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Because sex steroids and growth hormone play
2020-06-05

Because sex steroids and growth hormone play an important role in the development and maintenance of hepatic CYP450 enzyme expression and ER expression, it is possible that exposure to endocrine active agents during gestation and perinatally could alter expression of these proteins. Therefore, these
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Here we discuss implications of
2020-06-05

Here, we discuss implications of several major families of RING-type E3 ubiquitin ligases (MDM, Cullin, GRAIL, TRAF, TRIM) as targets in inflammation and immunity, and provide insights into potential small molecule interventions to mediate the cellular responses (summarized in Table 1). We briefly c
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In the context of E
2020-06-05

In the context of E3 ligase drug discovery, it is critical to identify the appropriate E2/E3 substrate pairing to ensure the development and use of the most physiologically relevant screening assay. There have been many reports of limited E2/E3 activity profiling with a small number of E2 and E3 Exo
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In general cellular senescence is considered a
2020-06-05

In general, cellular senescence is considered a programmed response to stress that can be activated by oxidative stress, irradiation or action of substances or drugs. These stressors cause DNA damage and, through the action of specific proteins (p53 and p21), lead to cell senescence (di Fagagna, 200
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br Acknowledgment This work was supported by the Estonian Sc
2020-06-05

Acknowledgment This work was supported by the Estonian Science Foundation (Grant ETF8862). Introduction In higher eukaryotes ionizing-radiation (IR) induced DNA double-strand breaks (DSB) are primarily repaired by the non-homologous end joining (NHEJ) pathway [1]. Ku, a heterodimeric protein
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iap apoptosis Here we investigate in more detail
2020-06-05

Here we investigate in more detail how Dot1 function contributes to the regulation of DNA damage tolerance. We find that Dot1 modulates the response to the alkylating agent MMS through its catalytic activity on H3K79. In fact, progressively reduced levels of H3K79 tri-methylation result in gradually
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Thus DGK active sites remain ill defined and
2020-06-05

Thus, DGK-active sites remain ill-defined and, combined with the lack of crystal structures for mammalian DGKs, have limited our understanding of substrate and inhibitor binding. As a result, current DGK inhibitors consist of compounds with poor specificity within the DGK superfamily (de Chaffoy de
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The in vivo IC M in the adipose
2020-06-05

The in vivo IC (0.0003μM) in the adipose tissue assay is in very good agreement with the in vitro IC (0.0005μM), and it is larger than the one measured in the OLTT assay (0.00005μM) for this compound. These differences in in vivo IC between OLTT and TAG synthesis are expected as we used free dpp-4 i
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However there are still some issues
2020-06-05

However, there are still some issues that remain poorly understood. For instance, how TGF-β modulates DDR2 expression and whether Smads participate in the regulation. How does DDR2 regulate the expression of PTHrP via Runx2? Is there any other kinase downstream of DDR2 participating in PTHrP regulat
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CysLTs trigger contractile and inflammatory processes throug
2020-06-05

CysLTs trigger contractile and inflammatory processes through the specific interaction with cell surface receptors belonging to the rhodopsin family of the G protein-coupled receptor (GPCR) genes. Until now, two receptor subtypes have been cloned, namely CysLT1 and CysLT2[8]. In particular, when the
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The changes in the chemokine receptors CCR and
2020-06-05

The changes in the chemokine receptors CCR-5 and CXCR-4 in women and men with PTSD are completely different. In the group of women with PTSD alone the level of this Nocodazole increased six times, whereas, in women with APD and PTSD, the level of the receptor CCR-5 was eight times higher than in th
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Mechanistically GW treatment modulated cytokine expression w
2020-06-05

Mechanistically, GW2580 treatment modulated cytokine expression within the kidney. We noted a decrease in the levels of TNF, MCP-1, IL-1β, IL-27, and GM-CSF in GW2580 treated mice. Decreased levels of these proinflammatory cytokines likely contributed to the attenuated proteinuria and improved renal
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Apart from neutrophil mediated inflammation
2020-06-05

Apart from neutrophil-mediated inflammation, the production of pro-inflammatory cytokines and chemokines from PGD2/CRTH2 activated macrophages could further aggravate LPS-induced lung injury (Eguchi et al., 2011; Jandl et al., 2016). Interestingly, genetic ablation of CRTH2 diminishes the TNF-α prod
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The intricate roles and neural
2020-06-05

The intricate roles and neural systems and mechanisms involved in the CRF1 and CRF2 mediation of spontaneous and stress-induced anxiety behavior remain to be defined. Of particular relevance are studies evaluating the behavioral actions of CRF1 and CRF2 receptors separately as well as together. For
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Two major mechanisms including apoptosis
2020-06-05

Two major mechanisms including apoptosis and oxidative stress have been suggested for MTX-induced cytotoxicity (Hafez et al., 2015; Neuman et al., 1999; El-Sheikh et al., 2015). It has been reported that MTX promotes cell death via apoptosis in both cancerous and non-transformed cells (Mazur et al.,
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