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One effective approach to fine tuning the
2021-10-25
One effective approach to fine-tuning the lipophilicity profile of FFA1 agonists is to ‘decorate’ the 3-phenylpropahoic Dehydroepiandrosterone scaffold with polar heterocyclic moieties. Alternatively, this scaffold could be replaced with heterocyclic isosteres (as in Takeda’s compounds 1,2 and 3 as
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FPR activation stimulates multiple signal
2021-10-25
FPR1 activation stimulates multiple signal transduction pathways responsible for various neutrophil functions, such as adhesion, chemotaxis, phagocytosis, GW5074 of secretory granules, and superoxide anion radical (O2) production, which contribute to the physiological inflammatory response associate
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As an inflammatory mediator histamine plays a pivotal role i
2021-10-25
As an inflammatory mediator, histamine plays a pivotal role in nociceptive processes in both the central and peripheral nervous systems (Gemkow et al., 2009; Hough & Rice, 2011; Tiligada et al., 2009). In this respect, the participation of H3Rs in modulating pain, especially neuropathic pain, has at
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In order to study the role of haspin
2021-10-25
In order to study the role of haspin’s kinase activity in mitosis (and other cellular processes) and its potential role in cancer, we sought to identify and optimize inhibitors. Utilizing a recently developed time-resolved fluorescence resonance energy transfer (TR-FRET) high throughput screening (H
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tachykinin br Conflict of interest statements br Acknowledge
2021-10-25
Conflict of interest statements Acknowledgements Introduction Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and is the major cause for cancer morbidity and mortality in developing countries. Age standardized incidence rate in India is 12.6 per 100 000 populat
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The calculations for the R substrate showed
2021-10-25
The calculations for the R substrate showed that, like the S substrate, the coordination shell of the Zn nf-κb pathway is more symmetric than in the HIC-SG crystal structure. This symmetry indicates that the enzyme could use the same reaction mechanisms as for the S substrate, but with exchanged rol
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The mechanisms by which NEIL and NEIL excise bulky adducts
2021-10-25
The mechanisms by which NEIL1 and NEIL3 excise bulky adducts and unhook ICLs are unclear. Structures of NEIL1 are available only in complex with DNA containing small lesions 79., 80., 81., and the single available structure of NEIL3 lacks DNA (Figure 5D,E) [73]. Nonetheless, comparison of the two st
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Xie et al b reported that the combination
2021-10-25
Xie et al. (2009b) reported that the combination of diagnostic ultrasound impulses and cyclic RGD-bearing MBs targeted for GP IIb/IIIa resulted in the successful recovery of epicardial and microvascular blood flow in swine models with acute thrombotic occlusion. It is well known that the stability o
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The following are the supplementary data
2021-10-25
The following are the supplementary data related to this article. Conflict of interest Acknowledgements This work was supported by JSPS KAKENHI Grant Numbers 24770068 and 15K07152. Introduction Aminoacyl-tRNA synthetases (aaRSs) help maintain the genetic code by recognizing their cognate
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It is generally considered that elevated blood glucose
2021-10-25
It is generally considered that elevated blood glucose due to insulin resistance is an important factor in islet compensation to high fat feeding [27]. However, we have shown recently that insulin resistance induced in mice by hydrocortisone injection provokes significant islet MTT sale in the absen
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sevelamer hcl Interestingly transgenic mice that constitutiv
2021-10-23
Interestingly, transgenic mice that constitutively express active FXR in the intestine (iVP16FXR) are protected from chemically-induced and genetically-induced cholestasis. This protective effect is attributed to the induction of intestinal FGF15 and repression of hepatic Cyp7a1 expression, downregu
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However at variance with the well studied
2021-10-23
However, at variance with the well-studied R form of FBP1 which is flat, the R state of FBP2 is diametrically different, with a perpendicular orientation of the upper and lower dimers (Barciszewski et al., 2016). The cruciform-like R state of FBP2 is stabilized by a unique hydrophobic motif called ‘
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YAP TAZ nuclear function is also
2021-10-23
YAP/TAZ nuclear function is also influenced by interaction with the TEAD family of transcription factors [96, 97, 98, 99, 100, 101]. The RAC1 flumethasone synthesis exchange factor protein TIAM1 has recently been linked to YAP/TAZ regulation in the nucleus and cytoplasm. Nuclear TIAM1 inhibits YAP/
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Cordycepin br GC C and cGMP of mice and
2021-10-23
GC-C and cGMP: of mice and men As is usually the case for many genes, most of the studies that relate to GC-C have to date been carried out in mouse models, or in cell lines derived from human colorectal cancer tissue. What appeared to be a lacuna was any report of a human disorder that resulted
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22(R)-hydroxy Cholesterol br TGR Agonists br FXR TGR Dual Ag
2021-10-23
TGR5 Agonists FXR/TGR5 Dual Agonists In 2010, a FXR/TGR5 dual agonist, 51 (INT-767), was reported [57]. Using an AlphaScreen coactivator recruitment assay, the potency of 51 at FXR was 30nM. In NCI-H716 cells, 51 stimulated intracellular cAMP secretion with an EC50 of 0.63μM. Its TGR5 potency
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