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The second approach to optimizing
2022-07-15
The second approach to optimizing microsomal stability in this series involved the strategic positioning of steric bulk along the tether as a means of encumbering the access of oxidative enzymes to the methylene bridge. This approach has been employed in other P2-P4 macrocyclic inhibitors of NS3/4A
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Hepatitis C virus HCV is a
2022-07-15
Hepatitis C virus (HCV) is a frequent cause of infectious chronic hepatitis. Unlike hepatitis A and B, there is no vaccine to prevent hepatitis C infection yet. According to WHO, around 200 million people are infected with HCV worldwide [1], in addition to three to four million newly infected patien
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It has been known for some
2022-07-15
It has been known for some time that an oral salt load given to mammals induces a much greater natriuresis than the intravenous administration of an equivalent amount of saline (Carey et al., 1976, Singer et al., 1998). In addition, oral administration of salt to rats has been reported to augmented
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The use of antiinflammatory agents has been suggested as
2022-07-15
The use of antiinflammatory agents has been suggested as a potential treatment in HF. One strategy targeted tumor necrosis factor (TNF) in HF,, but the negative results of the clinical trials have been discouraging., Other clinical trials have attempted to suppress proinflammatory cytokine product
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Glycogen synthase kinase GSK is an evolutionarily
2022-07-15
Glycogen synthase kinase-3β (GSK-3β) is an evolutionarily conserved serine/threonine kinase that plays multifaceted role in diverse cellular and neurophysiological processes [8]. GSK-3β is regulated by inhibitory serine and stimulatory tyrosine phosphorylation on Ser9 and Tyr216 respectively [9]. Dy
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br Materials and methods br Results br Discussion In this
2022-07-15
Materials and methods Results Discussion In this study, we demonstrated that zaprinast (a cGMP-PDE inhibitor) induced the intracellular calcium mobilization in the ciprofloxacin australia coexpressing GPR35 and Gqi5, Gqo5, or Gα16. Induction of intracellular calcium mobilization by zaprina
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br Discussion Our findings indicated that starting ART
2022-07-15
Discussion Our findings indicated that starting ART for asymptomatic HIV-infected pregnant women before their CD4 count falls below 500cells/mm3 is beneficial for CD4 normalization (CD4 recovery to 750cells/mm3 or more) in resource-limited settings. Women who started ART at lower baseline CD4 cou
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To overcome these limitations investigators have developed
2022-07-15
To overcome these limitations, investigators have developed novel strategies for identifying and purifying gonadotropes from transgenic mouse models. For example, FSH-producing gonadotropes have been tagged in vivo with a transgenic cell surface antigen (H-2Kk) so that they can be purified in vitro
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GnRH ant have been designed to obtain
2022-07-15
GnRH-ant have been designed to obtain pharmacological compounds to block the pituitary–gonadal axis without the undesirable flare effect exerted by GnRH itself or by the GnRH-a (see Section 2.2). GnRH-ant competitively block the binding of GnRH to GnRHRs (Schally, 1999; Tan & Bukulmez, 2011); they p
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Due to the therapeutic potential of GlyT inhibitors numerous
2022-07-15
Due to the therapeutic potential of GlyT1 inhibitors, numerous drug screening campaigns have been started - and are still going on - which aimed at the identification of compounds with biological activity at or affinity for this drug target. For characterization of biological activity at GlyT1, tran
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br Introduction Depression is a prevalent and disabling psyc
2022-07-14
Introduction Depression is a prevalent and disabling psychiatric illness that affects millions of individuals worldwide, resulting in enormous personal suffering and public health costs [1]. Traditional antidepressants such as monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake
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Human Glucocorticoid Receptor hGR was first cloned in Hollen
2022-07-14
Human Glucocorticoid Receptor (hGR) was first cloned in 1985 (Hollenburg et al., 1985). It is a modular protein comprised of an N-terminal trans-activating domain (NTD), a C-terminal ligand-binding domain (LBD) and a central DNA- binding domain (DBD). The DBD is highly conserved and has two zinc fin
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The genes for the receptors for peptides similar
2022-07-14
The genes for the receptors for peptides similar to glucagon are dispersed on three human chromosomes, with two on chromosome 17 (GCGR and GLP2R) and one each on chromosomes 6 (GLP1R) and 19 (GIPR) (see Table S1). The exon–intron gene structures of these genes are similar, as are the genes for other
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br Introduction G protein coupled receptors GPCRs represent
2022-07-14
Introduction G-protein coupled receptors (GPCRs) represent one of the largest family of receptors involved in cell membrane signal transduction and have become one of the leading therapeutic targets worldwide (Chakraborty and Chattopadhyay, 2015; Bouvier, 2001; Sriram and Insel, 2018). GPCRs sign
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br Conclusions There are a number of
2022-07-14
Conclusions There are a number of factors that affect the transit of solutes through gap junction channels. Fig. 4 provides a simplified illustration of those factors. First is the cytoplasmic vestibule through which all permeable solutes must pass to gain access to the pore. In an equivalent cir
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