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Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis

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Acta Pharmacologica Sinica 2006年第1期27卷 111-118页

作者： Yong-qiu ZHENG~2 Wei WEI~(2,3,4) Min DAI~2 Lei ZHU~2 Xiao-yi JIA~2 Yuan WANG1 Institute of Clinical Pharmacology,Anhui Medical University.hefei 230032,China 3 Key Laboratory of Anti-inflammation and Immunopharmacology in Anhui Province,hefei 230032.China Institute of Clinical Pharmacology Anhui Medical University Hefei China Key Laboratory of Anti-inflammation and Immunopharmacology in Anhui Province Hefei China

Aim:To investigate the mechanisms of interleukin-1 receptor antagonist （IL-1ra）in the treatment of adjuvant arthritis （AA）.Methods:AA was induced in rats bytreatment with Freund's complete adjuvant （FCA）.Rats were given an intracuta-neous injection of IL-1ra （2.5,10,40mg/kg,3 times per day） from d 14 to d 21 *** proliferation and the activity of IL-1 were determinedby using MTT *** necrosis factor alpha （TNF-α） and prostaglandin E2（PGE2） concentrations were measured by *** ultrastructureof synoviocytes was observed by using a transmission electron *** of c-Jun N-terminal kinase （JNK）,extracellular regulating kinase（ERK） and p38 kinase were detected by Western blot ***:IL-1ra （10and 40 mg/kg,ic,d 14-21） modulated the secondary inflammatory reaction（P<0.01）,ultrastructure of synoviocytes and mitogen-activated protein kinase（MAPK） phosphorylation in AA *** administration of IL-1ra （10 and 40mg/kg,ic,d 14-21） in AA rats significantly decreased the production of IL-1,PGE2and TNF-α by macrophage-like synoviocytes （MLS）（P<0.01）.IL-1ra （2.5 mg/kg）also decreased the production of PGE2（P<0.01） and TNF-α（P<0.05） by MLS inAA *** increased phosphorylation of MAPK and cell proliferation in fibro-blast-like synoviocytes （FLS） stimulated by supernatants of MLS in AA rats wasalso inhibited by IL-1ra （10 and 40 mg/kg,ic.d 14-21）.Conclusion:IL-1ra hasanti-inflammatory effects because it modulates the ultrastructure of synoviocytes,decreases the production of pro-inflammatory mediators by MLS,and inhibits thephosphorylation of MAPK in FLS.

关键词： interleukin-1 receptor experimental arthritis mitogen-activated protein kinase synovial membrane

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Pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes in mice

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Acta Pharmacologica Sinica 2005年第2期26卷 250-256页

作者： Yong JIN,Jun LI~2,Long-fu RONG,Xiong-wen L(?),Yan HUANG,Shu-yun XUInstitute of Clinical Pharmacology,School of Pharmacy,Anhui Medical University,hefei 230032,China Institute of Clinical Pharmacology School of Pharmacy Anhui Medical University Hefei China

Aim:To study the pharmacokinetics and tissue distribution of 5-fluorouracil en-capsulated by galactosylceramide liposomes(5-Fu-GCL)in ***:Theconcentration of 5-fluorouracil(5-Fu)in serum was detected by high performanceliquid chromatography after 5-Fu-GCL(80,40,20 mg/kg)and free 5-Fu(40mg/kg)were injected intravenously into *** tissue distribution of 5-Fu-GCL(40mg/kg)and free 5-Fu(40mg/kg)was investigated,and concentration-timeprofile of the two preparations in the liver were *** were analyzed by3p97 ***:Serum concentration-time curves of 5-Fu-GCL and free5-Fu conformed to one compartment model of first order absorption.5-Fu-GCLat 80,40,and 20 mg/kg had T1/2Keof 25.8±4.2,27.3±4.4,and 28.2±5.6 min;C0of24.9±4.9,17.7±3.6,and 11.5±2.7 mg/L;and AUC of 990.0±45.2,622.5±38.3,and 340.4±25.6 ***.L-1,*** contrast free 5-Fu at 40 kg/mg hadT1/2Keof 15.8±2.2min,C0of 35.8±6.2mg/L,AUC of 639.0±35.9 *** distribution of 5-Fu-GCL in the liver and immune organs was significantlyincreased,while in heart and kidney it was remarkably *** AUC of 5-Fu-GCL in the liver was 3 times higher than that of free ***:Thepharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-re-lated and dose-dependent,and exhibits sustained-release and hepatic targetcharacteristics.

