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MRcKO mice showed a comparable
2022-06-29
MRcKO mice showed a comparable degree of cardiac remodeling compared to control (MRf/f) mice. Moreover, the worse cardiac remodeling in pressure-overloaded GRcKO mice is not due to compensatory activation of cardiomyocyte MR, because GRMRdcKO mice displayed cardiac remodeling to the same extent as G
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br Hedgehog HH signaling plays
2022-06-29
Hedgehog (HH) signaling plays an important role both during embryonic development and adult life. It is involved in the regulation of cell differentiation, cell proliferation and tissue polarity, as well as in the maintenance of stem cells, tissue repair, and regeneration (, ). Three ligands, Indi
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br Acknowledgements This work was
2022-06-29
Acknowledgements This work was supported by a fellowship to C.H. under the ‘100 Foreign Expert’ scheme of the Shanxi province government(R100456). Conflict of interest: Dr. Holscher is a named inventor on a patent submitted by Lancaster University on the use of dual GLP-1/GIP analogues in neurode
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More polar substituents introduced on the position of
2022-06-29
More polar substituents introduced on the 5-position of the aniline ring (e.g., dimethyl amine in ) decreased the lipophilicity of the compounds (4.3 for vs 5.1 for ), but did not affect their potency. For instance, was highly potent in vitro and demonstrated a surprising 51% lowering of Aβ42 in mic
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Zn is the second most abundant trace metal
2022-06-29
Zn2+ is the second most abundant trace metal in many cells and neurons in the brain. It regulates cellular functions such as gene expression, epigenetic enzymatic activity, protein structural stability, and neuronal plasticity. Zn2+ is particularly abundant in the cortex and limbic system, including
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An advantage of photolabeling with
2022-06-29
An advantage of photolabeling with tritiated photoprobes followed by microsequencing with Edman degradation is the ability to both identify the photolabeled 3466 and to quantify photoincorporation which enables assessment of pharmacological specificity and allosteric interactions with other ligands
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Histamine receptors were largely linked with allergic and in
2022-06-28
Histamine receptors were largely linked with allergic and inflammatory reactions before the recognition of the histamine H3R in 1983 that proved its function as auto- as well as heteroreceptor at pre- and postsynaptic membranes and demonstrated its intense regulating influence on release of numerous
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CTGF is an established YAP
2022-06-28
CTGF is an established YAP/TAZ target gene which plays a central role in tissue remodeling. Downregulation of CTGF mediates collagen loss in chronologically-aged human skin whereas persistent activation of CTGF can result in excessive deposition of collagen and fibrotic disorders [63]. The authors f
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br Materials and methods br Results Heterologous expression
2022-06-28
Materials and methods Results Heterologous expression of P. locustae Hxk in methylotrophic yeast P. pastoris was not accompanied by nuclear localization of parasite protein (Fig. 1). The addition of leptomycin B, a specific inhibitor of nuclear export in fission yeast Schizosaccharomyces pombe
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Unlike many interacting proteins NRG was the only one
2022-06-28
Unlike many interacting proteins, NRG1 was the only one observed to undergo cleavage by NS3/4A. NRG1 is one of four proteins in the neuregulin family that act on the ErbB member of the EGFR (EGF receptor) family. NRG1 has several isoforms produced by alternative splicing of pro-NRG1, which allows it
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CONUT score is an effective detector of
2022-06-28
CONUT score is an effective detector of predicting OS and RFS in HCC patients. We found that patients with a damaged immune-nutrition status had significantly poor OS and RFS. Our initial literature review also retrieved other studies evaluating the survival of HCC patients using CONUT score [36,48,
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Introduction Soluble guanylyl cyclase sGC is a key
2022-06-28
Introduction Soluble guanylyl cyclase (sGC) is a key protein in the regulation of multiple physiological functions in mammalian physiology [1,2]. Upon stimulation by nitric oxide (NO) [3], sGC generates cyclic guanosine monophosphate (cGMP) from guanosine-5′ triphosphate and activates protein kinas
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br Materials and methods br
2022-06-28
Materials and methods Results Discussion Directly modulating specific target proteins and signaling pathways with small-molecule drugs or agonistic GSK2606414 is widely used for cancer metastasis therapies [[39], [40], [41]]. ANXA7 acts as a metastasis suppressor in prostate cancer. Howeve
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Two different genes encode GSK isoforms
2022-06-28
Two different genes encode GSK-3 isoforms α and β that have very similar catalytic domains but significantly differ in their N- and C-termini. The α and β isoforms split from a common precursor approximately at the emergence of vertebrates, suggesting that at least one of the isoforms took on a new
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br Conclusion In this report we describe the synthesis and
2022-06-28
Conclusion In this report, we describe the synthesis and evaluation of oxadiazole-based GSK3 inhibitors. Occupation of the ATP-binding pocket in its entirety led to the identification of several potent and selective compounds. These compounds are characterized by IC50 values in the low nanomolar
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