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- Fredholm, BB
(författare)
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Targeting adenosine receptors
- 2006
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Ingår i: ACTA PHARMACOLOGICA SINICA. - 1671-4083. ; 27, s. 26-26
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Kang, Nai-xin, et al.
(författare)
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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses
- 2022
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Ingår i: Acta Pharmacologica Sinica. - : Springer Nature. - 1671-4083 .- 1745-7254. ; 43, s. 977-991
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Tidskriftsartikel (refereegranskat)abstract
- Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 mu M) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 +/- 0.05 mu M against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-beta response, since knockdown of IFN-beta abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg center dot kg(-1) center dot d(-1), i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-gamma, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-beta by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.
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- Khayyal, MA, et al.
(författare)
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Towards rational use of drugs in Egypt
- 2006
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Ingår i: ACTA PHARMACOLOGICA SINICA. - 1671-4083. ; 27, s. 206-207
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Luo, Cheng, et al.
(författare)
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Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial
- 2005
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Ingår i: Acta Pharmacologica Sinica. - : Springer Science and Business Media LLC. - 1671-4083 .- 1745-7254. ; 26:8, s. 926-933
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Tidskriftsartikel (refereegranskat)abstract
- COX-2(cyclooxygenase-2) has sparked a surge in pharmaceutical interest since its discovery at the beginning of the 1990s. Several COX-2 selective inhibitors that avoid gastrointestinal side effects have been successfully launched into the market in recent years. The first selective COX-2 inhibitor, celecoxib, entered the market in December 1998 [corrected] However, there are a few organs that physiologically and functionally express COX-2, particularly the glomeruli of the kidney and the cortex of the brain. Inhibition of COX-2 expression in these organs possibly causes heart attack and stroke in long-term COX-2 inhibitor users. Recently, a USA Food and Drug Agency (FDA) advisory panel re-evaluated COX-2 inhibitors and unanimously concluded that the entire class of COX-2 inhibitors increase the risk of cardiovascular problems. Thus the use of COX-2 inhibitors is still controversial, and there is a challenge for not only pharmacologists, but also the pharmaceutical industry, to develop improved painkilling and anti-inflammatory drugs. This may involve exploring a new generation of COX-2 inhibitors with different inhibitory mechanisms through computer-aided design, screening different sources of inhibitors with lower selectivity, or seeking completely new targets. Synthetic COX-2 inhibitors have high selectivity and the advantage of irreversible inhibition, whereas naturally derived COX-2 inhibitors have lower selectivity and fewer side effects, with the medical effects in general not being as striking as those achieved using synthetic inhibitors. This review discusses the mechanism of COX-2 inhibitor therapy and a possible new way of exploration in the development of anti-inflammatory, analgetic, and antipyretic drugs.
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- Pilon, Marc, 1966, et al.
(författare)
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Development of Caenorhabditis elegans pharynx, with emphasis on its nervous system
- 2005
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Ingår i: Acta Pharmacologica Sinica. - : Springer Science and Business Media LLC. - 1745-7254 .- 1671-4083. ; 26:4, s. 396-404
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Tidskriftsartikel (refereegranskat)abstract
- The Caenorhabditis elegans pharynx is a neuromuscular tube of which the function is to pump and crush bacteria, and inject them into the intestine. The 80-cell pharynx develops via the morphogenesis and differentiation of the cells that compose its semi-spherical primordium, and requires the activity of several evolutionarily conserved genes, such as pha-4 (the homolog to the Drosophila forkhead and vertebrate FoxA), ceh-22 (the homolog to the Drosophila tinman and vertebrate Nkx2.5), and pha-2 (the homolog to the vertebrate Hex). There are 20 neurons in the pharynx, each with a reproducible unique trajectory. Developmental genetic analysis of axon guidance in the pharynx indicates that some axon trajectories are in part established without growth cones, whereas other parts necessitate growth cone function and guidance. Here we provide an overview of the developmental genetics of the Caenorhabditis elegans pharynx, with an emphasis on its nervous system.
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- Sun, Xian-qiang, et al.
