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IC values were obtained for an expanded version of
2024-09-12

IC50 values were obtained for an expanded version of the fragment library using the previously described mobility shift assay. Subsequently, Ki values were estimated from IC50 values to allow better comparison of the activity against targets which were measured at different substrate concentrations
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Another factor that is involved in the severity
2024-09-12

Another factor that is involved in the severity of EAE is apoptosis signal-regulating kinase 1 (ASK1), which is one of a growing number of mitogen-activated protein kinase (MAPK) kinase kinases identified in the upstream of the c-Jun N-terminal kinase and p38 MAPK pathways [12]. We previously report
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In addition enhanced AT receptor function
2024-09-11

In addition, enhanced AT1 receptor function abnormally increases central and sympathetic activity, contributing to cardiac and renal disease, which in turn alters homeostasis, increases vulnerability to stress, and further injures the brain, and that AT1 receptor blockade ameliorates excessive sympa
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The zinc transporter proteins are members
2024-09-11

The zinc transporter proteins are members of the SLC superfamily of metal transporters, and comprise two structurally and functionally different groups, the zinc-importer (ZIP; Zrt-, Irt-like proteins) family (SLC39A), which regulate zinc transport into the cytoplasm from outside the cell and from i
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Detailed analysis of the dose dependence of A effects reveal
2024-09-11

Detailed analysis of the dose dependence of Aβ effects revealed that at low amounts, Aβ can also act as a positive regulator of presynaptic activity, enhancing the neurotransmitter release probability and increasing the neuronal excitability [2]. The facilitator effects of low Aβ dose on excitatory
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Platelet derived growth factor PDGF
2024-09-11

Platelet-derived growth factor (PDGF) and ciliary neurotrophic factor (CNTF) are expressed by glial 94 8 and are important to neuron survival and the maintenance of oligodendrocytes. These neurotrophic factors contribute to the remyelination process by increasing the proliferation of oligodendrocyt
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br Depletion of serum amino acids Currently the only antican
2024-09-11

Depletion of serum amino acids Currently, the only anticancer agents that directly target amino atp gamma s metabolism are bacterial l-asparaginases (from Escherichia coli and Erwinia chrysanthemi), which are FDA-approved for treatment of pediatric and adult ALL. A potential complication of using
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br Conflict of interest br Introduction
2024-09-11

Conflict of interest Introduction Colorectal cancer (CRC) is one of the major cause of tumor-related morbidity and mortality worldwide. Poor prognosis and consequences of its metastatic spread make CRC the second most common cause of cancer-related deaths in western countries [1]. Apart from o
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To further clarify the vascular cell types
2024-09-11

To further clarify the vascular cell types expressing AR subtypes, double immunofluorescence staining for ARs and vascular endothelial Kaempferol mg or vascular smooth muscles was performed. As shown in Fig. 3, Fig. 4, overlay images show the expression of all ARs subtypes that we examined in vascul
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Endogenous adenosine systems have largely been implicated in
2024-09-11

Endogenous adenosine systems have largely been implicated in drug actions by the demonstration that caffeine (non-selective A1R and A2AR antagonist) (see Section The issue of caffeine), in doses up to 7.5–10mg/kg, inhibits antinociception, and when this occurs, it Calcium Ionophore I synthesis is g
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br AChE variants and their functions
2024-09-11

AChE variants and their functions The AChE gene generates several splice variants of AChE which are designated as hydrophobic (H), readthrough (R) and tailed (T) forms differing in membrane association and also localisation on a tissue and sub-cellular level. They all undergo significant posttran
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br Conflict of interest br Acknowledgements We thank
2024-09-10

Conflict of interest Acknowledgements We thank Ann Jackman, Mike Ormerod and members of Julian Downward's and Alan Ashworth's groups for helpful discussions. This work was supported by grant number PEM/GME/D391/40 from the Kidani Trust (S. Kaye) and by Keele University. Introduction Autota
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In the current study we provide evidence that
2024-09-10

In the current study, we provide evidence that enhanced ATX activity correlates well with increased ATX protein concentration during cholestasis and pregnancy (Fig. 1). Hereby we have ruled out the possibility of ATX enzyme activation in these conditions, e.g. by circulating cholephiles. ATX clearan
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br Acknowledgments br Introduction Cancer is the leading cau
2024-09-10

Acknowledgments Introduction Cancer is the leading cause of mortality in the United States for those between the ages of 40–79 years, surpassing heart diseases by more than 100,000 deaths [1]. The cause of most cancer subtypes remains idiopathic and may arise out of ‘bad luck’ among otherwise
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If the lack of specificity and
2024-09-10

If the lack of specificity and the high pleiotropy may represent a problem in view of the potential chemotherapeutic features of autophagy-inducing agents, it Paxilline may switch into an advantage in the case of chemopreventive strategies. In fact, as non-pharmacologic interventions such as limite
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