关键词： 5-fluorouracil galactosylceramide liposomes pharmacokinetics

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No association between IRF3 polymorphism and susceptibility to hepatitis B virus infection in Chinese patients

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World Journal of Gastroenterology 2012年第4期18卷 388-392页

作者： Fang Yan,Feng Lv,Xu Li,Hua-Fa Yin,Department of Infectious Diseases,The First Affiliated Hospital of Anhui Medical University,hefei 230032,Anhui Province,China Yu-Feng Gao,Department of Hepatopathy,The Second Affiliated Hospital of Anhui Medical University,hefei 230601,Anhui Province,China Tian-Chen Zhang,Department of Epidemiology and Biostatistics,School of Public Health,Anhui Medical University,hefei 230032,Anhui Province,China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Hefei 230032 Anhui Province China.

AIM:To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in inter-feron regulatory factors (IRF3) and the genetic suscep-tibility to chronic hepatitis B virus (HBV) ***:We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as *** tagSNPs in IRF3 (rs10415576,rs2304204,rs2304206) were genotyped with the Multiplex SNaPshot *** genotype and allele frequencies were calculatedand ***:The three SNPs showed no significant geno-type/allele associations with chronic HBV *** allele P values were:rs10415576,P=0.0908,odds ratio (OR) [95% confidence interval (CI)]=1.1798 (0.9740-1.4291);rs2304204,P=0.5959,OR (95% CI)=1.0597 (0.8552-1.3133);rs2304206,P=0.8372,OR (95% CI)=1.0250 (0.8097-1.2976).Overall genotype P values were:rs10415576,P=0.2106;rs2304204,P=0.8458;rs2304206,P=*** were no statisti-cally significant differences between patients with chron-ic HBV infection and *** generated by these three SNPs were also not significantly different between the two ***:The three tagSNPs of IRF3 are not asso-ciated with HBV infection in the Han Chinese population.

关键词： Chronic hepatitis B virus infection Interferon regulatory factors tag single nucleotide polymorphisms Genetic susceptibility Haplotype

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Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guérin and lipopolysaccharide

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Acta Pharmacologica Sinica 2005年第6期26卷 745-752页

作者： Hua WANG, Wei WEI~3, Sheng-yi ZHANG~2, Yu-xian SHEN, Ni-ping WANG, Li YUE, Shu-yun XU Institute of Clinical Pharmacology, Anhui Medical University, hefei 230032, China ~2Department of Chemistry, Anhui University, hefei 230039, China. Institute of Clinical Pharmacology Anhui Medical University Hefei China Department of Chemistry Anhui University Hefei China

Aim: Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guerin (BCG)/ lipopolysaccharide (LPS). Methods: The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate aminotransferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homo-genate were assayed by spectrophotometry. The content of tumor necrosis fac-tor (TNF) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed. Results: In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5,10, or 20 mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF and IL-1 levels in the liver and inhibited the production of TNF and IL-1 by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed. Conclusion: MT-Se showed a hepatic protective action on immunological liver injury in mice.

关键词： melatonin selenium liver superoxide dismutase glutathione peroxidase nitric oxide tumor necrosis factor interleukin-1

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Blocking effects of siRNA on VEGF expression in human colorectal cancer cells

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World Journal of Gastroenterology 2010年第9期16卷 1086-1092页

作者： Yu Yin,Li-Yu Cao,Wen-Qing Wu,Hao Li,Yan Jiang,Hong-Fu Zhang,Department of Pathology,Anhui Medical University,hefei 230032,Anhui Province,China Wen-Qing Wu,Department of Pathology,Anhui Provincial Hospital,hefei 230001,Anhui Province,China Department of Pathology Anhui Medical University Hefei 230032 Anhui Province China.

