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br Conclusion Growth survival and invasion of most PCs
2024-04-10
Conclusion Growth, survival, and invasion of most PCs have been shown to be androgen-dependent at the onset of castration therapy [31]. Thus, castration therapy has been central to systemic therapy and remains the standard approach to PC treatment. Even after progression to a castration-resistant
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Another significant group of reductase inhibitors is
2024-04-10
Another significant group of 5α-reductase inhibitors is the steroidal 3-carboxylic Dorsomorphin derivatives (relevant examples in Fig. 5), which were designed to mimic the putative enzyme-bound enolate intermediate. This was achieved by introducing sp2-hybridized centers at C3 and C4 and an anionic
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Our previous studies found that
2024-04-10
Our previous studies found that some steroid mimetic structures such as stilbene, biphenyl, naphthalene and benzothiophene rings were suitable for lipophilic moieties of 17,20-lyase inhibitors, and several inhibitors obtained using a steroid A, C-ring mimetic approach have already been published. Du
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Introduction An association of elevated
2024-04-10
Introduction An association of elevated branched-chain MK-3207 HCl synthesis (BCAA—Leu, Val, Ile) with obesity and insulin resistance was first reported nearly 50 years ago (Felig et al., 1969). With the advent of metabolomics technologies, it has since become apparent that the association of BCAA
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Recent studies have demonstrated that
2024-04-10
Recent studies have demonstrated that in response to IR, hundreds of substrates are phosphorylated in an ATM-dependent manner, clearly demonstrating the complexity of the ATM-mediated DDR pathways (Matsuoka et al., 2007, Bennetzen et al., 2010, Bensimon et al., 2010). However, evidence suggesting th
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br Experimental Procedures br Acknowledgments This work
2024-04-10
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
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AT signaling is distinct to that
2024-04-10
AT2 signaling is distinct to that of AT1 (Kaschina and Unger, 2003). As shown here, opposite to the stimulating effect of AT1 signaling, it inhibits apelin secretion. Activation of AT2 receptor, which is also G-protein coupled, is known to decrease cAMP and cGMP levels by inhibiting adenylyl cyclase
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MAPs require divalent transition metal ions
2024-04-09
MAPs require divalent transition metal ions as cofactors for activity [21]. Previous studies on MAPs from different organisms indicate cobalt ions to be the most preferred divalent metal activator [22]. However, MAPs also exhibit activity with other divalent cations like Mn(II), Ca(II), Ni(II) or Fe
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UM171 Aldose reductase ALR EC the first enzyme in the polyol
2024-04-09
Aldose reductase (ALR2, EC1.1.1.21), the first enzyme in the polyol pathway, is a monomeric oxidoreductase that catalyses the NADPH-dependent reduction of a wide variety of carbonyl compounds, especially glucose. In this metabolism pathway, glucose is firstly reduced to sorbitol catalyzed by ALR2 wi
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ALDHs also act as opposite roles in the initiation
2024-04-09
ALDHs also act as opposite roles in the initiation and development of carcinoma. For example, ALDH2, as a key enzyme which oxidises acetaldehyde, participates in alcohol metabolism and is associated with alcohol-mediated carcinogenesis [37]. It has been reported that up to 8% of the world's populati
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Blocking the action of CREB with the C inhibitor
2024-04-09
Blocking the action of CREB with the C646 inhibitor together with increasing Akt activation with the SC79 agonist is particularly interesting as it significantly reduced wound closure time from 7 days (which is required for complete closure of control hTECs exposed to DMSO) to only 4 days (when hTEC
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PF-670462 br ABCA mRNA expression is elevated in Niemann
2024-04-09
ABCA2 mRNA expression is elevated in Niemann-Pick type C and familial hypercholesterolemia fibroblasts Niemann-Pick Type C disease is a neurological disorder of adolescents due to autosomal-recessive mutations in either one or both Niemann-Pick-2 (NPC2) and NPC1 genes, which, like ABCA2, are loca
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Mass spectrometry MS analysis and selective
2024-04-09
Mass spectrometry (MS) analysis and selective enrichment methods of phosphorylated proteins are powerful tools that can help address these challenges. Recent advances in MS have made it possible to analyze signaling pathways by facilitating high-throughput identification of phosphorylation sites wit
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br Material and methods br
2024-04-09
Material and methods Results Discussion GRK2 activity has increasingly been shown to contribute to the progression of numerous diseases and organ dysfunction [5], [6]. For instance, a large body of work over the last two decades has identified GRK2 as a major regulator of cardiac dysfunctio
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The assay performance was estimated
2024-04-09
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
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