• HCV is a highly diverse virus with seven

  2022-02-10

  

  HCV is a highly diverse virus with seven known genotypes (GT1–7) and multiple subtypes (Gower et al., 2014, Messina et al., 2015, Smith et al., 2014). Patients infected with HCV develop a heterogeneous population of viral species known as quasispecies due to low fidelity of the RNA-dependent RNA pol

• GPR has been implicated in neuropathic and

  2022-02-10

  

  GPR55 has been implicated in neuropathic and inflammatory pain (Staton et al., 2008) and bone remodeling (Whyte et al., 2009). Thus delineating the pharmacology of this receptor and the discovery of selective agonists and antagonists merits further study and could lead to new therapeutics. Ackno

• br NMDA receptor LBDs The

  2022-02-10

  

  NMDA receptor LBDs The study of GluA2 was later expanded to include NMDA receptors [22]. NMDA receptors are obligate heterotetramers that are composed of two glutamate-binding subunits and two glycine-, or d-serine-, binding subunits. In this study, crystal structures of the NMDA receptor glycine

• Many investigators have noted structural similarities betwee

  2022-02-09

  

  Many investigators have noted structural similarities between certain flavonoids and benzodiazepines, such as diazepam, that are the most widely studied positive modulators of GABAA receptors. Benzodiazepines can act on these receptors via ‘two distinct and separable mechanisms’ (Walters, Hadley, Mo

• DAMPs are endogenous danger signals that can initiate

  2022-02-09

  

  DAMPs are endogenous danger signals that can initiate and perpetuate a noninfectious pfk mg during cell death [23]. HMGB1 is a well-studied nuclear DAMP in various types of regulated necrosis and has been implicated in the pathogenesis of infection and sterile inflammation. Our current data indicat

• The cytotoxicity of these compounds against

  2022-02-09

  

  The cytotoxicity of these compounds against Hep3B cells was assessed using the MTT assay. As shown in , compounds in series and (except ), which retained the carboxyl at C-17, showed no appreciable cytotoxic activity (IC > 100 μM), whereas compounds in series (except ,) were modestly cytotoxic, i

• br HO and cerebral malaria In

  2022-02-09

  

  HO-1 and cerebral malaria In a post-mortem evaluation of human cerebral (falciparum) malaria, strong HO-1 immunostaining was consistently noted in microglia/macrophages within and surrounding the pathognomonic Durck’s granulomas (Schluesener et al., 2001). As witnessed in cerebral trauma specimen

• In addition to the importance

  2022-02-09

  

  In addition to the importance of heme as an enzymatic cofactor, heme also acts as an important iron source. In order to access the iron within heme, S. aureus encodes heme degrading enzymes known as heme oxygenases (Skaar et al., 2004b; Wu et al., 2005). The two heme oxygenases encoded by S. aureus,

• br Concluding Remarks and Future Perspectives Our understand

  2022-02-09

  

  Concluding Remarks and Future Perspectives Our understanding of substrate targeting mechanisms utilized by kinases has grown tremendously in the past few years, but challenges still remain in relating these mechanisms to the organization of complex signaling networks. Substrate prediction based o

• The different NO stimulated and

  2022-02-09

  

  The different NO-stimulated and ODQ-inhibited cNMP patterns in terms of absolute and relative magnitude and time course reported herein suggest distinct functional roles of cGMP, cCMP and cUMP. Therefore, it will be necessary to dissect cellular effects of these cNMPs in numerous cell systems. For t

• br Introduction The signaling molecule

  2022-02-09

  

  Introduction The signaling molecule nitric oxide (NO) plays an essential role in vessel homeostasis by initiating vasodilation [1], [2], [3]. After biosynthesis in endothelial cells, NO diffuses into the subjacent smooth muscle layer to reach its target enzyme, soluble guanylyl cyclase (sGC, EC 4

• Here we show that lactate activates the

  2022-02-09

  

  Here we show that lactate activates the Gi-coupled receptor GPR81, which is exclusively expressed on adipocytes, and that lactate released from adipocytes in response to glucose and insulin mediates insulin-induced antilipolysis by activation of GPR81. Results Discussion Nutrients and their m

• We recently reported that the human derived PancCa

  2022-02-09

  

  We recently reported that the human-derived PancCa cell line PANC-1 and the human-derived hepatocellular HepG2 cell line express GPR55 mRNA and protein [21]. In PANC-1 and HepG2 cells, knockdown of GPR55 with specific siRNAs abrogates cellular uptake of Tocrifluor 1117, a selective GPR55 ligand [21]

• As part of our discovery efforts searching for

  2022-02-09

  

  As part of our discovery efforts searching for small molecule GPR119 agonists, we analyzed active pharmacophores of known agonists from the literature, and found that -methylsulfonylphenyl and substituted 4-hydroxyl piperidine are common fragments. In our initial efforts, we linked these two fragme

• Like other RNA viruses HCV also exhibits a high

  2022-02-08

  

  Like other RNA viruses HCV also exhibits a high degree of genetic diversity, creating a major challenge for the development of both HCV vaccines and pan-genotypic therapeutics (Timm and Roggendorf, 2007). The virus has a total of seven genotypes, with >50 subtypes and millions of quasispecies (Cuype

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