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https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#1
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28642293/random-squat-stand-maneuvers-a-novel-approach-for-assessment-of-dynamic-cerebral-autoregulation
#2
Sam C Barnes, Naomi Ball, Victoria Joanna Haunton, Ronney B Panerai, Thompson G Robinson
BACKGROUND: Squat-stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed-frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA, and to determine the reproducibility of FF and RFSSMs. METHOD: 29 healthy volunteers (19 male, mean age 23.0 [4.9] years) completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2 and angle of the squat movement were measured...
June 22, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28638347/bile-acids-do-not-contribute-to-the-altered-calcium-homeostasis-of-platelets-from-rats-with-biliary-cirrhosis
#3
Paola Romecín, Esther G Navarro, M Clara Ortiz, David Iyú, Joaquín García-Estañ, Noemí M Atucha
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28623316/revealing-protein-networks-and-gene-drug-connectivity-in-cancer-from-direct-information
#4
Xian-Li Jiang, Emmanuel Martinez-Ledesma, Faruck Morcos
The connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611532/progress-towards-a-more-predictive-model-for-hohlraum-radiation-drive-and-symmetry
#5
O S Jones, L J Suter, H A Scott, M A Barrios, W A Farmer, S B Hansen, D A Liedahl, C W Mauche, A S Moore, M D Rosen, J D Salmonson, D J Strozzi, C A Thomas, D P Turnbull
For several years, we have been calculating the radiation drive in laser-heated gold hohlraums using flux-limited heat transport with a limiter of 0.15, tabulated values of local thermodynamic equilibrium gold opacity, and an approximate model for not in a local thermodynamic equilibrium (NLTE) gold emissivity (DCA_2010). This model has been successful in predicting the radiation drive in vacuum hohlraums, but for gas-filled hohlraums used to drive capsule implosions, the model consistently predicts too much drive and capsule bang times earlier than measured...
May 2017: Physics of Plasmas
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#6
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28597991/lack-of-linear-correlation-between-dynamic-and-steady-state-cerebral-autoregulation
#7
Daan L K de Jong, Takashi Tarumi, Jie Liu, Rong Zhang, Jurgen A H R Claassen
The purpose of this study was to investigate the relationship between dynamic (dCA) and steady-state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid (ICA) and vertebral (VA) artery and cerebral blood flow velocity (CBFV) at the middle cerebral artery (MCA)...
June 9, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28597380/maternal-embryonic-metabolic-and-antioxidant-response-of-chapalichthys-pardalis-teleostei-goodeidae-induced-by-exposure-to-3-4-dichloroaniline
#8
Ana Laura Carbajal-Hernández, Roberto Carlos Valerio-García, Erika Berenice Martínez-Ruíz, Víctor Hugo Jarquín-Díaz, Fernando Martínez-Jerónimo
Chapalichthys pardalis is a viviparous fish, microendemic to the Tocumbo Region in the state of Michoacán, Mexico. Despite the peculiar type of reproduction of goodeid fish and their mother-embryo interaction, the effects on embryos induced by maternal exposure to aquatic xenobiotics are still unknown. The objective of the present work was to determine the maternal-embryonic metabolic and antioxidant response of C. pardalis exposed to 3,4-dichloroaniline (3,4-DCA), a compound considered highly noxious to the environment because of its high toxicity and persistence, which has been used as reference toxicant in toxicological bioassays...
June 8, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28596137/reshaping-antibiotics-through-hydrophobic-drug-bile-acid-ionic-complexation-enhances-activity-against-staphylococcus-aureus-biofilms
#9
Stefano Giovagnoli, Donatella Pietrella, Lanfranco Barberini, Claudio Santi, Andrea Carotti, Alessandro di Michele, Maurizio Ricci
The antibiotic era is on the verge of a profound change and facing a ground shaking crisis. The frequent failures of antibiotic treatments are often associated with biofilm formation, which is responsible for chronic infections, exacerbation as well as reinfection. So far, albeit the large number of valuable strategies employed to combat biofilm formation, little success has been recorded. In this work, we propose a simple approach, based on hydrophobic ionic complexation with the bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), to enhance anti-biofilm activity of well-known antibiotics, namely kanamycin (K), amikacin (A) and vancomycin (V)...
June 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28595656/ros-production-induced-by-braf-inhibitor-treatment-rewires-metabolic-processes-affecting-cell-growth-of-melanoma-cells
#10
Giulia Cesi, Geoffroy Walbrecq, Andreas Zimmer, Stephanie Kreis, Claude Haan
BACKGROUND: Most melanoma patients with BRAF(V600E) positive tumors respond well to a combination of BRAF kinase and MEK inhibitors. However, some patients are intrinsically resistant while the majority of patients eventually develop drug resistance to the treatment. For patients insufficiently responding to BRAF and MEK inhibitors, there is an ongoing need for new treatment targets. Cellular metabolism is such a promising new target line: mutant BRAF(V600E) has been shown to affect the metabolism...
