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https://www.readbyqxmd.com/read/28088457/preformulation-characterization-stabilization-and-formulation-design-for-the-acrylodan-labeled-glucose-binding-protein-sm4-ac
#1
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 (cIEF), peptide mapping and reversed phase high performance liquid chromatography (RP-HPLC)...
January 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#2
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28067526/extraction-of-thermodynamic-parameters-of-protein-unfolding-using-parallelized-differential-scanning-fluorimetry
#3
Thaiesha A Wright, Jamie M Stewart, Richard Christopher 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 9, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28064151/supervised-disulfiram-s-superior-effectiveness-in-alcoholism-treatment-ethical-methodological-and-psychological-aspects
#4
REVIEW
Colin Brewer, Emmanuel Streel, Marilyn Skinner
Disulfiram (DSF) causes the ALDH-mediated deterrence of alcohol consumption. We review recent meta-analyses showing the superior effectiveness of supervised disulfiram (SD) in alcoholism treatment compared with oral naltrexone or acamprosate (ACP). The success of SD is also consistent with the almost complete absence of alcoholism in Japanese homozygotes for 'inefficient' ALDH. However, SD is an underused treatment and some clinicians have ethical objections to DSF. We examine these objections and argue that they are based on a misunderstanding of how DSF works...
January 7, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28057017/the-brain-penetrating-cxcr4-antagonist-prx177561-increases-the-antitumor-effects-of-bevacizumab-and-sunitinib-in-preclinical-models-of-human-glioblastoma
#5
Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
BACKGROUND: Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28052684/discordance-between-clinical-and-pathological-tnm-classification-influence-on-results-of-treatment-and-prognosis-in-patients-with-laryngeal-cancer
#6
P Celakovsky, D Kalfert, K Smatanova, P Kordac, J Laco, V Chrobok
The goals of this retrospective cohort study were to compare the results of clinical and pathological TNM staging in patients with laryngeal squamous cell carcinoma and to determine the impact of the discordance on prognosis and treatment results. A total of 124 patients with laryngeal cancer, primarily indicated for surgical treatment, were enrolled. The concordance or discordance between the clinical and pathological staging was compared with the frequency of cancer relapse and disease-specific survival. Other potential prognostic factors, like age, the stage and location of the primary tumor, the status of neck lymph nodes, histological margins, and an indication for postoperative radiotherapy, were also evaluated...
January 5, 2017: Neoplasma
https://www.readbyqxmd.com/read/28003428/evaluation-of-compound-selectivity-of-aldo-keto-reductases-using-differential-scanning-fluorimetry
#7
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...
December 21, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/27987908/oriented-cellulose-nanopaper-ocnp-based-on-bagasse-cellulose-nanofibrils
#8
Seyed Rahman Djafari Petroudy, Esmaeil Rasooly Garmaroody, Hamidreza Rudi
The purpose of this study is to explore the suitability of bagasse fiber for production of Cellulose Nanofiber (CNF) and Oriented Cellulose Nanopaper (OCNP) for the first time. Different types of CNF were thus produced either mechanically by homogenization or with enzymatic pre-treatment followed by homogenization. The CNF was thereafter used for the production of nanopapers through two approaches; i) Dispersion Casting (DC) and ii) Dynamic Sheet Former (DSF). Then, the prepared nanopapers were characterized in terms of surface, structural, morphological and mechanical properties...
February 10, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27979499/the-dsf-family-of-quorum-sensing-signals-diversity-biosynthesis-and-turnover
#9
REVIEW
Lian Zhou, Lian-Hui Zhang, Miguel Cámara, Ya-Wen He
The diffusible signaling factor (DSF)-based quorum sensing (QS) system has emerged as a widely conserved cell-cell communication mechanism in Gram-negative bacteria. Typically, signals from the DSF family are cis-2-unsaturated fatty acids which regulate diverse biological functions. Recently, substantial progress has been made on the characterization of new members of this family of signals. There have also been new developments in the understanding of the biosynthesis of these molecules where dual enzymatic activities of the DSF synthase and the use of various substrates have been described...
