• br Experimental br Acknowledgments This project was

  2022-06-14

  

  Experimental Acknowledgments This project was generously supported by Grünenthal GmbH and IECB. We also thank the staff members of the technical platform of IECB and Grünenthal GmbH for their availability and their skills. Introduction Glucocorticoids (GCs) are essential steroid hormones t

• br Materials and methods br Results br Discussion

  2022-06-14

  

  Materials and methods Results Discussion Prior studies established that Notch signaling regulates the differentiation of hair cells and supporting cells during inner ear development (reviewed in Kiernan (2013)). Notch signaling is a multistep process that requires the interaction between a

• The highest metabolic stability observed for compound k EC

  2022-06-14

  

  The highest metabolic stability observed for compound 4k (EC50=0.41μM corresponding to 218ng/mL) among the four selected frontrunner candidates was the principal decisive point in nominating this compounds for pharmacokinetic characterization in mice at the dosage of 10mg/kg (administered intravenou

• br STAR Methods br Introduction Arsenite

  2022-06-14

  

  STAR★Methods Introduction Arsenite is a well-recognized toxic metalloid that commonly presents in the natural environment. Chronic exposure to arsenite can lead to a wide range of adverse health effects to human, including cancers, cardiovascular diseases, diabetes, skin lesion and neurodegene

• EZH mutations or amplifications have been found

  2022-06-14

  

  EZH2 mutations or amplifications have been found in a broad spectrum of human cancers including B cell lymphoma, ovarian cancer, breast cancer, melanoma, bladder cancer, gastric cancer, and other cancers (Kim and Roberts, 2016). Given the evidence of EZH2 as a cancer driver, numerous efforts have be

• Substrate affinity and specificity can be enhanced by dockin

  2022-06-13

  

  Substrate affinity and specificity can be enhanced by docking interactions, in which regions distal to the site of mglur antagonist bind to grooves, pockets, or surfaces outside of the kinase catalytic cleft 1, 2, 5, 6. Like catalytic site interactions, docking interactions can involve recognition o

• DNA methylation is a kind of epigenetic

  2022-06-13

  

  DNA methylation is a kind of epigenetic modifications that can be described as a heritable alteration in gene expression, without any changes in the DNA sequence. Recent evidences suggest that the regulation of DNA methylation status is a frequent and early event in prostate carcinogenesis. For exam

• The beta catenin TCF complex is an important target in

  2022-06-13

  

  The beta-catenin/TCF complex is an important target in the Wnt/beta-catenin pathway. This complex has proven challenging to target. However, natural inhibitors of this complex have been identified. One group of inhibitors is called the inhibitors of Wnt response (IWR-1/2). IWR-1/2 targets Axin and s

• br Conclusion and future perspectives

  2022-06-13

  

  Conclusion and future perspectives The nicotinic wnt signaling pathway receptor GPR109A and its close relatives GPR109B and GPR81 are primarily expressed in adipocytes and are coupled to Gi-type G proteins. Recently, the ketone body β-hydroxy-butyrate, the β-oxidation intermediate 3-hydroxy octa

• As part of our discovery efforts searching

  2022-06-13

  

  As part of our discovery efforts searching for small molecule GPR119 agonists, we analyzed active pharmacophores of known agonists from the literature, and found that -methylsulfonylphenyl and substituted 4-hydroxyl piperidine are common fragments. In our initial efforts, we linked these two fragme

• Compared to methadone or morphine buprenorphine is a partial

  2022-06-13

  

  Compared to methadone or morphine, buprenorphine is a partial mu-opioid agonist, which shows high affinity for, and slow dissociation from, mu-opioid receptors. This maintenance of homeostasis may help to counter the development of an overt withdrawal syndrome, and may explain the lower risk of deve

• In this study we examined

  2022-06-13

  

  In this study, we examined whether zebrafish ionocytes might also share other types of similarity in transport function with kidney cells. In addition to ion transport, mammalian kidney marbofloxacin also play key roles in xenobiotic elimination, through the action of ATP-Binding Cassette (ABC) tra

• br Acknowledgements br Introduction Glucagon

  2022-06-13

  

  Acknowledgements Introduction Glucagon, a 29-amino Fmoc-Val-OPfp mg peptide, is released from the pancreatic islets, intestine and stomach. Glucagon is released under hypoglycemic conditions and then elevates blood glucose levels, serving as a major counter hormone [1]. The regulation of gluc

• Due to the versatility of the ghrelin system and its

  2022-06-13

  

  Due to the versatility of the ghrelin system and its multiple functions, dysregulation in some of the components of the ghrelin system, such as ghrelin, GOAT, and GHSR, might lead to pathogenesis of many endocrine-related diseases, including obesity, short stature, cancer, inflammatory, and cardiova

• The secretase complex comprises four core subunits presenili

  2022-06-10

  

  The γ-secretase complex comprises four core subunits: presenilin (PS), nicastrin (NCT), anterior pharynx-defective 1 (Aph1), and presenilin enhancer 2 (Pen2) [7], [8]. PS is the catalytic subunit of γ-secretase, and many PS mutations associated with familial AD result in a high Aβ42/Aβ40 ratio [5].

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