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Our previous high throughput screening HTS campaign
2020-09-28
Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based Ozagrel assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [22], [23],
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It is well established that a number of
2020-09-28
It is well established that a number of intracellular signaling pathways mediate sensitization of sensory neurons (Gold and Gebhart, 2010, Richardson and Vasko, 2002). This redundancy could be advantageous since it provides diversity in initiating and maintaining hypersensitivity in response to inju
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br Introduction Prostaglandin E PGE signals
2020-09-28
Introduction Prostaglandin E2 (PGE2) signals through 4 separate G-protein coupled receptor sub-types (EP1, EP2, EP3 and EP4) to elicit a variety of physiological and pathophysiologic effects. EP2 and EP4 increase cAMP levels in the cell via adenylate cyclase activation, whereas EP3 inhibits cAMP
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For immobilization of enzymes natural polymers depict
2020-09-28
For immobilization of enzymes, natural polymers depict several outstanding features as support. These materials are inert, non-toxic, biodegradable and biocompatible. As well as, they can be treated with different functional groups easily by chemical reactions that occur under gentle conditions in a
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br Substrate characterization of candidate peptide reporters
2020-09-28
Substrate characterization of candidate peptide reporters in a library Measurement of resistance to intracellular proteases Use of capillary zone electrophoresis for assay readout Selection of lead peptide from small library screen Characterization of final reporter Additional modif
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Apart from the ET system s role
2020-09-28
Apart from the ET system\'s role in regulating blood vessel tone, it is also involved in a variety of cellular processes that are relevant to DR. For example, the ET receptors influence the survival of retinal ganglion mma f (McGrady et al., 2017; Tonari et al., 2012), development of the retinal va
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Initially we ascertained that if the dose of elastase was
2020-09-28
Initially, we ascertained that if the dose of elastase was sufficient to cause pulmonary emphysema, then pulmonary emphysema could be maintained throughout the study. We found that elastase at 3U was sufficient to cause emphysema that remained over 35 days. In this experimental design of lung diseas
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The concept of GPCRs and
2020-09-28
The concept of GPCRs and EGFRs existing as heteromers is consistent with previous studies. Co-immunoprecipitation studies have shown that agonist stimulation (both AngII and EGF) promotes a multi-protein complex containing the AT1R and EGFR, however these endpoint assays were not in live cells or in
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AP1903 Interestingly our analyses of human
2020-09-28
Interestingly, our analyses of human PBMCs using a monoclonal antibody against EBI2 showed that the expression pattern of human EBI2 is largely overlapping with that in mice. Especially Th17 AP1903 showed homogeneous high expression of EBI2 compared with Th1 cells, which contained a fraction of cel
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The differences between ground and transition state properti
2020-09-28
The differences between ground and transition state properties are exemplified by a comparison of our human–yeast results with those of a structural study of possible differences in ubiquitin-Uba-1 binding in yeast (known structure) with human (simulated in [12]). Their discussion focuses on Ubiquit
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Classical DHFR inhibitors such as
2020-09-27
Classical DHFR inhibitors such as methotrexate (MTX) bind tightly to the enzyme and possess adequate clinical pharmacokinetics. MTX bind to the DHFR binding site through the formation of hydrogen bonds with Asn64, Lys68, Arg28, Arg70, Val115 and Ile7 amino neuraminidase inhibitor residues as well a
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Mechanistically GW treatment modulated cytokine expression
2020-09-27
Mechanistically, GW2580 treatment modulated cytokine expression within the kidney. We noted a decrease in the levels of TNF, MCP-1, IL-1β, IL-27, and GM-CSF in GW2580 treated mice. Decreased levels of these proinflammatory cytokines likely contributed to the attenuated proteinuria and improved renal
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In the course of our program which
2020-09-27
In the course of our program, which was aimed at developing CRTH2 antagonists for the treatment of allergic diseases, we have been pursuing a new class of potent and selective CRTH2 antagonist lead based on the structures of CRTH2 antagonists known to date (, , ). Using a fused 6–6-membered ring sys
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br Conflict of interest br
2020-09-27
Conflict of interest Acknowledgments Part of this work was supported by Institut Francais en Egypte, and the Academy of Scientific Research and Technology in Egypt under the frame of “Imhotep Project N°: 31681XL” and “STDF/IFE project N° 30630″ Introduction NSAIDs play an important role in
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Introduction The COMT gene is located on
2020-09-27
Introduction The COMT gene is located on chromosomal band 22q11.2, extends over 28 kb, contains six exons, and encodes for catechol-O-methyl-transferase (Weinshilboum and Raymond, 1977; Grossman et al., 1992; Lundström et al., 1995; Bearden et al., 2005). This enzyme plays a major role in regulatio
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