimize high-performance photocatalysts based on graphene oxide/titanium dioxide (GO/TiO2) nanocomposites for the effective degradation of aqueous pollutants. The catalytic activity was tested against the degradation of dichloroacetic acid (DCA), a by-product of disinfection processes that is present in many industrial wastewaters and effluents. GO/TiO2 photocatalysts were prepared using three different methods, hydrothermal, solvothermal, and mechanical, and varying the GO/TiO2 ratio in the range of 1 to 10%...
December 23, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29236244/evaluation-of-disinfection-by-product-formation-during-chlor-am-ination-from-algal-organic-matter-after-uv-irradiation
#2
Shi Chen, Jing Deng, Lei Li, Naiyun Gao
This study evaluated the effect of low-pressure ultraviolet (UV) irradiation on the formation of disinfection by-products (DBPs) from algal organic matter of Microcystis aeruginosa during subsequent chlorination and chloramination. The algal organic matter includes extracellular organic matter (EOM) and intracellular organic matter (IOM). The fluorescence excitation-emission matrix spectra indicated that the humic/fulvic acid-like organics of EOM and the protein-like organics of IOM may be preferentially degraded by UV treatment...
December 13, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29181155/comparison-of-the-effect-of-the-aerobic-glycolysis-inhibitor-dichloroacetate-and-of-the-krebs-cycle-inhibitor-lw6-on-cellular-and-humoral-alloimmunity
#3
Theodoros Eleftheriadis, Georgios Pissas, Athanasios Mavropoulos, Vassilios Liakopoulos, Ioannis Stefanidis
Cell metabolism is altered during T-cell and B-cell activation and differentiation. Clarifying the exact metabolic shifts may lead to the development of new immunosuppressive medications. In this study, the effect of the aerobic glycolysis inhibitor dichloroacetate (DCA) and of the Krebs cycle enzyme malate dehydrogenase 2 (MDH2) inhibitor LW6 on T-cell alloimmune clonal expansion and on alloantibody production, was evaluated. T-cell clonal expansion was assessed in two-way mixed lymphocyte reaction (MLR). Humoral alloimmunity was evaluated by the alloantibody production in one-way MLR...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29143921/dichloroacetate-induced-intracellular-acidification-in-glioblastoma-in-vivo-detection-using-aacid-cest-mri-at-9-4%C3%A2-tesla
#4
Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha
Intracellular pH (pHi) plays an important role in the maintenance of normal cell function, and is maintained within a narrow range by the activity of transporters located at the plasma membrane. Modulation of tumor pHi may influence proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on cellular pH. Amine and amide concentration-independent detection (AACID) is a recently developed CEST contrast method that is intracellular pH (pHi) weighted...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29137417/inhibition-of-retinoic-acid-receptor-%C3%AE-signaling-confers-glycolytic-dependence-and-sensitization-to-dichloroacetate-in-melanoma-cells
#5
Cecilie Abildgaard, Christina Dahl, Ahmad Abdul-Al, Annette Christensen, Per Guldberg
Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129554/development-of-a-novel-observer-reported-outcome-tool-as-the-primary-efficacy-outcome-measure-for-a-rare-disease-randomized-controlled-trial
#6
Peter W Stacpoole, Jonathan Shuster, John L P Seamus Thompson, Sara Jo Nixon, Robert A Prather, Lee Ann Lawson, Baiming Zou, Richard Buchsbaum
We developed an Observer-Reported Outcome (ObsRO) survey instrument to be applied in a multicenter, placebo-controlled, crossover randomized controlled trial of dichloroacetate in children with pyruvate dehydrogenase complex deficiency. The instrument quantifies a subject's at-home level of functionality, as reported by a parent/caregiver, who were instrumental in providing the clinical descriptors and domains that formed the instrument's content. Feasibility testing of the ObsRO tool showed it to be easy to use and comprehensive in capturing the major clinical functional limitations of affected children and requires less than 5min for a parent/caregiver to complete daily...
November 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29107351/drinking-water-disinfection-by-products-during-pregnancy-and-child-neuropsychological-development-in-the-inma-spanish-cohort-study
#7
Cristina M Villanueva, Esther Gracia-Lavedan, Jordi Julvez, Loreto Santa-Marina, Nerea Lertxundi, Jesús Ibarluzea, Sabrina Llop, Ferran Ballester, Ana Fernández-Somoano, Adonina Tardón, Martine Vrijheid, Mònica Guxens, Jordi Sunyer
BACKGROUND: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. OBJECTIVES: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4-5years of age. METHODS: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003-2008)...