(författare)
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Structure-based ensemble-QSAR model : a novel approach to the study of the EGFR tyrosine kinase and its inhibitors
- 2014
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Ingår i: Acta Pharmacologica Sinica. - : Springer Science and Business Media LLC. - 1671-4083 .- 1745-7254. ; 35:2, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To develop a novel 3D-QSAR approach for study of the epidermal growth factor receptor tyrosine kinase (EGFR TK) and its inhibitors. Methods: One hundred thirty nine EGFR TK inhibitors were classified into 3 clusters. Ensemble docking of these inhibitors with 19 EGFR TK crystal structures was performed. Three protein structures that showed the best recognition of each cluster were selected based on the docking results. Then, a novel QSAR (ensemble-QSAR) building method was developed based on the ligand conformations determined by the corresponding protein structures. Results: Compared with the 3D-QSAR model, in which the ligand conformations were determined by a single protein structure, ensemble-QSAR exhibited higher R2 (0.87) and Q2 (0.78) values and thus appeared to be a more reliable and better predictive model. Ensemble-QSAR was also able to more accurately describe the interactions between the target and the ligands. Conclusion: The novel ensemble-QSAR model built in this study outperforms the traditional 3D-QSAR model in rationality, and provides a good example of selecting suitable protein structures for docking prediction and for building structure-based QSAR using available protein structures.
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| 27. |
- Wan, Yi-Hong, et al.
(författare)
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[1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation
- 2020
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Ingår i: Acta Pharmacologica Sinica. - : Springer Science and Business Media LLC. - 1671-4083 .- 1745-7254. ; 41:5, s. 706-718
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Tidskriftsartikel (refereegranskat)abstract
- Dengue fever is an acute infectious disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. There is no effective vaccine or antiviral drug available to date to prevent or treat dengue disease. Recently, RNA-dependent RNA polymerase (RdRp), a class of polymerases involved in the synthesis of complementary RNA strands using single-stranded RNA, has been proposed as a promising drug target. Hence, we screened new molecules against DENV RdRp using our previously constructed virtual screening method. Mol-5, [1,2,4]triazolo[1,5-a]pyrimidine derivative, was screened out from an antiviral compound library (~8000 molecules). Using biophysical methods, we confirmed the direct interactions between mol-5 and purified DENV RdRp protein. In luciferase assay, mol-5 inhibited NS5-RdRp activity with an IC50 value of 1.28 ± 0.2 μM. In the cell-based cytopathic effect (CPE) assay, mol-5 inhibited DENV2 infectivity with an EC50 value of 4.5 ± 0.08 μM. Mol-5 also potently inhibited DENV2 RNA replication as observed in immunofluorescence assay and qRT-PCR. Both the viral structural (E) and non-structural (NS1) proteins of DENV2 were dose-dependently decreased by treatment with mol-5 (2.5-10 μM). Mol-5 treatment suppressed DENV2-induced inflammation in host cells, but had no direct effect on host defense (JAK/STAT-signaling pathway). These results demonstrate that mol-5 could be a novel RdRp inhibitor amenable for further research and development.
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| 29. |
- Zhang, D., et al.
(författare)
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Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating beta-catenin
- 2013
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Ingår i: Acta Pharmacologica Sinica. - : Springer Science and Business Media LLC. - 1671-4083 .- 1745-7254. ; 34:1, s. 176-184
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression. Methods: Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of β-catenin, Akt/pAkt, GSK-3β/pGSK-3β, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively. Results: Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of β-catenin, leaving the mRNA level of β-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3β, and suppressed the mRNA and protein levels of MMP-9 in the cells. Conclusion: Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/β-catenin signaling pathway and Akt phosphorylation.
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| 30. |
- Zhang, Xiaoqun, et al.
(författare)
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Repeated l-DOPA treatment increases c-fos and BDNF mRNAs in the subthalamic nucleus in the 6-OHDA rat model of Parkinson's disease
- 2006
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 27, s. 96-96
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Tidskriftsartikel (refereegranskat)abstract
- The subthalamic nucleus and the striatum are input regions of the basal ganglia. This study used the unilateral 6-OHDA rat model of Parkinson's disease to examine effects of l-DOPA on the expression of c-fos and BDNF mRNAs in these nuclei. Dopamine depletion per se did not affect c-fos or BDNF. Both a single and repeated injections of l-DOPA induced c-fos, but not BDNF, in the dopamine-depleted striatum. However, repeated l-DOPA treatment increased c-fos and BDNF in the dopamine-depleted subthalamic nucleus. These molecular adaptations may reflect changes in neuronal plasticity that underlie some therapeutic actions and/or side effects of l-DOPA in Parkinson's disease.
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