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br Discussion br Conflict of interest
2021-12-08
Discussion Conflict of interest Acknowledgements We thank Rosetta Barkley for expert technical assistance. We thank Robin Maser, James Calvet, Darren Wallace, and Jovanka Koo for many helpful discussions and expert technical advice. This work was supported by National Institutes of Health,
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There are several limitations in our study First only the
2021-12-08
There are several limitations in our study. First, only the naturally occurring resistance-associated mutations in patients coinfected with HIV/HCV KPT-185 1b were analyzed. The result was only applicable to HCV genotype 1b, but not the HCV genotype 1a patients. We did not analyze the effect of gen
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The CNP pGC B cGMP
2021-12-08
The CNP/pGC-B/cGMP pathway has been reported to be potent inhibitor of fibrosis, from an intrinsic compensatory protective response as well as a therapeutic in cardiorenal injury and disease states [6,12,13,22,30]. Indeed, fibrosis is a progressive process leading to increased risk for morbidity and
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br Materials and methods br Results br Discussion The
2021-12-08
Materials and methods Results Discussion The compound P7C3 has been reported to activate NAMPT (Wang et al., 2014) and augment NAD+ levels, thereby promoting the survival of mature neurons and postnatal neurogenesis throughout the post-ischemic Gap19 (Loris et al., 2017). However, it has b
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As part of our discovery efforts searching
2021-12-08
As part of our discovery efforts searching for small molecule GPR119 agonists, we analyzed active pharmacophores of known agonists from the literature, and found that -methylsulfonylphenyl and substituted 4-hydroxyl piperidine are common fragments. In our initial efforts, we linked these two fragme
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Autophagy as an important cellular
2021-12-08
Autophagy as an important cellular process has drawn attentions to its role in cardiovascular systems [16]. Autophagy is a self-digestion and degradation process that recycles the contents of the cytosol, including macromolecules and cellular organelles, resulting in self-repair and conservation for
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br Recent insights into EAAT structure function aspects The
2021-12-08
Recent insights into EAAT structure/function aspects The EAATs are secondary-active transporters coupling the movement of one Glu with the symport of three Na+ and one proton and the counter-transport of one K+ [3, 4]. The transporters are trimeric assemblies of protomers that function independen
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br Materials and methods br Results Aberrant A has
2021-12-08
Materials and methods Results Aberrant Aβ has been suggested to be an initiating factor for glutamate excitotoxicity in AD pathology. To investigate whether Aβ1-42 alters glutamate uptake in astrocytes, neurons, and astrocyte-neuron co-cultures, we used synthetic Aβ1-42 peptide. Aβ1-42 has fa
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In a meta analysis of genome wide association
2021-12-08
In a meta-analysis of genome-wide association studies, a variant (rs10423928) in the GIPR gene has been found to be associated with elevated postprandial glucose and insulin (Saxena et al., 2010) as well as lean body composition including decreased BMI, lean mass and waist circumference (Lyssenko et
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br Materials and methods br
2021-12-08
Materials and methods Results Discussion Ghrelin is reported to regulate a number of processes related to cancer progression including tumor cell proliferation, apoptosis and metastasis [3,7,[15], [16], [17], [18], [19], [20], [21], [22]]. In the present study, we examined the potential eff
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Reversine During the course of the
2021-12-08
During the course of the development of aminothiazole-derived small molecule GSMs, SGSM-36 (Fig. 1A) was discovered and exhibited good activity for suppressing the production of Aβ42 (Aβ42 IC50=63nM) (Rynearson et al., 2016; Wagner et al., 2014). In addition, SGSM-36 exhibited improved physicochemic
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So far only few studies report
2021-12-08
So far only few studies report about GAL in the visual system: GAL has been detected in the cornea of rat (Jones and Marfurt, 1998), mouse (Henken and Martin, 1992) and pig (Stone et al., 1988), and in the uvea of rat (Strömberg et al., 1987), pig (Stone et al., 1988) and cat (Grimes et al., 1994),
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br Results and discussion br
2021-12-08
Results and discussion Conclusion In summary, we designed and discovered a series of novel GPR40 agonists containing 3,5-dimethylisoxazole with improved tPSA and ideal cLog P. Most of these compounds were confirmed as excellent GPR40 agonists in vitro. Especially, compound 11k exhibited robust
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Despite the central role of mitochondria in oxidative metabo
2021-12-08
Despite the central role of mitochondria in oxidative metabolism, it remains unclear whether mitochondria play a central role in ferroptosis. Supporting this possibility, ferroptosis is associated with dramatic morphological changes of mitochondria, including mitochondrial fragmentation and cristae
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Dysregulation of the HPA axis resulting in alteration
2021-12-08
Dysregulation of the HPA axis, resulting in alteration to both baseline and stress-induced glucocorticoid levels (e.g., cortisol and corticosterone), has been implicated in several diseases and psychopathologies, including anxiety (McEwen et al., 2015, 2016; Shin and Liberzon, 2010). For example, ba
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