• In summary we have designed and optimized a new

  2021-09-24

  

  In summary, we have designed and optimized a new series of 1,4-dioxycyclohexane GPR119 agonists. SAR studies led to the discovery of the preferred molecule that has potent and efficacious GPR119 activity across species. This lead compound exhibited an excellent ADME and safety profile, and demonstra

• The effects of opioids such as morphine

  2021-09-24

  

  The effects of opioids such as morphine are mediated through the opioid receptors. Opioid receptors are widely expressed both peripherally and in the CNS (Chen et al., 1993, Evans et al., 1992). The opioid agonist morphine has been shown to amplify the effect of the tubular cell-gp120 interaction on

• br Acknowledgments This work was

  2021-09-24

  

  Acknowledgments This work was supported by the Slovak grant agency VEGA, Grant 2/0084/13. We would like to thank Dr. J. Bauer for careful reading of the manuscript. Introduction Glycine is an important neurotransmitter which regulates both GSK1904529A inhibitory neurotransmission and excitat

• br Characterization and regional localization

  2021-09-24

  

  Characterization and regional localization of Glu transporters Molecular studies led to the description of five subtypes of plasma membrane Glu transporters termed in accordance to their human or rodent origin (Kanai and Hediger, 1992, Pines et al., 1992, Storck et al., 1992). In humans, these tr

• 3,3',5'-Triiodo-L-thyronine mg Shikonin represents n

  2021-09-24

  

  Shikonin represents naphtoquinonic compound isolated from the Chinese plant Lithospermum erythrorhizon[20]. Shikonin treatment inhibits AKT and ERK signaling pathways and induces apoptosis through FOXO transcription factors and mitochondrial pathway [21], [22]. Recent results suggest inhibition of l

• A number of GCK activators

  2021-09-24

  

  A number of GCK activators for treating T2D have been developed and tested but not progressed successfully from clinical trials into therapy [45]. Our observations suggest that increased risk of hypoglycemia might be possible, particularly if drugs penetrate into brain. A further possibility is that

• Recently multiple receptor agonists have been

  2021-09-24

  

  Recently, multiple receptor agonists have been developed to treat type II diabetes (Finan et al., 2013, Finan et al., 2015). We have tested novel dual GLP-1/GIP receptor agonists that showed good neuroprotective effects that are superior to single GLP-1 analogues (Cao et al., 2016, Jalewa et al., 20

• One of the main mechanisms enabling recycling of

  2021-09-24

  

  One of the main mechanisms enabling recycling of intracellular redox-active iron is lysosomal degradation of ferritin in the process of autophagy, often referred to as ‘ferritinophagy’ [128]. Autophagy was suggested to contribute to ferroptotic cell death by promoting the degradation of iron storage

• Next we aimed to investigate if the cardiac

  2021-09-24

  

  Next, we aimed to investigate if the cardiac apoptosis induced by CO-HFD, LA, T1DM or hyperglycemia involves up-regulation and activation of Fas/FasL-mediated cell death and if such effects are mediated by ROS and/or Ca+2/calcineurin/NFAT signaling axis. Similar to previous reports, [8], [9], [10],

• Although angiogenesis is crucial for cerebral

  2021-09-24

  

  Although angiogenesis is crucial for cerebral ischemic rehabilitation, the mechanism underlying NGF promotion of angiogenesis is not clear. Previous studies showed that angiogenesis can be promoted by FAK, in a breast cancer model [19]. Recent studies showed that FAK phosphorylation participated in

• br Venous thromboembolism VTE is a

  2021-09-24

  

  Venous thromboembolism (VTE) is a rare but potentially life-threatening complication of total joint arthroplasty (TJA) . With modern chemoprophylaxis, the incidence of VTE after primary total hip (THA) or total knee (TKA) arthroplasty is commonly estimated between 0.5% and 1%, and VTE is now consi

• Hyperactivation of Notch pathway can

  2021-09-24

  

  Hyperactivation of Notch1 pathway can give rise to transformation into T-ALL in murine models. In more than 50% of acute T-cell lymphoblastic leukemias oncogenic activating mutations of Notch1 have been detected and inactivation of Notch1 signaling impairs leukemia cell proliferation and promotes ap

• A small number of patients had

  2021-09-24

  

  A small number of patients (11%) had accessory integrase mutations (E157Q, G163R, L74IM, and/or V151I) that confer potential or low-level resistance and generally only when they occur in combination with other high/intermediate level resistance mutations. This is a somewhat higher incidence than tha

• In T cells whereas SETDB is implicated

  2021-09-24

  

  In T cells, whereas SETDB1 is implicated in OX40-dependent repression of the Il17a locus in Th17 cells (Xiao et al., 2016), SUV39H1 controls Th2 cell stability by depositing H3K9me3 at the Ifng promoter (Allan et al., 2012). However, the deregulation of the Ifng locus observed in Suv39h1−/− cells ca

• Upon LPS stimulation ERK and STAT signaling

  2021-09-23

  

  Upon LPS stimulation, ERK and STAT3 signaling pathways were activated in a time-dependent manner, and the phosphorylation of Y705 occurred later than that of S727 (Supplementary Fig. S5B). STAT3 is known to be phosphorylated on serine 727 (S727) by the mitogen-activated protein (MAP) kinase pathway

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