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The clinical impact of our findings is also supported by
2024-03-25
The clinical impact of our findings is also supported by our earlier report that the level of 12-LOX expression was correlated with the tumor stage and grade [17], [52] and that overall, 38% of patients demonstrated elevated levels of 12-LOX in prostate cancer tissue compared with their matching nor
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Through an extensive SAR optimization campaign with the hydr
2024-03-25
Through an extensive SAR optimization campaign with the 4-((2-hydroxy-3-methoxybenzyl)amino)-benzenesulfonamide-based scaffold researchers have developed ML355 ((N-benzo[d]thiazol-2-yl)-4((2-hydroxy-3 methoxybenzyl)amino)benzenesulfonamide) [5]. ML355 is a nonreductive, noncompetitive, reversible 12
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Due to metabolic variations it is important to consider
2024-03-25
Due to metabolic variations, it is important to consider arginine metabolism and dependency in specific contexts to identify precise patterns. This is best illustrated for ASS: while ASS deficiency correlates with worse prognosis in sarcomas, ASS levels positively correlate with a poor prognosis in
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The proposed formulation is however
2024-03-25
The proposed formulation is, however, challenging to solve since the structured sparsity-inducing norms are non-smooth. In order to solve the new objective function, we consider two different approaches: proximal averaging, which takes the average the solutions from the proximal operator for the ind
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Synthesis of the pterin carboxamides was achieved as shown
2024-03-25
Synthesis of the pterin-7-carboxamides was achieved, as shown in , based on a previously reported method that utilizes DBU as a key additive to dissolve pterin in organic solvents and accelerate the reaction., With this method, the pterin-amino WAY-600 conjugates (–) were readily obtained by simpl
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Although several studies indicate that ALDH protects the hea
2024-03-25
Although several studies indicate that ALDH2 protects the heart from injury and maladaptive remodeling (reviewed in [11], [12], [13]), accumulating evidence indicates that deficiency of the enzyme could be protective as well. For example, mice expressing the defective Aldh2*2 mutation show lower ald
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The fact that Yoda can activate
2024-03-25
The fact that Yoda1 can activate Piezo1 in the absence of other cellular components other than a cell membrane [2], suggests that it may directly interact with and activate Piezo1. However, this does not preclude Yoda1 from interacting and activating non-Piezo channels, particularly in endothelial c
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Pregnane X receptor PXR is a nuclear receptor
2024-03-25
Pregnane X receptor (PXR) is a nuclear receptor that plays an important role in regulation of metabolism and disposition of structurally diverse xenobiotics as well as endogenous steroids and bile acids (Bertilsson et al., 1998, Kliewer et al., 1998, Lehmann et al., 1998). PXR regulates the metaboli
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Ozone induced innate inflammatory responses in the lung
2024-03-25
Ozone-induced innate inflammatory responses in the lung involve neutrophil extravasation through enhanced trans-endothelial migration (Krishna et al., 1997). Catecholamines and glucocorticoids, which are increased by ozone inhalation (Bass et al., 2013, Miller et al., 2015, Miller et al., 2016a, Mil
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Adiponectin also suppresses inflammatory stimuli induced NF
2024-03-25
Adiponectin also suppresses inflammatory stimuli-induced NF-kappaB activation, which may significantly contribute to the anti-diabetic and anti-atherogenic effects of adiponectin (Ouchi et al., 2000). The downstream mediators of AdipoR1 and AdipoR2, RPPAR and AMPK increase inflammatory responses by
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Adiponectin also works on AdipoR inducing extracellular Ca
2024-03-25
Adiponectin also works on AdipoR1, inducing extracellular Ca2+ influx necessary for activation of Ca2+/calmodulin-dependent protein kinase kinase (CaMKK)β, AMPK (Fig. 1). This step is then followed by activation of SirT1 and increased expression and decreased acetylation of PPARγ coactivator (PGC)-1
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The assay performance was estimated using Z
2024-03-25
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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Earlier studies revealed an interaction between HSP
2024-03-25
Earlier studies revealed an interaction between HSP90β and ACK1 [15]. In the proteomic approach, we show that ACK1 associates with HSP90α and HSP90β. Additionally, we confirm the existence of a HSP90-ACK1 complex with co-IP experiments. We further analysed whether an inhibition of HSP90 affected the
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A combination of factors might however
2024-03-22
A combination of factors might, however, account for the low rate of success of drug development for neuropsychiatric disorders. First, in most neuropsychiatric disorders, the symptomatology is heterogeneous and the neurobiology remains poorly understood, making therapeutic targets difficult to iden
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Thirty six of the analogs
2024-03-22
Thirty-six of the analogs synthesized showed ATX inhibition greater than 50% at 10μM with FS-3, twelve of which had improved potency over the lead (Fig. 5). Of these, 22 was sub-micromolar (IC50 670nM). The 3,5-dichlorophenoxy ring of 22 is reminiscent of the 3,5-dichlorophenylthiourea ring in Hoegl
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