June 8, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28589225/characterization-of-the-newly-isolated-%C3%AF-oxidizing-yeast-candida-sorbophila-ds02-and-its-potential-applications-in-long-chain-dicarboxylic-acid-production
#11
Heeseok Lee, Yohanes Eko Chandra Sugiharto, Seunghoon Lee, Gyuyeon Park, Changpyo Han, Hyeran Jang, Wooyoung Jeon, Heejoon Park, Jungoh Ahn, Kyungbo Kang, Hongwoen Lee
α, ω-Dicarboxylic acids (DCAs) are multipurpose chemicals widely used in polymers, perfumes, plasticizers, lubricants, and adhesives. The biotransformation of DCAs from alkanes and fatty acids by microorganisms has attracted recent interest, since synthesis via chemical oxidation causes problems in terms of the environment and safety. We isolated an ω-oxidizing yeast from a wastewater disposal facility of a petrochemical factory by chemostat enrichment culture. The haploid strain identified as Candida sorbophila DS02 grew on glucose and dodecane, exhibiting greater cell shrinkage on the latter...
June 6, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28585279/serum-bile-acid-level-and-fatty-acid-composition-in-chinese-children-with-non-alcoholic-fatty-liver-disease
#12
Li Ping Lu, Yan Ping Wan, Peng Cheng Xun, Ke Jun Zhou, Cheng Chen, Si Yang Cheng, Min Zhong Zhang, Chun Hua Wu, Wei Wei Lin, Ying Jiang, Hai Xia Feng, Jia Lu Wang, Ka He, Wei Cai
OBJECTIVE: To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD) METHODS: Seventy-six children aged 4-17 years were categorized into three groups: none NAFLD (control), mild, and moderate/severe NAFLD groups respectively based on liver ultrasonography. Serum BAs and FAs were quantified by mass spectrometry and gas chromatography separately. General linear models were performed to assess the differences across groups...
June 6, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28583875/quantitative-profiling-of-19-bile-acids-in-rat-plasma-liver-bile-and-different-intestinal-section-contents-to-investigate-bile-acid-homeostasis-and-the-application-of-temporal-variation-of-endogenous-bile-acids
#13
Tingting Yang, Ting Shu, Guanlan Liu, Huifang Mei, Xiaoyu Zhu, Xin Huang, Luyong Zhang, Zhenzhou Jiang
Bile acid homeostasis is maintained by liver synthesis, bile duct secretion, microbial metabolism and intestinal reabsorption into the blood. When drug insults result in liver damage, the variances of bile acids (BAs) are related to the physiological status of the liver. Here, we established a method to simultaneously quantify 19 BAs in rat plasma, liver, bile and different intestinal section contents (duodenum, jejunum, ileum, cecum and colon) using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the pattern of bile acid homeostasis in the enterohepatic circulation of bile acids in physiological situations...
June 2, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28582972/the-impact-of-do-and-salinity-on-microbial-community-in-poly-butylene-succinate-denitrification-reactors-for-recirculating-aquaculture-system-wastewater-treatment
#14
Ya-Le Deng, Yun-Jie Ruan, Song-Ming Zhu, Xi-Shan Guo, Zhi-Ying Han, Zhang-Ying Ye, Gang Liu, Ming-Ming Shi
The interactions between environmental factors and bacterial community shift in solid-phase denitrification are crucial for optimum operation of a reactor and to achieve maximum treatment efficiency. In this study, Illumina high-throughput sequencing was applied to reveal the effects of different operational conditions on bacterial community distribution of three continuous operated poly(butylene succinate) biological denitrification reactors used for recirculating aquaculture system (RAS) wastewater treatment...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28572638/mitochondrial-targeting-by-dichloroacetate-improves-outcome-following-hemorrhagic-shock
#15
Kumar Subramani, Sumin Lu, Marie Warren, Xiaogang Chu, Haroldo A Toque, R William Caldwell, Michael P Diamond, Raghavan Raju
Hemorrhagic shock is a leading cause of death in people under the age of 45 and accounts for almost half of trauma-related deaths. In order to develop a treatment strategy based on potentiating mitochondrial function, we investigated the effect of the orphan drug dichloroacetate (DCA) on survival in an animal model of hemorrhagic shock in the absence of fluid resuscitation. Hemorrhagic shock was induced in rats by withdrawing 60% of the blood volume and maintaining a hypotensive state. The studies demonstrated prolonged survival of rats subjected to hemorrhagic injury (HI) when treated with DCA...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28569842/giant-barocaloric-effect-in-the-ferroic-organic-inorganic-hybrid-tpra-mn-dca-3-perovskite-under-easily-accessible-pressures