January 2018: Environment International
https://www.readbyqxmd.com/read/29093638/inhibition-of-hif1%C3%AE-and-pdk-induces-cell-death-of-glioblastoma-multiforme
#8
Jiwon Esther Han, Pyung Won Lim, Chul Min Na, You Sik Choi, Joo Young Lee, Yona Kim, Hyung Woo Park, Hyo Eun Moon, Man Seung Heo, Hye Ran Park, Dong Gyu Kim, Sun Ha Paek
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29070699/inhibition-of-pyruvate-dehydrogenase-kinase-improves-pulmonary-arterial-hypertension-in-genetically-susceptible-patients
#9
Evangelos D Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, Ian Paterson, Richard B Thompson, Kelvin Chow, Declan P O'Regan, Lan Zhao, John Wharton, David G Kiely, Adam Kinnaird, Aristeidis E Boukouris, Chris White, Jayan Nagendran, Darren H Freed, Stephen J Wort, J Simon R Gibbs, Martin R Wilkins
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a high mortality rate. It is characterized by an occlusive vascular remodeling due to a pro-proliferative and antiapoptotic environment in the wall of resistance pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is up-regulated as the major source of adenosine triphosphate production. This multifactorial mitochondrial suppression leads to inhibition of apoptosis and downstream signaling promoting proliferation...
October 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29059435/therapeutic-targeting-of-the-pyruvate-dehydrogenase-complex-pyruvate-dehydrogenase-kinase-pdc-pdk-axis-in-cancer
#10
REVIEW
Peter W Stacpoole
The mitochondrial pyruvate dehydrogenase complex (PDC) irreversibly decarboxylates pyruvate to acetyl coenzyme A, thereby linking glycolysis to the tricarboxylic acid cycle and defining a critical step in cellular bioenergetics. Inhibition of PDC activity by pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation has been associated with the pathobiology of many disorders of metabolic integration, including cancer. Consequently, the PDC/PDK axis has long been a therapeutic target. The most common underlying mechanism accounting for PDC inhibition in these conditions is post-transcriptional upregulation of one or more PDK isoforms, leading to phosphorylation of the E1α subunit of PDC...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29024715/proposal-of-a-flow-scheme-for-the-chemical-form-based-quantitative-analysis-of-chlorine-compounds-in-pulp-for-sanitary-products-and-verification-of-safety
#11
Takeharu Wada, Kei Iwasaki, Yasushi Minobe, Mitsuhiro Wada, Shigeo Imai, Satoko Ishii
To determine the amounts and chemical forms of chlorine compounds in elemental chlorine-free (ECF) bleached pulp for sanitary products, a chemical-form-based quantitative analysis flow scheme was created. The scheme involves quantitative determination of compounds eluted in elution tests assuming dermal exposure. The results indicated that most of the chlorine compounds in pulp used for sanitary products were insoluble organically bound chlorine and water-soluble chlorides consisting of chloride ions. The total amount of chlorine obtained by analysis of the total chlorine in the pulp products was close to the sum of the amounts of water-soluble chlorides, residual chlorine, chloroacetic acids, and insoluble organically bound chlorine...
October 9, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29023340/associations-between-disinfection-by-product-exposures-and-craniofacial-birth-defects
#12
John A Kaufman, J Michael Wright, Amanda Evans, Zorimar Rivera-Núñez, Amy Meyer, Michael G Narotsky
OBJECTIVE: Examine associations between craniofacial birth defects (CFDs) and disinfection by-product (DBP) exposures, including the sum of four trihalomethanes (THM4) and five haloacetic acids (HAA5) (i.e., DBP9). METHODS: We calculated first trimester adjusted odds ratios (aORs) for different DBPs in a matched case-control study of 366 CFD cases in Massachusetts towns with complete 1999-2004 THM and HAA data. RESULTS: We detected elevated aORs for cleft palate with DBP9 (highest quintile aOR = 3...
