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About epilepsy no specific seizure type has been identified
2021-09-13

About epilepsy, no specific seizure type has been identified because GLUT1-DS is associated with a wide range of epilepsies: patients develop seizures in infancy and early childhood, which are, frequently, do not respond to anticonvulsant medication. In infants, seizures are described as brief, subt
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The widespread involvement of HH GLI in
2021-09-13

The widespread involvement of HH/GLI in human malignancies has initiated a remarkable effort to identify selective HPIs. As shown in Table 2.1, most of these small molecule inhibitors target the essential effector protein SMO, which should lead to pathway abrogation by eventually decreasing the GLIA
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We speculated modulation of redox
2021-09-13

We speculated modulation of redox balance in brain, by activation of GIP receptor pathway. QA is known to mediate production of ROS, lipid peroxidation by its interactions with Fe2+ and formation of QA-Fe2+ complex (Braidy et al., 2010, Rios and Santamaria, 1991, Stipek et al., 1997). QA induces NOS
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EPZ004777 australia Conversely we find that dysfunction
2021-09-13

Conversely, we find that dysfunction in lysosomal-autophagy system observed in human APP and PSEN1 mutant neurons can be reversed by β-secretase inhibition, which reduces the supply of APP-β-CTF to the late endosome and/or lysosome (Jiang et al., 2010). These data argue that accumulation and/or alte
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Clinical trials of all GSIs have ended prematurely
2021-09-13

Clinical trials of all GSIs have ended prematurely, raising the question on our understanding of their target, the γ-secretase/presenilin. Development of compounds to target γ-secretase and reduce Aβ production is complicated by the fact that γ-secretase/presenilin has critical biological function,
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Inflammatory pain is very common in the clinic A
2021-09-13

Inflammatory pain is very common in the clinic. A study demonstrated that galanin was upregulated after nerve injury or inflammation (Ma and Bisby, 1997). It has been reported that galanin plays an important role in the transmission of nociceptive information in the spinal cord of rats with inflamma
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Many investigators have noted structural similarities betwee
2021-09-13

Many investigators have noted structural similarities between certain flavonoids and benzodiazepines, such as diazepam, that are the most widely studied positive modulators of GABAA receptors. Benzodiazepines can act on these receptors via ‘two distinct and separable mechanisms’ (Walters, Hadley, Mo
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TXNIP interacts with various proteins including NLRP Yoshiha
2021-09-13

TXNIP interacts with various proteins, including NLRP3 (Yoshihara et al., 2014, Zhou et al., 2010). Emerging evidence suggests that TXNIP plays a role in ER stress-mediated cell death and in the NLRP3 inflammasome activation step (Abderrazak et al., 2015, Lerner et al., 2012, Oslowski et al., 2012,
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In the present studies we found
2021-09-13

In the present studies, we found that genistein did not antagonize fMLF-induced Ca2+ mobilization in FPR1-HL60 VO-Ohpic trihydrate and human neutrophils. Thus, the previously reported inhibitory effect of genistein on fMLF-stimulated degranulation, aggregation, and reactive oxygen species (ROS) prod
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Factor Xa FXa has emerged as a particularly promising
2021-09-13

Factor Xa (FXa) has emerged as a particularly promising target for the development of effective anticoagulant drugs because FXa acts at the convergence point of the extrinsic and intrinsic coagulation pathways. It efficiently catalyzes the conversion of prothrombin to thrombin with one molecule of F
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Mitochondrial is the main source for
2021-09-13

Mitochondrial is the main source for ROS and ATP generation, and the loss of mitochondrial membrane potential is involved in the alteration of mitochondrial metabolism and mitochondrial failure-induced cell death [33,34]. In this study, we showed that upregulated ZNF32 sustained mitochondrial membra
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br Heme oxygenase inhibitors Historically the first class
2021-09-11

Heme oxygenase-1 inhibitors Historically, the first class of competitive HO-1 inhibitors was represented by MPs, heme analogs in which the central iron UCM05 of heme is exchanged by another element, such as zinc, cobalt, tin, or chromium. These molecules compete with heme for binding to the enzy
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We have previously reported on the effects of replacing
2021-09-11

We have previously reported on the effects of replacing the isoquinoline P2∗ moiety with a naphthalene ring and modifying the connectivity for this element to the P2 proline ring, as demonstrated by compounds – (). Therein, it was hypothesized that the reduced potency observed with – when compared t
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br Conclusions br Conflicts of Interest br Introduction Myal
2021-09-11

Conclusions Conflicts of Interest Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem illness of unconfirmed cause. ME/CFS has largely been diagnosed from Fukuda CFS criteria and/or the Canadian ME/CFS criteria. The Institute of Medicine in 2015
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br Advanced Glycation Endproducts As glucose levels rise
2021-09-11

Advanced Glycation Endproducts As glucose levels rise within sensory neurons as a result of hyperglycemia, normal metabolic pathways become overwhelmed and excess glucose is shunted into other ancillary pathways that, under these conditions, become damaging. One consequence of hyperglycemia is th
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