Enhancing cellular immune response to HBV M DNA vaccine in mice by codelivery of interleukin-18 recombinant

Objective: To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines. Methods: BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA; splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro. Results: The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone, but there was not significantly different (P>0.05). Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05). Conclusion: The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.     

“P53 Codon 72 Single Base Substitution in Viral Hepatitis C and Hepatocarcinoma Incidences”

Viral infection with hepatitis C virus (HCV) has a high propensity in becoming chronic and it is the major cause of hepatocellular carcinoma (HCC) worldwide. This review was basically established to illustrate the putative role of the P53 gene Arg72Pro polymorphism on various cancer models and viral infections, focusing on HCV and HCC incidences. Authors studied the 72 G/C single base substitution of P53 gene at codon 72 using various polymorphic techniques. Intriguingly, authors investigated that the P53 codon 72 plays a crucial role as risk factor in several cancer models. Others found that there is no association between codon 72 genotypes and HCV disease severity or liver cancer. Moreover, the lack of a significant relationship between this polymorphism and risk of HCC shows that it does not predispose towards hepatocarcinogenesis and the frequent loss of the proline allele in HCV-associated carcinogenesis of the liver plays some critical role in hepatocarcinogenesis. Amazingly, there is a significant correlation between male homozygotes for P53 72Pro with HCV type 1b infection. However, there was no significant difference between the P53 polymorphism and HCV genotypes 2a and 2b. It was concluded that the P53 gene polymorphism at codon 72 has been investigated as potential risk factor in several cancer models and HCV infections.     

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

The present study evaluated the plausible role of circulating biomarkers in immune pathogenesis of chronic hepatitis considered a priority in clinical hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) patients was quantified and correlation studies were performed with circulating levels of Th1/Th2 cytokines; C reactive protein and circulating nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our knowledge, the study is first among its kind that validates strong positive correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV infections. Although, multi-centric studies including large cohorts are required for translating our findings to clinical practice, however, role of these biomarkers with potential diagnostic or prognostic significance might be helpful in clinical assessment of high-risk individuals, thereby, designing interventional strategies, towards development of personalized medicare. The results of our study also offer valuable insights of immune signaling mediators engaged in development of hepatocellular carcinoma.     

复方甘草甜素(美能)注射液治疗慢性乙型肝炎临床疗效观察

[目的]观察复方甘草甜素(美能)对慢性乙型肝炎的治疗作用.[方法]将病人随机分为为两组,治疗组10例,用美能40 m l/d.iv.3周后改为口服美能片75 mg,每日3次.对照组1 0例,使用甘利欣150 mg/d,VD.3周后改为口服甘利欣100 mg,每日3次.[结果]治疗组治疗后症状缓解率75%;血清ALT水平由306.70±229.33 u/L降为105.00±86.11 u/L;血清AST水平由137.90±71.44 u/L降为64.30±34.93 u/L;血清SB水平由31.80±28.90 umol/L降为16.20±3.43 umol/L.对照组治疗后症状缓解率为66.7%;血清ALT水平由208.20±160.13 u/L降为77.20±65.92 u/L;血清AST水平由92.60±61.19 u/L降为51.20±31.38 u/L;血清SB水平由20.60±5.08 umol/L降为11.70±2.06 umol/L.[结论]复方甘草甜素(美能)的临床疗效与国内同类产品(甘利欣)相仿,具有较好的保肝、降酶作用,有一定的优势.     

New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy

Infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide. However, no vaccine or immunoglobulin is currently available for the prevention of HCV infection. The standard of care (SOC) involving pegylated interferon-α (PEG-IFN α) plus ribavirin (RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1, the most prevalent type of HCV in North America and Europe. Recently, reliable in vitro culture systems have been developed for accelerating antiviral therapy research, and many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are being evaluated in clinical trials. These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration. The aim of this review is to summarize the current developments in new anti-HCV drugs.     

Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults

Objective: To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination. Methods: Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination. Results: A total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ ²=2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116). Conclusions: Domestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.     

Science Letters： Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy

Herein, solid lipid nanoparticles (SLN) were proposed as a new drug delivery system for adefovir dipivoxil (ADV). The octadecylamine-fluorescein isothiocynate (ODA-FITC) was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15. The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system. About 15wt% drug entrapment efficiency (EE) and 3wt% drug loading (DL) could be reached in SLN loading ADV. Comparing with free ADV, the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels in vitro were significantly enhanced.     

