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Effects of blueberry on hepatic fibrosis and transcription factor Nrf2 in rats

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World Journal of Gastroenterology 2010年第21期16卷 2657-2663页

作者： Wang, Yu-Ping Cheng, Ming-Liang Zhang, Bao-Fang Mu, Mao Wu, Jun Guiyang Med Coll Dept Infect Dis Guiyang 550004 Guizhou Prov Peoples R China

AIM:To investigate the effects of blueberry on hepatic fibrosis and NF-E2-related factor 2(Nrf2) transcription factor in ***:Forty-five male Sprague-Dawley rats were randomly divided into control group(A);CCl4-induced hepatic fibrosis group(B);blueberry prevention group(C);Dan-shao-hua-xian capsule(DSHX) prevention group(D);and blueberry + DSHX prevention group(E).Liver fibrosis was induced in rats by subcutaneous injection of CCl4 and a high-lipid/low-protein diet for 8 wk(except the control group).The level of hyaluronic acid(HA) and alanine aminotransferase(ALT) in serum was *** activity of superoxide dismutase(SOD),glutathione-S-transferase(GST) and malondialdehyde(MDA) in liver homogenates was *** degree of hepatic fibrosis was evaluated by hematoxylin and eosin and Masson *** of Nrf2 and NADPH quinone oxidoreductase 1(Nqo1) was detected by real-time reversed transcribed-polymerase chain reaction,immunohistochemical techniques,and western ***:Compared with group B,liver indices,levels of serum HA and ALT of groups C,D and E were reduced(liver indices:0.038 ± 0.008,0.036 ± 0.007,0.036 ± 0.005 vs 0.054 ± 0.009,P<0.05;HA:502.33 ± 110.57 ng/mL,524.25 ± 255.42 ng/mL,499.25 ± 198.10 ng/mL vs 828.50 ± 237.83 ng/mL,P<0.05;ALT:149.44 ± 16.51 U/L,136.88 ± 10.07 U/L,127.38 ± 11.03 U/L vs 203.25 ± 31.62 U/L,P<0.05),and SOD level was significantly higher,but MDA level was lower,in liver homogenates(SOD:1.36 ± 0.09 U/mg,1.42 ± 0.13 U/mg,1.50 ± 0.15 U/mg vs 1.08 ± 0.19 U/mg,P<0.05;MDA:0.294 ± 0.026 nmol/mg,0.285 ± 0.025 nmol/mg,0.284 ± 0.028 nmol/mg vs 0.335 ± 0.056 nmol/mg,P<0.05).Meanwhile,the stage of hepatic fibrosis was significantly weakened(P<0.05).Compared with group A,the activity of GST liver homogenates and expression levels of Nrf2 and Nqo1 in group B were elevated(P<0.05).The expression level of Nrf2 and Nqo1 in groups C,D,and E were increased as compared with group B,but the difference was not significant

关键词： Blueberry Hepatic fibrosis NF-E2-related factor 2 NADPH quinone oxidoreductase 1 GlutathioneS-transferase

Relationship between HBV genotypes and anti-viral therapeutic efficacy of interferon-alpha

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Hepatobiliary & Pancreatic diseases International 2007年第2期6卷 166-171页

作者： Ma, Jin-Chun Wang, Lu-Wen Li, Xin-Jian Liao, Yong-Feng Hu, Xi-Ya Gong, Zuo-Jiong Wuhan Univ Renmin Hosp Dept Infect Dis State Key Lab Virol Wuhan 430060 Peoples R China Huangshi Aikang Hosp Dept Infect Dis Huangshi 435000 Peoples R China

BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.

关键词： hepatitis B virus genotype gene variation interferon-alpha anti-viral therapy

Detection of hepatitis E virus RNA in sera of patients with hepatitis E by polymerase chain reaction

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Hepatobiliary & Pancreatic diseases International 2007年第1期6卷 38-42页

作者： Zhao, Zhen-Yu Ruan, Bing Shao, Hui Chen, Zhen-Juan Liu, She-Lan Zhejiang Univ Affiliated Hosp 1 Sch MedMinistry Publ Hlth Key Lab Infect DisDept Infect Dis Hangzhou 310003 Peoples R China

BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of HEV infection more thoroughly. METHODS: HEV RNA was detected in the serum samples of hospitalized patients with acute hepatitis E by reverse transcriptase-nested polymerase chain reaction (RT-nPCR) using two pairs of primers from open reading frame (ORF) I of the HEV genome. RESULTS: The serum samples from 44 (70%) of 62 patients were positive for HEV RNA. Thirty-two of these patients, with 288 serial serum specimens, were followed up for the whole process, and 24 patients (75%) were positive for HEV RNA. The positive rates declined with the course of the disease, serum HEV RNA persisting for 20.6 days on average after onset of illness. Serum HEV RNA remained positive in 36 (81.8%) of the 44 patients at the time their alanine aminotransferase (ALT) began to decrease. There was no difference in HEV RNA positivity between serum with high levels of HEV antibody (peak P/N ratio >= 4.0) and that with low levels (peak P/N ratio 4.0), with 25 out of 35 and 19 out of 27 (71.4% vs. 70.4%, P>0.05), respectively. CONCLUSIONS: There is a relatively long period of HEV viremia in patients with hepatitis E. The proportion of HEV viremia and its duration are not directly related to serum ALT values or HEV antibody levels.

