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Metformin prevents hormonal and metabolic disturbances and 1,2-dimethylhydrazine-induced colon carcinogenesis in non-diabetic rats

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Cancer Biology & Medicine 2017年第1期14卷 100-107页

作者： Viktoria V.Bekusova Vasily M.Patsanovskii Alexander D.Nozdrachev Alexandr P.Trashkov Margarita R.Artemenko Vladimir N.Anisimov Department of Physiology St.Petersburg State UniversitySt.Petersburg 197183Russia I.P.Pavlov Institute of Physiology Russian Academy of Sciences St.Petersburg 199034Russia deparment of experimental pharmacology I.M.Sechenov Institute of Evolutionary Physiology and BiochemistryThe Russian Academy of SciencesSt.Petersburg 194223Russia Department of Carcinogenesis and Oncogerontology N.N.Petrov Research Institute of OncologySt.Petersburg 197758 Russia

Effects of two doses of the anti-diabetic drug, metformin （MF）, on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine （DMH）-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin- like growth factor-l, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin. Treatment with two doses of MF normalized maiority of these changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH treatment. The only exception was the decreased triglyceride levels in MF-treated rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and decreased endophytic tumors compared with untreated rats. Moreover, both MF doses increased DMH-induced and highly differentiated tumors and decreased the invasiveness of colon carcinomas compared with rats provided with DMH and water. Therefore, effects of MF on metabolic homeostasis are critical for preventing colon cancer.

关键词： Colon cancer prevention 1,2-dimethylhydrazine mefformin rat

Cancer chemoprevention through dietary avonoids: what's limiting?

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Chinese Journal of Cancer 2017年第10期36卷 455-467页

作者： Haneen Amawi Charles R. Ashby Jr Amit K. Tiwari Department of pharmacology and Systems Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43560USA Pharmaceutical Sciences College of Pharmacy St. John’s UniversityQueens NY 11432 USA Department of pharmacology and experimental Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43614 USA

Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their e ective use, including(1) the isolation and purification of flavonoids from their natural resources;(2) demonstration of the e ects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and(3) numerous pharmacokinetic challenges(e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and e orts that are being made to surmount these challenges.

关键词： Flavonoids Chemoprevention Silybin Silymarin Natural product drug development Pharmacokinetic challenges

Hot aqueous leaf extract of Lasianthera africana(Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity

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Journal of Integrative Medicine 2018年第4期16卷 263-272页

作者： Lucky Legbosi Nwidu Raphael Ellis Teme Department of experimental pharmacology and Toxicology Faculty of Pharmaceutical Sciences University of Port Harcourt Histopathology Laboratory Braithwaite Memorial Specialist Hospital Medical Laboratory Science Department Faculty of Science Rivers State University of Science and Technology

Objectives： The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana （lcacinaceae） against isoniazid （INH） and rifampicin （RlF）-induced liver damage in rats. Methods： The hepatoprotective effects of hot aqueous L. africana （HALA） leaf extract （0.1-1 g/kg） and sily-matin （50 mg/kg） were assessed in a model of oxidative liver damage induced by RIF and INH （100 mg/kg each） in Wistar rats for 28 days. Biochemical markers of hepatic damage such as alanine aminotrans- ferase （ALT）, aspartate aminotransferase （AST） and alkaline phosphatase （ALP） were assessed. The antiox- idant statuses of plasma glutathione peroxidase （GSPx）, glutathione reductase （GSH）, catalase （CAT） and superoxide dismutase （SOD） and lipid peroxidation were evaluated. Results： The pretreatment of INH and RIF decreased hematological indices and the antioxidant levels （P〈 0.001） and increased the levels of liver marker enzymes （P〈 0.001）. However, pretreatment with HALA extract and silymarin provoked significant elevation of hematological indices. The levels of AST, ALT, and ALP were depressed （P 〈 0.001 ）. Total triglycerides, total cholesterol, total bilirubin and low-density lipoprotein were decreased （P 〈 0.001）. However, high-density lipoprotein, bicarbonate, and electrolytes like chloride and potassium were elevated （P 〈 0.001）, but sodium was depressed （P 〈 0.05）. Additionally, GSH, GSPx, SOD and CAT were elevated （P 〈 0.01） and malondialdehyde was depressed （P 〈 0.001 ） when compared to the R1F-INH-treated rats. Histopathological evaluations support hepatoprotective activity. Conclusion： This study demonstrated that HALA leaf extract attenuated RIF-INH-induced hepatotoxicity. L, africana could be exploited in management of RIF-INH-induced hepatitis.

