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https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#1
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29050650/glycaemic-response-after-intake-of-a-high-energy-high-protein-diabetes-specific-formula-in-older-malnourished-or-at-risk-of-malnutrition-type-2-diabetes-patients
#2
Hamid Laksir, Mirian Lansink, Sophie C Regueme, Johan de Vogel-van den Bosch, Andreas F H Pfeiffer, Isabelle Bourdel-Marchasson
BACKGROUND & AIMS: Several studies with diabetes-specific formulas (DSFs) for hyperglycaemic patients in need of nutritional support have been conducted in non-malnourished patients, mainly comparing products with varying macronutrient compositions. Here, the effect of a high energy, high protein DSF on postprandial responses was compared to a product with a similar macronutrient composition in malnourished or at risk of malnutrition patients with type 2 diabetes. METHODS: In this randomised, double-blind cross-over study, 20 patients were included...
October 6, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28986384/mass-spectrometry-for-fragment-screening
#3
REVIEW
Daniel Shiu-Hin Chan, Andrew J Whitehouse, Anthony G Coyne, Chris Abell
Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography...
October 6, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28946828/retention-of-the-structure-and-function-of-heparan-sulfate-biomaterials-after-gamma-irradiation
#4
Raymond A A Smith, R J E Chua, Susan M Carnachan, Clarissa Ling Ling Tan, Ian M Sims, Simon F R Hinkley, Victor Nurcombe, Simon Cool
Heparan sulfate (HS) is a highly heterogeneous polysaccharide implicated in many important biological processes. Our previous work has demonstrated that a particular affinity-selected HS (referred to henceforth as 'HS3') is capable of enhancing the osteogenic effects of bone morphogenetic protein 2 (BMP2). Here, we gamma-irradiated HS with 26 kGy of ionizing radiation to determine how this affected the structure, composition and function. Initial structural studies were performed on a commercial preparation of HS as a proof-of-concept...
September 25, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28791001/novel-in-vitro-screening-system-based-on-differential-scanning-fluorimetry-to-search-for-small-molecules-against-the-disassembly-or-assembly-of-hiv-1-capsid-protein
#5
Yasuyuki Miyazaki, Naoya Doi, Takaaki Koma, Akio Adachi, Masako Nomaguchi
Varieties of in vitro systems have been used to study biochemical properties of human immunodeficiency virus Gag-capsid protein (HIV Gag-CA). Recently, we have comparatively characterized HIV-1 and HIV-2 Gag-CA proteins using such technology, and have demonstrated that the NaCl-initiated CA-polymerization in vitro and the stability of CA N-terminal domain as judged by differential scanning fluorimetry (DSF) are inversely correlated. In this study, we found that ZnCl2 works as a competent initiator of the in vitro HIV-1 CA-polymerization at much lower concentrations than those of NaCl frequently used for the polymerization initiation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28740306/comparative-study-of-the-quality-characteristics-of-defatted-soy-flour-treated-by-supercritical-carbon-dioxide-and-organic-solvent
#6
Sung-Won Kang, M Shafiur Rahman, Ah-Na Kim, Kyo-Yeon Lee, Chan-Yang Park, William L Kerr, Sung-Gil Choi
Defatted soy flour is a potential source of food protein, amino acids, ash and isoflavones. The supercritical carbon dioxide (SC-CO2) and a traditional organic solvent extraction methods were used to remove fat from soy flour, and the quality characteristics of a control soy flour (CSF), defatted soy flour by SC-CO2 (DSFSC-CO2) and defatted soy flour by an organic solvent (DSF-OS) were compared. The SC-CO2 process was carried out at a constant temperature of 45 °C, and a pressure of 40 MPa for 3 h with a CO2 flow rate of 30 g/min...
July 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28637248/expression-and-comparison-of-codon-optimised-aspergillus-tubingensis-amylase-variants-in-saccharomyces-cerevisiae
#7
Rosemary A Cripwell, Shaunita H Rose, Willem H van Zyl
The expression of codon optimised genes is a popular genetic engineering approach for the production of industrially relevant proteins. This study investigates and compares the expression of codon optimised and codon adapted amylase variants. The Aspergillus tubingensis raw starch hydrolysing α-amylase (amyA) and glucoamylase (glaA) encoding genes were redesigned using synonymous codons and expressed in Saccharomyces cerevisiae Y294. Codon optimisation to favour S. cerevisiae codon bias resulted in a decrease in extracellular enzyme activity of 72% (30...