关键词： hepatitis E viremia HEV RNA duration

Betaine inhibits Toll-like receptor 4 expression in rats with ethanol-induced liver injury

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World Journal of Gastroenterology 2010年第7期16卷 897-903页

作者： Shi, Qing-Zhao Wang, Lu-Wen Zhang, Wei Gong, Zuo-Jiong Wuhan Univ Renmin Hosp Dept Infect Dis Wuhan 430060 Hubei Province Peoples R China

AIM:To test whether ethanol feeding could induce Toll-like receptor 4(TLR4)responses,assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver ***:Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control,model,low and high dose betaine *** control group,all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 *** was administered intragastrically after exposure of ethanol for 4 *** changes of liver histology were *** expression of TLR4 mRNA and protein was detected by RT-PCR and Western blotting,*** serum aminotransferase activity alanine transarninase(ALT),aspartate aminotransferase(AST),serum endotoxin,and liver inflammatory factors tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-18(IL-18)were also ***:Compared with control group,rats of model group developed marked liver injury,accompanied by an increase of ALT(159.41±7.74 U/L vs 59.47± 2.34 U/L,P<0.0001),AST(248.25±1.40 U/L vs 116.89±3.48 U/L,P<0.0001),endotoxin(135.37± 30.17 ng/L vs 44.15±7.54 ng/L,P<0.0001),TNF-α(20.81±8.58 pg/mL vs 9.34±2.57 pg/mL,P=0.0003),IFN-γ(30.18±7.60 pg/mL vs 16.86±9.49 pg/mL,P= 0.0039)and IL-18(40.99±8.25 pg/mL vs 19.73±9.31 pg/mL,P=0.0001).At the same time,the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption(1.45±0.07 vs 0.44±0.04,P<0.0001;1.83±0.13 vs 0.56±0.08,P<0.0001).Compared with model group,betaine feeding resulted in significant decreases of ALT(64.93 ±6.06 U/L vs 159.41±7.74 U/L,P<0.0001),AST(188.73±1.11 U/L vs 248.25±1.40 U/L,P<0.0001),endotoxin(61.80±12.56 ng/L vs 135.37±30.17 ng/L,P<0.0001),TNF-α(9.79±1.32 pg/mL vs 20.81± 8.58 pg/mL,P=0.0003),IFN-γ(18.02±5.96 pg/mL vs 30.18±7.60 pg/mL,P=0.0008)and IL-18(18.23±7.01 pg/mL vs 40.99±8.25 pg/mL,P<0.0001).Betaine also improved liver *** expression levels of TLR4 mRNA

关键词： Betaine Toll-like receptor 4 Alcoholic liver injury Expression

The MELD scoring system for predicting prognosis in patients with severe hepatitis after plasma exchange treatment

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Hepatobiliary & Pancreatic diseases International 2007年第5期6卷 492-496页

作者： Yu, Jian-Wu Wang, Gui-Qiang Zhao, Yong-Hua Sun, Li-Jie Wang, Shu-Qin Li, Shu-Chen Harbin Med Coll Dept Infect Dis Affiliated Hosp 2 Harbin 150086 Peoples R China Peking Univ First Hosp Dept Infect Dis Beijing 100034 Peoples R China

BACKGROUND: Hepatic failure caused by severe hepatitis is a clinical syndrome where the major liver functions, particularly detoxification, synthetic functions, and metabolic regulation are impaired to different degrees, and may result in major life-threatening complications such as hepatic encephalopathy, ascites, jaundice, cholestasis, bleeding and hepatorenal syndrome. Plasma exchange (PE) has been found useful in treating patients with fulminant hepatic failure by removing hepatic toxins and replacement of clotting factors, so PE treatment has temporary supportive effects on liver failure caused by severe viral hepatitis. in this study, our aim was to predict the prognosis of patients with severe hepatitis after PE treatment using the end-stage liver disease (MELD) scoring system. METHODS: Two hundred and twenty patients were randomly divided into PE and control groups, and the MELD score was calculated for each patient according to the original formula. The efficacy of PE was assessed by mortality or improvement in biochemical parameters and MELD score. RESULTS: The levels of total bilirubin and international normalised ratio (INR) in patients whose MELD scores were between 30 and 39 were lower than those before PE treatment, as those in patients whose MELD scores were 40 or higher. The mortality of patients in the PE group with MELD scores from 30 to 39 was 50.0%, while it was 83.3% in the control group (P0.05). CONCLUSIONS: PE treatment can decrease the serum total bilirubin level and INR and MELD score of patients with severe hepatitis and improve liver function. Compared with the control group, PE can significantly decrease the mortality of patients with MELD scores from 30 to 39, but has no effect in patients with MELD scores of 40 or higher.

