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https://www.readbyqxmd.com/read/29566027/microrna-expression-in-serum-samples-of-sulfur-mustard-veterans-as-a-diagnostic-gateway-to-improve-care
#1
Sedigheh Gharbi, Shahriar Khateri, Mohammad Reza Soroush, Mehdi Shamsara, Parisa Naeli, Ali Najafi, Eberhard Korsching, Seyed Javad Mowla
Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids...
2018: PloS One
https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#2
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29374256/screening-a-small-molecule-library-to-identify-inhibitors-of-nf-%C3%AE%C2%BAb-inducing-kinase-and-pro-labor-genes-in-human-placenta
#3
Bingbing Wang, Nataliya Parobchak, Adriana Martin, Max Rosen, Lumeng Jenny Yu, Mary Nguyen, Kseniya Gololobova, Todd Rosen
The non-canonical NF-κB signaling (RelB/p52) pathway drives pro-labor genes in the human placenta, including corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), making this a potential therapeutic target to delay onset of labor. Here we sought to identify small molecule compounds from a pre-existing chemical library of orally active drugs that can inhibit this NF-κB signaling, and in turn, human placental CRH and COX-2 production. We used a cell-based assay coupled with a dual-luciferase reporter system to perform an in vitro screening of a small molecule library of 1,120 compounds for inhibition of the non-canonical NF-κB pathway...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29364271/detecting-estrogenic-ligands-in-personal-care-products-using-a-yeast-estrogen-screen-optimized-for-the-undergraduate-teaching-laboratory
#4
Thea M Edwards, Howard E Morgan, Coralia Balasca, Naveen K Chalasani, Lauren Yam, Alison M Roark
The Yeast Estrogen Screen (YES) is used to detect estrogenic ligands in environmental samples and has been broadly applied in studies of endocrine disruption. Estrogenic ligands include both natural and manmade "Environmental Estrogens" (EEs) found in many consumer goods including Personal Care Products (PCPs), plastics, pesticides, and foods. EEs disrupt hormone signaling in humans and other animals, potentially reducing fertility and increasing disease risk. Despite the importance of EEs and other Endocrine Disrupting Chemicals (EDCs) to public health, endocrine disruption is not typically included in undergraduate curricula...
January 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29313412/physicochemical-screening-for-chemical-stabilizer-of-erythropoietin-to-prevent-its-aggregation
#5
Mehri Mortazavi, Mohammad Ali Shokrgozar, Soroush Sardari, Kayhan Azadmanesh, Reza Mahdian, Hooman Kaghazian, Seyed Nezamedin Hosseini, Elnaz Shams
Recombinant protein aggregation is a problematic issue and can provoke immunological response. The aim of this study was to analyze the stability of erythropoietin (EPO), as a therapeutic protein expressed in mammalian cells, in the presence of different chemicals and find a specific stabilizer for EPO. The effects of several chemicals, including mannitol, betaine, trehalose, taurine, linoleic acid, beta-cyclodextrin, copper sulfate, spermidine, maltose, maltodextrin, sucrose, dextran, beta-alanine, myo-inositol, and cysteine, on protein stabilization through the thermally induced aggregation of EPO were monitored...
February 7, 2018: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/29295894/a-computational-based-approach-to-identify-estrogen-receptor-%C3%AE-%C3%AE-heterodimer-selective-ligands
#6
Carlos G Coriano, Fabao Liu, Chelsie K Sievers, Muxuan Liang, Yidan Wang, Yoongho Lim, Menggang Yu, Wei Xu
The biologic effects of estrogens are transduced by two estrogen receptors (ERs), ER α and ER β , which function in dimer forms. The ER α / α homodimer promotes and the ER β / β inhibits estrogen-dependent growth of mammary epithelial cells; the functions of ER α / β heterodimers remain elusive. Using compounds that promote ER α / β heterodimerization, we have previously shown that ER α / β heterodimers appeared to inhibit tumor cell growth and migration in vitro. Further dissection of ER α / β heterodimer functions was hampered by the lack of ER α / β heterodimer-specific ligands...
