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	1. NGF contribute to acid-induced articular chondrocytes apoptosis by modulating ASIC1a/NLRP1/Caspase-1 signaling axis
	HU Wei
	Pharmacy 14 May 2018
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	Abstract:Objective: Nerve growth factor (NGF) is key regulators in the pathogenesis of the rheumatoid arthritis (RA) diseases. However, the potential role of NGF in RA remains unclear. It has been shown that ASIC1a is an extracellular pH sensor in articular chondrocytes and RA. Moreover, NGF modulates the expression of ASICs in sensory neurons sensitization. In this study, we examined whether NGF contribute to ASIC1a expression could affect acid-induced apoptotic injury to articular chondrocytes. Methods: The primary rat articular chondrocytes were isolated from Sprague-Dawley rats. Apoptosis of chondrocytes was observed by the terminal deoxyribonucleotidyl transferase- mediated dUTP nick-end labeling method as well as propidium iodide labeling methods. Treatment of articular chondrocytes with NGF, ASIC1a-siRNA and acid, the expression levels of NGF, ASIC1a, NLRP1 and Caspase-1 were examined by qRT-PCR and western blotting, respectively. Results: We found that up-regulation of ASIC1a in acid-induced articular chondrocytes is associated with NGF treatment. Knockdown of ASIC1a inhibited NLRP-1 expression in acid-induced articular chondrocytes. Knockdown of ASIC1a suppressed acid-induced articular chondrocytes apoptosis. Moreover, we investigated the effect of ASIC1a on NLRP1/Caspase-1 pathway. Our results demonstrated that NGF contribute to acid-induced articular chondrocytes apoptosis by modulating ASIC1a/NLRP1/Caspase-1 signaling axis. Conclusion: Taken together, these results indicated that NGF promotes acid-induced articular chondrocytes apoptosis by up-regulation of ASIC1a/NLRP1/Caspase-1 signaling axis.
	TO cite this article:HU Wei. NGF contribute to acid-induced articular chondrocytes apoptosis by modulating ASIC1a/NLRP1/Caspase-1 signaling axis[OL].[14 May 2018] http://en.paper.edu.cn/en_releasepaper/content/4745087


	2. Discovery of quercetin derivatives as metal ions chelators with potent anti-HCV activities
	ZHONG Dongwei,LIU Mingming,CAO Yang,ZHOU Lu,YE Deyong
	Pharmacy 08 May 2017
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	Abstract:The α,γ-diketoacid (DKA) analogues or isosteres show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of flavonoid quercetin (2) could partly be attributed to its structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel quercetin analogues, 7-O-arylmethyl quercetin and quercetin-3-O-benzoic acid-ester, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.
	TO cite this article:ZHONG Dongwei,LIU Mingming,CAO Yang, et al. Discovery of quercetin derivatives as metal ions chelators with potent anti-HCV activities[OL].[ 8 May 2017] http://en.paper.edu.cn/en_releasepaper/content/4730625


	3. Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents
	SONG Wuhui,LIU Mingming,ZHONG Dongwei,YE Deyong,ZHOU Lu,YUAN Zhenghong
	Pharmacy 28 April 2017
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	Abstract:In this paper, a series of diketo tetrazoles and diketo triazoles were designed and synthesized as bioisosteres of α, γ-diketo acid, the active site inhibitor of HCV (Hepatitis C virus) polymerase NS5B. Among the synthesized compounds, 4-(4-fluorobenzyloxy)phenyl diketo triazole (30) exhibited anti-HCV activity with an EC50 value of 3.9 μM and an SI value more than 128. The reduction of viral protein and mRNA levels were also validated, supportingthe anti-HCV activity of compound 30. These results provide convincing evidence that the diketo tetrazoles and diketo triazoles can be developed as bioisosteres of α,γ-diketo acid to exhibit potent inhibitory activity against HCV.
	TO cite this article:SONG Wuhui,LIU Mingming,ZHONG Dongwei, et al. Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo tetrazoles and diketo triazoles as anti-HCV agents[OL].[28 April 2017] http://en.paper.edu.cn/en_releasepaper/content/4730608


	4. Acid-sensing ion channel 1a regulates matrix metabolism of rat
	weihu,Cheng Sun,shiming wang
	Pharmacy 25 April 2017
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	Abstract:Objectives: ASIC1a has a wide range of biological functions, plays an important role in cell metabolic activity, Our research has shown that extracellular pH plays an important role in matrix synthesis and metabolism in articular chondrocytes by activated ASIC1a. However, little is kown about the underlying mechanism of ASIC1a on matrix synthesis and metabolism in articular chondrocytes. The present study was undertaken to investigate the mechanism of ASIC1a on matrix synthesis and metabolism in articular chondrocytes by acidosis. Down-regulation of GAG, HYP, MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA expression and production was abolished by inhibit acidosis- elicited increase in intracellular Ca2+ concentration. Pretreatment with BAPTA-AM (Ca2+ chelator) abolished acidosis induced ERK1/2, p38 MAPK, c-jun and c-fos activation. PD98059 (ERK1/2 inhibitor) attenuate c-jun activation and rest

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