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br Introduction The principal pathways
2023-09-21
Introduction The principal pathways of adrenal and gonadal steroidogenesis have been known for over 50 years (reviewed by Miller and Auchus, 2011). Cholesterol is first converted to pregnenolone via three reactions, 20-hydroxylation, 22-hydroxylation and scission of the 20,22 carbon–carbon bond,
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Thirty six of the analogs
2023-09-21
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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Our data indicate that the D domain only needs to
2023-09-21
Our data indicate that the D1 domain only needs to hydrolyze ATP a few times, or perhaps even just once, during the processing of a given substrate molecule, whereas the D2 domain hydrolyzes ATP many times. Consistent with this model, only D2 contains the canonical aromatic pore loop residues implic
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Tumor suppressor ARF regulates the activity of
2023-09-21
Tumor suppressor ARF regulates the activity of p53 by inhibiting the functions of Mdm2. ARF is induced by hyperproliferative signals emanating from oncogenic Ras, overexpressed c-myc, and from deregulated E2F . ARF prevents p53 degradation and leads to increased p53 function by sequestering Mdm2 to
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Many coumarin derivatives can be found in
2023-09-21
Many coumarin derivatives can be found in nature. There are more than 1300 types of those purely derived from plants, and if synthetic products are included, their number is immeasurable. According to the earliest existing records extant, herbs containing Psoralen-type compounds, e.g., methoxsalen,
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The enzyme Arginase ARG plays a role in
2023-09-21
The enzyme Arginase 1 (ARG1) plays a role in the hepatic urea cycle by hydrolyzing L-arginine to L-ornithine and urea [13]. In the context of macrophages and MDSCs, ARG1 expression redirects L-arginine metabolism to abolish cytotoxic nitric oxide production [14], suppress T-cell function [15], [16],
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Two major categories of arginase inhibitors
2023-09-21
Two major categories of arginase inhibitors have been distinguished (Fig. 3): the first category comprises synthetic arginase inhibitors, which have been developed from the substrate l-arginine [35]; and the second category includes inhibitors derived from natural products [36]. The category of synt
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br Conflicts of interest br Contributors br Introduction
2023-09-21
Conflicts of interest Contributors Introduction Lipid oxidation and enzymatic activities are some of the most significant problems in the food industry. These reactions lead to changes in chemical composition which in turn reduce the quality and shelf life of food products. Most of the anti
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While there is much in vivo work on prion
2023-09-21
While there is much in vivo work on prion-like Aβ, it has not been shown that one can induce inclusions of Aβ in cultured cells as has been shown for tau and α-synuclein. One reason is practical; Aβ is a low molecular weight metabolite cleaved from within the larger amyloid precursor protein (APP) a
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In a recent issue of Minokoshi and colleagues have
2023-09-21
In a recent issue of , Minokoshi and colleagues have added more light to our understanding of the role of hypothalamic AMPK in the regulation of energy balance. Previous seminal work from the same group suggested that AMPK in the PVH might be involved in the modulation of feeding . Here, they show
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Prednisone Heat shock protein Hsp is a
2023-09-20
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a central role in regulating the maturation, activation and stability of numerous “client proteins” that drive the development and progression of many cancers. Therefore, inhibition of Hsp90 would result in degradation of the client p
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AKT has been shown to be important
2023-09-20
AKT1 has been shown to be important for G1-S checkpoint transition and proliferation, whereas AKT2 regulates cell-cycle exit through its interaction with p21 (Héron-Milhavet et al., 2006). In a recent study in triple negative breast cancer, AKT3, rather than AKT1 activity was most important for cell
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The AHR potentially enhances IDO expression possibly via
2023-09-20
The AHR potentially enhances IDO-expression, possibly via crosstalk with several inflammatory signaling pathways (shown by now for IL6 and ‘signal transducer and activator of transcription’ (STAT) 3, and for NFκB, toll like receptor-pathways) [56,59,60]. IDO metabolizes Trp to kynurenines, which are
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Mechanistically NAergic signaling in the VTA modulates neuro
2023-09-20
Mechanistically, NAergic signaling in the VTA modulates neuronal activity presumably via α1-AR. The majority of α1-ARs are found in the VTA are located presynaptically on unmyelinated hcv protease inhibitor and axon terminals of glutamatergic and GABAergic neurons. However, α1-ARs are also found on
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Previous studies have demonstrated the presence of soluble N
2023-09-20
Previous studies have demonstrated the presence of soluble NTPDases, 5′-nucleotidase and adenosine deaminase in rat blood serum as well as in human blood (Doleski et al., 2016; Oses et al., 2004; Yegutkin, 1997; Yegutkin et al., 2007). In addition, our earlier reports have shown that these membrane-
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