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Here we report discovery of highly selective pan Aurora kina
2023-11-15
Here we report discovery of highly selective pan-Aurora kinase inhibitors through phenotypic screening. The co-crystal structure of mexiletine hcl bound in the ATP binding site of Aurora A is described, and provides insight into the possible structural basis for the selectivity of the interaction.
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filgotinib The therapeutic potential of ML induced
2023-11-15
The therapeutic potential of ML327-induced MET against filgotinib of mesenchymal origin has not been explored. In the present study, we hypothesized that induction of MET using ML327 would block the growth of ES cells and sensitize to TRAIL-mediated apoptosis. Herein, we report that ML327 induces a
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br The role of apelin in hepatic diseases The involvement
2023-11-15
The role of apelin in hepatic diseases The involvement of the apelin/APJ system in liver physiology and pathology has been proven in numerous studies (Table 6). For instance, in the experiment of Emam et al. [63] on rats suffering from hepatic injury, apelin decreased the levels of ALT, AST and L
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Although apelin g kg shows negative early and positive
2023-11-15
Although apelin 60μg/kg shows negative (early) and positive (late) inotropic effects, since ERK1/2 phosphorylation starts at the min 5 of administration [6], ERK1/2 phosphorylation mediate positive inotropic effects of apelin 60μg/kg. After the simultaneous inhibition of KOR and APJ the phosphoryla
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br Materials and method br Results and discussion
2023-11-15
Materials and method Results and discussion Conclusion The adsorption behaviors of 5 antibiotics on 5 types of microplastic particles were investigated using batch type experiments. Our results showed that adsorption capacities varied among antibiotics, plastic types, and environmental cond
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br Experimental procedures br Results br Discussion Our biop
2023-11-15
Experimental procedures Results Discussion Our biophysical and cellular analyses of mutant Aβ1–42 peptides support a role of the N-terminus of Aβ in peptide aggregation and toxicity. We demonstrate that double mutations constructed to humanize the rodent Aβ1–42 sequence result in a signific
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Immunohistochemistry Hearts from young and aged
2023-11-15
Immunohistochemistry: Hearts from young and aged mice were collected at the indicated times, fixed overnight in 10% formalin, and embedded in paraffin. Serial 5-μm heart sections from each group were analyzed. Samples were stained with H&E for routine histologic examination. Immunohistochemical stai
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br AMPK as a druggable target
2023-11-15
AMPK as a druggable target AMPK signaling has attracted considerable attention within the past decades, owing to the capacity of pharmacological compounds (e.g., 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside [AICAR] and metformin) or natural compounds (e.g., resveratrol) to activate AMPK in
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Recently a Phase III study demonstrated that alectinib the s
2023-11-15
Recently, a Phase III study demonstrated that alectinib, the second-generation ALK inhibitor, might have a better response to ALK-rearrangement patients than crizotinib [10]. Should alectinib replace crizotinib as the frontline treatment for ALK-rearranged patients? Or should those patients be treat
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BITC significantly enhanced the gene expression of
2023-11-15
BITC significantly enhanced the gene expression of the Nrf2-dependent genes, such as NQO1 and HO-1 (Fig. 4), as well as the ALDH genes (Fig. 2). Nrf2 is a key transcriptional factor which activates the expression of the genes that contain ARE in their promoter. Nrf2 translocates to the nucleus where
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Growing evidence indicates that GRKs can exert different eff
2023-11-15
Growing evidence indicates that GRKs can exert different effects within the cell depending on the stimulus, cell type, and localization [97], [121]. In this sense, we were the first to demonstrate a mitochondrial localization for GRK2 [122], later confirmed by other investigators [123], establishing
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Introduction The cytoskeleton allows cells to establish main
2023-11-14
Introduction The cytoskeleton allows cells to establish, maintain and transform their shape. In neurons, these include cell differentiation, migration, polarization and development of their unique arborization. Axons are very thin (~1 μm), long (up to 1m) and highly branched (>95% of the plasma mem
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It is interesting that Li et al
2023-11-14
It is interesting that Li et al. (2008) reported that AChR-immunized FcγRIIB knock out (KO) mice are significantly resistant to antibody-mediated EAMG. This is in contrast with previous studies, but does not contradict the results presented here. Despite their observation that the incidence and seve
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Fluticasone propionate br Materials and methods br
2023-11-14
Materials and methods Results Bilateral microinjections (n = 6) of 10 mM ACh (300–500 pmol) and 5 mM physostigmine (150–250 pmol) at the two selected caudal NTS sites caused within 1 min significant increases in respiratory frequency (from 54.5 ± 1.7 to 70.9 ± 4.1 breaths/min; +30.8 ± 7.0%; P
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Finasteride has been shown to
2023-11-14
Finasteride has been shown to be a mechanism-based inhibitor of 5AR-2 [9]. Finasteride acts as an alternate substrate for 5AR-2 and is initially bound in an extremely stable enzyme-bound NADP-dihydrofinasteride adduct which is ultimately processed to dihydrofinasteride. The NADP-dihydrofinasteride a
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