AIM:To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptors Fmslike tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1) in colorectal carcinoma (CRC),and the blocking effects of small interfering RNAs (siRNAs) on VEGF expression in human colorectal cancer HCT116 ***:Immunohistochemical staining for VEGF,FLT-1 and FLK-1 proteins was performed in 82 cases of CRC and 14 normal colorectal mucosae.A siRNA targeting VEGF was synthesized and transfected into HCT116 cells using lipofectamine *** staining and Western blotting analyses were performed to detect the expression of VEGF *** suppressive effect of the siRNA on cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltertrazolium bromide (MTT) *** apoptosis was detected using flow cytometry (FCM).RESULTS:The expression of VEGF,FLT-1 and FLK-1 in tumor tissues was significantly higher than that in normal tissues (P=0.008,P=0.000,P=0.000).The expression of VEGF was positively correlated with both lymph node metastasis and clinical stage (P=0.009 and P=0.025,respectively).Immunocytochemistry showed that the expression of VEGF was weakly positive and Western blotting indicated a significant reduction in VEGF-siRNA cell protein ***-siRNA cell growth inhibition was assessed by the MTT assay,and the tumor cell proliferation rate was significantly different at 24,48,and 72 h after *** results showed that the VEGF-siRNA group had an apparent aneuploid ***:VEGF,FLT-1 and FLK-1 are associated with colorectal *** silencing of the VEGF gene suppresses proliferation,and induces apoptosis in HCT116 *** results suggest that VEGF may be a new gene therapy target for colorectal cancer.

关键词： Colorectal carcinoma Vascular endothelial cell growth factor Fms-like tyrosine kinase 1 Fetal liver kinase 1 Small interfering RNA

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Therapeutic effects of glucosides of Cheanomeles speciosa on collagen-induced arthritis in mice

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Acta Pharmacologica Sinica 2004年第11期 111-117页

作者： Ling-ling ZHANG, Wei WEI, Shang-xue YAN, Xiang-yang HU, Wu-yi SUNInstitute of Clinical Pharmacology, Anhui Medical University, hefei 230032, China

AIM: To investigate the therapeutic effect of the glucosides of Cheanomeles speciosa (GCS) on the collagen-induced arthritis (CIA) in mice. METHODS: Mice were divided randomly into six groups, including normal, CIA, CIA+GCS (60, 120, and 240 mg/kg) and CIA+glucosides of Tripterygium wilfordii (GTW) groups. CIA model was based on mice. The effect of GCS in CIA mice was measured by paw-swelling, arthritis scores, and histo-pathological assessment of synovium. Indices of thymus and spleens were measured. Thymocytes and splenocytes proliferation, activity of interleukin-1 (IL-1), and interleukin-2 (IL-2) were assayed by MTT and [3H]TdR method. The level of anti-collagen type Ⅱ (CII) antibody in serum and prostaglandin E (PGE) in ankle were assayed by ELISA and ultraviolet spectrophotometer method, respectively. RESULTS: The onset of paw-swelling was on d 24 after injection of emulsion. The peak of secondary inflammation appeared on d 36 and then declined after d 40. GCS and GTW significantly reduced paw-swe

关键词： glucosides Cheanomeles speciosa experimental arthritis inflammation immunity

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Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflarnmatory factors

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Acta Pharmacologica Sinica 2004年第9期 80-83页

作者： Li YUE, Hua WANG, Li-hua LIU, Yu-xian SHEN2, Wei WEIInstitute of Clinical Pharmacology, Anhui Medical University, hefei 230032, China

AIM: To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis. METHODS: The model of rat AA was induced by injection of intradermal complete Freund’s adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin-1 (IL-1) and IL-2 were measured by the assay of thymocytes proliferation. IL-1β and tumor necrosis factor-a (TNF-α) produced

关键词： rats experimental arthritis endostatin angiogenesis inhibitors cytokines

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Gain-of-function mutant SHP-2 might enhance mouse leukemogenesis and leukemia cells malignant behaviors

Gain-of-function mutant SHP-2 might enhance mouse leukemogen...

