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https://www.readbyqxmd.com/read/28346092/screening-for-protein-protein-interaction-inhibitors-using-a-bioluminescence-resonance-energy-transfer-bret-based-assay-in-yeast
#1
Caroline Corbel, Sara Sartini, Elisabetta Levati, Pierre Colas, Laurent Maillet, Cyril Couturier, Barbara Montanini, Stéphane Bach
The bioluminescence resonance energy transfer (BRET) technology is a widely used live cell-based method for monitoring protein-protein interactions as well as conformational changes within proteins or molecular complexes. Considering the emergence of protein-protein interactions as a new promising class of therapeutic targets, we have adapted the BRET method in budding yeast. In this technical note, we describe the advantages of using this simple eukaryotic model rather than mammalian cells to perform high-throughput screening of chemical compound collections: genetic tractability, tolerance to solvent, rapidity, and no need of expensive robotic systems...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345579/inhibition-of-delta-secretase-improves-cognitive-functions-in-mouse-models-of-alzheimer-s-disease
#2
Zhentao Zhang, Obiamaka Obianyo, Elfriede Dall, Yuhong Du, Haian Fu, Xia Liu, Seong Su Kang, Mingke Song, Shan-Ping Yu, Chiara Cabrele, Mario Schubert, Xiaoguang Li, Jian-Zhi Wang, Hans Brandstetter, Keqiang Ye
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345250/the-application-of-constitutively-solvent-tolerant-p-taiwanensis-vlb120%C3%AE-c%C3%AE-ttgv-for-stereospecific-epoxidation-of-toxic-styrene-alleviates-carrier-solvent-use
#3
Jan Volmer, Andreas Schmid, Bruno Bühler
For whole-cell biotransformations involving toxic organic compounds, two-liquid phase setups are typically applied employing an apolar extractive phase. Bis(2-ethylhexyl)phthalate (BEHP) has proven to be an ideal solvent for stereospecific styrene epoxidation with recombinant E. coli, providing excellent extractive properties and a high biocompatibility. In eco-efficiency evaluations, BEHP, however, has been identified as a critical factor regarding costs and environmental impact. In this study, the constitutive solvent tolerance of P...
March 27, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28344492/cyp2c9-cypc19-and-cyp2d6-gene-profiles-and-gene-susceptibility-to-drug-response-and-toxicity-in-turkish-population
#4
Merve Arici, Gül Özhan
Pharmacogenetics is a vast field covering drug discovery research, the genetic basis of pharmacokinetics and dynamics, genetic testing and clinical management in diseases. Pharmacogenetic approach usually focuses on variations of drug transporters, drug targets, drug metabolizing enzymes and other biomarker genes. Cytochrome P450 (CYP) enzymes, an essential source of variability in drug-response, play role in not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds such as steroids, vitamins and fatty acids...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28342858/aqueous-extract-from-leaf-of-artocarpus-altilis-provides-cardio-protection-from-isoproterenol-induced-myocardial-damage-in-rats-negative-chronotropic-and-inotropic-effects
#5
Chukwuemeka Nwokocha, Javier Palacios, Mario J Simirgiotis, Jemesha Thomas, Magdalene Nwokocha, Lauriann Young, Rory Thompson, Fredi Cifuentes, Adrian Paredes, Rupika Delgoda
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. MATERIAL AND METHODS: Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-hour period...
March 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28340740/quantification-of-polybrominated-diphenyl-ethers-pbdes-in-food-a-review
#6
REVIEW
Wojciech Jerzy Pietroń, Paweł Małagocki
The polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), are food contaminants of animal origin. Interest in food matrices analysis is growing due to the toxicity of PBDEs and European Commission (EC) recommendation (118/2014/EU). Here we review papers concerning methods of PBDEs analysis while focusing on extraction, clean up, chromatographic separation and detection techniques. The emphasis is put on EC recommendation, the congeners and the efficiency of different detection systems...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28340455/toxicological-and-behavioral-responses-as-a-tool-to-assess-the-effects-of-natural-and-synthetic-dyes-on-zebrafish-early-life
#7
Flavia R Abe, Jacqueline N Mendonça, Luiz A B Moraes, Gisele A R de Oliveira, Carlos Gravato, Amadeu M V M Soares, Danielle P de Oliveira
Organic dyes extracted from natural sources have been widely used to develop safety and eco-friendly dyes as an alternative to synthetic ones, since the latter are usually precursors of mutagenic compounds. Thereby, toxicity tests to non-target organisms are critical step to develop harmless dyes to environment and in this context, zebrafish early life stages are becoming an important alternative model. We aimed to assess the toxic effects of the synthetic dye Basic Red 51 (BR51, used in cosmetic industry), the natural dye erythrostominone (ERY, a potential commercial dye extracted from fungi) and its photodegradation product (DERY), using zebrafish early life assays...