关键词： Hepatoprotection Hepatotoxicity RifampicinIsoniazid Lasianthera africana Tuberculosis Rats

A nanobody-based blocking enzyme-linked immunosorbent assay for detecting antibodies against pseudorabies virus glycoprotein E

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Journal of Integrative Agriculture 2024年第4期23卷 1354-1368页

作者： Huanhuan Lü Pinpin Ji Siyu Liu Ziwei Zhang Lei Wang Yani Sun Baoyuan Liu Lizhen Wang Qin Zhao Department of Preventive Veterinary Medicine College of Veterinary MedicineNorthwest A&F University/Shaanxi Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic TechnologyMinistry of Agriculture and Rural AffairsYangling 712100China

Pseudorabies(PR)is an acute infectious disease of pigs caused by the PR virus(PRV)and results in great economic losses to the pig industry *** glycoprotein E(gE)-based enzyme-linked immunosorbent assay(ELISA)has been used to distinguish gE-deleted vaccine-immunized pigs from wild-type virus-infected pigs to eradicate PR in some *** has the advantages of small size and easy genetic engineering and has been a promising diagnostic ***,there were few reports about developing nanobody-based ELISA for detecting anti-PRV-gE *** the present study,the recombinant PRV-gE was expressed with a bacterial system and used to immunize the Bactrian ***,two nanobodies against PRV-gE were screened from the immunized camel by phage display ***,two nanobody-HRP fusion proteins were expressed with HEK293T *** PRV-gE-Nb36-HRP fusion protein was selected as the probe for developing the blocking ELISA(bELISA)to detect anti-PRV-gE *** optimizing the conditions of bELISA,the amount of coated antigen was 200 ng per well,and dilutions of the fusion protein and tested pig sera were separately 1:320 and 1:*** cut-off value of bELISA was 24.20%,and the sensitivity and specificity were 96.43 and 92.63%,*** detecting 233 clinical pig sera with the developed bELISA and a commercial kit,the results showed that the coincidence rate of two assays was 93.99%.Additionallly,epitope mapping showed that PRV-gE-Nb36 recognized a conserved conformational epitope in different reference PRV ***,great stability and low-cost nanobody-based bELISA for detecting anti-PRV-gE antibodies were *** bELISA could be used for monitoring and eradicating PR.

关键词： nanobody nanobody-HRP blocking ELISA PRV-gE antibody

A new self-adaptive remeshing approach

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High Technology Letters 2006年第2期12卷 154-159页

作者：吴勇 He Yuanjun Zhang Lin deparment of Computer Science ＆ Engineering Shanghai Jiaotong University Shanghai 200030 P.R. China

This paper proposes a self-adaptive approach to converting irregular genus-O meshes into those with subdivision connectivity. To assure a maximal utilization of the multiresolution techniques on the remesh, we map the original mesh onto the unit sphere and construct a base mesh with only four vertices. We also introduce a self-adaptive relocation operation, which is used to adapt the vertex distribution of the spherical subdivision mesh to that of the parameterized mesh, to improve the visual appearance of the remesh. The experimental results show that our method can not only make the number of irregular vertices in the remesh as small as possible, but also preserve the details of the original mesh well.

关键词： self-adaptive remeshing subdivision connectivity spherical parametrization multiresolution

Evaluation of Lentinan on Cytochrome P450 activity by Cocktail method

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Evaluation of Lentinan on Cytochrome P450 activity by Cockta...

Antiviral activity of Jinchai capsule against influenza virus

浙江省药理学高峰论坛暨浙江省药理学会、浙江省药学会药理专业委员会2017年会

作者： Yiping Lin Yanli Wei Xiaoxia Hu Meiling Wu Jingchan Yao Xiaoqian Ying Xiaoyan Fu Mingxing Ding Liman Qiao deparment of pharmacology Jinhua Polytechnic deparment of pharmacy Jinhua Central Hospital deparment of pharmacy The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University

The purpose of this study was to find out whether lentinan influences the effect on rat cytochrome P450(CYP)enzymes(CYP1A2,CYP2Cg,CYP2C19,CYP2D6and CYP3A4)by using cocktail probe drugs in vivo.A co

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Journal of Traditional Chinese Medicine 2013年第2期33卷 200-204页

作者： Juying Zhong Xiaolan Cui Yujing Shi Yingjie Gao Hongxin Cao experimental Research Center China Academy of Chinese Medical Sciences pharmacology laboratory Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Graduate School of China Academy of Chinese Medical sciences

OBJECTIVE:To evaluate the effect on influenza virus of Jinchai,a capsule made of Traditional Chinese ***:Madin-darby canine kidney(MDCK) cells were infected with the FM1 strain of influenza virus A(subtype H1N1) in *** were used to explore how Jinchai affected cell adsorption,cell membrane fusion,transcription and replication of the influenza ***(HA) protein,intracellular pH,and influenza virus protein acid(PA) polymerase subunit were detected with confocal microscopy and real-time fluorescent quantitative polymerase chain ***:Jinchai significantly reduced the expression of HA and PA polymerase subunit mRNA in infected MDCK *** also significantly decreased intracellular pH in infected ***:Jinchai had strong anti-influenza activity against the influenza *** weakened the ability of the influenza virus to adsorb to cell wall and fuse with cell membranes in the early infection stage,and inhibited the transcription and replication of the virus.

