• Optimization of the tetrahydroindazole series

  2021-09-09

  

  Optimization of the tetrahydroindazole series led to the discovery of two moderately potent γ-secretase modulators, 2-cyclobutane and 2-hydroxy-2-methylpropane which were subsequently evaluated in a kinetic aqueous solubility assay. Unfortunately, neither analog demonstrated improved solubility ()

• To obviate the mitogenic FGF

  2021-09-09

  

  To obviate the mitogenic FGF19 activity, several engineered FGF19 variants have been generated aiming to maintain the metabolic activity excluding the protumorigenic ones. One variant, M70, that differs from wild-type FGF19 by 5-amino acids deletion at the N-terminus and the substitution of 3-amino

• Data of initial analogs have been shown

  2021-09-09

  

  Data of initial analogs (±)-– have been shown in wherein SAR was observed for the intended change of the right-hand side pyridin-3-yl ring of to various other -containing heteroaryl ring (Ar) disposing the ring- at different directions. Based on consistent human and rat FAAH potency as well as int

• br Acknowledgments We thank Drs

  2021-09-09

  

  Acknowledgments We thank Drs. Yasuhiro Saito and Mitsuru Futakuchi for helpful discussion. We also thank Drs. Kohei Miyazono and Tadashi Matsuda for cells. This work was supported by Grant-in-Aids for Scientific Research on Innovative Area (16H06373; 16K15273) from MEXT, Japan (to M.H.) and by Pr

• The transcription factor Nrf is a master regulator

  2021-09-09

  

  The transcription factor Nrf2 is a master regulator of cytoprotective responses to endogenous and exogenous stresses caused by reactive oxygen species (ROS) and electrophiles [6]. Nrf2 promoter polymorphisms are significantly associated with the development of gastric mucosal inflammation, either in

• There is evidence for an adverse

  2021-09-09

  

  There is evidence for an adverse sympatho-stimulatory effect in the medulla oblongata mediated by the α1/β1 isoform, implying a possible benefit of selective α2/β1 activation [19]. While the stimulator BAY 41–2272 increases NO-sensitivity of both isoforms [20], a prevalence of the α1/β1 isoform comp

• All the compounds and were assayed for their potential cytot

  2021-09-09

  

  All the compounds –, , , –, , – and – were assayed for their potential cytotoxicity at a single dose of 10 µM on Huh7 cells. Interestingly, all compounds proved to be non toxic, with the exception of and which exhibited high cellular toxicity and therefore were excluded from further experiments (a

• Our aim was to gain insight

  2021-09-08

  

  Our aim was to gain insight into mechanisms that underlie the contribution of thrombospondin-1 (TSP1) to progression of CKD. TSP1 is the most-studied member of the thrombospondin family of matricellular proteins. Previous studies have demonstrated that pharmacological suppression or genetic depletio

• br Materials and methods br Results and discussion

  2021-09-08

  

  Materials and methods Results and discussion We recently found that the GlyT1 N-terminal and C-terminal sequences could be modified by phophorylation, or partially lost under pathological conditions by calcium-dependent proteolysis (Baliova and Jursky, 2005, Baliova and Jursky, 2010). While re

• In summary activated A AR

  2021-09-08

  

  In summary, activated A2AR exacerbated the reverse transport function of endothelial EAATs through a direct or indirect pathway depending on PKA and glutamate levels in response to OGD in vitro, but A2AR inhibition quickly restored the normal transport function. Moreover, the key mechanisms by which

• br Glucocorticosteroid receptor structure and function The g

  2021-09-08

  

  Glucocorticosteroid receptor structure and function The gene encoding for the human GR is composed of 9 exons (Oakley and Cidlowski, 2011) and the translated protein is described as having 4 functional regions. The protein contains a highly conserved central DNA-binding domain (DBD) or C-domain,

• GLI proteins activate or repress transcription of

  2021-09-08

  

  GLI proteins activate or repress transcription of their target genes by binding to a similar sequence motif within a cis-regulatory module (CRM) (Hallikas and Taipale, 2006, Peterson et al., 2012). Transcriptional responses to the HH pathway can be elicited either by de-repression of GLI-R or in oth

• casr Recently results obtained by our group have

  2021-09-07

  

  Recently, results obtained by our group have demonstrated that hEECs are able to secrete NPY into the extracellular medium and that this peptide can induce an increase in the [Ca]i of these cells (Jacques et al., 2003b). In light of these results and those obtained in this study, we can speculate th

• br Conclusion br Author contributions br Acknowledgements We

  2021-09-07

  

  Conclusion Author contributions Acknowledgements We thank Hydrochlorothiazide USC Center for Craniofacial Molecular Biology (CCMB) for their extensive guidance and teaching in biochemical techniques. We acknowledge Laurel Fisher, PhD for her contribution to statistical analysis of the data

• A common principle to ameliorate underquantification because

  2021-09-07

  

  A common principle to ameliorate underquantification because of primer or probe mismatching is to employ multiple targets for detection or quantification of blood borne viruses [14]. Dual targeting real time PCRs have become common for quantification of HIV-1 [15], [16]. In a recent paper arguing fo

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