乙型肝炎患者机体抗氧化能力的变化

目的:探讨乙型肝炎患者机体抗氧化能力的变化及其与病情的关系.方法: 门诊乙型肝炎患者共124例和健康者30例,均经放射免疫方法检测后加以确诊.乙型肝炎患者分为三组:乙型肝炎病毒复制组、乙型肝炎病毒恢复组、乙型肝炎合并肝癌组.患者组和对照组均经7150型全自动生化分析仪测定血清ALT、AST含量,应用改良TBA微量法测定血清丙二醛(MDA),以黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)、Cu/Zn-SOD及Mn-SOD水平的变化.结果: 乙型肝炎病毒复制组、乙型肝炎病毒恢复组、乙型肝炎合并肝癌组三组患者血清MDA水平均显著高于对照组(P<0.01),而血清SOD、Cu/Zn-SOD及Mn-SOD水平均显著低于对照组(P<0.01);乙型肝炎病毒复制组、乙型肝炎合并肝癌组患者血清MDA水平均显著高于乙型肝炎病毒恢复组(P<0.01),而血清SOD、Cu/Zn-SOD及Mn-SOD水平均显著低于乙型肝炎病毒恢复组(P<0.01);乙型肝炎合并肝癌组患者血清MDA水平均显著高于乙型肝炎病毒复制组(P<0.01),而血清SOD、Cu/Zn-SOD及Mn-SOD水平均显著低于乙型肝炎病毒复制组(P<0.01).但血清MDA水平与ALT、AST水平(r=0.151),血清SOD、Cu/Zn-SOD及Mn-SOD水平与ALT、AST水平(r=-0.218)均无相关性(P>0.05).结论: 乙型肝炎患者出现明显抗氧化能力的异常.通过血清MDA、SOD、Cu/Zn-SOD及Mn-SOD水平的检测,可为乙型肝炎的临床防治及疗效观察提供一定的依据.     

Character of HBV （hepatitis B virus） polymerase gene rtM204V／I and rtL180M mutation in patients with lamivudine resistance

Objectives: To investigate the relationship between HBV (hepatitis B virus) polymerase gene 180 and 204 sites mutation and lamivudine resistance. Methods: One hundred forty-one patients with lamivudine resistance after lamivudine treatment and 60 chronic hepatitis B patients without lamivudine treatment were enrolled in this study. The serum HBV DNA mutation was analyzed by sequence detection via polymerase chain reaction (PCR). The sequences of the same patient were analyzed before and after lamivudine treatment. Results: One hundred and nine lamivudine resistance patients had HBV YMDD (tyrosine-methionine-aspartate-aspartate) mutation. Among them, 45 patients had rtL180M/M204V mutation (41.28%), 28 patients had rtL 180M/M204I mutation (25.70%) and 36 patients had rtM204I mutation (33.02%). There were 6 patients with rtL180M mutation in 32 lamivudine resistance patients. Sixty chronic hepatitis patients without lamivudine treatment had no mutations. Conclusions: HBV mutations, which play an important role in lamivudine resistance usually locate at polymerase gene 204 site; 180 site mutation was also observed in these patients. Evaluation of the anti-virus therapy by surveillance of the two sites mutations is of importance.     

乙肝专题文献知识库的创新构建

信息整合与数据挖掘技术在文献数据库创新性建设领域具有非常重要的意义,这已在国外同行的应用中取得了较好的效果,但国内对此项技术的研究和应用才刚刚起步。该研究通过广泛调研,制定了文献专题知识数据库的期刊和文献收录标准,以及数据库框架结构和数据录入标准。在此基础上,收集了国内外乙肝相关文献,借助期刊和文献影响力及专家内容分析等筛选方法筛选了近1．5万篇左右文献信息,构建了一个知识覆盖面广、文章质量高和分类标引好的乙肝专题文献知识库,并进一步通过构建文本挖掘工具字典,成功实现了乙肝专题文献知识库与国内外科学数据型数据库的关联与整合,从而初步实现了乙肝病毒相关蛋白质的知识