October 11, 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28964917/redox-imbalance-due-to-the-loss-of-mitochondrial-nad-p-transhydrogenase-markedly-aggravates-high-fat-diet-induced-fatty-liver-disease-in-mice
#13
Claudia D C Navarro, Tiago R Figueira, Annelise Francisco, Genoefa A Dal'Bó, Juliana A Ronchi, Juliana C Rovani, Cecilia A F Escanhoela, Helena C F Oliveira, Roger F Castilho, Anibal E Vercesi
The mechanisms by which a high fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunctions and redox imbalance. We hypothesized that a HFD would increase mitochondrial reliance on NAD(P)-transhydrogenase (NNT) as the source of NADPH for antioxidant systems that counteract NAFLD development. Therefore, we studied HFD-induced liver mitochondrial dysfunctions and NAFLD in C57Unib.B6 congenic mice with (Nnt(+/+)) or without (Nnt(-/-)) NNT activity; the spontaneously mutated allele (Nnt(-/-)) was inherited from the C57BL/6J mouse substrain...
September 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28962523/metabolic-disruption-early-in-life-is-associated-with-latent-carcinogenic-activity-of-dichloroacetic-acid-in-mice
#14
Leah C Wehmas, Anthony B DeAngelo, Susan D Hester, Brian N Chorley, Gleta Carswell, Greg R Olson, Michael H George, Julia H Carter, Sandra R Eldridge, Anna Fisher, Beena Vallanat, Charles E Wood
Early-life environmental factors can influence later-life susceptibility to cancer. Recent evidence suggests that metabolic pathways may mediate this type of latency effect. Previously, we reported that short-term exposure to dichloroacetic acid (DCA) increased liver cancer in mice 84 weeks after exposure was stopped. Here, we evaluated time course dynamics for key events related to this effect. This study followed a stop-exposure design in which 28-day-old male B6C3F1 mice were given the following treatments in drinking water for up to 93 weeks: deionized water (dH2O, control); 3...
October 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28943110/therapies-for-mitochondrial-diseases-and-current-clinical-trials
#15
REVIEW
Ayman W El-Hattab, Ana Maria Zarante, Mohammed Almannai, Fernando Scaglia
Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better understanding of the etiology and mechanism of these diseases, there are still no satisfactory therapies available for mitochondrial disorders. Treatment for mitochondrial diseases remains largely symptomatic and does not significantly alter the course of the disease...
September 18, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28934276/enhanced-pyruvate-dehydrogenase-activity-improves-cardiac-outcomes-in-a-murine-model-of-cardiac-arrest
#16
Lin Piao, Yong-Hu Fang, Manfred M Kubler, Michael W Donnino, Willard W Sharp
RATIONALE: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA) hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28928817/dichloroacetate-induces-protective-autophagy-in-esophageal-squamous-carcinoma-cells
#17
Hong-Yu Jia, He-Nan Wang, Feng-Yu Xia, Yan Sun, Hong-Li Liu, Li-Li Yan, Shan-Shan Li, Dong-Chun Jiang, Mei-Mei Xu
Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28915065/targeting-hif-1%C3%AE-pdk1-axis-by-dichloroacetate-dca-suppresses-bleomycin-induced-pulmonary-fibrosis
#18
Justin Goodwin, Hyunsung Choi, Meng-Hsiung Hsieh, Michael L Neugent, Jung-Mo Ahn, Heather N Hayenga, Pankaj K Singh, David B Shackelford, In-Kyu Lee, Vladimir Shulaev, Shanta Dhar, Norihiko Takeda, Jung-Whan Kim
RATIONALE: Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences such as hypoxia contribute to their sustained activation and differentiation is poorly understood. OBJECTIVES: As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the pre-clinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis...
September 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28914978/model-informed-dose-optimization-of-dichloroacetate-for-the-treatment-of-congenital-lactic-acidosis-in-children
#19
Naveen Mangal, Margaret O James, Peter W Stacpoole, Stephan Schmidt
Dichloroacetate (DCA) is an investigational drug used to treat congenital lactic acidosis and other mitochondrial disorders. Response to DCA therapy in young children may be suboptimal following body weight-based dosing. This is because of autoinhibition of its metabolism, age-dependent changes in pharmacokinetics, and polymorphisms in glutathione transferase zeta 1 (GSTZ1), its primary metabolizing enzyme. Our objective was to predict optimal DCA doses for the treatment of congenital lactic acidosis in children...
September 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28881758/suppression-of-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#20
Hong Sun, Anyou Zhu, Xiang Zhou, Fengchao Wang
Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells...
August 8, 2017: Oncotarget
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