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br Conclusion br Acknowledgement This study was supported by
2024-11-20
Conclusion Acknowledgement This study was supported by NIH/NINDSR01 NS036812-16. 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 gene
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Introduction Lipoxygenases LOXs are key enzymes
2024-11-20
Introduction Lipoxygenases (LOXs) are key enzymes that catalyze the polyunsaturated fatty acids (PUFAs) such as arachidic S63845 (AA), linoleic acid (LA) and others unsaturated fatty acids (Brash, 1999). LOXs are expressed in immune, neural, epithelial, tumor cells and other cells (Claesson, 2009)
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At the organismal level skeletal muscle lung and adipose
2024-11-20
At the organismal level, skeletal muscle, lung and adipose tissues mediate net de novo synthesis and release of glutamine, whereas net glutamine catabolism occurs in the kidney [7]. The liver exhibits net glutamine consumption coupled to urea production in the post-absorptive state, and net glutamin
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br Comparison to IWG In addition to the NIA AA
2024-11-20
Comparison to IWG In addition to the NIA AA, the other group that has established diagnostic guidelines for AD that incorporate biomarkers is the IWG [64,74,75]. In the most recent formal IWG document, published in 2014 [75], the diagnosis of AD required the presence of cognitive symptoms plus an
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Obesity is defined as a
2024-11-19
Obesity is defined as a body mass index (BMI) of 30kg/m2 or higher and is known to have a very close association with the risk of developing cancers (Hsueh and Deng, 2016). Several theories exist as to how this link is defined with respect to various cancers, one of which involves the effect of obes
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Introduction Diabetic nephropathy is a rapidly growing cause
2024-11-19
Introduction Diabetic nephropathy is a rapidly growing cause of end-stage renal disease [1]. Glomerular, tubular and vascular toxicity resulting from hyperglycemia (glucotoxicity) have been evaluated extensively at the molecular level as contributing factors for diabetic nephropathy [[1], [2], [3]]
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The extent to which GPCR oligomerization is
2024-11-19
The extent to which GPCR oligomerization is a regulated process still remains unclear. Reported effects of ligands on both GPCR homo- and heteromers are highly variable and depend on GPCR subtypes and the specific ligand used. According to our data, chronic treatment of mice with both paroxetine or
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The cellular mechanism underlying the CGS mediated inhibitio
2024-11-19
The cellular mechanism underlying the CGS12066-mediated inhibition of glutamate release from hippocampal nerve terminals through presynaptic 5-HT1B receptors remains to be elucidated. 5-HT1B receptors are coupled to PTX-sensitive G proteins (Gi or Go) that have been shown to inhibit AC activity as w
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In the previous study we demonstrated the importance
2024-11-19
In the previous study, we demonstrated the importance of the mPFC postsynaptic 5-HT1A receptor in the sustained antidepressant effects, because a sustained antidepressant effect was obtained with intra-mPFC injection, but not systemic injection of 8-OH-DPAT, a 5-HT1A receptor agonist (Fukumoto et al
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br GMF Remodels Actin Networks at the Leading
2024-11-19
GMF Remodels Actin Networks at the Leading Edge How are the conserved activities of GMF used in vivo to regulate branched BTL-105 australia networks (e.g., at sites of endocytosis and at the leading edge) (Figure 2A,B)? In animal cells, the regulatory effects of GMF on actin networks appear to g
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Several tertiary prevention studies are currently underway e
2024-11-19
Several tertiary prevention studies are currently underway examining the use of dutasteride for prostate cancer treatment: (1) during expectant management of prostate cancer, (2) after radical prostatectomy in men at high risk for relapse, and (3) in men with metastatic disease. The Reduction by Dut
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In fact serotonin is a major modulator of
2024-11-19
In fact, serotonin is a major modulator of dopaminergic (DA) neuronal activity through the 5-HT2C receptor. Studies have shown that the selective 5-HT2C receptor agonist Ro60-0175 blocks the burst-firing of mesolimbic DA neurons, which project from the ventral tegmental area (VTA) to the nucleus acc
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Having taken a step back from affinity
2024-11-19
Having taken a step back from affinity to gain better exposure and solubility, we started work to replace the unstable oxazolinone, and address the selectivity over the hERG channel. Keeping in mind the binding mode of the series from crystal structures, triazole was identified as another mildly aci
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It has also been reported that defects in ATM
2024-11-19
It has also been reported that defects in ATM or ATR signalling are synthetically lethal with PARP inhibition (Turner et al., 2008, Peasland et al., 2011, Yap et al., 2011, Michels et al., 2014), suggesting that combined inhibition of PARP and ATM or ATR may be an effective therapeutic strategy. In
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Several structural classes of ASK inhibitors mostly from
2024-11-19
Several structural Demethoxycurcumin of ASK1 inhibitors, mostly from industry but also from academia, have been identified over the last decade. In 2012, Terao et al. (Takeda) reported imidazo[1,2-α]pyridine () as a potent ASK1 inhibitor derived from structure-based drug design. GSK, Merck and Gil
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