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br Acknowledgments br Free fatty acids FFAs
2022-06-20
Acknowledgments Free fatty acids (FFAs) are not only essential nutritional components, but they also function as signaling molecules. Recently, a G protein-coupled receptor (GPCR) de-orphanizing strategy successfully identified multiple receptors for FFAs, which function on the cell surface and
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Expression and translocation of GLUT are regulated
2022-06-20
Expression and translocation of GLUT4 are regulated by various mechanisms including protein kinase C isoforms (PKCs) and mitogen-activated protein kinase (MAPK) signals [22], [23], but the real mechanism that statins alter expression and function of GLUT4 has not been fully identified. It is general
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To directly address whether pharmacological attenuation of p
2022-06-18
To directly address whether pharmacological attenuation of physiological GIP provides therapeutic benefits in obese mice, we pursued a selective long-acting antagonist to complement the work we report on GIPR agonism. We report a GIP analog of sufficient aqueous solubility that employs a shortened N
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Primarily because secretase was a therapeutic target in AD
2022-06-18
Primarily because γ-secretase was a therapeutic target in AD, a plethora of γ-secretase inhibitors (GSIs) have been developed that effectively inhibit γ-secretase cleavage in humans [16]. Indeed, “druggability” of γ-secretase has not been an issue even when the identity of the target was unknown in
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Preliminary explorations focused on the
2022-06-18
Preliminary explorations focused on the linker of 2 (Table 1). Lilly reported that the methylene between the phenyl and the piperidyl group was metabolically susceptible to N-dealkylation, so we replaced the methylene with a carbonyl moiety to block the metabolic site [23,48] (Fig. 2). In addition,
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In general FPSs require Mg or Mn as
2022-06-18
In general, FPSs require Mg2+ or Mn2+ as a cofactor for GPP and FPP synthesis. Co2+ also acts as a cofactor in EuFPSs, as in the case for PcFPS and Abies grandis FPS [29], [44]. Co2+ enhanced the activity of EuFPS1 more than the activity of EuFPS2: Mg2+, Mn2+ and Co2+ had approximately the same effe
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One PKC target that controls cortical actin structure is a
2022-06-18
One PKC target that controls cortical dabigatran etexilate mesylate structure is a well-known actin crosslinking protein, myristoylated alanine-rich C-kinase substrate (MARCKS). MARCKS cross-links actin and binds PIP2 and this binding activity is regulated by PKC phosphorylation [82]. Activation of
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br Materials and methods br
2022-06-18
Materials and methods Results Estimations of OMP generated by the proposed mechanism (Fig. 1) were first performed for the range of 0.001–2 mM of Liproxstatin-1 concentration in the cytosol. It was assumed that only 5% of all VDACs in MOM form the ANT-VDAC1-HKI contact sites, and that the fra
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br Conclusion Whilst acknowledging that forensic science
2022-06-18
Conclusion Whilst acknowledging that forensic science critically needs strategic investment across every domain [27], forensic science needs to bring both ‘hedgehog’ and ‘fox’ approaches together to address the roots of the major challenges the discipline faces. Addressing these challenges in a w
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The effect of microtubule inhibitors
2022-06-18
The effect of microtubule inhibitors on HBV infection and replication were reported previously. In the study by Dr. Ai-Long Huang's group, microtubule inhibitors promoted HBV replication in Hep2.2.15 and HepG2-HBV1.1, in which HBV DNA is integrated into the chromosomal DNA (Xu et al., 2015). Integra
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It is important to note that
2022-06-18
It is important to note that upon RIG-I activation, IRF-3, p38, and ERK were activated by 3p-siHBx, leading to upregulated IFN response (Fig. 6). This suggests that 3p-siHBx has specific effects on HBV replication. In addition, 3p-siHBx induced type III IFN response (Fig. 6D), which could also inhib
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br Materials and methods br
2022-06-18
Materials and methods Results Discussion Serum HBsAg is not only an important serological marker for the screening and diagnosis of HBV infection but also an important indicator for the treatment of hepatitis B [15]. Jaroszewicz et al. [4] and Nguyen et al. [8] reported that the HBsAg level
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The observed glucose intolerance and
2022-06-18
The observed glucose intolerance and elevated fasting blood glucose in this study is in consonance with earlier study (Ferris and Kahn, 2012). These have been the common features of GC exposure and are not unexpected. Previous researches that reported IR during GC exposure have shown controversy con
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An alternative approach to improving pharmacokinetic
2022-06-17
An alternative approach to improving pharmacokinetic profile while retaining high GlyT1 potency was also pursued. Libraries were prepared in which potency enhancing piperidine C4 substituents were combined with clearance lowering truncated alkyl sulfonamides. The result was the discovery of (). Unl
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br Acknowledgements The authors are
2022-06-17
Acknowledgements The authors are grateful for funding provided by the Health Research Council of New Zealand. Introduction Glucose is the most important energy carrier of the brain. Glucose transporter type 1 (Glut1) is located at the blood–brain barrier and assures the energy-independent, fa
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