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One effective approach to fine tuning the lipophilicity prof
2022-05-23
One effective approach to fine-tuning the lipophilicity profile of FFA1 agonists is to ‘decorate’ the 3-phenylpropahoic imidazoline scaffold with polar heterocyclic moieties. Alternatively, this scaffold could be replaced with heterocyclic isosteres (as in Takeda’s compounds 1,2 and 3 as well as Am
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The highest metabolic stability observed
2022-05-23
The highest metabolic stability observed for compound 4k (EC50=0.41μM corresponding to 218ng/mL) among the four selected frontrunner candidates was the principal decisive point in nominating this compounds for pharmacokinetic characterization in mice at the dosage of 10mg/kg (administered intravenou
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Ning et al showed that LPC appeared to increase insulin
2022-05-23
Ning et al. showed that LPC 18:1 appeared to increase insulin release through both GPR119-dependent and -independent mechanisms (Ning et al., 2008). In our study, we have shown that not only GPR119 but also GPR40 and GPR55 participate in LPC-stimulated insulin secretion (Fig. 4, Fig. 5) and target p
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Introduction Type diabetes T D
2022-05-23
Introduction Type 2 diabetes (T2D) has been seriously affecting the health life of 415 million people and 193 million undiagnosed people [1]. Importantly, this disease was found to cause death at least 1.5 million annually, and has brought about an extensive health concern throughout the world [2,3
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Moreover long term treatment of
2022-05-23
Moreover, long term treatment of leukemia cells with imatinib activates AKT, ERK and STAT5 signaling pathway and induce upregulation of EZH2 protein in patients with CML, Ph + ALL and human eosinophilic leukemia cell line (EOL-1 cells) [142]. So, resistance to tyrosine kinase inhibitor (TKI) imatini
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In the current study Olfml knockdown increased YAP but decre
2022-05-23
In the current study, Olfml1 knockdown increased YAP but decreased the respective target genes of canonical Wnt signaling and Hedgehog signaling, Axin2 and Gli1. YAP suppresses canonical Wnt via binding to Dishevelled and/or β-catenin [[39], [40], [41], [42]]. Tariki et al. reported that adenovirus-
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It is important to note that the
2022-05-21
It is important to note that the GC-C expression is retained in colon tumours, and therefore GC-C expression can be used as a marker to diagnose metastatic colon cancer [42]. However, expression of uroguanylin and guanylin is often lost in colorectal cancer progression [43]. Therefore, the anti-prol
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Molecular mechanisms of decidualization have been studied fo
2022-05-21
Molecular mechanisms of decidualization have been studied for years, revealing numerous signaling pathways and transcriptional factors participated in the regulation [37,38]. As a central controller of deicdualization, FOXO1 regulates the transcription of a large number of target genes, which are in
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Our exploration of Domain focused on the role
2022-05-21
Our exploration of Domain 1 focused on the role of the carbonyl linker in (). We found that replacement of this group by a methylene unit as in or direct attachment of the thiophene ring to the central aromatic core as in did not significantly impact potency. The thiophene ring in could be repla
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br Significant efforts are currently focused on
2022-05-21
Significant efforts are currently focused on non-dopaminergic strategies to address the unmet medical needs in schizophrenia, and targeting -methyl--aspartate (NMDA) proteasome hypofunction has garnered a great deal of attention., , Elevation of synaptic glycine levels near NMDA-containing synapse
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Elimination of the Q R bridge significantly affected the
2022-05-21
Elimination of the Q234–R244 bridge significantly affected the protein MHC class II antigen (45-57) [Homo sapiens] but had little effect on its activity at a permissive temperature, which may seem contrary to the known functional importance of this motif in Fpg. However, since the mutants fully or p
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glycoprotein inhibitors To maintain low Glu concentrations
2022-05-21
To maintain low Glu concentrations in the synaptic cleft below the affinity of its receptors, this amino glycoprotein inhibitors is rapidly removed from the extracellular space by a family of sodium-dependent high-affinity transport systems located mainly in the plasma membrane of perisynaptic astr
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EPZ005687 Cx is a phosphoprotein that is predominantly phosp
2022-05-21
Cx43 is a phosphoprotein that is predominantly phosphorylated in the control state. Cx43 can be phosphorylated by a number of kinases and dephosphorylated by protein phosphatases such as PP1 and PP2A [6], [10]. Posttranslational phosphorylation of Cx43 is thought to influence intercellular coupling
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SNL in rats led to
2022-05-21
SNL in rats led to upregulated Panx1 mRNA and protein level in DRG but not in spinal cord, and immunostaining revealed increased Panx1 in DRG neurons [50]. Although it was not emphasized, Panx1 labeling in SGCs was also increased in this pain model. Intrathecal injection of Panx1 blockers or Panx1-s
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Nano biocatalyst prepared by assembling an enzyme on
2022-05-21
Nano-biocatalyst, prepared by assembling an enzyme on nanomaterial (NM) carriers is an emerging innovation in the field of nanobiotechnology. Some of the advantages of using NM as supports in Chlorothiazide to conventional porous supports are effective enzyme loading due to large surface area with
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