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Valproic acid VPA is a first line treatment for
2020-11-04
Valproic Mitochondrial DNA Isolation Kit (VPA) is a first-line treatment for epilepsy and bipolar disorder, although its therapeutic mechanism of action is not fully understood. Considerable evidence suggests that VPA can act through the GABAergic system, NMDA receptors, and/or sodium channels (for
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The most significant source of DAG originates from the
2020-11-04
The most significant source of DAG originates from the PLC family of enzymes, which produces DAG in an agonist-regulated reaction. PLCs constitute a wide family of enzymes acting on both phosphatidilinositols (PI) and phosphatidilcoline (PC) (Li et al., 2010) in the plasma membrane and other intrace
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The current study provides evidence for a previously unknown
2020-11-04
The current study provides evidence for a previously unknown role for DHODH as a growth/survival factor in KRAS mutant tumors. While many aspects of the link between DHODH inhibition and survival of KRAS mutant cells remain to be established, de novo pyrimidine biosynthesis appears to be a crucial p
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br Four active site residues of
2020-11-04
Four active site residues of Δ1-KSTD1 are fully conserved in Δ1-KSTDs from different species (Supplementary Figure S2). These residues are Tyr-119, Tyr-487, and Gly-491 from the FAD-binding domain and Tyr-318 from the catalytic domain. The structure of the Δ1-KSTD1•ADD complex revealed that the hy
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One possible explanation for differences in the binding abil
2020-11-04
One possible explanation for differences in the binding ability of monomeric versus dimeric forms of DDR2 ECD to collagen could be that the monomeric form only binds to the primary GVMGFO site, whereas dimeric (and oligomeric) DDR2 ECD binds to additional sites on the collagen triple-helical molecul
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br Introduction Noncanonical nucleoside triphosphates NTPs s
2020-11-04
Introduction Noncanonical nucleoside triphosphates (NTPs; such as deoxyinosine triphosphate (dITP), deoxyxanthosine triphosphate (dXTP), 8-oxo-deoxyguanosine triphosphate, and 2-oxo-deoxyadenosine triphosphate are produced from oxidation, deamination, or other modifications of canonical nucleotid
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Animal studies investigating the role of D
2020-11-04
Animal studies investigating the role of D1 dopamine receptors in the PFC have focused on delayed response tasks, which require online maintenance of a previously presented stimulus. Striatal dopamine is thought to be important for flexibility and updating goal representations when new information i
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A growing body of data indicates that endothelial NOS
2020-11-04
A growing body of data indicates that endothelial NOS (eNOS) is a rate-limiting enzyme for the synthesis of nitric oxide (NO), its downstream Nitazoxanide molecule. High pathological concentrations of NO produced from inducible NO synthase (iNOS) induce apoptosis, whereas a reduction in the concentr
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br ET Antagonist for the
2020-11-04
ET Antagonist for the Future: Macitentan and Atresentan Macitentan is an insurmountable antagonist, resulting from structure-activity studies to improve the efficacy and tolerability of bosentan, and gained approval in the United States in 2013 for the treatment of PAH. Actelion describes the com
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To function as Ub ligases E proteins
2020-11-04
To function as Ub-ligases, E3 proteins must interact with E2s. As compared to the extensive studies on E3s, functional studies on E2s are relatively rudimentary in higher plants. We previously reported that there are 48 genes encoding Ub-conjugating (UBC) fold-containing putative E2 proteins in the
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We next focused our design building into
2020-11-03
We next focused our design building into the ribose binding site, which had not been yet utilized in this effort. Compounds bearing a series of five-membered aromatic heterocycles (compound , ) showed reduced inhibition of the Gram-positive isozymes compared with compound , but a 20-fold improved po
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HPF We show that direct contact with MSCs is necessary and
2020-11-03
We show that direct contact with MSCs is necessary and sufficient to induce DDR2 upregulation in breast cancer cells. DDR2 expression in MSC is required for collagen deposition and leads to increased DDR2 expression and activation in breast cancer cells. This paracrine-autocrine MSC-cancer cell axis
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Edrophonium chloride Next we evaluated the therapeutic
2020-11-03
Next, we evaluated the therapeutic potential of compound () using the mouse model of collagen-induced arthritis (CIA model), which is the pathological model for RA. Consequently, oral once-daily dosing of 3 mg/kg reduced the overall progression of the clinical score, including inflammation and bone
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Besides the enhanced expression of costimulatory and adhesio
2020-11-03
Besides the enhanced expression of costimulatory and adhesion proteins, also the expression of the CD83 surface molecule is strongly enhanced during DC maturation (Banchereau and Steinman 1998; Banchereau et al. 2000). In fact, CD83 is a major cell surface marker for fully mature DC, as it can not b
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vitamin d receptor VEGF inhibition causes vascular regressio
2020-11-03
VEGF inhibition causes vascular regression and tissue hypoxia in tumor tissues and their surrounding healthy adipose tissues. In this regard, tumors in steatotic livers and adjacent to adipose tissues would experience more hypoxia than non-adipose tumors. Indeed, our present experimental results sup
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