June 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28464377/bile-salts-and-alkaline-ph-reciprocally-modulate-the-interaction-between-the-periplasmic-domains-of-vibrio-cholerae-toxr-and-toxs
#8
Charles R Midgett, Salvador Almagro-Moreno, Maria Pellegrini, Ronald K Taylor, Karen Skorupski, F Jon Kull
ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood...
July 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28454708/functional-characterisation-of-burkholderia-pseudomallei-biotin-protein-ligase-a-toolkit-for-anti-melioidosis-drug-development
#9
Thomas E H Bond, Alanna E Sorenson, Patrick M Schaeffer
Burkholderia pseudomallei (Bp) is the causative agent of melioidosis. The bacterium is responsible for 20% of community-acquired sepsis cases and 40% of sepsis-related mortalities in northeast Thailand, and is intrinsically resistant to aminoglycosides, macrolides, rifamycins, cephalosporins, and nonureidopenicillins. There is no vaccine and its diagnosis is problematic. Biotin protein ligase (BirA) which is essential for fatty acid synthesis has been proposed as a drug target in bacteria. Very few bacterial BirA have been characterized, and a better understanding of these enzymes is necessary to further assess their value as drug targets...
June 2017: Microbiological Research
https://www.readbyqxmd.com/read/28427840/aav-id-a-rapid-and-robust-assay-for-batch-to-batch-consistency-evaluation-of-aav-preparations
#10
Simon Pacouret, Mohammed Bouzelha, Rajani Shelke, Eva Andres-Mateos, Ru Xiao, Anna Maurer, Mathieu Mevel, Heikki Turunen, Trisha Barungi, Magalie Penaud-Budloo, Frédéric Broucque, Véronique Blouin, Philippe Moullier, Eduard Ayuso, Luk H Vandenberghe
Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency. Currently, there is no facile, fast, and robust characterization assay enabling to probe the identity of AAV products at the protein level...
June 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28371560/differential-scanning-calorimetry-and-fluorimetry-measurements-of-monoclonal-antibodies-and-reference-proteins-effect-of-scanning-rate-and-dye-selection
#11
Brian E Lang, Kenneth D Cole
Differential scanning calorimetry (DSC) and differential scanning fluorimetry (DSF) were used to measure the transition temperatures of four proteins: RNase A, invertase, rituximab, and the NISTmAb (NIST Reference Material, RM 8671). The proteins were combined with several different fluorescent dyes for the DSF measurements. This study compares the results of DSC and DSF measurements of transition temperatures with different types of proteins, dye combinations, and thermal scan rates. As protein unfolding is often influenced by kinetic effects, we measured the transition temperatures of the proteins using DSC over a range of temperature scan rates and compared them to the data obtained from DSF over comparable temperature scan rates...
April 3, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28355693/-influence-of-occupational-aluminum-exposure-on-cognitive-function-and-glutamate-receptor-protein-expression-in-workers
#12
P Ren, R Li, Y Z Yuan, X T Lu, Q Niu
Objective: To investigate the influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in peripheral blood lymphocytes in workers and the possibility of glutamate receptor being used as a biomarker for cognitive impairment in aluminum workers. Methods: From October to December, 2014, cluster sampling was performed to select 121 workers in aluminum electrolysis workshop as exposure group and 231 workers in thermoelectric workshop and logistics department as control group...
February 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#13
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
August 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28244030/characterization-of-a-bacillus-thuringiensis-chitinase-that-binds-to-cellulose-and-chitin
#14
Shotaro Honda, Toshiyuki Kunii, Kenta Nohara, Satoshi Wakita, Yasusato Sugahara, Masao Kawakita, Fumitaka Oyama, Masayoshi Sakaguchi
Bacillus thuringiensis is a Gram-positive soil bacterium that is known to be a bacterial biopesticide that produces insecticidal proteins called crystal proteins (Cry). In the insecticidal process, chitinases are suggested to perforate the peritrophic membrane barrier to facilitate the invasion of the Cry proteins into epithelial membranes. A chitinase gene from B. thuringiensis was successfully expressed in a soluble form in Escherichia coli, and the gene product was purified and characterized. The purified recombinant enzyme, BthChi74, hydrolyzed an artificial substrate, 4-nitrophenyl N,N'-diacetyl-β-D-chitobioside [4NP-(GlcNAc)2], and the natural substrates, colloidal chitin and crystalline α-chitin, but it did not hydrolyze cellulose...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28151054/the-effect-of-organic-shock-loads-on-the-stability-of-anaerobic-granular-sludge
#15
Yangcheng Ding, Huajun Feng, Dongsheng Shen, Na Li, Meizhen Wang, Yuyang Zhou
This study investigated the effect of organic shock loads on the stability of anaerobic granular sludge (AnGS). At double and triple shock intensity (8 and 12 kg COD/m(3)d organic loading rate (OLR), respectively), the accumulation of volatile fatty acids resulted in the decreasing pH of the reactors. The unstable performances of AnGS also appeared in the macroscopic properties, including the decreasing contents of relative hydrophobicity (RH), granular strength and diameter, and the fluctuation of EPS production...
