Abstract:Adult hippocampal neurogenesis is modulated by stress and various antidepressants. Neuronal stem cells express high levels of telomerase in adult hippocampus. Here, we used 3'-azido-deoxythymidine (AZT), a nucleoside reverse transcriptase inhibitor, and constructed recombinant adenovirus vector expressing mouse telomerase reverse transcriptase (Ad-mTERT-GFP) to investigate whether hippocampal telomerase implicate in pathophysiology of depression by regulating hippocampal neurogenesis. We found that infusion of AZT into hippocampal DG resulted in a decrease of neurogenesis in the hippocampus without causing neuronal degeneration, whereas infusion of Ad-mTERT-GFP into hippocampal DG upregulated hippocampal neurogenesis. The mice infused with AZT exhibited depression-like behaviors whereas the mice infused with Ad-mTERT-GFP exhibited antidepression-like behaviors both about 4 weeks after infusion. In addition, chronic stress resulted in a decrease in mTERT content in the hippocampus, reversed by chronic fluoxetine treatment. Furthermore, mTERT content in the SVZ, another telomerase expressed place in the adult brain, was unaffected after chronic stress exposure and infusion of AZT into SVZ did not induce depression-like phenotype. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult hippocampal neurogenesis.

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	1. Modulation of adult hippocampal neurognensis by telomerase: implication in depressive disorder
	ZHOU Qigang,HU Yao,LIU Mengying,JIN Xing,SUN Weixiang,ZHU Dongya
	Pharmacy 17 February 2012
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	Abstract:Adult hippocampal neurogenesis is modulated by stress and various antidepressants. Neuronal stem cells express high levels of telomerase in adult hippocampus. Here, we used 3'-azido-deoxythymidine (AZT), a nucleoside reverse transcriptase inhibitor, and constructed recombinant adenovirus vector expressing mouse telomerase reverse transcriptase (Ad-mTERT-GFP) to investigate whether hippocampal telomerase implicate in pathophysiology of depression by regulating hippocampal neurogenesis. We found that infusion of AZT into hippocampal DG resulted in a decrease of neurogenesis in the hippocampus without causing neuronal degeneration, whereas infusion of Ad-mTERT-GFP into hippocampal DG upregulated hippocampal neurogenesis. The mice infused with AZT exhibited depression-like behaviors whereas the mice infused with Ad-mTERT-GFP exhibited antidepression-like behaviors both about 4 weeks after infusion. In addition, chronic stress resulted in a decrease in mTERT content in the hippocampus, reversed by chronic fluoxetine treatment. Furthermore, mTERT content in the SVZ, another telomerase expressed place in the adult brain, was unaffected after chronic stress exposure and infusion of AZT into SVZ did not induce depression-like phenotype. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult hippocampal neurogenesis.
	TO cite this article:ZHOU Qigang,HU Yao,LIU Mengying, et al. Modulation of adult hippocampal neurognensis by telomerase: implication in depressive disorder[OL].[17 February 2012] http://en.paper.edu.cn/en_releasepaper/content/4466920


	2. Synthesis and Biological Evaluation of Heterocyclic Ring Fused Betulinic Acid Derivatives as Novel Inhibitors of Osteoclast Differentiation and Bone Resorption
	Xu Jun,Li Zhenxi,Luo Jian,Yang Fan,Liu Ting,liu Mingyao,Qiu Wen-Wei,Tang Jie
	Pharmacy 19 January 2012
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	Abstract:A series of betulinic acid (BA) derivatives were synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects of RANKL-induced osteoclastogenesis were evaluated by using a cell-based tartrate-resistant acid phosphatase (TRAP) activity assay. Compared with BA, most of these compounds exhibited a dramatic increase in inhibitory potency. Especially compound 20, which showed 66.9% inhibition even at low concentration of 0.1 M, was about 200-fold more potent than lead compound BA. The cytotoxicity assay on RAW264.7 suggested that the action of 20 on osteoclast differentiation was not result from its cytotoxicity. The primary mechanistic study indicated that 20 could inhibit osteoclastogenesis-related marker gene expression levels of cathepsin K and TRAP. Importantly, this compound attenuated bone loss of ovariectomy mouse in vivo. These BA derivatives could be used as potential leads for the development of a new type of antiosteoporosis agents.
	TO cite this article:Xu Jun,Li Zhenxi,Luo Jian, et al. Synthesis and Biological Evaluation of Heterocyclic Ring Fused Betulinic Acid Derivatives as Novel Inhibitors of Osteoclast Differentiation and Bone Resorption[OL].[19 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4463179

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	3. Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B
	Li Hui,Zou-Hui,Gao Lixin,Liu Ting,Yang Fan,Li Jingya,Li Jia,Qiu Wen-Wei,Tang Jie
	Pharmacy 18 January 2012
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	Abstract:A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring fused at C-2, C-3 positions showed a dramatic increase in inhibition, the two most potent PTP1B inhibitors 19 (IC50 = 0.91 μM) and 21 (IC50 = 0.98 μM) showed about 3-fold more potent than lead compound OA. Some compounds with C-ring modified showed high selectivity for PTP1B over TCPTP, among them, 50 possessed the best selectivity of 6.6-fold.
	TO cite this article:Li Hui,Zou-Hui,Gao Lixin, et al. Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B[OL].[18 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4463053


