• br Acknowledgements MC and PD were funded by the Michael

  2023-12-12

  

  Acknowledgements MC and PD were funded by the Michael J Fox Foundation (Grant ID 9969). We would like to thank Pierluigi Saba, Francesco Traccis and Barbara Tuveri for their technical assistance. Introduction In the prostate, androgens play a crucial role in normal, BPH and cancerous growth b

• Small kinase inhibitors have been developed

  2023-12-12

  

  Small kinase inhibitors have been developed to block AXL by interacting with the kinase cytoplasmic ATP binding site. Up to date, no AXL selective kinase inhibitors are marketed. As depicted in , some marketed kinase inhibitors such as Bosutinib and Cabozantinib or kinase inhibitors in clinical pha

• The inhibition of ACLY induces an

  2023-12-12

  

  The inhibition of ACLY induces an anticancer effect that has been reported to be involved in mitochondrial reactive oxygen species (ROS) generation [14], [16], dual blockade of mitogen-activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways [11], and the glycolytic phenotype of tumor

• AP26113 Investigating these possibilities will illuminate

  2023-12-12

  

  Investigating these possibilities will illuminate whether AP26113 possess mechanisms to differentially detect ACLY-generated versus ACSS2-generated acetyl-CoA as well as define the functional relationship between histone acetylation levels and cellular functions and phenotypes. Given that ACLY domi

• exemplifies three of the compounds

  2023-12-12

  

  exemplifies three of the compounds investigated in the selection for a candidate drug (CD). Our first criteria was an IC The LY364947 as such did not show any genotoxicity in the SOS/umu assay, but this does not say anything about any possible genotoxicity of its metabolites or degradation product

• In addition to drawing attention to

  2023-12-12

  

  In addition to drawing attention to Ser454 of ACL as a phosphosite that is regulated by both BDK and PPM1K, our phospho-proteomics screen identified several additional sites in other proteins. For example, Ser25, Ser29, and Ser79 of the lipogenic enzyme acetyl-coA carboxylase 1 (ACC1) were found to

• br Introduction Lipoxygenases LOXs are a heterogeneous famil

  2023-12-12

  

  Introduction Lipoxygenases (LOXs) are a heterogeneous family of enzymes that catalyze the peroxidation of polyunsaturated fatty acids (PUFAs). By oxidizing free PUFAs, they were shown to contribute to the generation of various bioactive lipid mediators. However, LOX-mediated oxidation of PUFAs es

• From an historical perspective ligands for GPCRs adrenaline

  2023-12-12

  

  From an historical perspective, ligands for GPCRs (adrenaline, serotonin, induced pluripotent stem cell or morphine, to name a few) have been identified before their receptor counterparts, at a time when the concept of receptor itself was controversial [15]. Although many cognate receptors for endo

• br ASK in Huntington s disease and other polyglutamine disea

  2023-12-12

  

  ASK1 in Huntington's disease and other polyglutamine diseases The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding regions of specific genes, leading to the production

• PD research involves the use of many animal models

  2023-12-12

  

  PD research involves the use of many animal models, which can be categorized into two main types: toxic models—among which the two most widely used are the classical 6-hydroxydopamine (6-OHDA) model in rats and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model in mice and monkeys—and gen

• MMAF br Conclusions In summary the present results showed th

  2023-12-12

  

  Conclusions In summary, the present results showed that ageing diminished arginase activity only in clearance tissues and that l-arginine supplementation did not induce major changes in arginase activity thus refuting a role of arginase in the potential deleterious effects of l-arginine supplemen

• faah inhibitor Introduction Cytochrome P CYP aromatase catal

  2023-12-12

  

  Introduction Cytochrome P450 19 (CYP19; aromatase) catalyzes the conversion of androgens to estrogens in a three-reaction sequence, where each step depends on NADPH and O2 [[1], [2], [3]]. The first two steps are accepted to be hydroxylations of the steroid C19 methyl group, whereas the final step

• There is limited information regarding hyperargininemia

  2023-12-12

  

  There is limited information regarding hyperargininemia incidence or prevalence. Reports of incidence vary by an order of magnitude: 0.5 to 5.0 per million [5], [6]. A relatively large U.S. study estimated 1.1 cases per million births [7], but it used an indirect methodology that introduces uncertai

• br Implementation of sacubitril valsartan into clinical prac

  2023-12-12

  

  Implementation of sacubitril/valsartan into clinical practice Following on from the results of PARADIGM-HF, sacubitril/valsartan was given regulatory approval for use in patients who conform to the main inclusion criteria of the trial; NYHA functional class II–IV, reduced left ventricular ejectio

• Hyperactivity of the hypothalamus pituitary adrenal

  2023-12-12

  

  Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is well described in MDD (Pariante and Lightman, 2008, Marques et al., 2009), is also observed in AD and results in increased glucocorticoid (GC, cortisol in primates) levels in blood and CSF (Davis et al., 1986, Martignoni et al.

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