December 2017: Environmental Technology
https://www.readbyqxmd.com/read/28143565/disulfiram-overcomes-bortezomib-and-cytarabine-resistance-in-down-syndrome-associated-acute-myeloid-leukemia-cells
#16
Ranjan Bista, David W Lee, Oliver B Pepper, David O Azorsa, Robert J Arceci, Eiman Aleem
BACKGROUND: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL...
February 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28088457/preformulation-characterization-stabilization-and-formulation-design-for-the-acrylodan-labeled-glucose-binding-protein-sm4-ac
#17
Neha Sahni, Rajoshi Chaudhuri, John M Hickey, Prakash Manikwar, Ajit D'Souza, Andrew Metters, Sangeeta B Joshi, C Russell Middaugh, David B Volkin
This study describes the physicochemical characterization, stabilization, and formulation design of SM4-AC, an acrylodan-labeled glucose/galactose-binding protein for use in a continuous glucose monitoring device. The physical stability profile of SM4-AC as a function of pH and temperature was monitored using a combination of biophysical techniques and the resulting physical stability profile was visualized using an empirical phase diagram. Forced degradation chemical stability studies (Asn deamidation, Met oxidation) of SM4-AC were performed using a combination of capillary isoelectric focusing, peptide mapping, and reversed-phase HPLC...
January 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28067526/extraction-of-thermodynamic-parameters-of-protein-unfolding-using-parallelized-differential-scanning-fluorimetry
#18
Thaiesha A Wright, Jamie M Stewart, Richard C Page, Dominik Konkolewicz
Thermodynamic properties of protein unfolding have been extensively studied; however, the methods used have typically required significant preparation time and high protein concentrations. Here we present a facile, simple, and parallelized differential scanning fluorimetry (DSF) method that enables thermodynamic parameters of protein unfolding to be extracted. This method assumes a two-state, reversible protein unfolding mechanism and provides the capacity to quickly analyze the biophysical mechanisms of changes in protein stability and to more thoroughly characterize the effect of mutations, additives, inhibitors, or pH...
January 12, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28003428/evaluation-of-compound-selectivity-of-aldo-keto-reductases-using-differential-scanning-fluorimetry
#19
Aurangazeb Kabir, Satoshi Endo, Naoki Toyooka, Mayuko Fukuoka, Kazuo Kuwata, Yuji O Kamatari
Inhibitors of AKR1B10 belonging to the aldo-keto reductase (AKR) superfamily are considered promising candidates for anti-cancer drugs. AKR1B1, a structurally similar isoform of AKR1B10, is involved in glucose metabolism. Thus, selective inhibition of AKR1B10 is required for the development of anti-cancer drugs. In this study, we first compared correlations between melting temperature and the 50% inhibition concentration obtained from differential scanning fluorimetry (DSF) and an enzyme inhibitory experiment, respectively, and a good correlation was found, except for compounds with low solubility...
February 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/27813538/the-use-of-differential-scanning-fluorimetry-in-the-rational-design-of-plastic-antibodies-for-protein-targets
#20
Jon Ashley, Yunus Shukor, Ibtisam E Tothill
The development of molecularly imprinted polymer nanoparticles (MIP-NPs), which specifically bind biomolecules, is of great interest in the area of biosensors, sample purification, therapeutic agents and biotechnology. Polymerisation techniques such as precipitation polymerisation, solid phase synthesis and core shell surface imprinting have allowed for significant improvements to be made in developing MIP-NPs which specifically recognise proteins. However, the development of MIP-NPs for protein templates (targets) still require lengthy optimisation and characterisation using different ratios of monomers in order to control their size, binding affinity and specificity...
November 14, 2016: Analyst
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