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The regulation of the stem
2022-03-29
The regulation of the stem cell compartment in CML is dynamic, in particular, during disease progression to a blast crisis and might involve a complex cross-regulation of Hh, Wnt, Notch, and hox signaling pathways (). Significant upregulation of Ptch1 and cyclin D1, upon other proteins, marks the bl
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To directly address whether pharmacological attenuation
2022-03-29
To directly address whether pharmacological attenuation of physiological GIP provides therapeutic benefits in obese mice, we pursued a selective long-acting antagonist to complement the work we report on GIPR agonism. We report a GIP analog of sufficient aqueous solubility that employs a shortened N
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br Materials and methods br Results
2022-03-29
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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3466 A group of small molecule with a more promising therape
2022-03-29
A group of small molecule with a more promising therapeutic mechanism are known as γ-secretase modulators (GSMs), which modulate the cleavage activity of γ-secretase (and likely a host of other substrates) and specifically reduce the levels of the fibrillogenic Aβ42 peptide without altering the ε-si
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The overall decrease in consummatory drive
2022-03-29
The overall decrease in consummatory drive seen in rodents treated with naltrexone in previous studies is in accordance with the effects seen with mice treated with SNAP 37889 in this study. While it may seem inappropriate to use a broad-acting drug like SNAP 37889 that suppresses overall consummato
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We hypothesize that HBO increases GABA activity
2022-03-29
We hypothesize that HBO2 increases GABA activity at the GABAA receptor via a nitric oxide dependent mechanism. Blotting for the phosphorylated β3 subunit of the GABAA receptor should theoretically be increased when there is more GABA activity at the receptor (McDonald et al., 1998). We expected that
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Encouraged by the observation obtained from
2022-03-29
Encouraged by the observation obtained from region A, we selected the structure of 1 as the next template to successively pursue the SAR on regions B-D of 1 (lower side of Fig. 2). Next, we turned attention to the external aromatic ring of 1 to verify the impact on the antagonistic activity and prep
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OCA has recently been approved for the
2022-03-29
OCA has recently been approved for the treatment of patients with PBC and is under study for diseases such as NASH, PSC and biliary atresia [30], [49]. Up to now, the beneficial effects of OCA have been related to its anti-cholestatic, anti-inflammatory and anti-fibrotic properties. We have here rep
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In the light of the above mentioned considerations it is
2022-03-29
In the light of the above-mentioned considerations, it is interesting to note that the FPR-related research with regards to bias agonism did not prosper during considerably during the last decade (possible exceptions are [[8], [9], [10], [11]]. However, with new insights in receptor chemistry and fu
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br Significance Metabolites present in the extracellular env
2022-03-29
Significance Metabolites present in the extracellular environment can potently modulate cellular phenotypes and potentially serve as therapeutics for various diseases. Ferroptosis is a non-apoptotic cell death process characterized by the generation of toxic lipid reactive oxygen species (ROS). I
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Acetylation of histones by histone acetyltransferases stimul
2022-03-28
Acetylation of histones by histone acetyltransferases stimulates gene expression by relaxing Dextran sulfate sodium salt mg structure, allowing access of transcription factors to DNA, whereas deacetylation of histones by histone deacetylases promotes chromatin condensation and transcriptional repres
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In tumor cells HK II induction is mediated
2022-03-28
In tumor cells HK-II induction is mediated by Akt/mTOR pathway [6], [11]. HK-II dynamically shuttles between the mitochondria and cytoplasm under different metabolic conditions. In cardiomyocytes, Akt enhances HK-II binding to mitochondria, setting the heart at a state resistant to ischemic injury [
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HER genotype was determined in breast cancer tissue of
2022-03-28
HER2 genotype was determined in breast cancer tissue of 73 breast cancer patients. As previously reported, Ile655Val and Ala1170Pro genotypes measured in breast cancer tissues were available for 71 and 69 breast cancer patients, respectively. Briefly, 77.5% (55/71) of patients were homozygous for th
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The rationale for developing HDACi as anticancer agents was
2022-03-28
The rationale for developing HDACi as anticancer agents was based on their ability to induce the hyperacetylation of histones and nonhistone proteins, resulting in increased differentiation, apoptosis, and Tideglusib arrest of cancer cells 1, 2, 3. HDACi have been used in the treatment of hematolog
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Heavy alcohol consumption reported by
2022-03-28
Heavy alcohol consumption, reported by three of five referred patients with chronic HCV infection and cirrhosis, is a risk factor for cirrhosis in p.C282Y homozygotes [19], [47] and adults with chronic HCV infection [48]. Although none of the present referred patients were diagnosed to have porphyri
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