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https://www.readbyqxmd.com/read/28094765/selective-antagonism-of-muscarinic-receptors-is-neuroprotective-in-peripheral-neuropathy
#1
Nigel A Calcutt, Darrell R Smith, Katie Frizzi, Mohammad Golam Sabbir, Subir K Roy Chowdhury, Teresa Mixcoatl-Zecuatl, Ali Saleh, Nabeel Muttalib, Randy Van der Ploeg, Joseline Ochoa, Allison Gopaul, Lori Tessler, Jürgen Wess, Corinne G Jolivalt, Paul Fernyhough
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28094552/glucose-metabolism-in-cancer-and-ischemia-possible-therapeutic-consequences-of-the-warburg-effect
#2
Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed...
January 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28074362/the-determination-and-fate-of-disinfection-by-products-from-ozonation-chlorination-of-fulvic-acid
#3
Xin Zhong, Chongwei Cui, Shuili Yu
Ozonation of fulvic acid (FA) can result in diverse intermediate oxidation by-products, significantly affecting disinfection by-product (DBP) formation following chlorination. The objective of this study was to provide insight into ozone reaction intermediates and reveal the possible formation pathway of DBPs from ozonation of FA due to the formation of intermediate oxidation by-products. Aldehydes, aromatic acids, short-chain acids, chloroform, and dichloroacetic acid were detected at various ozone dosage additions...
January 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28040265/pyruvate-dehydrogenase-kinase-4-deficiency-attenuates-cisplatin-induced-acute-kidney-injury
#4
Chang Joo Oh, Chae-Myeong Ha, Young-Keun Choi, Sungmi Park, Mi Sun Choe, Nam Ho Jeoung, Yang Hoon Huh, Hyo-Jeong Kim, Hee-Seok Kweon, Ji-Min Lee, Sun Joo Lee, Jae-Han Jeon, Robert A Harris, Keun-Gyu Park, In-Kyu Lee
Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression...
December 28, 2016: Kidney International
https://www.readbyqxmd.com/read/27996252/the-formation-and-occurrence-of-n-chloro-2-2-dichloroacetamide-a-previously-overlooked-nitrogenous-disinfection-byproduct-in-chlorinated-drinking-waters
#5
Yun Yu, David A Reckhow
Haloacetamides (HAMs) are a class of newly identified nitrogenous disinfection byproducts (N-DBPs) whose occurrence in drinking waters has recently been reported in several DBP surveys. As the most prominent HAM species, it is commonly acknowledged that 2,2-dichloroacetamide (DCAM) is mainly generated from dichloroacetonitrile (DCAN) hydrolysis because the concentrations of these two compounds are often well correlated. Instead of DCAM, a previously unreported N-DBP, N-chloro-2,2-dichloroacetamide (N-Cl-DCAM), was confirmed in this study as the actual DCAN degradation product in chlorinated drinking waters...
December 20, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/27939695/ag311-a-small-molecule-inhibitor-of-complex-i-and-hypoxia-induced-hif-1%C3%AE-stabilization
#6
Anja Bastian, Satoshi Matsuzaki, Kenneth M Humphries, Gavin A Pharaoh, Arpit Doshi, Nilesh Zaware, Aleem Gangjee, Michael A Ihnat
Cancer cells have a unique metabolic profile and mitochondria have been shown to play an important role in chemoresistance, tumor progression and metastases. This unique profile can be exploited by mitochondrial-targeted anticancer therapies. A small anticancer molecule, AG311, was previously shown to possess anticancer and antimetastatic activity in two cancer mouse models and to induce mitochondrial depolarization. This study defines the molecular effects of AG311 on the mitochondria to elucidate its observed efficacy...
December 8, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913098/succinyl-coa-synthetase-sucla2-deficiency-in-two-siblings-with-impaired-activity-of-other-mitochondrial-oxidative-enzymes-in-skeletal-muscle-without-mitochondrial-dna-depletion
#7
Xiaoping Huang, Jirair K Bedoyan, Didem Demirbas, David J Harris, Alexander Miron, Simone Edelheit, George Grahame, Suzanne D DeBrosse, Lee-Jun Wong, Charles L Hoppel, Douglas S Kerr, Irina Anselm, Gerard T Berry
Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype...
