1.Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice
Weifan YAO ; Mingyan LIU ; Xin ZHONG ; Shilun YANG ; Ke DU ; Ruikun MAO ; Minjie WEI
Chinese Pharmacological Bulletin 2016;32(4):473-479,480
Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.
2.Generation of Japanese Encephalitis Virus-like Particle Vaccine and Preliminary Evaluation of Its Protective Efficiency.
Yanfang ZHANG ; Ruikun DU ; Shaomei HUANG ; Tao ZHANG ; Jinliang LIU ; Bibo ZHU ; Hualin WANG ; Fei DENG ; Shengbo CAO
Chinese Journal of Virology 2016;32(2):150-155
The cDNA fragment of JEV prME gene was cloned into the baculovirus shuttle vector (bacmid) to construct a recombinant baculovirus vector, defined as AcBac-prME. Then the recombinant baculovirus Ac-prME was obtained by transfecting Sf9 cells with AcBac-prME. Western blot analysis and immunofluorescence results indicated that both prM and E proteins were efficiently expressed in Sf9 cells. Electron microscopy suggested that prME was assembled into JEV-VLPs. To further evaluate the potential of JEV-VLPs as vaccine, the mice were immunized with JEV-VLPs and then challenged with lethal JEV. The results of mice survival and pathological changes demonstrated that the JEV-VLPs performed complete protection against JEV-P3 strain and relieved pathological changes in the mice brain significant. This study suggest that JEV-VLPs would be a potential vaccine for Japanese encephalitis virus.
Animals
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Antibodies, Viral
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immunology
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Encephalitis Virus, Japanese
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genetics
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immunology
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Encephalitis, Japanese
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immunology
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prevention & control
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virology
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Humans
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Japanese Encephalitis Vaccines
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administration & dosage
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genetics
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immunology
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Mice
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Mice, Inbred BALB C
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Sf9 Cells
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Vaccination
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Vaccines, Virus-Like Particle
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administration & dosage
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genetics
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immunology
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Viral Envelope Proteins
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administration & dosage
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genetics
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immunology
3.SARS-CoV-2 cell entry and targeted antiviral development.
Zinuo CHEN ; Ruikun DU ; Jazmin M GALVAN ACHI ; Lijun RONG ; Qinghua CUI
Acta Pharmaceutica Sinica B 2021;11(12):3879-3888
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19), which threatens human health and public safety. In the urgent campaign to develop anti-SARS-CoV-2 therapies, the initial entry step is one of the most appealing targets. In this review, we summarize the current understanding of SARS-CoV-2 cell entry, and the development of targeted antiviral strategies. Moreover, we speculate upon future directions toward next-generation of SARS-CoV-2 entry inhibitors during the upcoming post-pandemic era.