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中国病理生理学会受体、肿瘤和免疫专业委员会联合学术会议

作者： Si-Ying Wang Anhui Medical University,hefei,Anhui,230032

Leukemia is the most frequent malignant tumor in *** often relapses or metastasizes because of invasion,drug resistance and hyper-proliferation of leukemia cells,which leading to treatment failure in these pediatric *... 详细信息

关键词： SHP Gain-of-function mutant SHP-2 might enhance mouse leukemogenesis and leukemia cells malignant behaviors GOF

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N-Acetylcysteine attenuates lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice

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Acta Pharmacologica Sinica 2007年第11期28卷 1803-1809页

作者： Hua WANG~2,De-xiang XU~(2,3,4),Jin-wei LU~2,Lei ZHAO~2,Cheng ZHANG~2,Wei WEI~(3,4)~2 Department of Toxieology and ~2 Institute of Clinical Pharmacology Anhui Medical University,hefei 230032,China Department of Toxicology Anhui Medical University Hefei China Institute of Clinical Pharmacology Anhui Medical University Hefei China

Aim:To investigate the effects of N-acetylcysteine on D-galactosamine (Ga1N)/lipopolysaccharide (LPS)-induced apoptotic liver injury in ***:Whengiven together with a low dose of LPS,Ga1N highly sensitizes animals to produceapoptotic liver injury with severe hepatic congestion,resulting in rapid *** Ga1N/LPS model,TNF-α is the major mediator leading to apoptotic liver *** oxygen species (ROS) are involved in Ga1N-induced sensitization toTNF-α-evoked hepatocyte apoptosis.N-acetylcysteine (NAC) is an antioxidantand a glutathione (GSH) *** this study,we investigated the effects ofNAC on LPS-induced apoptotic liver injury in Ga1N-sensitized ***:Pretreatment with NAC significantly reduced Ga1N/LPS-induced elevation ofserum alanine aminotransferase *** parallel,Ga1N/LPS-induced hepaticnecrosis and congestion were obviously improved by ***,NACpretreatment significantly alleviated Ga1N/LPS-induced hepatic apoptosis,mea-sured by the inhibition of hepatic caspase-3 activity and attenuation of *** pretreatment had no effect on LPS-evoked nitric oxide productionin Ga1N-sensitized *** in serum TNF-α concentration,which wereobserved in Ga1N/LPS-treated mice,were not significantly reduced by *** NAC pretreatment significantly alleviated LPS-induced hepatic GSHdepletion,DL-buthionine-(SR)-sulfoximine,an inhibitor of GSH synthesis,did notinfluence the protective effect of NAC on Ga1N/LPS-induced apoptotic liver ***:NAC attenuates Ga1N/LPS-induced apoptotic liver injury via its strongROS scavenging and anti-apoptotic effects.

关键词： N-acetylcysteine lipopolysaccharide apoptosis liver injury antioxidant

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Preliminary research on myosin light chain kinase in rabbit liver

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World Journal of Gastroenterology 2001年第6期7卷 868-871页

作者： Bin Ren~1 Hua-Qing Zhu~2 Zhao-Feng Luo~1 Qing Zhou~2 Yuan Wang~2 Yu-Zhen Wang~1 1 Department of Biochemistry and Molecular Biology,University of Science and Technology of China,hefei 230027,Anhui Province,China2 Laboratory of Molecular Biology,Anhui Medical University,hefei 230032,Anhui Province,China Department of Biochemistry and Molecular Biology University of Science and Technology of China Hefei 230027 Anhui Province China.

AIM: To study preliminarily the properties of myosin light chain kinase (MLCK) in rabbit liver. METHODS: The expression of MLCK was detected by reverse transcription-polymerase chain reaction(RT-PCR); the MLCK was obtained from rabbit liver, and its activity was analyzed by gamma-(32)P incorporation technique to detect the phosphorylation of myosin light chain. RESULTS: MLCK was expressed in rabbit liver, and the activity of the enzyme was similar to rabbit smooth muscle MLCK, and calmodulin-dependent. When the concentration was 0.65 mg x L(-1), the activity was at the highest level. CONCLUSION: MLCK expressed in rabbit liver may catalyze the phosphorylation of myosin light chain, which may play important roles in the regulation of hepatic cell functions.

关键词： Animals Hepatocytes Liver Myosin Light Chains Myosin-Light-Chain Kinase Phosphorylation Rabbits Research Support, Non-U.S. Gov't

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