March 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28337797/standardized-sophora-pachycarpa-root-extract-enhances-osteogenic-differentiation-in-adipose-derived-human-mesenchymal-stem-cells
#8
Samaneh Mollazadeh, Vajiheh Neshati, Bibi Sedigheh Fazly Bazzaz, Mehrdad Iranshahi, Majid Mojarrad, Hojjat Naderi-Meshkin, Mohammad Amin Kerachian
Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21 days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity...
March 24, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#9
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28334285/control-of-the-bradysia-odoriphaga-diptera-sciaridae-with-allyl-isothiocyanate-under-field-and-greenhouse-conditions
#10
Cai-Hua Shi, Jing-Rong Hu, Wen Xie, Yu-Ting Yang, Shao-Li Wang, You-Jun Zhang
The botanical compound allyl isothiocyanate (AITC) is toxic to many microorganisms and insects. The aim of this study was to assess the effects of AITC on the Bradysia odoriphaga (Diptera: Sciaridae), as well as the seeds and seedlings of Chinese chive. AITC was toxic to all four stages of B. odoriphaga. The adult was significantly more sensitive (LC50 = 7.43 µl liter-1) to AITC than the other three stages, which had no difference in sensitivity to the chemical. The control efficacy of AITC against B. odoriphaga was much better in the greenhouse than that in the field...
March 2, 2017: Journal of Economic Entomology
https://www.readbyqxmd.com/read/28334192/insecticidal-properties-of-essential-oils-and-some-of-their-constituents-on-the-turkestan-cockroach-blattodea-blattidae
#11
Sudip Gaire, Mary O'Connell, Francisco O Holguin, Anup Amatya, Scott Bundy, Alvaro Romero
The Turkestan cockroach, Blatta lateralis (Walker), has become the most important peridomestic species in urban areas of the Southwestern United States. The aim of this study was to evaluate the use of botanical compounds to control this urban pest. We tested the acute toxicity and repellency of six botanical constituents and three essential oils on Turkestan cockroach nymphs. Chemical composition of the essential oils was also determined. Topical and fumigant assays with nymphs showed that thymol was the most toxic essential oil constituent, with a LD50 of 0...
March 3, 2017: Journal of Economic Entomology
https://www.readbyqxmd.com/read/28334022/effects-of-clothianidin-on-aquatic-communities-evaluating-the-impacts-of-lethal-and-sublethal-exposure-to-neonicotinoids
#12
Jesse C Miles, Jessica Hua, Maria S Sepulveda, Christian H Krupke, Jason T Hoverman
The widespread usage of neonicotinoid insecticides has sparked concern over their effects on non-target organisms. While research has largely focused on terrestrial systems, the low soil binding and high water solubility of neonicotinoids, paired with their extensive use on the landscape, puts aquatic environments at high risk for contamination via runoff events. We assessed the potential threat of these compounds to wetland communities using a combination of field surveys and experimental exposures including concentrations that are representative of what invertebrates experience in the field...
2017: PloS One
https://www.readbyqxmd.com/read/28333458/declining-trends-of-polychlorinated-naphthalenes-in-seabird-eggs-from-the-canadian-arctic-1975-2014
#13
Birgit M Braune, Derek C G Muir
There are relatively few studies of polychlorinated naphthalenes (PCNs) for biota in polar regions and even fewer reports of temporal trends. We determined concentrations of PCNs in eggs of thick-billed murres (Uria lomvia) collected from the Canadian high Arctic between 1975 and 2014 and calculated their associated toxic equivalents (TEQs). Concentrations of Σ67PCN decreased significantly in the murre eggs between 1975 and 2014 at an average annual rate of -14.9 pg g(-1) wet weight. Although the penta- and tetra-CNs (predominantly CN-52/60 and CN-42) dominated the PCN profile, the hexa-CNs (mainly CN-66/67) accounted for the majority of the Σ67TEQ-PCN, concentrations of which also decreased significantly between 1975 to 2014...