November 12, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27874079/crosstalk-among-proteome-acetylome-and-succinylome-in-colon-cancer-hct116-cell-treated-with-sodium-dichloroacetate
#8
Danxi Zhu, Lidan Hou, Bin Hu, Hang Zhao, Jie Sun, Jianhua Wang, Xiangjun Meng
Protein lysine acetylation and succinylation play important regulatory roles in cells, both of which or each other has a close relationship. Dichloroacetate (DCA), a well-known pyruvate dehydrogenase kinase (PDK) inhibitor, has the potential to be used as anti-cancer drugs for several tumors including colorectal cancer. However, little is known about the potential mechanism of DCA-based cancer therapy by protein posttranslational modifications (PTM) including global proteome, acetylome and succinylome. Here the combinations with stable isotope labeling (SILAC), antibody affinity enrichment and high resolution LC-MS/MS analysis were performed in human colon cancer HCT116 cells...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27849909/267-dichloroacetic-acid-improves-neurologic-outcomes-in-a-rat-model-of-asphyxia-cardiac-arrest
#9
Peng Wang, Mingdi Chen, Zhengfei Yang, Jiali Lin, Zitong Huang, Wanchun Tang
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27803917/long-term-stabilization-of-stage-4-colon-cancer-using-sodium-dichloroacetate-therapy
#10
Akbar Khan, Douglas Andrews, Anneke C Blackburn
Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death)...
October 16, 2016: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/27785718/detection-of-genotoxic-effects-of-drinking-water-disinfection-by-products-using-vicia-faba-bioassay
#11
Yu Hu, Li Tan, Shao-Hui Zhang, Yu-Ting Zuo, Xue Han, Na Liu, Wen-Qing Lu, Ai-Lin Liu
Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk...
October 26, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27774434/fatal-liver-and-bone-marrow-toxicity-by-combination-treatment-of-dichloroacetate-and-artesunate-in-a-glioblastoma-multiforme-patient-case-report-and-review-of-the-literature
#12
Martin Uhl, Stefan Schwab, Thomas Efferth
A 52-year-old male patient was treated with standard radiochemotherapy with temozolomide for glioblastoma multiforme (GBM). After worsening of his clinical condition, further tumor-specific treatment was unlikely to be successful, and the patient seeked help from an alternative practitioner, who administered a combination of dichloroacetate (DCA) and artesunate (ART). A few days later, the patient showed clinical and laboratory signs of liver damage and bone marrow toxicity (leukopenia, thrombocytopenia). Despite successful restoration of laboratory parameters upon symptomatic treatment, the patient died 10 days after the infusion...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27771434/therapeutic-applications-of-dichloroacetate-and-the-role-of-glutathione-transferase-zeta-1
#13
REVIEW
Margaret O James, Stephan C Jahn, Guo Zhong, Marci G Smeltz, Zhiwei Hu, Peter W Stacpoole
Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen...
October 19, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27760379/a-combined-biochemical-and-computational-studies-of-the-rho-class-glutathione-s-transferase-sll1545-of-synechocystis-pcc-6803
#14
Tripti Pandey, Rohit Shukla, Harish Shukla, Amit Sonkar, Timir Tripathi, Arvind Kumar Singh
Peroxides are one of the most important radicals that cause oxidative stress. Certain Glutathione S-transferases (GSTs) have been reported to show peroxidase activity. We report a novel peroxidase activity of Synechocystis GST- sll1545. The recombinant protein was purified to homogeneity and characterized. Low Km (0.109μM) and high Vmax (0.663μmolmin(-1)) values suggest a high preference of sll1545 for cumenehydroperoxide. Disc inhibition assay confirmed the ability of the enzyme to protect cells against peroxide-induced damage...
January 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27757958/dichloroacetate-induces-regulatory-t-cell-differentiation-and-suppresses-th17-cell-differentiation-by-pyruvate-dehydrogenase-kinase-independent-mechanism
#15
Naoyuki Makita, Jun Ishiguro, Keisuke Suzuki, Futoshi Nara
OBJECTIVES: Recently, there has been a growing interest in the mechanism of action of dichloroacetate (DCA) for T-cell differentiation; however, this mechanism has not been elucidated in detail. Therefore, this study aimed to investigate the mechanism of action of DCA for Treg and Th17 differentiation with pyruvate dehydrogenase kinase (PDHK) inhibitor (AZD7545) and PDHK knockdown. METHODS: Inhibitory activity of DCA and AZD7545 against recombinant PDHK and intracellular PDH phosphorylation was measured...
