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Aconitase clusters are prone to oxidations and are
2024-10-26
Aconitase clusters are prone to oxidations and are among the first to undergo a change in transition state during stages of electrophilic stress rendering them inactive [31]. Aconitase activity in LETO and OLETF did not differ at T0 suggesting that the early onset of insulin resistance may not be at
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Structural and functional imaging studies
2024-10-26
Structural and functional imaging studies searching for specific cortical areas related to each cognitive function domain have provided clues to the spreading patterns of cognitive dysfunction (Domoto-Reilly et al., 2012, Firbank et al., 2016, Li et al., 2012, Machulda et al., 2003, Mandal et al., 2
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In pancreatic islets we found
2024-10-26
In pancreatic islets we found an increase in protein expression of leukocyte 12/15-LO that paralleled the metabolic decline characterized by severe hyperglycemia and reduced islet numbers. Similar increase in 12/15-LO expression by Western blot was found in the control mice, which have a normal meta
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The lactam emerged as lead candidate due to
2024-10-26
The lactam (6) emerged as lead candidate due to its high selectivity, outstanding potency (against ALK or in clinically known ALK mutants), low in vitro clearance, and low efflux potential. The lactam (6) was selected for further profiling against the resistant ALK mutants. Preclinical rat pharmacok
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In the vasculature it is known that A A and
2024-10-26
In the vasculature, it is known that A2A and A2B adenosine receptors are stimulatory for adenylyl-cyclase, leading to cyclic-AMP (cAMP) production and vasodilation, while the A1 and A3 adenosine receptors are linked to the inhibitory Gi, suppressing adenylyl-cyclase and favoring contraction. However
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AdipoRon is an orally active synthetic small molecule that
2024-10-26
AdipoRon is an orally active, synthetic small molecule that activates adiponectin receptor (AdipoR). It mimics the antidiabetic effects of adiponectin, exhibiting its effect through the activation of AMPK and PPARα pathways via AdipoR1 and AdipoR2, respectively (Fig. 2) [62]. AdipoR activation has r
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gp120 Inactivation of the proton pump comes with
2024-10-25
Inactivation of the proton pump comes with luminal alkalinization of the targeted vesicles such as lysosomes (Fig. 2b). Lysosome pH can also be raised stoichiometrically by addition of a membrane-permeable weak gp120 such as methylamine or chloroquine which accumulates in its protonated, non-membran
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ATP citrate lyase ACLY is a cytosolic enzyme that catalyzes
2024-10-25
ATP citrate lyase (ACLY) is a cytosolic enzyme that catalyzes the generation of acetyl-CoA from citrate [15]. Acetyl-CoA is the building block for the biosynthesis of fatty acids and cholesterol, and also serves as a substrate of the acetylation reaction of various molecules, including histones and
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Fig summarizes the oxidative metabolism
2024-10-25
Fig. 1 summarizes the oxidative metabolism of arachidonic Z-DQMD-FMK by lipoxygenases cyclooxygenases and cytochrome P450. Lipoxygenases in humans are expressed in a tissue-specific fashion: 5-LOX is mainly expressed in leukocytes, 12-LOX in platelets, and 15-LOX-1 in reticulocytes, eosinophils, an
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A unique finding in this study is that LO influences
2024-10-25
A unique finding in this study is that 12/15-LO influences CREB phosphorylation in the murine brain. While previous reports have found that knockout of 5-lipoxygenase, a related enzyme that also uses arachidonic cdc42 inhibitor for substrate, can regulate CREB phosphoryation in the context of Alzhei
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There is a delicate balance between ROS generation
2024-10-25
There is a delicate balance between ROS generation and scavenging by the protective antioxidant defenses in the cell. Antioxidant systems present in the herpes simplex virus type 1 include enzymes like superoxide dismutase (SOD), catalases, glutathione peroxidases (GPxs) and peroxiredoxins (PRxs) (
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Although little is known about the etiopathogenesis of preec
2024-10-25
Although little is known about the etiopathogenesis of preeclampsia, this syndrome has a major impact on maternal and fetal health worldwide, since it is responsible for 10–15% of maternal deaths [16], [17], preterm births, intrauterine growth restriction (IUGR), and fetal deaths [2]. In developing
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br Introduction Heart Failure HF is a major
2024-10-25
Introduction Heart Failure (HF) is a major and growing health challenge in India and the developing countries. It is one of the most important causes of morbidity and mortality in the industrialized world. The incidence and prevalence estimates of HF are unreliable in India because of the lack of
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Amyloid fibrils are insoluble high molecular weight non
2024-10-25
Amyloid fibrils are insoluble, high-molecular-weight, non-crystalline aggregates and traditional experimental techniques for structure determination such as X-ray and solution NMR cannot resolve their high resolution structures [64], [68]. However, amyloid fibrils exhibit various advantageous featur
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The RAS may have different functions
2024-10-25
The RAS may have different functions depending on whether we consider the circulatory component or the different local tissue systems (including brain) well described previously [29]. The cardiovascular control and hydroelectrolytic balance (among other functions), are largely the result of the infl
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