• Regulation of pancreatic and cell mass has

  2022-05-26

  

  Regulation of pancreatic α and β cell mass has been extensively studied and hotly debated, due to potential therapeutic implications. Early claims of Angptl8 as “betatrophin” and Angptl4 as a regulator of glucagon secretion and α cell proliferation (Yi et al., 2013, Ben-Zvi et al., 2015) have not st

• Here we used chemogenetic modulation

  2022-05-26

  

  Here, we used chemogenetic modulation of MBH GHSR neurons to address the role of the endogenous ghrelin system in the normal, hyperphagic response to a short-term fast. Studies demonstrating the requirement of an intact ghrelin-GHSR system for the rebound food intake following fasting have been inco

• Conversely we find that dysfunction in lysosomal autophagy s

  2022-05-26

  

  Conversely, we find that dysfunction in lysosomal-autophagy system observed in human APP and PSEN1 mutant neurons can be reversed by β-secretase inhibition, which reduces the supply of APP-β-CTF to the late endosome and/or lysosome (Jiang et al., 2010). These data argue that accumulation and/or alte

• br Ethics approval br Availability of data and materials

  2022-05-26

  

  Ethics approval Availability of data and materials Consent for publication Competing interests Authors contributions Introduction Glucose supply to tissues is maintained through a complex regulatory network mostly driven by the pancreatic hormones insulin and glucagon which control

• uPAR promotes cell associated proteolysis by binding to uPA

  2022-05-26

  

  uPAR promotes cell-associated proteolysis by binding to uPA which locally converts plasminogen into active plasmin [10]. Ligand-engaged uPAR also acts as a potent regulator of cell migration and matrix attachment. Being a membrane receptor, uPAR needs to interact with extracellular matrix (ECM) prot

• In principle an ideal Fenton reaction element

  2022-05-26

  

  In principle, an ideal Fenton reaction element should have multiple oxidation states to form a redox cycle in the process of H2O2 decomposition to HO•. Although iron is very effective in catalyzing Fenton reaction, it requires a low pH value (pH 2-4) to reach the optimal catalytic efficiency, which

• Classical drugs target the viral

  2022-05-26

  

  Classical drugs target the viral Sulfo-NHS-SS-Biotin synthesis reverse transcriptase (RT), protease and integrase (IN) [[4], [5], [6]]. Raltegravir (ISENTRESS/MK-0518) is the prototypical integrase strand transfer inhibitor (INSTI) leading to an extremely strong reduction in viral load [7] and it ha

• br Conflict of interest statement

  2022-05-26

  

  Conflict of interest statement References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: Acknowledgements We thank Urann Chan for assistance with the figures. This work was supported in part by National Institutes of

• br Pharmacological anti aging approaches and the Hippo

  2022-05-25

  

  Pharmacological anti-aging approaches and the Hippo pathway Aging and age-related pathologies are the main causes of disabilities and death. As Magalhañes and colleagues suggest, the challenges of developing anti-aging pharmacological therapies may, in part, be due to the complexity of aging mole

• Interestingly myorelaxation and the stimulation of cGMP prod

  2022-05-25

  

  Interestingly, myorelaxation and the stimulation of cGMP production are properties also reported for sGC stimulators, such as YC-1 and BAY 41–2272 (i.e., indazole compounds that were discovered in the 1990s) [35]. They relax aortic ring contractions induced by phenylephrine, and their effects are si

• Our study has strengths and limitations We believe

  2022-05-25

  

  Our study has strengths and limitations. We believe we are the 1st to report a novel model of secondary hypogonadism. Several animal models for hypogonadotropic hypogonadism (kisspeptin and the kisspeptin receptor knockout) exist but we are unaware of animal models of secondary hypogonadism with dif

• br Introduction br Mitochondrial dysfunction

  2022-05-25

  

  Introduction Mitochondrial dysfunction and cancer Lactate and succinate as oncometabolites Intracellular actions of lactate and succinate as tumor promoters Cell-surface receptors for lactate and succinate and their role in cancer GPR109A as the receptor for butyrate and β-hydroxybu

• Further our study provides the first evidence that zaprinast

  2022-05-25

  

  Further, our study provides the first evidence that zaprinast and kynurenic PR171 administration not only prevented the development of thermal and mechanical hypersensitivity but also enhanced morphine antinociceptive properties. Morphine is considered to be one of the most effective analgesic drugs

• br Next we explored the SAR around the aryl

  2022-05-25

  

  Next, we explored the SAR around the aryl ring attached to the pyrrole nitrogen in the presence of the 3-CF and the 2,6-difluorophenylpropionic Pranlukast receptor sidechain (). The EC value of the unsubstituted phenyl was about 100 nM. The 4-methyl was 2-fold more potent, however ethyl and br

• Despite having potent activity and good solubility showed

  2022-05-25

  

  Despite having potent activity and good solubility, showed inhibitory activities against cytochrome P450 (CYP) 2C8, 2C9, and 2C19 with an IC value of less than 10 μM. In general, the specificity of the compound to the target should improve and the off-target risk such as CYP inhibitory activity sho

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