January 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27748833/the-effect-of-dichloroacetate-in-canine-prostate-adenocarcinomas-and-transitional-cell-carcinomas-in-vitro
#16
Tatjana Harting, Mandy Stubbendorff, Saskia Willenbrock, Siegfried Wagner, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte
The Warburg effect describes the ability of cancer cells to produce energy via aerobic glycolysis instead of oxidative phosphorylation of pyruvate. This deviation in mitochondrial metabolism inhibits apoptosis, allowing increased proliferation under conditions of reduced oxygen levels. Dichloroacetate (DCA) was successfully used in several human cancer cell lines to reactivate oxidative phosphorylation in mitochondria. The aim of this study was the characterization and response of canine cancer cell lines after DCA exposure...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27734577/elevated-acetyl-coa-by-amino-acid-recycling-fuels-microalgal-neutral-lipid-accumulation-in-exponential-growth-phase-for-biofuel-production
#17
Lina Yao, Hui Shen, Nan Wang, Jaspaul Tatlay, Liang Li, Tin Wee Tan, Yuan Kun Lee
Microalgal neutral lipids [mainly in the form of triacylglycerols (TAGs)], feasible substrates for biofuel, are typically accumulated during the stationary growth phase. To make microalgal biofuels economically competitive with fossil fuels, generating strains that trigger TAG accumulation from the exponential growth phase is a promising biological approach. The regulatory mechanisms to trigger TAG accumulation from the exponential growth phase (TAEP) are important to be uncovered for advancing economic feasibility...
October 13, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27726087/tio2-structures-doped-with-noble-metals-and-or-graphene-oxide-to-improve-the-photocatalytic-degradation-of-dichloroacetic-acid
#18
Paula Ribao, Maria J Rivero, Inmaculada Ortiz
Noble metals have been used to improve the photocatalytic activity of TiO2. Noble metal nanoparticles prevent charge recombination, facilitating electron transport due to the equilibration of the Fermi levels. Furthermore, noble metal nanoparticles show an absorption band in the visible region due to a high localized surface plasmon resonance (LSPR) effect, which contributes to additional electron movements. Moreover, systems based on graphene, titanium dioxide, and noble metals have been used, considering that graphene sheets can carry charges, thereby reducing electron-hole recombination, and can be used as substrates of atomic thickness...
October 11, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27685525/2-deoxy-d-glucose-enhances-dichloroacetate-antitumor-action-against-lewis-lung-carcinoma
#19
O N Pyaskovskaya, D L Kolesnik, A G Fedorchuk, I V Prokhorova, G I Solyanik
UNLABELLED: Aerobic glycolysis that supports high proliferation rate and survival of tumor cells in unfavorable conditions is among fundamental features of tumor metabolism. The search for active modulators of energetic metabolism capable of suppressing tumor growth and metastasis could result in higher effectiveness of anticancer therapy. AIM: To study antitumor and antimetastatic activity of the modulators of energetic metabolism dichloroacetate (DCA) and 2-deoxy-D-glucose (2DG) used in combination treatment of Lewis lung carcinoma (LLC)...
September 2016: Experimental Oncology
https://www.readbyqxmd.com/read/27669387/toxicity-of-2-6-dichloro-1-4-benzoquinone-and-five-regulated-drinking-water-disinfection-by-products-for-the-caenorhabditis-elegans-nematode
#20
Yu-Ting Zuo, Yu Hu, Wei-Wei Lu, Jing-Jing Cao, Fan Wang, Xue Han, Wen-Qing Lu, Ai-Lin Liu
Scarce toxicological data are available for 2,6-dichloro-1,4-benzoquinone (DCBQ), an emerging water disinfection by-product (DBP) that is of potential public health concern. This study investigated the effects of DCBQ on the lethality, respiration rate, and DNA damage in the Caenorhabditis elegans nematode. Meanwhile, the toxic effects of five regulated DBPs, dichloroacetic acid (DCA), trichloroacetic acid (TCA), monobromoacetic acid (MBA), dibromoacetic acid (DBA), and N-nitrosodimethylamine (NDMA), have also been evaluated...
September 17, 2016: Journal of Hazardous Materials
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