• nmda receptor ALK fusion positive NSCLC is clinically action

  2023-05-24

  

  ALK fusion-positive NSCLC is clinically actionable because it can be targeted by several FDA-approved drugs, including the first generation TKI crizotinib, which is a dual inhibitor to MET and ALK [15], and the second generation inhibitors, alectinib and ceritinib, both of which are highly-selective

• To guide our attempts at achieving AKT potency

  2023-05-24

  

  To guide our attempts at achieving AKT potency and selectivity against p70S6K and other kinases from (p70 S6K IC: 0.004 μM) and , we took advantage of exploiting the subtle sequence differences in the active sites of the AGC family kinases, we utilized the information around crystal structure of AKT

• The results of cell culture models were

  2023-05-24

  

  The results of cell culture models were further supported by in vivo studies in mice treated with PXR and/or AhR agonists, PCN and β-NF. In these mice, AhR-regulated cyp1a1, and cyp1a2 were suppressed by PXR activation as determined by real time Q-PCR (Fig. 3). The level of PXR mRNA was not changed

• Pregnane X receptor PXR is a nuclear receptor that plays

  2023-05-24

  

  Pregnane X receptor (PXR) is a nuclear receptor that plays an important role in regulation of metabolism and disposition of structurally diverse xenobiotics as well as endogenous steroids and bile acids (Bertilsson et al., 1998, Kliewer et al., 1998, Lehmann et al., 1998). PXR regulates the metaboli

• Unlike in humans hepatic expression of

  2023-05-24

  

  Unlike in humans, hepatic expression of FGF21 increases in mice consuming KD and is a necessary mediator of the physiologic adaptations to the diet. FGF21 knockout (KO) mice gain, rather than lose weight on the diet [6]. FGF21 also activates BAT in part by increasing SNS drive [3,7]. In addition, th

• Medium spiny neurons MSNs in the striatum start from

  2023-05-24

  

  Medium spiny neurons (MSNs) in the striatum start from a deeply hyperpolarized resting membrane potential, slowly depolarize and show a delayed start of firing during a current injection (Kawaguchi, 1993, Nisenbaum and Wilson, 1995, Planert et al., 2013). The firing pattern during the current inject

• The hypothalamic pituitary adrenal HPA axis

  2023-05-24

  

  The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that is central to regulating responses to stress (Palazidou, 2012). In older persons, a high dysfunction of the HPA axis is observed (Otte et al., 2005) which may be enhanced by stimulatory effects of genes involved in the axi

• NSAIDs induce gastrointestinal toxicity and evoke asthma

  2023-05-24

  

  NSAIDs induce gastrointestinal toxicity and evoke natural aromatase inhibitors by decreasing the production of gastroprotective prostanoids and by redirecting the COX substrate AA into LT biosynthesis, thereby causing vasoconstriction in gastric mucosa and airways (Celotti and Laufer, 2001; Koeberle

• Chronic inflammation is associated with both

  2023-05-24

  

  Chronic inflammation is associated with both initiation and progression of many neoplastic conditions [149], and ATX may be a player in the process. ATX/LPA signaling is positively correlated with the invasive and metastatic potential of several cancers including melanoma, breast cancer, ovarian can

• br Experimental section br Competing interests br Author s

  2023-05-24

  

  Experimental section Competing interests Author's contributions Acknowledgement This research is partially supported by a seed fund for the Center for Drug Discovery and Translational Research (LS) and a research grant by Fujifilm (VPS and LS). The Sponsors played no roles in study desig

• In previous years evidence emerged that inferred

  2023-05-24

  

  In previous years, evidence emerged that inferred secondary metabolites in plants might exhibit a potential arginase inhibition [36]. In a recent study, Pham and co-workers showed the inhibitory activity of chlorogenic (-)-p-Bromotetramisole Oxalate (7) and piceatannol (8) (Fig. 3b) on mammalian ar

• br Introduction Hepatocellular carcinoma HCC is an

  2023-05-24

  

  Introduction Hepatocellular carcinoma (HCC) is an aggressive and malignant cancer detected in clinical practice, as it is the third key reason of tumor-related deaths worldwide, with > 800, 000 mortalities every year (Torre et al., 2015). Current treatments for HCC are surgical therapy, liver tra

• br Does TIPARP contribute to the diverse species

  2023-05-17

  

  Does TIPARP contribute to the diverse species sensitivity to TCDD toxicity? In chick embryo hepatocytes TIPARP was reported to mediate the TCDD-dependent suppression of hepatic gluconeogenesis, by reducing cellular NAD+ levels and reducing PCK1 expression, suggesting that ADP-ribosylation enhance

• The srd a isoforms showed unique

  2023-05-17

  

  The srd5a isoforms showed unique expression profiles in early FHM development (Fig. 2). Similar to amphibian embryos, there was a high abundance of both srd5a1 and srd5a3 at 1dpf in FHMs, suggesting that mRNA for these enzymes may be maternally deposited and that these enzymes may play a key role in

• Because LTs are proved to mediate multiple biological and

  2023-05-17

  

  Because LTs are proved to mediate multiple biological and pathological responses in various disease states, the 5-LO biosynthetic pathway producing LTs from AA have been the target of drug discovery efforts for over two decades. As observed from literature, a pile of research efforts has been direct

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