关键词： severe hepatitis model for end-stage liver disease plasma exchange mortality

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

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Hepatobiliary & Pancreatic diseases International 2010年第5期9卷 499-507页

作者： Wang, Lu-Wen Chen, Hui Gong, Zuo-Jiong Wuhan Univ Renmin Hosp Dept Infect Dis Wuhan 430060 Peoples R China

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with c

关键词： high mobility group box-1 protein regulatory T cells chronic hepatitis B liver failure

Effects of Dan-shao-hua-xian on expression of PPAR-gamma and NF-kappa B in rat liver fibrosis

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Hepatobiliary & Pancreatic diseases International 2008年第2期7卷 179-184页

作者： Wang, He-Yan Cheng, Ming-Liang Affiliated Hosp Guiyang Med Coll Dept Infect Dis Guiyang 550004 Peoples R China

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor kappa B (NF-kappa B) play important roles in liver fibrosis. This study aimed to investigate the effects of Dan-shao-hua-xian, a preparation of traditional Chinese medicine, on the expression of PPAR-gamma and NF-kappa B in the fibrotic livers of rats. METHODS: Seventy Wistar rats were randomly divided into 4 groups: treatment (model, 8 weeks+treatment, 8 weeks; group A), natural recovery (model, 8 weeks+ saline, 8 weeks; group B), model (model only, 8 weeks; group Q, and control (normal, untreated, 16 weeks; group D). Each group consisted of 20 rats (except for group D, which had 10). Fibrotic liver models were induced in rats by subcutaneous injection of CCI4, oral administration of alcohol and a high-lipid/low-protein diet for 8 weeks. After the models were established, the rats in group A were orally given Dan-shao-hua-xian capsules daily for another 8 weeks. Then, the liver indices serum hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) were measured. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the liver tissue was determined. The expression of PPAR-gamma was detected by immunohistochemical techniques. The protein levels of PPAR-gamma and NF-kappa B were determined by Western blotting. RESULTS: The concentrations of serum HA, TNF-alpha and Hyp in group C increased compared with group D (P<0.05), and they decreased in group A compared with group C (P<0.05). The expression of PPAR-gamma in group C decreased compared with group D (P<0.05), and it increased in group A compared with groups B and C (P<0.05). Similarly, Western blotting showed that the expression of PPAR-gamma in group C decreased compared with group D, and it increased in group A compared with group C. The expression of NF-kappa B increased in group C compared with group D (P<0.05), and it decreased in group A compa

关键词： Dan-shao-hua-xian capsules peroxisome proliferator-activated receptors NF-kappa B hepatic fibrosis

Lactosamination of liposomes and hepatotropic targeting research

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World Journal of Gastroenterology 2000年第4期6卷 593-596页

作者： Chen YP Zhang L Lu QS Feng XR Luo KX First Mil Med Univ Dept Infect Dis Nanfang Hosp Guangzhou Guangdong Prov Peoples R China

Site-specific delivery of therapeutic drugs to their target cells is a major scientific challenge for the pharmaceutical sciences. It offers a number of advantages over conventional drug administration. With drug targeting, high local concentrations of the drug can be achieved, thus circumventing many unwanted side effects. Various carriers have been suggested for the delivery of drugs, including liposomes[1 - 5] and (neo ) glycoproteins[6-8]. The asialoglycoprotein receptor (ASGP-R) has frequently been utilized for targeting drugs to the parenchymal liver cell[6- 12]. Liposomes have several advantageous characteristics as drug carrier, and particularly, ligandtacked liposomes achieve a highly effective targeting[13]. Hara et al reported that asialofetuin (AF)-tacked liposomes distributed to rat hepatocytes selectively in vivo[14], and ASGP-R mediated the uptake of AF-liposomes encapsulating IFN-γ by isolated rat hepatocytes in vitro[15]. Lactosaminated human serum albumin (L-HSA) is a neoglycoprotein taking number of galactose residue as terminal sugar[6].

关键词： liposomes asialoglycoprotein liver interferon-alpha antigens viral drug carriers drug therapy rats

Transfusion transmitted virus infection in general populations and patients with various liver diseases in south China

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World Journal of Gastroenterology 2000年第5期6卷 738-741页

作者： Chen YP Liang WF Zhang L He HT Luo KX First Mil Med Univ Nanfang Hosp Dept Infect Dis Guangzhou 510515 Guangdong Provi Peoples R China

INTRODUCTIONAlthough several specific detecting methods hadbeen applied to determine the hepatitis virus,therewas a lot of cryptogenic hepatitis without anyknown hepatitis infectious *** of hepatitis G virus (HGV) (also knownas GB-C virus) infection has been reported to be 5%-13% in patients with non-A-E hepatitis andcirrhosis,however,there is little evidencesuggesting that HGV causes hepatitis in human.

关键词： transfusion-transmitted virus liver disease/etiology DNA virus polymerase chain reaction serodiagnosis hepatitis viruses