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In summary we have successfully identified
2021-11-22
In summary, we have successfully identified a series of potent and selective GSNOR inhibitors having imidazole and tetrazole functional groups in both end of the core structure and many compounds have been identified with IC: low hERG activity, minimal off-target (POR) activity and reasonable oral
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T lymphocytes play an important role in
2021-11-22
T lymphocytes play an important role in cellular and humoral immunity and immune responses (Shin and Iwasaki, 2013; Schenkel and Masopust, 2014). T BQ-123 mature after complex selection and differentiation in the thymus. They can express various membrane proteins, such as CD3, CD4, and CD8 molecule
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Glutamate activates cationic glutamate gated channels i e
2021-11-22
Glutamate activates cationic glutamate-gated channels (i.e. ionotropic glutamate receptors) that mediate the fast excitatory actions of glutamate. It also activate G protein-coupled receptors, named metabotropic glutamate receptors (mGluRs) (Pin and Bettler, 2016). The eight subtypes of mGluRs are k
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Long non coding RNAs lncRNAs are mRNA like transcripts of
2021-11-22
Long non-coding RNAs (lncRNAs) are mRNA-like transcripts of greater than 200 nucleotides (nt), with little or no protein-coding potential [13,14]. LncRNAs have been suggested to participate in transcription and post-transcription regulation as scaffolds, guides, decoys or repressors, activators, and
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Introduction Human pathogenic Leishmania protozoa comprise d
2021-11-22
Introduction Human pathogenic Leishmania protozoa comprise 20 different species that are distributed throughout the world and cause the disease leishmaniasis [1]. Transmission primarily occurs through the bite of a female sand fly and clinical manifestations of the disease span from cutaneous lesio
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The development of metabolic stable non peptidergic galanin
2021-11-22
The development of metabolic stable, non-peptidergic galanin agonists could be the basis to clinical diagnosis and treatment of tumors with high levels of galanin receptor expression like gliomas and pituitary tumors. As for gliomas, penetration of the blood brain barrier by the compounds might be p
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In the course of our ongoing attempts to
2021-11-22
In the course of our ongoing attempts to photolabel allosteric binding sites of γ-aminobutyric all trans retinoic acid synthesis type A (GABAA) receptors, we were met with the need for relatively large (near mg) quantities of recombinant protein. Rather than establishing a stable cell line we sough
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Natural product based drug discovery can
2021-11-22
Natural-product-based drug discovery can be enhanced with computational methods [205]. Because most of the reported small-molecule natural inhibitors of fMLF-induced functional responses were not evaluated in ProteOrange binding assays, we used molecular modeling to predict how well these compounds
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First identified in as the second mammalian
2021-11-22
First identified in 1982 as the second mammalian glutathione peroxidase [23], we and Stockwell's group demonstrated in 2014 that the selenoperoxidase GPX4 is the key upstream regulator of ferroptosis [12], [13]. The role of GPX4 as the main regulator in the ferroptotic process is based on its unique
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Although it is well documented
2021-11-20
Although it is well documented that FAAH substrates can elicit analgesic effects [for review see [47,48] and that systemic poly I:C administration induces mechanical allodynia in rats [14], to our knowledge this is the first study to demonstrate that enhancing FAAH substrate levels can modulate TLR3
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br Materials and methods br Results br Discussion In general
2021-11-20
Materials and methods Results Discussion In general, we have demonstrated that the CRISPR/dCas9-based system, fused with 2 × PP7 and PCP-EZH2, could stably and precisely methylate the H3K27 at specific locus of C/ebpα to silence gene expression and inhibit adipogenic differentiation in 3T3
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More direct evidence of a role for Hat in the
2021-11-20
More direct evidence of a role for Hat1 in the acetylation of newly synthesized histone H4 has come from a number of recent studies that have shown that Hat1 is responsible for at least a portion of the acetylation that occurs on histone H4 lysines 5 and 12 in the pool of cytosolic histones. In chic
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Consistent with other studies on
2021-11-20
Consistent with other studies on the metabolic effects of an OM3 enriched diet [26,104,105], irrespective of gender, the lowest glucose levels were seen in the Bob-Cat groups fed OM3 diet. Sexual dimorphism was observed in insulin levels. The highest average levels were in the HFD fed [Tg(CAT)±] mal
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GnRH receptor GnRH R levels are elevated in decidualized str
2021-11-20
GnRH receptor (GnRH-R) levels are elevated in decidualized stromal cells, suggesting a function for the GnRH–GnRH-R pathway in the early implantation events. Both GnRH and GnRH-R have been shown to be present in preimplantation embryos and the fallopian tubes at both mRNA and protein levels (). Two
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While the apparent complexity of gap junction
2021-11-19
While the apparent complexity of gap junction regulation presents challenges, new technologies continue to propel the field forward. Advances in microscopy are increasingly able to capture rapid dynamics at the plasma membrane (e.g., biosensors [67] and lattice light sheet microscopy [100]) and to d
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