March 23, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28332847/phase-behavior-and-physical-properties-of-new-biobased-ionic-liquid-crystals
#14
Ariel Antonio Campos Toledo Hijo, Guilherme José Maximo, Mariana Conceição Costa, Rosiane Lopes Cunha, Jorge Fernando Brandão Pereira, Kiki Adi Kurnia, Eduardo A Caldas Batista, Antonio J A Meirelles
Protic ionic liquids (PILs) have emerged as promising compounds and attracted the interest of the industry and the academy community, due to their easy preparation and unique properties. In the context of green chemistry, the use of biocompounds, such as fatty acids for their synthesis could disclose a possible alternative way to produce ILs with low or non-toxic effect and consequently, expanding their applicability in bio-based processes or in the development of bioproducts. This work addressed efforts to a better comprehension of the complex Solid-Liquid-Crystal-Liquid thermodynamic equilibrium of twenty new PILs synthesized by using fatty acids commonly found in vegetable oils, as well as their rheological profile and self-assembling ability...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28330245/co-metabolism-of-thiocyanate-and-free-cyanide-by-exiguobacterium-acetylicum-and-bacillus-marisflavi-under-alkaline-conditions
#15
Lukhanyo Mekuto, Oluwadara Oluwaseun Alegbeleye, Seteno Karabo Obed Ntwampe, Maxwell Mewa Ngongang, John Baptist Mudumbi, Enoch A Akinpelu
The continuous discharge of cyanide-containing effluents to the environment has necessitated for the development of environmentally benign treatment processes that would result in complete detoxification of the cyanide-containing wastewaters, without producing additional environmental toxicants. Since biological detoxification of hazardous chemical compounds has been renowned for its robustness and environmental-friendliness, the ability of the Exiguobacterium acetylicum (GenBank accession number KT282229) and Bacillus marisflavi (GenBank accession number KR016603) to co-metabolise thiocyanate (SCN(-)) and free cyanide (CN(-)) under alkaline conditions was evaluated...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330176/molecular-dissection-of-pathway-components-unravel-atisine-biosynthesis-in-a-non-toxic-aconitum-species-a-heterophyllum-wall
#16
Varun Kumar, Nikhil Malhotra, Tarun Pal, Rajinder Singh Chauhan
Aconitum heterophyllum is an important component for various herbal drug formulations due to the occurrence of non-toxic aconites including marker compound, atisine. Despite huge pharmacological potential, the reprogramming of aconites production is limited due to lack of understanding on their biosynthesis. To address this problem, we have proposed here the complete atisine biosynthetic pathway for the first time connecting glycolysis, MVA/MEP, serine biosynthesis and diterpene biosynthetic pathways. The transcript profiling revealed phosphorylated pathway as a major contributor towards serine production in addition to repertoire of genes in glycolysis (G6PI, PFK, ALD and ENO), serine biosynthesis (PGDH and PSAT) and diterpene biosynthesis (KO and KH) sharing a similar pattern of expression (2-4-folds) in roots compared to shoots vis-à-vis atisine content (0-0...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329446/in-vitro-intrinsic-permeability-a-transporter-independent-measure-of-caco-2-cell-permeability-in-drug-design-and-development
#17
Linda Fredlund, Susanne Winiwarter, Constanze Hilgendorf
In-vitro permeability data have a central place in absorption risk assessments in drug discovery and development. For compounds where active efflux impacts permeability in vitro, the inherent passive membrane permeability ("intrinsic permeability"), gives a concentration-independent measure of the compound's permeability. This work describes the validation of an in-vitro intrinsic permeability assay and application of the data in a predictive in-silico model. Apparent intrinsic permeability (Papp) across Caco-2 cell monolayers is determined in presence of an optimized cocktail of chemical inhibitors towards the three major efflux transporters ABCB1, ABCC2, and ABCG2...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28326551/cyclic-imine-toxins-from-dinoflagellates-a-growing-family-of-potent-antagonists-of-the-nicotinic-acetylcholine-receptors
#18
REVIEW
Jordi Molgó, Pascale Marchot, Rómulo Aráoz, Evelyne Benoit, Bogdan I Iorga, Armen Zakarian, Palmer Taylor, Yves Bourne, Denis Servent
We present an overview of the toxicological profile of the fast-acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore, the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28326124/adverse-effects-of-hydroalcoholic-extracts-and-the-major-components-in-the-stems-of-impatiens-balsamina-l-on-caenorhabditis-elegans
#19
Hong-Fang Jiang, Zi-Heng Zhuang, Bei-Wei Hou, Bao-Jun Shi, Cheng-Jie Shu, Lei Chen, Guo-Xin Shi, Wei-Ming Zhang
Impatiens balsamina L. (Balsaminaceae), an annual herb found throughout China, has been extensively used in traditional Chinese medicine (TCM). However, our knowledge regarding the adverse effects of I. balsamina in vivo is very limited. In this present study, the nematode Caenorhabditis elegans model was employed to fully assess the adverse effects of hydroalcoholic (EtOH 55%) extracts of I. balsamina stems (HAEIBS) in vivo. After exposure to 10 mg/mL HAEIBS, the major organism-level endpoints of C. elegans of percent survival, frequency of head thrash and body bends, and reproduction had decreased by 24%, 30%, and 25%, respectively...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28324276/the-cytotoxicity-and-genotoxicity-of-particulate-and-soluble-cobalt-in-human-urothelial-cells
#20
Rachel M Speer, Therry The, Hong Xie, Louis Liou, Rosalyn M Adam, John Pierce Wise
Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder...
March 21, 2017: Biological Trace Element Research
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