March 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29175591/linking-t-cell-epitopes-to-a-common-linear-b-cell-epitope-a-targeting-and-adjuvant-strategy-to-improve-t-cell-responses
#7
Sara M Mangsbo, Erika A K Fletcher, Wendy W C van Maren, Anke Redeker, Robert A Cordfunke, Inken Dillmann, Jasper Dinkelaar, Kahina Ouchaou, Jeroen D C Codee, Gijs A van der Marel, Peter Hoogerhout, Cornelis J M Melief, Ferry Ossendorp, Jan W Drijfhout
Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd...
January 2018: Molecular Immunology
https://www.readbyqxmd.com/read/28978013/microtubule-inhibitor-sp-6-27-inhibits-angiogenesis-and-induces-apoptosis-in-ovarian-cancer-cells
#8
Arpita Kulshrestha, Gajendra K Katara, Safaa A Ibrahim, Renukadevi Patil, Shivaputra A Patil, Kenneth D Beaman
In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903496/editor-s-highlight-development-of-novel-neural-embryonic-stem-celltests-for-high-throughput-screening-of-embryotoxic-chemicals
#9
Kumiko Kobayashi, Noriyuki Suzuki, Kiyoshi Higashi, Akane Muroi, Florian Le Coz, Hirohisa Nagahori, Koichi Saito
There is a great demand for appropriate alternative methods to rapidly evaluate the developmental and reproductive toxicity of a wide variety of chemicals. We used the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes as a basis for establishing a rapid and highly reproducible invitro embryotoxicity test known as the Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST). In this study, we developed novel neural-Luc ESTs using two marker genes for neural development, tubulin beta-3 (Tubb3) and Reelin (Reln), and evaluated the capacity of these tests to predict developmental toxicity...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28870238/bet-bromodomain-inhibitors-and-agonists-of-the-beta-2-adrenergic-receptor-identified-in-screens-for-compounds-that-inhibit-dux4-expression-in-fshd-muscle-cells
#10
Amy E Campbell, Jonathan Oliva, Matthew P Yates, Jun Wen Zhong, Sean C Shadle, Lauren Snider, Nikita Singh, Shannon Tai, Yosuke Hiramuki, Rabi Tawil, Silvère M van der Maarel, Stephen J Tapscott, Francis M Sverdrup
BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs that enhance the repression of DUX4 and prevent its expression in skeletal muscle cells therefore represent candidate therapies for FSHD. METHODS: We screened an aggregated chemical library enriched for compounds with epigenetic activities and the Pharmakon 1600 library composed of compounds that have reached clinical testing to identify molecules that decrease DUX4 expression as monitored by the levels of DUX4 target genes in FSHD patient-derived skeletal muscle cell cultures...
September 4, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28545020/microtubule-inhibitor-sp-6-27-inhibits-angiogenesis-and-induces-apoptosis-in-ovarian-cancer-cells
#11
Arpita Kulshrestha, Gajendra K Katara, Safaa A Ibrahim, Renukadevi Patil, Shivaputra A Patil, Kenneth D Beaman
In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533985/metabarcoding-monitoring-analysis-the-pros-and-cons-of-using-co-extracted-environmental-dna-and-rna-data-to-assess-offshore-oil-production-impacts-on-benthic-communities
#12
Olivier Laroche, Susanna A Wood, Louis A Tremblay, Gavin Lear, Joanne I Ellis, Xavier Pochon
Sequencing environmental DNA (eDNA) is increasingly being used as an alternative to traditional morphological-based identification to characterize biological assemblages and monitor anthropogenic impacts in marine environments. Most studies only assess eDNA which, compared to eRNA, can persist longer in the environment after cell death. Therefore, eRNA may provide a more immediate census of the environment due to its relatively weaker stability, leading some researchers to advocate for the use of eRNA as an additional, or perhaps superior proxy for portraying ecological changes...
2017: PeerJ
https://www.readbyqxmd.com/read/28253977/high-throughput-quantification-of-gfp-lc3-dots-by-automated-fluorescence-microscopy
#13
J M Bravo-San Pedro, F Pietrocola, V Sica, V Izzo, A Sauvat, O Kepp, M C Maiuri, G Kroemer, L Galluzzi
Macroautophagy is a specific variant of autophagy that involves a dedicated double-membraned organelle commonly known as autophagosome. Various methods have been developed to quantify the size of the autophagosomal compartment, which is an indirect indicator of macroautophagic responses, based on the peculiar ability of microtubule-associated protein 1 light chain 3 beta (MAP1LC3B; best known as LC3) to accumulate in forming autophagosomes upon maturation. One particularly convenient method to monitor the accumulation of mature LC3 within autophagosomes relies on a green fluorescent protein (GFP)-tagged variant of this protein and fluorescence microscopy...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28230988/retraction-of-design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#14
Vibha Pathak, Corinne E Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
No abstract text is available yet for this article.
