Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study.

BACKGROUND: Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis. However, few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites. AIM: To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism. METHODS: A total of 75 cirrhotic patients with refractory ascites were enrolled in the study (50 in a rifaximin and 25 in a control group). Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics (19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics). All patients received conventional treatment for refractory ascites, while patients in the rifaximin group received oral rifaximin-α 200 mg four times daily for at least 2 wk. The ascites grade, fasting weight, liver and kidney function, and inflammatory factors in the plasma were evaluated before and after treatment. In addition, the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment. The patients were followed for 6 mo. RESULTS: Compared with the control group, the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin (P = 0.011 and 0.009, respectively). The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group (P = 0.048). The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group (P = 0.024). The abundance of Roseburia, Haemophilus, and Prevotella was significantly reduced after rifaximin treatment, while the abundance of Lachnospiraceae_noname, Subdoligranulum, and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics. The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics. CONCLUSION: Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites. A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria, thus improving the systemic inflammatory state.

[Mechanisms of tanshinone â ¡_A in reducing 4-HNE-induced hepatocyte damage by activating PPARα].

Tanshinone Ⅱ_A( Tan Ⅱ_A),the liposoluble constituents of Salvia miltiorrhiza,can not only ameliorate the lipidic metabolism and decrease the concentration of lipid peroxidation,but also resist oxidation damage,scavenge free radicals and control inflammation,with a protective effect on prognosis after liver function impairment. Therefore,the studies on the exact mechanism of Tan Ⅱ_A in protecting the liver can provide important theoretical and experimental basis for the prevention and treatment effect of Tan Ⅱ_A for liver injury. In the present study,the protective effects and mechanism of Tan Ⅱ_A on 4-hydroxynonenal( 4-HNE)-induced liver injury were investigated in vitro. Normal liver tissues NCTC 1469 cells were used to induce hepatocytes oxidative damages by 4-HNE treatment. The protective effect of Tan Ⅱ_A on hepatocytes oxidative damages was detected by release amount of lactate dehydrogenase( LDH) analysis and hoechst staining. The protein expression changes of peroxisome proliferator-activated receptor α( PPARα) and peroxisome proliferator response element( PPRE) were analyzed by Western blot analysis in NCTC 1469 cells before and after Tan Ⅱ_A treatment. The gene expression changes of fatty aldehyde dehydrogenase( FALDH) were analyzed by Real-time polymerase chain reaction( PCR) analysis. The results showed that 4-HNE increased the release amount of LDH,lowered the cell viability of NCTC 1469 cells,and Tan Ⅱ_A reversed 4-HNE-induced hepatocyte damage. Western blot analysis and RT-PCR analysis results showed that 4-HNE decreased the expression of PPARα and FALDH and increased the expression of 4-HNE. However,the expression of PPARα and FALDH were increased significantly and the expression of 4-HNE was decreased obviously after Tan Ⅱ_A treatment. This study confirmed that the curative effect of Tan Ⅱ_A was obvious on hepatocytes damage,and the mechanism may be associated with activating PPARα and FALDH expression as well as scavenging 4-HNE.

Epimedin C Promotes Vascularization during BMP2-Induced Osteogenesis and Tumor-Associated Angiogenesis.

