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Drug resistance development often involves structurally un r
2023-09-13

Drug resistance development often involves structurally un-related drugs and, specifically both conventional and targeted agents. IGROV-1/Pt1 hiv fusion inhibitors are characterized by resistance to cisplatin and reduced sensitivity to inhibitors of EGF-R and MEK, the up-stream activator of ERK1/2,
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br Funding This work was supported by Arena Pharmaceuticals
2023-09-13

Funding This work was supported by Arena Pharmaceuticals, Inc, San Diego, CA, USA. Introduction 5-hydroxytryptamine 1B (5-HT1B) receptors are widely distributed in the central nervous system (CNS); they have various modulatory functions in drug reinforcement, appetitive behaviors, stress, moo
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In earlier experiments on snails a
2023-09-13

In earlier experiments on snails, a behavioral model was employed of certain food rejection to study the mechanisms of the reconsolidation of long-term associative memory. It was found that conditioned food stimuli (reminder) presentation, combined with injections of NMDA glutamate receptor antagoni
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br Clinical realities br Commentary on uses of
2023-09-13

Clinical realities Commentary on uses of selective 17,20 lyase inhibitors If continued monitoring of these same parameters along with tracking of circulating ACTH in human trials confirms these new drugs are the long sought after 17,20 lyase inhibitors, then we may for the first time be able t
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At present drugs that specifically inhibit YAP
2023-09-13

At present, drugs that specifically inhibit YAP activity are not available. In fact, verteporfin, which was originally described as a specific inhibitor of YAP-TEAD interaction, has been recently shown to exert its activity through selective induction of proteotoxicity rather than through YAP inhibi
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We have recently reported a regulatory effect of quercetin
2023-09-13

We have recently reported a regulatory effect of quercetin on the AChE activity in the brainstem during the demyelination and remyelination process [17]. It has also been observed that there is a protective effect on lipid peroxidation and worsening of motor functions caused by loss of myelin in the
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MLN 8237 The downstream targets of ATR involved in mediating
2023-09-13

The downstream targets of ATR involved in mediating human telomerase recruitment have not yet been identified. Under stalled fork conditions, activated ATR is able to phosphorylate and activate ATM (Stiff et al., 2006, and Figures 4C and 4D); whether this MLN 8237 of ATM participates in a positive
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Further validation for a role
2023-09-12

Further validation for a role in 12/15-LOX pathway in mediating adipocyte function comes from studies revealing a regulatory role of lipocalin-2 on 12/15-LOX activity. Lipocalin-2, a glycoprotein member of the lipocalin superfamily, is a novel abundant adipokine implicated in obesity-mediated inflam
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We next developed a system for staging
2023-09-12

We next developed a system for staging severity. Our guiding principles were the following. Two types of information about the research participant are staged independently from each other: (1) grading disease severity using biomarkers and (2) grading the severity of cognitive impairment. Measures u
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The present study determined the effect
2023-09-12

The present study determined the effect of DCA on VSMC calcification in vitro and in atherosclerotic ApoE-/- mice in vivo. We found that Iberin australia non-toxic concentrations of DCA, did not affect VSMC viability, induced calcification of VSMC in culture and increased atherosclerotic vascular c
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Unlike in humans hepatic expression of FGF
2023-09-12

Unlike in humans, hepatic expression of FGF21 increases in mice consuming KD and is a necessary mediator of the physiologic adaptations to the diet. FGF21 knockout (KO) mice gain, rather than lose weight on the diet [6]. FGF21 also activates BAT in part by increasing SNS drive [3,7]. In addition, th
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To validate the identified phosphorylation sites in
2023-09-12

To validate the identified phosphorylation sites in the mouse heart, we analyzed HEK 293T Triptolide transfected with Adrb1 based on the hypothesis that protein residues phosphorylated both in vivo and in vitro are more likely to be physiologically relevant. All of the phosphorylation sites identifi
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br A novel therapeutic strategy based on the APN
2023-09-12

A novel therapeutic strategy based on the APN and obesity paradoxes As shown above, the relationship of the serum APN concentration with health and disease states shows an inverted-U correlation, suggesting that moderate concentrations of serum APN are beneficial (Fig. 3). Given that both hypo- a
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The relatively high concentration of HT
2023-09-12

The relatively high concentration of 5-HT used in this study (100 µM) is consistent with the concentrations used in other published ex vivo studies (Ropert and Guy, 1991, Passani et al., 1994, Shen and Andrade, 1998). In our paradigm 5-HT was focally applied at the surface of the slice via a fast pe
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In summary we could identify and experimentally confirm two
2023-09-12

In summary, we could identify and experimentally confirm two novel SBEs within the 5-LO promoter and we were able to demonstrate that TGFβ and SMADs stimulate 5-LO promoter activity. Moreover, an elevated 5-LO expression has been linked to different forms of leukaemia. Therefore, the influence of ML
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