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The findings in mice were echoed in the human
2022-05-04

The findings in mice were echoed in the human studies, in which the effects of higher doses of LY3298178 caused greater weight loss than the selective GLP-1RA dulaglutide. In patients with T2DM, LY3298176 demonstrated meaningful weight loss after only four weeks of treatment. This was consistent wit
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br Materials and methods br Results br
2022-05-04

Materials and methods Results Discussion Prior studies established that Notch signaling regulates the differentiation of hair cells and supporting cells during inner ear development (reviewed in Kiernan (2013)). Notch signaling is a multistep process that requires the interaction between a
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To understand the impact of
2022-05-04

To understand the impact of alterations in Rapalink-1 zinc homeostasis, the role of Zn2+ as a neurotransmitter has to be appreciated. Certain regions of the brain including the neocortex and hippocampus harbour so-called “zincergic” (or “gluzinergic”) neurons, where Zn2+ is co-released with glutama
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nefiracetam br Results br Discussion Previous
2022-04-29

Results Discussion Previous studies have shown that all the components of ET system are expressed by various neuronal and non-neuronal structures throughout the CNS (McCumber et al., 1990; Giaid et al., 1991). In effect, endothelin-converting enzyme activity, mRNA, ET-1 and ET-3 immunoreactivi
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Fig illustrates the different signaling pathways elicited
2022-04-29

Fig. 1 illustrates the different signaling pathways elicited or modulated by H3R activation. Collectively, the modulation of the release of histamine and other neurotransmitters through H3R activation could be linked to several neurological disorders such as sleep disorders like narcolepsy, Alzheime
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Experimental conditions may be critical to explain one model
2022-04-29

Experimental conditions may be critical to explain one model or the other. The matter of Hippo-driven cytoplasmic sequestration (Varelas et al., 2008) of active SMAD complexes (Varelas et al., 2008) vs. TßR basolateral relocalization upon epithelial polarization (Nallet-Staub et al., 2015) as mechan
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MAP Ks act at the level of
2022-04-29

MAP4Ks act at the level of MST1/2 to phosphorylate LATS1/2 and regulate the Hippo pathway (Box 1). Of particular interest is the involvement of MAP4K4, a key metabolic regulator [88] and common polymorphisms in the MAP4K4 locus are associated with T2D and insulin resistance [89] in adipogenesis. In
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br Statistical analysis The mean standard
2022-04-29

Statistical analysis The mean, standard deviation, median, range, frequency, and percentage were used for data description. The chi-square (x2) test was used for analyses the differences in categorical variables in the 2-way table. Overall survival (OS) was defined as the time interval between t
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br Conclusions br Acknowledgements This work was
2022-04-29

Conclusions Acknowledgements This work was supported by grants from the Polish National Science Center: 2014/14/E/NZ1/00139 (to A. Jazwa-Kusior) and 2015/17/N/NZ1/00041 (to M. Tomczyk) and National Centre for Research and Development (STRATEGMED2/269415/11/NCBR/2015) (to J. Dulak). Faculty of
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Given the overexpression of HO in some
2022-04-29

Given the overexpression of HO-1 in some tumors, such as CML, and its potential involvement in chemoresistance to classical chemotherapeutic agents, compounds 4 and 8f were tested in CML cell lines resistant to IM, a classical TK inhibitor used in CML. Compounds 4 and 8f, in combination with IM, sho
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In the Hedgehog signaling pathway cholesterol is required to
2022-04-29

In the Hedgehog signaling pathway, cholesterol is required to activate SMO (Cooper et al., 2003), the downstream target of PTCH1. A previous study (Bidet et al., 2011) reported that Patched expression in yeast p 00 mg increased extrusion of a fluorescent boron dipyromethanene sterol derivative (BODI
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BMS 195614 Epigenetic drugs such as HDAC inhibitors regulate
2022-04-29

Epigenetic drugs, such as HDAC inhibitors, regulate gene expression by affecting the activity of histone or DNA modifying enzymes and their associated transcriptional response [141]. BET bromodomain protein inhibition is another epigenetic approach for blocking the Hedgehog pathway at the downstream
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Our overall goal is to develop selective compounds
2022-04-26

Our overall goal is to develop selective compounds for low-affinity/high-capacity transporters inhibitors (i.e. OCT1–3 and PMAT), and provide the field with much needed, specific pharmacological tools to study these transporters. In our initial efforts, we synthesized halogen substituted analogs and
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Ghrelin readily crosses the blood brain barrier
2022-04-25

Ghrelin readily crosses the blood Amoxapine barrier (Banks et al., 2002, Banks et al., 2008), and recent studies have identified central nervous system sites of action for ghrelin-mediated appetite and hyperphagia (Alvarez-Crespo et al., 2012, King et al., 2011, Schele et al., 2016, Skibicka et al.
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Most of the above mechanisms are implicated in
2022-04-25

Most of the above mechanisms are implicated in attenuation of myocardial I/R injury. However, the role of GalR2 receptor activation in cardioprotection remains unclear because of the lack of receptor subtype selectivity of peptides G2 and G3. It has been shown that Ala5-galanin (2–11) (G4) has a hig
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