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br Sources of funding This
2022-01-28
Sources of funding This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (No. MOP-111096) and from the Heart and Stroke Foundation of Canada awarded to Dr. Danielle Jacques. Disclosures Acknowledgments Introduction A large number of epidemiological, hu
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br Mechanisms of Resistance As
2022-01-28
Mechanisms of Resistance As with other cancer treatments in development, resistance is a concern with HHIs. Most observations regarding HHI resistance originate from patients with BCC [78]. In the clinic, resistance to vismodegib and sonidegib were observed when used to treat advanced BCC [78],
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Ergosterol australia br Trifluoromethylketones This group of
2022-01-28
Trifluoromethylketones This group of compounds was demonstrated to bind the zinc Ergosterol australia in the active site due to its easy hydration, forming the required chelating intermediate. Ontaria et al. [92] have proposed variations around the cap group of trifluoromethylthiophene as the co
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The Y H D A
2022-01-28
The Y56H/D168A variant was resistant to all tested PIs, and the inhibitor binding mode determined the molecular mechanism of resistance. Prior to the development of grazoprevir, PIs typically contained large heterocyclic P2 moieties that strongly interacted with S2-subsite residues (Ali et al., 2013
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Here we demonstrate an anti inflammatory
2022-01-28
Here we demonstrate an anti-inflammatory and anticancer function for Gpr109a in colon. Gpr109a signaling imposed anti-inflammatory properties in colonic antigen-presenting cells, which in turn induced differentiation of Treg 3-bromo-5-phenyl Salicylic Acid synthesis and IL-10-producing T cells. Gpr
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br Acknowledgments br Introduction Manipulating target prote
2022-01-28
Acknowledgments Introduction Manipulating target protein expression via either induction or suppression of gene expression is a powerful technology that has been widely used in the recent past in the field of neurobiology, both to study the pathophysiological significance of a target gene and
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The two competitive bivalent GlxI inhibitors polyBHG nM
2022-01-28
The two competitive bivalent GlxI inhibitors polyBHG2-62 (=1nM) and polyBHG2-54 (=0.3nM) () were designed based on the transition-state analog -(-bromophenyl--hydroxycarbamoyl) glutathione (BHG) by an examination of the X-ray crystal structure of human GlxI in complex with one CHG at each active sit
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In conclusion we have designed and characterized a novel
2022-01-28
In conclusion, we have designed and characterized a novel series of EAAT-blockers, exemplified by (-[4-(2-bromo-4,5-difluorophenoxy)phenyl]--asparagine)—a potent, selective, competitive non-substrate inhibitor of EAAT-2. As one of the most potent and selective EAAT-2 inhibitors identified to date,
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br Dysregulation of glutamate transporter expression and
2022-01-28
Dysregulation of glutamate transporter expression and function Aberrant glutamate transporter function and expression are associated with various neurological disorders. Therefore, understanding the underlying mechanisms of EAAT1/2 expression may provide therapeutic targets for treating neurologi
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About epilepsy no specific seizure type has been identified
2022-01-28
About epilepsy, no specific seizure type has been identified because GLUT1-DS is associated with a wide range of epilepsies: patients develop seizures in infancy and early childhood, which are, frequently, do not respond to anticonvulsant medication. In infants, seizures are described as brief, subt
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Solid tumors usually present insufficient supply of oxygen a
2022-01-28
Solid tumors usually present insufficient supply of oxygen, activating the hypoxia inducible factor-1 (HIF-1) pathway, which prompts an adaptive response on genes that regulate glycolytic metabolism, promoting glucose uptake through the transcription of GLUTs [54]. Increasing evidence indicates that
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In order to discover novel small molecule compounds
2022-01-28
In order to discover novel small-molecule compounds with the activity of GLUT4 translocation, we conducted a cell-based phenotype screening in L6-GLUT4-myc myoblasts by measuring appearance of GLUT4 on the plasma membrane (GLUT4 translocation activity). Evaluation of total 183,400 compounds gave sev
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br Results br Discussion Our cardiomyocyte specific
2022-01-28
Results Discussion Our cardiomyocyte-specific GR knockout mice did not show spontaneous cardiac hypertrophy unless pressure overload was given to the heart. This finding is somewhat different from previous work of a cardiomyocyte-specific GR Gastrodin australia mouse model using GR-floxed mic
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We conclude that a combination of GD specific CAR T
2022-01-27
We conclude that a combination of GD2-specific CAR T cell therapy with pharmacological EZH2 inhibition deserves investigation as a new therapeutic strategy in EwS and potentially other cancers with heterogeneous GD2 expression, including osteosarcoma, various soft tissue sarcomas, melanoma, lung can
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In the next set of experiments we sought to
2022-01-27
In the next set of experiments, we sought to determine the source of lysosomal Z-Ligustilide inhibition by oxidative stress. Lysosomal exocytosis probably involves multiple steps including vesicle positioning, delivery, docking and fusion. The previous evidence and data in Fig. 1C,D show that TRPML
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