• Tetrazole is one of the most commonly used bioisosteres

  2021-09-16

  

  1-Tetrazole is one of the most commonly used bioisosteres for carboxylic acids arising from their similarity in pKa (ca. 4.5–4.9 vs 4.2–4.4, respectively)., Metabolically, tetrazoles may exhibit an advantage over carboxylic acids because they form -glucuronides which are not as chemically reactive

• The ion conduction pathway reported herein accounts for

  2021-09-16

  

  The ion conduction pathway reported herein accounts for all known functional properties of EAAT/GltPh anion channels. Simulations reveal unitary current amplitudes and ion selectivities (Figures 3C and 3D) that resemble experimental results (Melzer et al., 2003, Wadiche and Kavanaugh, 1998). The cal

• By regulation of synaptic glutamate concentration glutamate

  2021-09-16

  

  By regulation of synaptic glutamate concentration, glutamate transporters play an important role in limiting glutamate signaling and controlling the activation of glutamate receptors (Rimmele and Rosenberg, 2016). Reduced glutamate transport is thought to underlie the pathogenesis of numerous neurol

• There are also data showing potential beneficial

  2021-09-16

  

  There are also data showing potential beneficial effects of SGLT2i on non-alcoholic fatty liver disease (NAFLD) [[14], [15], [16], [17]], a hepatic manifestation of the metabolic syndrome that has been linked to type 2 diabetes mellitus (T2DM) development and increased cardiovascular (CV) as well as

• Overnight mg dexamethasone suppression testing DST

  2021-09-16

  

  Overnight 1-mg dexamethasone suppression testing (DST) of the BclI polymorphism carriers found them to have lower cortisol levels, suggesting an increased sensitivity to GCs with respect to the transrepression effect of cortisol on the POMC gene of the corticotroph pituitary cells [28]. The exact me

• br Introduction Glucose homeostasis is primarily regulated b

  2021-09-16

  

  Introduction Glucose homeostasis is primarily regulated by the hormones insulin and glucagon, secreted from the pancreatic islets of Langerhans. Although insulin produced by β R406 mg is the blood glucose-lowering hormone, glucagon secreted from α cells acts as the major counter-regulatory hormo

• The stability of the i motif at the

  2021-09-15

  

  The stability of the i-motif at the neutral pH has been analyzed in our previous paper [31] by tracking the rmsd changes in unbiased calculations. Fig. 7 presents, just to confirm the conclusions drawn in [12], the changes in distances between atoms forming hydrogen bonds within the i-motif structur

• Based on the previous report that FXR regulated PEPCK

  2021-09-15

  

  Based on the previous report that FXR regulated PEPCK indirectly [20], we speculated that FXR may regulate gluconeogenesis by regulating some key transcription factors associated with gluconeogenesis. Finally, by using HS218 as a probe, we found that FXR binds to PGC-1α promoter and directly regulat

• br Declaration of interest br Acknowledgments

  2021-09-15

  

  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

• A common feature of ferroptosis is the iron dependent

  2021-09-15

  

  A common feature of ferroptosis is the iron-dependent accumulation of lipid-ROS and the subsequent depletion of polyunsaturated fatty molar equivalent phospholipids (PUFA-PLs) [118]. The PUFA chains of membrane lipids are more susceptible to both enzymatic and non-enzymatic oxidation, which results

• orthopox The EZH overexpression group exhibited upregulated

  2021-09-15

  

  The EZH2 overexpression group exhibited upregulated CEP55 expression but downregulated methylation, suggesting that changes in EZH2 expression in lung adenocarcinoma result in differences of CEP55 methylation and expression. Moreover, according to TCGA database and GSE27262 chip data, CEP55 expressi

• SecinH3 synthesis A complimentary approach with Per Luc cell

  2021-09-15

  

  A complimentary approach with Per2:Luc SecinH3 synthesis exposed to hypoxia as well as with mBmal1:Luc circadian reporter cells in which we overexpressed variants of HIF-1α and HIF-2α revealed that hypoxia and HIFs can not only shorten the period but also decrease the amplitude of the clock (Figure

• Epigenetic drugs such as HDAC inhibitors regulate

  2021-09-15

  

  Epigenetic drugs, such as HDAC inhibitors, regulate gene expression by affecting the activity of histone or DNA modifying enzymes and their associated transcriptional response [141]. BET bromodomain protein inhibition is another epigenetic approach for blocking the Hedgehog pathway at the downstream

• Pharmacologic approaches of inhibiting GSNOR activity have r

  2021-09-15

  

  Pharmacologic approaches of inhibiting GSNOR activity have reached the point of clinical development with the recent announcement of the first cystic fibrosis patients treated with the first-in-class GSNOR inhibitor, N6022 (N30 Pharmaceuticals). Clinical development is ongoing for other indications

• Importance of glucokinase in glucose homeostasis and a

  2021-09-14

  

  Importance of glucokinase in glucose homeostasis and a possibility to change its activity using the activators define the scientific interest in the development of new allosteric activators of GK (Liu et al., 2012, Pfefferkorn et al., 2011, Waring et al., 2013, Behera et al., 2015). Activation of gl

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