• The identification of novel kinase inhibitor scaffolds is

  2024-09-30

  

  The identification of novel kinase inhibitor scaffolds is highly desirable in order to develop selective kinase inhibitors. Small-molecule inhibitors of Interleukin-2-inducible T-cell kinase (Itk) that are based on the 3-aminopyridin-2-one fragment 1 have been reported. Despite derivatisation of 1 y

• br Experimental Procedures br Acknowledgments This work was

  2024-09-30

  

  Experimental Procedures Acknowledgments This work was supported by NIH/National Human Genome Research Institute (NHGRI)R00 HG006922 and NIH/NHGRIR01 HG008974 (to J.G.), the Huntsman Cancer Institute, and the Women’s Cancers Disease-Oriented Team at the Huntsman Cancer Institute. Research repor

• In humans the superior safety profile of lipid

  2024-09-29

  

  In humans, the superior safety profile of lipid-associated formulations is characterized by decreased acute infusion-related reactions and dose-related nephrotoxicity, allowing the administration of larger doses and therefore similar efficacy with fewer administrations. In vitro studies and human cl

• br STAR Methods br Acknowledgments We thank

  2024-09-29

  

  STAR★Methods Acknowledgments We thank Simcere Pharmaceuticals, Nanjing, China, for providing a rabbit anti-VEGF neutralizing monoclonal antibody. We thank Dr. Schlisio in the Ludwig Institute for Cancer Research, Karolinska Institute, for assistance with hypoxia assay. Y.C.’s laboratory is su

• br Experimental procedures br Results br Discussion Our

  2024-09-29

  

  Experimental procedures Results Discussion Our biophysical and cellular analyses of mutant Aβ1–42 peptides support a role of the N-terminus of Aβ in peptide aggregation and toxicity. We demonstrate that double mutations constructed to humanize the rodent Aβ1–42 sequence result in a signific

• br Introduction AMP activated protein

  2024-09-29

  

  Introduction AMP-activated protein kinase (AMPK) has been found to be a key character against cardiovascular diseases and cellular stress. When activated by certain stress, AMPK regulates sugars and fatty acids that are good or detrimental to the heart. For example, targeting AMPK phosphorylation

• In past Zebra fish Danio rerio has emerged as

  2024-09-29

  

  In past, Zebra fish (Danio rerio) has emerged as a suitable model for early vertebrate development, and a number of targeted mutations in the zebrafish genome led to phenotypic alterations that resemble human diseases [34]. A 12-LOX in Zebra fish has been cloned and knock down of this zf12-LOX enzym

• br Conflict of interest statement br Introduction The

  2024-09-29

  

  Conflict of interest statement Introduction The global prevalence of Alzheimer's disease (AD) is expected to increase to 106 million in 2050 from 30 million in 2010 (Brookmeyer et al., 2007), which will further impose a significant economic burden on health systems and society as a whole (Broo

• br Conclusions br Acknowledgments The authors are thankful t

  2024-09-29

  

  Conclusions Acknowledgments The authors are thankful to Hugo Santos, Olga Martinez and Ricardo Lacerda for the technical assistance provided in the maintenance of the aquaria. This work was supported by national funds, through FCT and co-funded by the European Regional Development Fund (ERDF)

• deoxyribonuclease i Does dietary caffeine interfere with ant

  2024-09-29

  

  (8) Does dietary caffeine interfere with antinociception by other modalities that alter pain (TENS, exercise, joint mobilization, water immersion therapy)? Caffeine and/or A1R antagonists inhibit antinociception by each of these modalities in preclinical studies, such that there is potential for int

• The assay performance was estimated

  2024-09-29

  

  The assay performance was estimated using Z′-factors (plotted in Fig. 2A) according to Zhang et al. calculated for each plate comparing positive (in the absence of an inhibitor) and negative controls (in the presence of an AdK inhibitor). The mean Z′-factor±SD was determined to be 0.7±0.1, indicativ

• Curcumin is the principal natural

  2024-09-29

  

  Curcumin is the principal natural polyphenol curcuminoid of turmeric (Curcuma longa) rhizome, a member of the ginger family (Zingiberaceae) [13]. Curcumin has a wide spectrum of therapeutic properties, and it has been shown to possess antioxidant, anti-inflammatory, anticancer, antiangiogenesis, che

• br Materials and methods br Results Bilateral microinjection

  2024-09-29

  

  Materials and methods Results Bilateral microinjections (n = 6) of 10 mM ACh (300–500 pmol) and 5 mM physostigmine (150–250 pmol) at the two selected caudal NTS sites caused within 1 min significant increases in respiratory frequency (from 54.5 ± 1.7 to 70.9 ± 4.1 breaths/min; +30.8 ± 7.0%; P 

• Application of the broad acting HTR antagonist methiothepin

  2024-09-29

  

  Application of the broad-acting 5-HTR antagonist methiothepin (Bard et al., 1996, Hoyer et al., 1994, Peroutka, 1990) converted the TBS-induced response of both thalamocortical and intracortical A1 synapses from LTP to LTD, an effect that was mimicked by the selective 5-HT2R antagonist ketanserin (L

• AG-1295 ASK has been identified as an ASK binding

  2024-09-28

  

  ASK2 has been identified as an ASK1 binding protein (Wang et al., 1998). ASK1 supports the stability and active configuration of ASK2 in the heteromeric complex, while ASK2 has been found to activate ASK1 by direct phosphorylation (Takeda et al., 2007). Unlike ASK1, which is ubiquitously expressed i

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