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With LML methyl oxo dihydropyridazin yl piperidin yl cyclobu
2021-12-15
With LML-134 (1-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate) containing drug-likeness properties (MW 375.47, five HBA, and MLogP 1.88), Novartis presents an additional drug-candidate to treat excessive sleepiness. A phase I clinical study was perform
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OS has a key role
2021-12-15
OS has a key role in the pathogenesis of micro- and macrovascular diabetic complications [3]. There is now convincing evidence that the enzymes that generate ROS and gasotransmitters, such as nitric oxide (NO) and CO, are redox regulated at both the transcription and activity levels, and are also im
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Studies with GSNOR knockout mice reported decreased CD
2021-12-15
Studies with GSNOR knockout mice reported decreased CD4+ pi3 kinase and increased CD19+ cells (B-cell) in the blood [31] as well as demyelination, neurodegeneration, and neuropathic pain [29]. To understand the basis of these differences in immune function of GSNOR knockout mice and GSNO treated mi
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As the material for in silico experiments we
2021-12-15
As the material for in silico experiments we used an amino Pamidronate Disodium sequence of a fragment of HIV1 surface glycoprotein gp120 corresponding to its less mutable B-cellular epitope: NMWKNNMVEQMHEDIISLWDQ. This sequence is the same as the sequence of the NQ21 and the biotin-NQ21 peptides (
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Alpha synuclein AS is a protein located in presynaptic termi
2021-12-15
Alpha synuclein (AS) is a protein located in presynaptic terminals of neurons that functions in recycling and storage of neurotransmitters [17]. Under conditions of inflammation and oxidative stress, AS proteins misfold and accumulate into vasopressin receptor [81], [90]. The aggregates of misfolded
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To further implicate the role of EAAT in morphine induced
2021-12-15
To further implicate the role of EAAT3 in morphine-induced place preference, the effects of morphine on EAAT3 cathepsin inhibitors was determined. Interestingly, morphine increased EAAT3 protein expression in the plasma membrane of mPFC, nucleus accumbens and VTA but not in the hippocampus of wild-
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Recent studies revealed that synthetic oligomeric A decrease
2021-12-15
Recent studies revealed that synthetic oligomeric Aβ1-42 decreased GLT-1 expression and promoted mislocalization of GLT-1 from the cell surface of primary astrocytes, leading to glutamate dyshomeostasis in synapses (Abdul et al., 2009, Scimemi et al., 2013). To address the cause for reduction of ast
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Apoptosis a form of programmed cell death is
2021-12-15
Apoptosis, a form of programmed cell death, is a critical component in maintaining homeostasis and growth in all tissues and plays a significant role in immunity and cytotoxicity [54,55]. Although GR are expressed in all immune cells, the physiological outcomes of GR activation are highly cell type-
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br Materials and methods br Conflicts
2021-12-15
Materials and methods Conflicts of interest Some of the peptidomimetic compounds in this work are the subject of the patent application “Peptidomimetics for Imaging the Ghrelin Receptor”, WO/2016/191865 A1, December 8th, 2016. Acknowledgements Special thanks go to Rebecca McGirr (Lawson He
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Hypertriglyceridemia is associated with an overproduction an
2021-12-15
Hypertriglyceridemia is associated with an overproduction and secretion of triglyceride-rich lipoproteins (TRLs), due to increased liver lipid substrate availability (Adiels et al., 2005, Choi and Ginsberg, 2011), and/or reduced catabolism of TRLs and their remnants, due to reduced lipoprotein lipas
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A relatively independent review of the history of the
2021-12-15
A relatively independent review of the history of the discovery of GABA (and L-glutamate) as neurotransmitters in the CNS can be found in ‘When and why amino acids?’ in the in 2010 by Kresimir Krnjevic , who spent a post-doc in Canberra in 1956–1958. Introduction The insect RDL GABA receptor is
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The normal function of the FBPase enzyme
2021-12-14
The normal function of the FBPase enzyme is to catalyze the hydrolysis of F1,6BP to F6P. This activity is induced by diabetes and starvation and is increased in diabetic rats. The level of FBPase can be normalized by insulin, however, similar information is not available from diabetic patients. FBPa
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To discriminate the peripheral and
2021-12-14
To discriminate the peripheral and central involvement of FAAH in paracetamol action, we proposed a pharmacological strategy challenging the analgesic action of paracetamol observed in an inflammatory context with either a peripherally-restricted FAAH inhibitor (URB937, Clapper et al., 2010, Moreno-
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Compound a substituted phenyl H pyrano
2021-12-14
Compound 6, a 5-(4-substituted-phenyl)-5H-pyrano[2,3-d:-6,5-d′]dipyrimidine derivative was invented previously to have significant efficacy to inhibit HIV integrase enzyme with 0.9 ± 0.4 μM of IC50 against 3′-processing and 16.1 ± 10.7 μM of IC50 against strand transfer suppression. The compound ind
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THZ1 Hydrochloride The stable association of Hat complexes w
2021-12-14
The stable association of Hat1 complexes with histones H3 and H4 raises a number of interesting issues. The first is the question of how Hat1 remains stably associated with histones H3 and H4. While the simple answer is that Hat1 remains bound to histones because of its association with histone chap
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