	4. STUDIES ON THE SYNTHESIS OF NICOTINAMIDE NUCLEOSIDE AND NUCLEOTIDE ANALOGUES AND THEIR INHIBITIONS TOWARDS CD38 NADASE
	CHEN Zhe,YANG Zhenjun,Zhang Liangren,LEE Hon Cheung,ZHANG Lihe
	Pharmacy 18 January 2012
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	Abstract:Nicotinamide adenine dinucleotide (NAD) analogues inhibit the NADase activity of CD38. In the current study, efficient protocols for the synthesis of substituted-nicotinamide nucleosides and nucleotides were developed. The one-pot phosphorylation-esterification strategy provides a convenient way of obtaining nicotinamide nucleoside phosphodiesters from the corresponding nucleosides. Structure-activity relationship information revealed that replacement of 3'-hydroxy group with F or N3 led to the considerably decrease of activity as compared with ara-F NMN. Phosphodiesterification of nicotinamide nucleosides lowers their inhibitory activities in some extent.
	TO cite this article:CHEN Zhe,YANG Zhenjun,Zhang Liangren, et al. STUDIES ON THE SYNTHESIS OF NICOTINAMIDE NUCLEOSIDE AND NUCLEOTIDE ANALOGUES AND THEIR INHIBITIONS TOWARDS CD38 NADASE[OL].[18 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4462595


	5. Effects of 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one on chemical-induced liver fibrosis in rats
	DING Hui,LI Erguang,SHI Dahua,WANG Yurong,WU Junhua
	Pharmacy 16 January 2012
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	Abstract:The aim of this study was to investigate the effects of 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one, the main component in Iris tectorum which has been used as a folk proven medicine for several centuries to treat some hepatic ailments in China, on chemical-induced liver fibrosis in rats and its possible mechanism. Liver fibrosis was induced in rats by carbon tetrachloride, plus a diet of fat, cholesterol and alcohol in the drinking water. 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one treatment significantly blocked the increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronate (HA), laminin (LN) and procollagen III N-termimal peptide (PIIIP) contents in serum and collagen contents in liver caused by chemical-induced liver fibrosis. Chemical-induced liver fibrosis led to the drop of serum albumin concentration and the ratio of albumin and globulin (A/G), and 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one made a slight increase except tectorigenin at 30 mg/kg making a remarkable increase. Tectorigenin could also remarkably block the increase of liver lipid peroxidation (LPO) production and the decrease of liver superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities caused by liver fibrosis. Furthermore tectorigenin shows no acute toxicity. In conclusion, 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one can effectively reverse chemically induced liver fibrosis in rats and it could be developed as a liver fibrosis therapeutic drug. The therapeutic effect of 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one on chemical-induced liver fibrosis in rats appears to be due, at least in part, to its antioxidant properties. These data also support the folkloric uses of I. tectorum in the treatment of hepatic diseases including hepatic fibrosis, liver cirrhosis and hepatocellular carcinoma.
	TO cite this article:DING Hui,LI Erguang,SHI Dahua, et al. Effects of 5,7-dihydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one on chemical-induced liver fibrosis in rats[OL].[16 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4461442


	6. Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells
	DING Hui,SHI Dahua,LI Erguang,WANG Yurong,JIANG Chunping,WU Junhua
	Pharmacy 16 January 2012
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	Abstract:Tectorigenin, a main isoflavone in the Iris tectorum rhizome which was used traditionally for treating liver-related diseases, was shown to inhibit the growth of human hepatoma HepG2 cells, and to induce the cell apoptosis. In the apoptotic process, the intracellular ROS and Ca2+ elevation acted as an early event followed by depolarization of mitochondrial membrane potential (MMP). And then cytochrome c was released to cytosol. Moreover, the tectorigenin treatment co-enhanced the caspase-3, -8 and -9 proteolytic activities. In conclusion, tectorigenin significantly inhibited the proliferation and induced apoptosis in human hepatocellular carcinoma HepG2 cells mainly via mitochondrial-mediated pathway. And the death receptor-dependent pathway might play a certain role in the apoptotic process. These observations indicated that tectorigenin is the active principle of Iris tectorum rhizome applied in the folk medicine for alleviating liver disorders, and that the isoflavone is a promising candidate for hepatocellular carcinoma chemotherapeutic and chemopreventive agent.
	TO cite this article:DING Hui,SHI Dahua,LI Erguang, et al. Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells[OL].[16 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4461207