#16
Juan M Bermúdez-García, Manuel Sánchez-Andújar, Socorro Castro-García, Jorge López-Beceiro, Ramón Artiaga, María A Señarís-Rodríguez
The fast growing family of organic-inorganic hybrid compounds has recently been attracting increased attention owing to the remarkable functional properties (magnetic, multiferroic, optoelectronic, photovoltaic) displayed by some of its members. Here we show that these compounds can also have great potential in the until now unexplored field of solid-state cooling by presenting giant barocaloric effects near room temperature already under easily accessible pressures in the hybrid perovskite [TPrA][Mn(dca)3] (TPrA: tetrapropylammonium, dca: dicyanamide)...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28557708/spontaneously-hypertensive-rat-chromosome-2-with-mutant-connexin-50-triggers-divergent-effects-on-metabolic-syndrome-components
#17
O Šeda, D Křenová, L Šedová, L Kazdová, M Krupková, B Chylíková, F Liška, V Křen
Metabolic syndrome is a frequent condition with multifactorial aetiology. Previous studies indicated the presence of genetic determinants of metabolic syndrome components on rat chromosome 2 (RNO2) and syntenic regions of the human genome. Our aim was to further explore these findings using novel rat models. We derived the BN-Dca and BN-Lx.Dca congenic strains by introgression of a limited RNO2 region from a spontaneously hypertensive rat strain carrying a mutation in the Gja8 gene (SHR-Dca, dominant cataract) into the genomic background of Brown Norway strain and congenic strain BN-Lx, respectively...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28554984/the-effect-of-deoxycholic-acid-on-secretion-and-motility-in-the-rat-and-guinea-pig-large-intestine
#18
Nam Hee Kim, Jung Ho Park, Jae-Soon Park, Yeun-Ho Joung
Background/Aims: Bile acid is an important luminal factor that affects gastrointestinal motility and secretion. We investigated the effect of bile acid on secretion in the proximal and distal rat colon and coordination of bowel movements in the guinea pig colon. Methods: The short-circuit current from the mucosal strip of the proximal and distal rat colon was compared under control conditions after induction of secretion with deoxycholic acid (DCA) as well as after inhibition of secretion with indomethacin, 1,2-bis (o-aminophenoxy) ethane-N, N,N',N'-tetra-acetic acid (an intracellular calcium chelator; BAPTA), and tetrodotoxin (TTX) using an Ussing chamber...
May 29, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28554617/dynamic-controlled-atmosphere-dca-interaction-between-dca-methods-and-1-methylcyclopropene-on-fuji-suprema-apple-quality
#19
Anderson Weber, Fabio Rodrigo Thewes, Rogerio de Oliveira Anese, Vanderlei Both, Elizandra Pivotto Pavanello, Auri Brackmann
The objective of the present work was to evaluate the appropriate respiratory quotient (RQ) value to achieve a safe lowest oxygen limit (LOL), during storage of 'Fuji Suprema' apples, in dynamic controlled atmosphere (DCA), treated with or without 1-methylcyclopropene (1-MCP). The apples were stored in DCA-RQ, a new technology for storing fruits, and were compared with the HarvestWatch™, a system based on chlorophyll fluorescence DCA (DCA-CF), and static controlled atmosphere. DCA-RQ1.5 is the most suited for the storage of 'Fuji Suprema' apples...
November 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28552691/identification-of-bile-acids-responsible-for-inhibiting-the-bile-salt-export-pump-leading-to-bile-acid-accumulation-and-cell-toxicity-in-rat-hepatocytes
#20
Kumiko Oizumi, Shuichi Sekine, Meiko Fukagai, Takeshi Susukida, Kousei Ito
Inhibition of bile salt export pump (BSEP) causes hepatic accumulation of toxic bile acid (BA), leading to hepatocyte death. We reported a sandwich-cultured hepatocyte (SCH)-based model that can estimate potential cholestatic-compounds by assessing their ability to induce hepatotoxicity in combination with a titrated amount of human 12 BA-species. However, there is little information about the specific BA(s) responsible for hepatotoxicity, when BSEP is inhibited. This study measured the accumulation of each BA in rat SCHs in the presence of 10μM cyclosporine A (CsA), which only inhibits BSEP, and 50μM CsA, which further inhibits basolateral BA efflux transporters...
May 25, 2017: Journal of Pharmaceutical Sciences
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