关键词： Antiviral agents Influenza A virus Jin-chai capsule

Does protracted antiviral therapy impact on HCV-related liver cirrhosis progression?

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World Journal of Gastroenterology 2007年第36期13卷 4903-4908页

作者： Giovanni Tarantino Antonio Gentile Domenico Capone Vincenzo Basile Marianna Tarantino Matteo Nicola Dario Di Minno Alberto Cuocolo Paolo Conca Department of Clinical and experimental Medicine Federico Ⅱ University Medical School of Naples Naples 80131 Italy Department of Biomorphological and Functional Sciences Pharmacology Section of Neuroscience Department Federico Ⅱ University Medical School of Naples Naples 80131 Italy

AIM: To study the outcomes of patients with compensated hepatitis C virus-related cirrhosis. METHODS: Twenty-four grade A5 and 11 grade A6 of Child-Pugh classification cirrhotic patients with active virus replication, treated for a mean period of 31.3 ± 5.1 mo with moderate doses of interferon-alpha and ribavirin, were compared to a cohort of 36 patients with similar characteristics, without antiviral treatment. Salivary caffeine concentration, a liver test of microsomal function, was determined at the starting and thrice in course of therapy after a mean period of 11 ± 1.6 mo, meanwhile the resistive index of splenic artery at ultra sound Doppler, an indirect index of portal hypertension, was only measured at the beginning and the end of study. RESULTS: Eight out of the 24 A5- (33.3%) and 5 out of the 11 A6- (45.45%) treated-cirrhotic patients showed a significant improvement in the total overnight salivary caffeine assessment. A reduction up to 20% of the resistive index of splenic artery was obtained in 3 out of the 8 A5- (37.5%) and in 2 out of the 5 A6- (40%) cirrhotic patients with an improved liver function, which showed a clear tendency to decrease at the end of therapy. The hepatitis C virus clearance was achieved in 3 out of the 24 (12.5%) A5- and 1 out of the 11 (0.091%) A6-patients after a median period of 8.5 mo combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but 3 patients (8.3%) had a worsening ofthe Child-Pugh score (P = 0.001).CONCLUSION: A prolonged antiviral therapy with moderate dosages of interferon-alpha and ribavirin shows a trend to stable liver function or to ameliorate the residual liver function, the entity of portal hypertension and the compensation status at acceptable costs.

关键词： Liver cirrhosis Hepatitis C virus infection Antiviral therapy

Protective effects of iptakalim,a novel ATP-sensitive potassium channel opener,on global cerebral ischemia-evoked insult in gerbils

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Acta Pharmacologica Sinica 2006年第6期27卷 665-672页

作者： Hua CHEN~(2,4)Yong YANG~(2,4)Hong-hong YAO~2 Xing-chun TANG~2 Jian-hua DING~2 Hai WANG~3 Gang HU~(2,5)2 Laboratory of Neuropharmacology,Department of Anatomy,Histology and pharmacology,Nanjing Medical University,Nanjing 210029,China 3 Department of Cardiovascular pharmacology,Beijing Institute of pharmacology and Toxicology,Beijing 100850,China Department of Anatomy Laboratory of Neuropharmacology Histology and Pharmacology Nanjing Medical University Nanjing China Department of Cardiovascular pharmacology Beijing Institute of Pharmacology and Toxicology Beijing China

Aim:To investigate the protective role of iptakalim,a novel ATP sensitive potas-sium channel opener,on global cerebral ischemia-evoked insult in gerbils andglutamate-induced PC 12 cell ***:Global cerebral ischemia was in-duced by occluding the bilateral common carotid arteries in gerbils for 5 *** field maze and T-maze were employed to investigate the experimental thera-peutic value of iptakalim on ischemic brain insult（n=8）.The pyramidal cells in thehippocampal CA1 regions were counted to assess the protective effects *** released from the gerbil hippocampus and PC12 cells weredetermined by *** calcium was measured by Fluo-3 AM with ABio-Rad Radiance 2100TM confocal system in conjunction with a Nikon *** glutamate uptake measurements were determined by liq-uid scintillation ***:Iptakalim（0.5-4.0 mg/kg per day,ip）couldreduce the high locomotor activity evoked by ischemia and improve global cere-bral ischemia-induced working memory *** studies revealedthat iptakalim could increase the survival neuron in the hippocampus CA1 zone ina dose-dependent ***,iptakalim could reverse ischemia-evokedincreases of glutamate in the hippocampus of *** an in vitro study,iptakalimprotected PC12 cells against glutamate-induced excitotoxicity,reduced the[Ca2+]iincreases,and enhanced the glutamate uptake activity of primary ***:Iptakalim plays a key role in preventing global cerebralischemia-evoked insults in gerbils and glutamate-induced PC12 cell injury by *** might be a promising novel candidate for the preventionand/or treatment of stroke.

关键词： ATP-sensitive potassium channel opener iptakalim global cerebral ischemia neuroprotection excitotoxicity