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28157684/cdk5-foxo3-axis-initially-neuroprotective-eventually-neurodegenerative-in-alzheimer-s-disease-models
#15
Chun Shi, Keith Viccaro, Hyoung-Gon Lee, Kavita Shah
Deregulated Cdk5 causes neurotoxic amyloid beta peptide (Aβ) processing and cell death, two hallmarks of Alzheimer's disease, through the Foxo3 transcriptional factor in hippocampal cells, primary neurons and an Alzheimer's disease mouse model. Using an innovative chemical genetic screen, we identified Foxo3 as a direct substrate of Cdk5 in brain lysates. Cdk5 directly phosphorylates Foxo3, which increased its levels and nuclear translocation. Nuclear Foxo3 initially rescued cells from ensuing oxidative stress by upregulating MnSOD (also known as SOD2)...
May 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#16
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27785713/i-cell-disease-mucolipidosis-ii-alpha-beta-from-screening-to-molecular-diagnosis
#17
Ankur Singh, Rajniti Prasad, Aditya Kumar Gupta, Anil Sharma, Sandra Alves, Maria Francisca Coutinho, Seema Kapoor, Om Prakash Mishra
Mucopolysaccharidosis (MPS) and Mucolipidosis (ML) share common phenotypes (coarse facial features, organomegaly, dysostosis multiplex) despite having different molecular basis. Thus, they pose great diagnostic challenge to treating clinicians. Differentiating between the two conditions requires a battery of tests from screening to molecular diagnosis. Besides discussing differential diagnosis of MPS like features with negative urinary Glycosaminoglycans (GAG), the authors also discuss the utility of p-nitrocatechol sulphate based chemical test as an important screening tool, besides establishing molecular basis in index case...
February 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/27693453/development-of-a-neuroprotective-potential-algorithm-for-medicinal-plants
#18
Weixi Liu, Hang Ma, Nicholas A DaSilva, Kenneth N Rose, Shelby L Johnson, Lu Zhang, Chunpeng Wan, Joel A Dain, Navindra P Seeram
Medicinal plants are promising candidates for Alzheimer's disease (AD) research but there is lack of systematic algorithms and procedures to guide their selection and evaluation. Herein, we developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Aβ) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation...
September 29, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27633901/screening-of-endocrine-activity-of-compounds-migrating-from-plastic-baby-bottles-using-a-multi-receptor-panel-of-in-vitro-bioassays
#19
Coraline Simon, Matthias Onghena, Adrian Covaci, Els Van Hoeck, Joris Van Loco, Tara Vandermarken, Kersten Van Langenhove, Heidi Demaegdt, Birgit Mertens, Karin Vandermeiren, Marie-Louise Scippo, Marc Elskens
Endocrine activity of 65 compounds migrating from polycarbonate replacement plastic baby bottles was assessed using in vitro cell based assays (reporter gene assays) involving 7 nuclear receptors, i.e. human steroid hormones receptors (oestrogen, androgen, progesterone and glucocorticoid receptors), human thyroid beta and peroxisome proliferator-activated gamma receptors, and the mouse aryl hydrocarbon receptor. The chemicals were tested at 4 concentrations ranging from 0.001mM to 1mM. Only twelve chemicals did not show any activity towards any of the nuclear receptors, while fifty three compounds showed a possible endocrine activity...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27528272/novel-cell-based-assay-for-detection-of-thyroid-receptor-beta-interacting-environmental-contaminants
#20
Diana A Stavreva, Lyuba Varticovski, Ludmila Levkova, Anuja A George, Luke Davis, Gianluca Pegoraro, Vicki Blazer, Luke Iwanowicz, Gordon L Hager
Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP)-tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TRβ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TRβ, this GFP-GR-TRβ chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3',5'-triiodothyronine, or rT3) was inactive...
August 10, 2016: Toxicology
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