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BITC significantly enhanced the gene expression of
2022-12-09
BITC significantly enhanced the gene expression of the Nrf2-dependent genes, such as NQO1 and HO-1 (Fig. 4), as well as the ALDH genes (Fig. 2). Nrf2 is a key transcriptional factor which activates the expression of the genes that contain ARE in their promoter. Nrf2 translocates to the nucleus where
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Many metalloenzyme inhibitors consist of two
2022-12-06
Many metalloenzyme inhibitors consist of two chemical components: the MBG, the portion of the inhibitor designed to bind to the metal, and the scaffold, the portion of the inhibitor recognized by the amino Chlorambucil synthesis residues that form the substrate-binding site of the metalloenzyme. Th
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Having established the structural requirements for
2022-12-06
Having established the structural requirements for potency in both the biochemical and biomarker (CRA) assays, we evaluated key compounds in the metabolic stability assay. Disappointingly, we found that all compounds had high intrinsic clearances in mouse microsomes. To ascertain whether the in vitr
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br Introduction The process of mitosis is
2022-12-06
Introduction The process of mitosis is highly complex and tightly regulated. This phase of the PD 151746 resulted in two identical daughter cells. The aurora kinases (aurora A, B, and C) are a family of three highly homologous serine-threonine protein kinases that play a key role in regulating t
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Lorlatinib is an orally active brain penetrant cyclic
2022-12-02
Lorlatinib is an orally active brain penetrant cyclic 2-aminopyridine derivative that is a type I½ B ALK inhibitor (Fig. 5F) [61]. This medicinal is an effective antagonist against the more common L1196M and G1269A crizotinib-resistant mutations as well as the less common T1151Ins, L1152R, C1156Y, F
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Our published data showed that in mouse heart
2022-12-02
Our published data showed that, in mouse heart, the protein level of WDR1 was highest during the embryonic stage, but became progressively decreased to a constant level from birth to adulthood (Yuan et al., 2014), indicating an important role of WDR1 in embryonic heart development. However, function
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br ACK signaling partners ACK interacts with
2022-12-02
ACK1 signaling partners ACK1 interacts with and tyrosine phosphorylates many cellular proteins regulating critical cellular processes [11]. While ACK1 shares common intracellular effectors such as AKT with other signaling pathways, it imparts specificity to signaling by phosphorylating effectors
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The Kelch like ECH associated protein Keap Nrf signaling
2022-12-02
The Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway functions as one of the key regulator of the cellular defense system against oxidative stress [26]. Nrf2 is a redox-sensitive transcription factor, that is sequestered in the cytoplam by binding to Keap1; however, under oxidative
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br Ataxia telangiectasia and Rad related as
2022-12-02
Ataxia–telangiectasia and Rad3 related as a therapeutic target Several concerns revolving around functional inhibition of ATR have hindered the exploitation of ATR as therapeutic target in cancer therapy and delayed the development of specific ATR kinase inhibitors. It was anticipated that pharma
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Another class of AMPK regulator is
2022-12-02
Another class of AMPK regulator is peptidyl-prolyl cis/trans isomerase (PPIase) NIMA-interacting 1 (Pin1), which binds to a number of proteins and regulates oncogenesis and metabolic diseases (Khanal et al., 2013; Zhou and Lu, 2016). Pin1 has been shown to bind to and inhibit AMPK; therefore, at lea
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br STAR Methods br Author Contributions br Acknowledgments
2022-12-02
STAR★Methods Author Contributions Acknowledgments This study is funded by National Institutes of Health (NIH) Grants NS028901 and DC004450 (to L.O.T.); N.L. Tartar Trust Fellowship (to H.-W.L.); DC014878 to T.S.B. We thank members of the Trussell lab for helpful discussions, Dr. Stephen Dav
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Compelling evidence now indicates that
2022-12-01
Compelling evidence now indicates that DR is a multifactorial disease that involves chronic inflammation at every stage, from initiation to progression and eventually to ischemia and NV [6,7]. Data from animal studies suggest that leukocyte-endothelial cell adhesion and entrapment (leukostasis) are
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According to their structures and substrate specificity
2022-12-01
According to their structures and substrate specificity, MMPs are divided into five major groups: collagenases (e.g., MMP1), gelatinases (e.g., MMP2, MMP9), stromelysins (e.g., MMP3, MMP10), matrilysins (e.g., MMP7), and membrane-type MMPs [7]. Among them, MMP1 is a major collagenase that degrades t
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HT modulates cortical and hippocampal pyramidal cell functio
2022-12-01
5-HT modulates cortical and hippocampal pyramidal cell function in a very complex manner, since most 5-HT receptor subtypes (excitatory as well as inhibitory) are expressed on pyramidal reference 4 as well as GABAergic interneurons that exert inhibitory control over pyramidal cells (Leiser et al.,
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The adult muscle type acetylcholine receptor
2022-12-01
The adult muscle-type zvad fmk receptor (AChR), the exemplar pLGIC, is a heteropentamer comprising two α subunits, and one each of the β, δ, and ɛ subunits (Sine, 2012). These five subunits come together in a counterclockwise α-ɛ-α-δ-β arrangement (Figure 1A). Binding of acetylcholine to the AChR's
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