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br Autophagy in the central nervous system
2024-07-01
Autophagy in the central nervous system The autophagic process appears to be very important for the cells of the central nervous system, as it allows to maintain the functional integrity of the nervous tissue. Indeed macroautophagy is involved in the regulation of homeostasis of the CNS, playing
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The identification of novel kinase inhibitor scaffolds
2024-07-01
The identification of novel kinase inhibitor scaffolds is highly desirable in order to develop selective kinase inhibitors. Small-molecule inhibitors of Interleukin-2-inducible T-cell kinase (Itk) that are based on the 3-aminopyridin-2-one fragment 1 have been reported. Despite derivatisation of 1 y
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br Breast cancer The interactions between
2024-07-01
Breast cancer The interactions between 15-LOX and COX enzymes also affect the outcome of breast cancer. Indomethacin, a COX-1 and COX-2 inhibitor, decreased the growth of human breast cancer (BC) cells in nude mice, as well as slowed the rate of lung metastasis formation [41]. The levels of 12-HE
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br STAR Methods br AMPK A
2024-06-28
STAR★Methods AMPK: A Therapeutic Target in the β Cell? Loss of pancreatic β cell function is a hallmark of the transition to a diagnosis of T2DM (see Glossary) 1, 2, 3, 4. AMPK activation has gained attention for the treatment of hyperglycemia in prediabetes as an insulin-sensitizing agent bec
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br Discussion Hepatic dysfunction in
2024-06-28
Discussion Hepatic dysfunction in the metabolic syndrome is a driver of negative patient outcomes that requires more therapeutic options. The complexity of liver alterations in this disease – elevated de novo synthesis of fatty acids and cholesterol, reduced clearance of circulating atherogenic L
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In large biopsies series from ALK NSCLC
2024-06-28
In large biopsies series from ALK+ NSCLC treated patients, the number of detected mutations increased after second generation ALKi (Gainor et al., 2016) and in one study were present in 56% of the entire cohort (Shaw et al., 2013b). For example, the rate of G1202R mutations increases from 2% in post
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MPI-0479605 br Results br Discussion Tapinarof GSK is a
2024-06-28
Results Discussion Tapinarof (GSK2894512) is a naturally derived investigational topical medicine with demonstrated clinical efficacy for patients with AD and psoriasis (Bissonnette et al., 2010, Bissonnette et al., 2012a). The drug substance is a polyphenol produced by bacteria that is struct
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The cavity volume of the
2024-06-28
The cavity volume of the binding pocket may differ not only between species but also among various AhR/ARNT isoforms within a single species. It is noteworthy that even a single amino PYR-41 mg substitution within a binding pocket may result in a change in the cavity volume. This, in turn, may affe
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In addition to plasma membrane sites
2024-06-28
In addition to plasma membrane sites, OCT3 was also observed associated with endomembranes, including mitochondrial membranes, with particularly strong expression in the outer nuclear membranes of both neurons and astrocytes (Gasser et al., 2017), indicating that, in addition to regulating extracell
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am680 Although the effects of adenosine receptor signaling
2024-06-28
Although the effects of adenosine receptor signaling in acute renal IRI have been attributed to the generation of high concentrations of adenosine, we have recently reported an increase in kidney levels of both AMP and adenosine, with a concomitant fall in ATP and ADP. We have also previously demons
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br Introduction Epilepsy is characterized by spontaneous
2024-06-28
Introduction Epilepsy is characterized by spontaneous recurrent seizures and represents one of the most frequent neurological diseases affecting about 60 million people worldwide (McNamara, 1999). It is estimated that up to 50% of all cases are triggered by “initial precipitating injuries”, such
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False positivity of Anti AChR Ab titers due
2024-06-28
False positivity of Anti-AChR Ab titers, due to cross reactivity with bungarotoxin, has previously been demonstrated. One such study reported that patients with amyotrophic lateral sclerosis, who had received long term snake venom therapy, had developed antibodies to bungarotoxin and hence demonstra
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The reaction of LOX with unlabeled AA generated products fro
2024-06-28
The reaction of 5-LOX with unlabeled AA generated products from hydrogen abstraction at C7 (95% 5-HETE) with minor products derived from abstraction at C10 (5% 8-HETE). With 7,7--AA the selectivity remained skewed towards C7 hydrogen abstraction (59%) compared to C10 hydrogen abstraction products (4
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Taken together BRP represents a novel chemotype of LT biosyn
2024-06-28
Taken together, BRP-187 represents a novel chemotype of LT biosynthesis inhibitors with outstanding potency in human PMNL and monocytes activated under pathophysiological relevant conditions and with effectiveness in vivo. Using the PLA that visualizes the in situ interaction between 5-LO and FLAP i
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Aromatization of the pyrrole ring
2024-06-27
Aromatization of the pyrrole ring after anion capturing, using acceptor atoms with electron deficiency (B & Be), and substitution of strong electron withdrawing groups such as CN were three strategies used to design a new class of anion receptors. Comparison of the anion affinities of these anion re
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