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While the specific set of challenges
2022-04-14
While the specific set of challenges associated with deorphanization and transforming each poorly characterized GPCR into a useful drug target will be unique, much can be learned by considering how these issues have been addressed for other receptors. One group of poorly characterized GPCRs that hav
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br Material and methods br Results The search for proteins
2022-04-14
Material and methods Results The search for proteins selectively expressed in pancreatic islet BADGE in the Human Protein Atlas (HPA) yielded 27 hits, including well-known islet cell markers such as insulin, glucagon and pancreatic polypeptide (Table 1). The search algorithm excluded islet cel
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To apply the recently developed GPR
2022-04-14
To apply the recently developed GPR35 ligands to CNS disorders, it is necessary to understand whether GPR35 is expressed by any identified cell types in the chemokine receptor and whether activation or blockade of this receptor has any consequence on the activity of the neuronal circuitry. To this
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As part of their ongoing effort in the
2022-04-14
As part of their ongoing effort in the field, Kalypsis recently disclosed that quinazolinones 5 [49], imidazo[1,2-a] [1,2]diazepin 6 [50] and quinolines 7 [51] all had activity as small molecule modulators of TGR5 (Figure 4). Intercept, however, disclosed different bile receptor tyrosine kinase der
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In this study we further expanded the
2022-04-14
In this study, we further expanded the antitumor bioactivity, with the BALB/c S-180 tumor model, which is long-established due to its highly aggressive in all strains of laboratory mice and rats (Cui et al., 2003). We investigated the tumor-regressing ability of β-glucan by different modes of admini
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br Discussion The pattern of activity exhibited by SSR
2022-04-14
Discussion The pattern of activity exhibited by SSR 504734 and Lu AA21279 in the MEST test was very similar. Both compounds were inactive at the lowest dose (3.0mg/kg), but exhibited robust increases (∼150%) at 10mg/kg followed by a maximal detectable response at 30mg/kg. Based on the magnitude o
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To further investigate its role in stresses tolerance OsGly
2022-04-14
To further investigate its role in stresses tolerance, OsGly I was overexpressed in transgenic rice. qRT-PCR and zymologic determination showed that K-115 sale level of OsGly I and the glyoxalase I activity were significantly increased to different extent in the transgenic overexpression lines (Fig
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EAAT glutamate uptake is driven by the co transport of
2022-04-14
EAAT glutamate uptake is driven by the co-transport of three sodium ions and one proton, as well as the counter-transport of one potassium ion (Fig. 1B). This complex stoichiometry frees up enough energy to permit NB-598 Maleate receptor of glutamate into the cell against a steep concentration grad
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Inflammatory pain is very common in the clinic
2022-04-13
Inflammatory pain is very common in the clinic. A study demonstrated that galanin was upregulated after nerve injury or inflammation (Ma and Bisby, 1997). It has been reported that galanin plays an important role in the transmission of nociceptive information in the spinal cord of rats with inflamma
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A relatively independent review of the history of the discov
2022-04-13
A relatively independent review of the history of the discovery of GABA (and L-glutamate) as neurotransmitters in the CNS can be found in ‘When and why amino acids?’ in the in 2010 by Kresimir Krnjevic , who spent a post-doc in Canberra in 1956–1958. Introduction The insect RDL GABA receptor is
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Main Text FFAR GPR is
2022-04-13
Main Text FFAR1 (GPR40) is a long-chain fatty selinexor (LCFA) receptor highly expressed and enriched in enteroendocrine cells, where it senses LCFAs generated from dietary triglycerides, and in pancreatic islet cells, where it acts as a powerful stimulator of insulin secretion. However, the physio
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Defining the cooperation between molecular pathways within h
2022-04-13
Defining the cooperation between molecular pathways within highly complex biological systems, such as those between immune cell networks and target tissues is certainly a hard task. Recently, there are many investigations in the pathogenesis of renal graft rejection, one of the most evident investig
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br Acknowledgments This research was supported by the Nation
2022-04-13
Acknowledgments This research was supported by the National Institutes of Health Grants GM58442 and GM084152, as well as the National Institutes of Health Predoctoral Training Grant 5T32GM008700-13. We thank Eric Oldfield (University of Illinois, Urbana-Champaign) for providing the FDPS inhibitor
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The anti platelet functions of ZGR
2022-04-13
The anti-platelet functions of ZGR were confirmed by the mechanistic studies such as the activation of PKC, intracellular Ca2+ mobilization, and the expressions of P-selectin and PAC-1. Further, rivaroxaban prolonged the generation of thrombin and reduced the thrombin burst produced in the propagati
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br Conclusion Discovery of an
2022-04-13
Conclusion Discovery of an ideal orally active antithrombotic drug has remained elusive till date. Research efforts in this direction led to the discovery of numerous coagulation enzyme inhibitors including various thrombin and FXa inhibitors. Several preclinical studies have highlighted the impo
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