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br Funding The authors disclose the following support for
2021-12-27
Funding The authors disclose the following support for the research and/or authorship of this article: This work was supported by the Canadian Institutes for Health Research (CIHR). TM is the recipient of a BMS/CTN postdoctoral fellowship and PKQ was funded by a CAHR/CIHR doctoral scholarship. A
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Metabolic adaptation is an important survival
2021-12-27
Metabolic adaptation is an important survival strategy for cancer cells within the hypoxic tumor environment. Under the condition of O2 limitation, metabolic pathways shift from energy-efficient oxidative phosphorylation to the anaerobic glycolysis pathway for the purpose of ATP generation [13,43].
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KT182 australia Chronic exposure of cells to
2021-12-27
Chronic exposure of cells to cytotoxic drugs can result in the selection of multiple phenotypic and genetic changes. Thus, the use of MCF7/VP cells, which were selected for resistance to VP-16, was potentially problematic. However, a thorough characterization of MCF7/VP cells demonstrated that they
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br Methods br Results br
2021-12-27
Methods Results Discussion Our results show that the DRG and the spinal cord express significant amount of GPR35, a previously orphan Gi protein coupled receptor whose stimulation with zaprinast or with KYNA may reduce inflammatory pain. The receptor is also expressed in primary cultures of
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The synthesized methoxyamide derivatives were evaluated for
2021-12-27
The synthesized -methoxyamide derivatives were evaluated for in vitro as GPR119 agonists (, , ) whereas GSK1292263 (II in ) was used as the reference standard. To identify novel sulfone or tetrazole surrogates, diverse functional groups including amide, -sulfonyl amide, hydrazide, -methoxy--methyla
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Methods br Results br Discussion The current study is the
2021-12-27
Methods Results Discussion The current study is the first to specifically investigate the role of hepatic GPR109A and GPR109B on HDL metabolism and response to niacin therapy. While niacin raises HDL-C levels in humans, it has been reported by others [20], [36] and confirmed by us here that n
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Initial evidence that cell contact mediated transmission
2021-12-27
Initial evidence that cell-contact-mediated transmission of HIV-1 is relevant for the generation of latently infected tak1 inhibitor was suggested in the context of transmission from dendritic cells to resting CD4+ T cells (Evans et al., 2013, Kumar et al., 2015). As dendritic cells probe for antig
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The top concern for the clinical use of
2021-12-27
The top concern for the clinical use of CRISPR-Cas9 technology is safety. Off-target alterations must be avoided to ensure genome integrity and proper cellular function. WGS found no off-target effects among the top 49 predicted off-target sites. WGS did find 4,658 indels and 1,891 SNVs in sgRNA1/2-
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In the present study both experimental
2021-12-27
In the present study, both experimental and theoretical studies were performed to explore the inhibitory mechanisms of indomethacin and its analogues towards GLOI. A remarkable correlation (=0.974) was derived for the four structurally similar NSAIDs and two curcumins between the experimental bindin
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In respect of clinical development Takeda has pioneered
2021-12-27
In respect of clinical development Takeda has pioneered the field with the GPR40 agonist TAK-875 or fasiglifam (Figure 2A), which in phase-II studies decreased HbA1c as efficiently as sulfonylurea without signs of hypoglycemia [24]. This was obtained with surprisingly little effect on systemic insul
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TAK-875 mg Here we reported series of
2021-12-27
Here, we reported series of carbohydrate-modified compounds containing a dibromo substituted benzene ring which was derived from the red alga (). The conformation flexibility of TAK-875 mg and their polyol structures give them many unique biological properties as we have described earlier. More in
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In order to discover novel small molecule compounds
2021-12-27
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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GKRP binds to the inactive super open
2021-12-27
GKRP binds to the inactive, super-open conformation of GCK, acting as a competitive inhibitor of glucose association with the enzyme (Fig. 3) [45]. Upon formation of the inhibitory complex with GKRP, GCK is sequestered into the hepatocyte nucleus [48]. The detailed mechanism by which GKRP mediates t
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Glucocorticoid is a major regulator of body s response
2021-12-27
Glucocorticoid is a major regulator of body's response to stress (Armario, 2006). Repeated injections of the glucocorticoid corticosterone (CORT) in mice have been shown to produce an animal model of depression (Zhao et al., 2008). Further study of this phenomenon suggested that prolonged CORT expos
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Further we examined the degradation of
2021-12-27
Further, we examined the degradation of Cx43. Autophagy and the proteasome system have previously been implicated in Cx43 degradation (Falk et al., 2014). DEX inhibited communication between 1661010 by promoting the degradation of Cx43 through autophagy in osteocytes (Gao et al., 2016). In our exper
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