	7. Synthesis and antidiabetic activity of 5,7-dihydroxyflavonoids and analogues
	Qin Nan,Chang Liushuan,Li Chunbao,Jin Meina,Duan Hongquan
	Pharmacy 15 January 2012
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	Abstract:Aim of the study: This is a study aiming to evaluate the structural elements essential to the antidiabetic activity of flavonoids. Methods: We synthesized two series of flavonoids, 5,7-dihydroxyflavanones and 5,7-dihydroxyflavones. Results: In a screening for in vitro potential antidiabetic activity, most of the flavonoids showed a remarkable in vitro activity, and compounds 5f, 7d, and 10c were significantly more effective than the positive control, metformin. Conclusion: The biological activity was mainly affected by introducing structural modification at the ring B moiety of the flavonoid skeleton. The results suggest that 5,7-dihydroxyflavonoids can be considered promising candidates in the development of new antidiabetic lead compounds.
	TO cite this article:Qin Nan,Chang Liushuan,Li Chunbao, et al. Synthesis and antidiabetic activity of 5,7-dihydroxyflavonoids and analogues[OL].[15 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4462427


	8. Preparation and characterization of novel pH-sensitive N-succinyl-chitosan/poly(vinyl alcohol) hydrogel
	FAN Lihong,WEN Feng,WU Penghui,WANG Libo,TAN Chang,SHA Mingming
	Pharmacy 15 January 2012
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	Abstract:Blended hydrogels have been widely used in biomedical fields due to their biocompatibility and biodegradability. In order to get a new kind of blended hydrogel using as deliver system for drugs, we prepared N-succinyl-chitosan (NSCS) and Poly (vinyl alcohol) blended hydrogels by freezing-thawing method. The hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Antibacterial activity of hydrogels composite within nanosilver was also investigated. The swelling degree of hydrogels was increased with the amount of NSCS. Protein release studies were performed in different pH solutions. The results showed that the release rate was slower under acid than under basic conditions, which could be attributed to the pH-sensitive of NSCS. It is suggesting that the NSCS/PVA hydrogels could be potentially applied as oral delivery systems for protein drugs.
	TO cite this article:FAN Lihong,WEN Feng,WU Penghui, et al. Preparation and characterization of novel pH-sensitive N-succinyl-chitosan/poly(vinyl alcohol) hydrogel[OL].[15 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4462334


	9. The Aggravatory Effect of Nicotine on Ethanol-Induced Acute Gastric Mucosa Injury: Role of Asymmetric Dimethylarginine
	LI Yuanjian,ZHANG Zhe,ZHOU Yuan,YANG Zhichun
	Pharmacy 04 January 2012
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	Abstract:effect of nicotine on ethanol-induced acute gastric injury. METHODS：Gastric mucosa injury was induced by an injection of ethanol (75%) in the stomach in Sprague-Dawley rats. Animals were pretreated with nicotine for 28 days. Nicotine was dissolved in tap water (0.05 mg/ml). The gastric mucosal ulcer index (UI), the level of ADMA and NO were determined. Mucosal epithelium cells were treated with nicotine (10 μM) for 24 h in the presence or absence of ethanol. The concentrations of ADMA in the culture medium and the rate of cell apoptosis were determined.RESULTS：In the rats treated with ethanol, the UI and ADMA level were increased and the NO level was decreased, and the effects of ethanol were intensified by pretreatment with nicotine. Incubation of nicotine (10 μM) with epithelial cells for 24 h further increased the elevated level of ADMA and rate of cell apoptosis due to ethanol. Exogenous ADMA directly induced cell apoptosis. CONCLUSIONS：The facilitatory effect of nicotine on ethanol-induced acute gastric mucosa injury is related to induction of cell apoptosis by stimulation of ADMA generation.
	TO cite this article:LI Yuanjian,ZHANG Zhe,ZHOU Yuan, et al. The Aggravatory Effect of Nicotine on Ethanol-Induced Acute Gastric Mucosa Injury: Role of Asymmetric Dimethylarginine[OL].[ 4 January 2012] http://en.paper.edu.cn/en_releasepaper/content/4459618


	10. Octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles as potential carriers for targeted antitumor drug delivery
	Zou Aifeng ,Meirong Huo,Yong Zhang,Jianping Zhou,Xiaoqiang Yin,Chengli Yao,Qinnv Zhu
	Pharmacy 09 October 2011
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	Abstract:Octreotide (OCT) was recently found to have high binding affinity to the positive tumor cells of somatostatin receptors (SSTRs). In this study, octreotide-polyethene glycol-stearic acid (OCT-Phe-PEG-SA) was first successfully synthesized and used as a targeting molecule for N-octyl-O, N-carboxymethyl chitosan (OCC). Doxorubicin (DOX) was loaded into OCT-modified OCC micelles (DOX-OCC-OCT). The drug-loaded micelles obtained exhibited spherical shape, small particle sizes and negative zeta potentials. The cytotoxicity of DOX-OCC-OCT micelles against MCF-7 cells (SSTRs expressing) was found to significantly increase with the increased amount of OCT modification, while no significant difference was observed against WI-38 cells (no SSTRs expressing). Results of flow cytometry, fluorescence microscopy and confocal laser scanning microscopy confirmed DOX-OCC-OCT micelles could remarkably increase the uptake of DOX in MCF-7 cells. All the results indicated that OCC-OCT micelles may be a promising intracellular targeting carrier for efficient delivery of antitumor drugs into tumor cells.
	TO cite this article:Zou Aifeng ,Meirong Huo,Yong Zhang, et al. Octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles as potential carriers for targeted antitumor drug delivery[J].

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