December 12, 2016: Trends in Microbiology
https://www.readbyqxmd.com/read/27915005/development-and-characterisation-of-disulfiram-loaded-plga-nanoparticles-for-the-treatment-of-non-small-cell-lung-cancer
#10
Mohammad Najlah, Zahima Ahmed, Mohammed Iqbal, Zhipeng Wang, Patrica Tawari, Weiguang Wang, Christopher McConville
Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4min) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27895076/mesothelial-cells-create-a-novel-tissue-niche-that-facilitates-gastric-cancer-invasion
#11
Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells...
November 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#12
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27882330/aldh2-inhibition-potentiates-high-glucose-stress-induced-injury-in-cultured-cardiomyocytes
#13
Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Suresh Selvaraj Palaniyandi
Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27831632/disulfiram-as-a-candidate-nf-%C3%AE%C2%BAb-and-proteasome-inhibitor-prevents-endometriotic-implant-growing-in-a-rat-model-of-endometriosis
#14
O Celik, A Ersahin, M Acet, N Celik, Y Baykus, R Deniz, E Ozerol, I Ozerol
OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27813538/the-use-of-differential-scanning-fluorimetry-in-the-rational-design-of-plastic-antibodies-for-protein-targets
#15
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
https://www.readbyqxmd.com/read/27803460/an-ophthalmic-formulation-of-disulfiram-nanoparticles-prolongs-drug-residence-time-in-lens
#16
Noriaki Nagai, Yu Mano, Yoshimasa Ito
Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27796875/molecular-and-spectroscopic-characterization-of-aspergillus-flavipes-and-pseudomonas-putida-l-methionine-%C3%AE-lyase-in-vitro
#17
Ashraf S A El-Sayed, Laura E Ruff, Salah E Abdel Ghany, Gul Shad Ali, Sadik Esener
Pseudomonas putida L-methionine γ-lyase (PpMGL) has been recognized as an efficient anticancer agent, however, its antigenicity and stability remain as critical challenges for its clinical use. From our studies, Aspergillus flavipes L-methionine γ-lyase (AfMGL) displayed more affordable biochemical properties than PpMGL. Thus, the objective of this work was to comparatively assess the functional properties of AfMGL and PpMGL via stability of their internal aldimine linkage, tautomerism of pyridoxal 5'-phosphate (PLP) and structural stability responsive to physicochemical factors...
October 29, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27794454/characterization-of-aminoacyl-trna-synthetase-stability-and-substrate-interaction-by-differential-scanning-fluorimetry
#18
REVIEW
Jamie A Abbott, Nathan M Livingston, Shawn B Egri, Ethan Guth, Christopher S Francklyn
Differential scanning fluorimetry (DSF) is a fluorescence-based assay to evaluate protein stability by determining protein melting temperatures. Here, we describe the application of DSF to investigate aminoacyl-tRNA synthetase (AARS) stability and interaction with ligands. Employing three bacterial AARS enzymes as model systems, methods are presented here for the use of DSF to measure the apparent temperatures at which AARSs undergo melting transitions, and the effect of AARS substrates and inhibitors. One important observation is that the extent of temperature stability realized by an AARS in response to a particular bound ligand cannot be predicted a priori...
October 26, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27789147/utilizing-direct-skin-feeding-assays-for-development-of-vaccines-that-interrupt-malaria-transmission-a-systematic-review-of-methods-and-case-study
#19
REVIEW
Elizabeth B Brickley, Mamadou Coulibaly, Erin E Gabriel, Sara A Healy, Jen C C Hume, Issaka Sagara, Sekou F Traore, Ogobara Doumbo, Patrick E Duffy
Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27765525/the-clinical-and-economic-impact-of-the-use-of-diabetes-specific-enteral-formula-on-icu-patients-with-type-2-diabetes
#20
Yin-Yi Han, Sheng-Ru Lai, Jamie S Partridge, Michael Y Wang, Suela Sulo, Fang-Wei Tsao, Refaat A Hegazi
BACKGROUND & AIMS: Patients admitted to intensive care units (ICUs) often need enteral nutrition (EN) support. For patients with type 2 diabetes (T2D), standard EN formulas may not provide ideal nutrients. The purpose was to investigate whether use of a diabetes-specific formula (DSF) could provide clinical and health economic benefits (compared to standard formulas) in critically ill patients with T2D. METHODS: This study was a retrospective analysis of medical records and expenditure data covering a 5-year period (2009-2013) from the hospitalization database of the National Taiwan University Hospital...
October 6, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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