• br Acknowledgments We thank Dr Kathleen Sullivan of Merck

  2022-01-26

  

  Acknowledgments We thank Dr Kathleen Sullivan of Merck Research Laboratories for providing the CHO-K1 nor-NOHA acetate expressing an NFAT-β-lactamase reporter and the Gα subunit Gqi5, Dr. Chen Liaw (Arena Pharmaceutical), Ms. Rebecca Kaplan, Mr. Frank Xiaodong Gan for technical assistance, Dr. A

• Pleuromutilin We have previously established the pharmacokin

  2022-01-26

  

  We have previously established the pharmacokinetic profile and effective dose of MNF in the rat [43] and demonstrated the effectiveness of MNF as an anticancer drug in Pleuromutilin and xenograft models [44]. Moreover, MNF was found to effectively block GPR55 signaling in tumor cells [21]. The comp

• br GR Is a Transcriptional Activator How GR

  2022-01-25

  

  GR Is a Transcriptional Activator How GR activates some genes while repressing others remains unsettled after decades of study. While significant controversy exists regarding GR-mediated repression, a consensus model for transcriptional activation has emerged: GR activates transcription through s

• Remarkably most of these molecules are also quite effective

  2022-01-25

  

  Remarkably, most of these molecules are also quite effective in interfering with the proliferation of the drug-resistant cancer cell lines, with IC50 values ranging from 0.59 to 2.93 μM against MCF-7/ADR cells, and from 0.160 to 1.17 μM against NSCLC-resistant H1975 cells. Among these molecules, com

• br Experimental procedures br Results br Discussion The data

  2022-01-25

  

  Experimental procedures Results Discussion The data herein confirm the well documented neuroinflammatory effect of TLR3 activation following systemic administration of the viral mimetic poly I:C and the associated acute sickness response which includes fever, reduced body weight and allodyn

• br STAR Methods br Acknowledgments We thank the

  2022-01-25

  

  STAR★Methods Acknowledgments We thank the Shanghai Synchrotron Radiation Facility (SSRF) BL18U for help with X-ray data collection. We thank Dr. Thomas F.J. Martin for providing the pcDNA3.1-CAPS-1 plasmid and Dr. Xiaofei Yang for providing the pFHUUIG_shortU6 (l309) plasmid. We thank Dr. Shun

• TLRs were originally identified as pathogen associated molec

  2022-01-25

  

  TLRs were originally identified as pathogen-associated molecular pattern recognition receptors that recognized exogenous ligands in response to infection [31]. In cirrhotic mice or patients, the gastrointestinal tract produces and absorbs considerable bacterial LPS with increased permeability of the

• The increased levels of proinflammatory cytokines in BALF ar

  2022-01-25

  

  The increased levels of proinflammatory cytokines in BALF are noted during ALI/ARDS, and the persistent elevation of these mediators may exaggerate systemic or focal inflammatory reaction with a worse outcome. These cytokines, particularly TNF-α and IL-6, play essential roles in ALI [16,17]. The ove

• ML-291 Intestinal epithelium renewal is tightly controlled b

  2022-01-25

  

  Intestinal epithelium renewal is tightly controlled by Hedgehog genes. Three Hedgehog genes are highly conserved in mouse and human, including Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh) [13]. Hedgehogs bind to Patched (PTCH) [[14], [15], [16]], which unlike conventional r

• br Direct effect of HDACs on contractile function by

  2022-01-25

  

  Direct effect of HDACs on contractile function by deacetylating cytoskeletal and contractile proteins Role of HDACs in electropathology by transcriptional reprogramming Next to deacetylation of α-tubulin by HDAC6 in experimental and human AF, there is also evidence for transcriptional reprogra

• As indicated by the wide variety of pharmaceuticals for

  2022-01-25

  

  As indicated by the wide variety of pharmaceuticals for IOP management (Table 1), each case of glaucoma is unique and requires a unique treatment regimen to effectively lower IOP. This often results in patients utilizing several medications at once and/or combining medications with surgical interven

• Like tBHQ and DEM treatment of Keap

  2022-01-25

  

  Like tBHQ and DEM, treatment of Keap1+/+ MEFs with SFN increased the abundance of Hmox1 and Nqo1 mRNA, and this was blunted by LY294002 and MK-2206 (Figure 2C). However, unlike the situation with tBHQ and DEM, treatment of Keap1−/− MEFs with SFN did not increase further the elevated basal levels of

• Finally we investigated increasing basicity as a way to

  2022-01-25

  

  Finally, we investigated increasing basicity as a way to improve solubility. We expected that conversion of the ether linkage of to an -methyl group could improve solubility. More than expected, A 205804 demonstrated significant improvement of values of solubility for the two media, especially fo

• Gene expression of both GPR A

  2022-01-25

  

  Gene expression of both GPR109A and GPR81 in adipocytes has been linked to PPARγ activation [22]. Treatment with the thiazolidinedione (TZD) PPARγ agonist, rosiglitazone, increases GPR109A and GPR81 expression, and knockdown of PPARγ suppresses receptor expression in fully differentiated human multi

• How changes in APP processing by

  2022-01-24

  

  How changes in APP processing by γ-secretase lead to AD is still not well understood. Deposition of amyloid beta (Aβ) peptide fragments of the amyloid precursor protein (APP) in amyloid plaques and hyperphosphorylated tau in neurofibrillary tangles are the cellular hallmarks of AD (O’Brien and Wong,

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