• FXR agonists represent an attractive

  2022-08-23

  

  FXR agonists represent an attractive class of drugs for patients with PFIC. Synthetic and semi-synthetic FXR agonists, with higher affinity and potency to activate FXR, have been successfully tested in animal models of cholestasis. In these murine models, the semi-synthetic steroidal FXR ligand obet

• In summary the SAR of a series of phenylpropanoic

  2022-08-23

  

  In summary, the SAR of a series of phenylpropanoic acid-free fatty Oxonic acid potassium salt receptor agonists is described which resulted in the identification of potent FFA4 agonists. The superior pharmacokinetic properties of compound led to its selection as an in vivo tool compound which afford

• br Discussion In response to an increase in glucose or

  2022-08-23

  

  Discussion In response to an increase in glucose or DHA concentration, FBPase showed nuclear import and recruitment in a peripheral cell compartment. Interestingly, FBPase and GS were co-recruited to the periphery of the cells. This is precisely the site where glycogen is initially synthesized an

• Regulation of gene expression in mammalian cells is governed

  2022-08-22

  

  Regulation of gene expression in mammalian cells is governed by the epigenetic machinery, which includes several distinctive yet entangled branches. DNA and histone modifying enzymes, non-coding regulatory RNAs, and ATPase-dependent chromatin remodeling proteins all contribute to the dynamic alterat

• Taken together the four HRs

  2022-08-22

  

  Taken together, the four HRs couple with several different signaling pathways modulating various G-proteins (Fig. 1). Histamine H1R The H1R, including many other biogenic amine receptors, is one of the GPCR family members (see for a complete list e.g. http://www.gpcr.org/7tm/ or http://tools.gpc

• Several recent studies have linked clock function with the c

  2022-08-22

  

  Several recent studies have linked clock function with the cell cycle and reported that clock components, such as PER1, PER2, BMAL1, and CRY1/2 decrease cell proliferation or improve the action of anti-cancer drugs in different cancer cell lines. Moreover, certain types of human cancer show an alter

• In vitro studies suggest that the increase in

  2022-08-22

  

  In vitro studies suggest that the increase in Hx activity seen in normal pregnancy may contribute to the down-regulation of the vascular expression of Angiotensin II receptor 1 thereby promoting a relaxed and dilated maternal vascular bed [25]. It has further been suggested that the decreased Hx act

• The characterization of Da CTSL shows that it preferentially

  2022-08-22

  

  The characterization of Da-CTSL1 shows that it preferentially cleaves Z-FR-AFC (Fig. 8), which has a 69 9 phenylalanine at P2 and Da-proCTSL1 is autocatalyzed at pH 8.0 releasing an activated Da-CTSL1 that exhibits optimal activity at pH 8 indicating that the enzyme when secreted by the foregut and

• LY 255283 As a measure of ROS formation we measured the

  2022-08-22

  

  As a measure of ROS formation we measured the extent by which Cu(I) affected the production of hydrogen peroxide and, at the same time, to ensure that there would not be shortage of NADH substrate. Our results show that H2O2 production is increased over time by LPS stimulation but it is not when mic

• br Acknowledgments br Introduction Obesity and type

  2022-08-22

  

  Acknowledgments Introduction Obesity and type 2 diabetes (T2D) are two major chronic non-communicable diseases that are increasing worldwide at an alarming rate; the majority of people with T2D are overweight or obese, and T2D associated with obesity is expected to have doubled by 2030 (Chen e

• Spatial working memory improved in the Balb

  2022-08-22

  

  Spatial working memory improved in the Balb/c strain at a dose of VU0410120 (i.e., 30mg/kg) that disrupted spatial working memory in the Swiss Webster comparator strain. Consistent with a recent PET study in rhesus macaques suggesting a relationship between the extent of the dose-dependent occupancy

• Sequences of hexokinases were initially deduced and

  2022-08-22

  

  Sequences of hexokinases were initially deduced and predicted based on cDNA clones (Andreone et al., 1989, Schwab and Wilson, 1989, Schwab and Wilson, 1991, Griffin et al., 1991, Thelen and Wilson, 1991). Analysis of genome sequence data identified, in CK 666 to the 4 expected known hexokinase enzy

• In general substrates that undergo regulated intramembrane

  2022-08-22

  

  In general substrates that undergo regulated intramembrane proteolysis are initially cleaved in the extracellular domain by sheddases such as TACE (TNFα converting enzyme) or ADAM (a disintegrin and metalloproteinase domain)/α-secretase, or by aspartyl proteases, such as BACE/β-secretase, before cle

• High lipophilicity of seems to cause poor PK profiles

  2022-08-19

  

  High lipophilicity of seems to cause poor PK profiles. First we replaced the phenyl ring of compound with various hetero aromatic rings to reduce lipophilicity, (). The synthesis of pyridine derivative was shown in . (2′,6′-Dimethylbiphenyl-3-yl)methanol () was reacted with 2,5-dibromopyridine i

• br Declaration of interest br Acknowledgments br

  2022-08-19

  

  Declaration of interest Acknowledgments This work was supported by grants from the Polish National Science Centre (PRELUDIUM grant no. 2013/11/N/NZ5/00270) and the European Commission FP7 Project Beta-JUDO (grant number 279 153), European Union EIT Health project DeTecT2D, Swedish Diabetes A

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