Epimedin C is one of the chemical markers and major flavonoids in Herba Epimedii (Yinyanghuo), which is traditionally used to treat bone diseases and gonadal dysfunction in China. Our previous study indicated that epimedin C could induce endothelial-like, but not osteogenic differentiation of C3H/10T1/2 cells in vitro. As vasculogenesis plays a pivotal role in bone formation, this study used the bone morphogenetic protein 2 (BMP2) induced ectopic bone formation model and mice 4T1 breast cancer cells co-implanted with luciferase labeled C3H/10T1/2 cells (4T1 [Formula: see text] C3H/10T1/2-Luc) model to examine the in vivo effects of Epimedin C on vasculogenesis. As a result, Epimedin C significantly increased the bone weight and blood perfusion of mice in the BMP2 induced ectopic osteogenesis model, and the bone in Epimedin C [Formula: see text] BMP2 group was more mature than that in BMP2 group. In addition, the tumor weight, blood perfusion and tumor-associated angiogenesis were also significantly increased in the Epimedin C treated 4T1 tumor bearing mice. The mRNA levels of endothelial markers, such as the platelet endothelial adhesive factor-1(CD31), the endothelial cell specific molecule-1(ESM-1), and the vascular von Willebrand factor (vWF) in mouse 4T1 mammary tumor tissue, were commonly found to occur alongside the luciferase (labeled in C3H/10T1/2 cells) expression and significantly increased after Epimedin C treatment. Taken together, Epimedin C can effectively promote vascularization both in the BMP2-depended bone formation model and in the 4T1 mammary tumor-bearing model by inducing an endothelial-like differentiation of C3H/10T1/2 in BALB/c nude mice.

The impact of gender difference on clinical and echocardiographic outcomes in patients with heart failure after cardiac resynchronization therapy: A systematic review and meta-analysis.

BACKGROUND: Cardiac resynchronization therapy(CRT) has been recommended as a standard treatment for patients with advanced heart failure. However, some studies have reported different clinical and echocardiographic outcomes between male and female patients who received CRT. This Meta-analysis is to determine whether gender difference has any significant impact on clinical and echocardiographic outcomes in patients with heart failure after CRT. METHODS AND RESULTS: PubMed, Embase, and the Cochrane library database were searched. A total of 149,259 patients in 11 studies were identified. Our analysis demonstrated that women showed lower all-cause mortality than men after CRT (odds ratio[OR] 0.50, 95% confidence interval [CI] 0.36 to 0.70). No significant difference was observed in the increment of New York Heart Association (NYHA) functional class(standard mean difference[SMD] -0.07,95% CI -0.15 to 0.01), 6-minitue walk distance (6-MWD) (SMD -0.05, 95% CI -0.07 to 0.17), and quality of life (QoL) (SMD -0.10, 95% CI -0.23 to 0.03). With respect to the echocardiographic parameters, women exhibited statistically significant improvement in left ventricular ejection fraction (LVEF) (SMD 0.25,95% CI 0.07 to 0.43), and decrement of left ventricular end diastolic diameter (LVEDD) (SMD -0.27, 95% CI -0.39 to -0.25) as compared with men. No significant difference was observed in left ventricular end diastolic volume (LVEDV) (SMD -0.08, 95% CI -0.28 to 0.08) and left ventricular end systolic volume (LVESV) (SMD -0.16, 95% CI -0.40 to 0.09) between men and women. CONCLUSION: Women seem to obtain greater benefits from CRT both in clinical and echocardiographic outcomes compared with men. But as this gender superiority could be observed only during long-term follow-up periods, further studies are needed to elucidate exact reasons for this phenomenon.

Measurement of serum procalcitonin levels for the early diagnosis of spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis.

BACKGROUND: It is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs. METHODS: Our cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers. RESULTS: Among the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84-0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively. CONCLUSION: Serum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3 contributes to the progress of HCC is largely unclear. The present study investigated the association between GPC3 expression and HCC clinicopathological characteristics, and particularly focused on the role and underlying mechanisms of GPC3 in HCC epithelial-mesenchymal transition (EMT). Remarkably elevated expression of GPC3 was demonstrated in HCC tumor tissues compared with paired non-tumor tissues in 45 patients with HCC by quantitative real-time PCR, immunohistochemistry, and western blotting, respectively. Furthermore, the tissue expression of GPC3 was increased during HCC progression from Barcelona Clinic Liver Cancer stage A or B to stage C. The enhanced levels of GPC3 in HCC tumor tissues were tightly correlated to the expression of the EMT-associated proteins and tumor vascular invasion. Patients with GPC3-high expression in tumor tissues displayed significantly shorter survival time than those with GPC3-low expression (P=0.001). Consistent with the findings in patients, HepG2 cells, which expressed high levels of GPC3, showed stronger capacity of migration and significant EMT-like changes when compared to those HCC cells with low levels of GPC3, e.g., Hep3B and Huh7 in scratch, Transwell assays and western blotting. Furthermore, administration with exogenous GPC3 in HCC cells activated extracellular signal-regulated kinase (ERK) and significantly enhanced cell migration and invasion. The behavior was significantly inhibited by the ERK inhibitor PD98059. Together, our studies show that GPC3 contributes to HCC progression and metastasis through impacting EMT of cancer cells, and the effects of GPC3 are associated with ERK activation.

Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients.

AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma. METHODS: Thirty-nine patients (mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan (15 mg/d for 5-14 d) and diuretics (40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B (69.2%), hepatitis C (7.7%) and alcohol-induced (23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan. RESULTS: Tolvaptan increased the mean urine excretion volume (1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment (from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.

Effect of curcumin on down-expression of thrombospondin-4 induced by oxidized low-density lipoprotein in mouse macrophages.

This study was designed to investigate the effect of curcumin on the expression of thrombospondin-4 (THBS-4) in mouse macrophages treated with oxidized low-density lipoprotein (oxLDL). The mouse macrophage cell line ANA-1 was treated with oxLDL. Cell viability was measured by MTT assay. ANA-1 cells were divided into five groups: control group, model group, 5 µM curcumin group, 15 µM curcumin group and 25 µM curcumin group. The gene and protein expression levels of THBS-4 in each group were determined by real-time quantitative polymerase chain reaction (PCR) and western blotting, respectively. MTT assay showed that curcumin concentrations up to 25 µM and oxLDL concentrations up to 20 µg/ml had no significant cytotoxic effects on macrophages at 24 h. Real-time quantitative PCR revealed that THBS-4 mRNA expression was markedly reduced by stimulation with oxLDL, but subsequently significantly increased by treatment with curcumin. Western blotting confirmed that curcumin (5, 15, and 25 µM) significantly prevented the decrease in THBS-4 expression induced by oxLDL (20 µg/ml) in macrophages. Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin.

Antiviral drug resistance increases hepatocellular carcinoma: a prospective decompensated cirrhosis cohort study.

AIM: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients. METHODS: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed. RESULTS: Among the antiviral treatment patients, 162 had a complete virological response (CVR), and 36 were drug-resistant (DR). The two-year cumulative incidence of hepatocellular carcinoma (HCC) in the DR patients (30.6%) was significantly higher than that in both the CVR patients (4.3%) and the control group (10.3%) (P < 0.001). Among the DR patients in particular, the incidence of HCC was 55.6% (5/9) in those who failed rescue therapy, which was extremely high. The rtA181T mutation was closely associated with rescue therapy failure (P = 0.006). The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline (8.9 ± 2.3 vs 6.0 ± 1.3, P = 0.043). CONCLUSION: This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients, especially in those who failed rescue therapy.

Expressions of type I collagen, α2 integrin and ß1 integrin in sclera of guinea pig with defocus myopia and inhibitory effects of bFGF on the formation of myopia.

AIM: To investigate the expressions of type I collagen, α2 integrin and ß1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and ß1 integrin. METHODS: After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and ß1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular -7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. RESULTS: The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular -7D lens could decrease the levels of type I collagen, α2 integrin and ß1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION: bFGF can prevent the formation and development of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and ß1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.

[Ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage: clinical features and prognostic implications].

OBJECTIVE: To investigate the incidence, clinical features and prognostic implications of ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. METHODS: By retrospective review of the medical records of all 264 inpatients with upper gastrointestinal hemorrhage of hepatitis B related liver cirrhosis from January 1st 2007 to November 30th 2008, 11 patients with ischemic hepatitis (IH) were identified. The clinical features and prognostic implications were compared between the IH patients and 30 patients without ischemic hepatitis (control group). RESULTS: The incidence of ischemic hepatitis was 4.17% in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. The patients in IH group were younger than those in control group, the average age was (43.1+/-5.7) in IH group and (52.3+/-11.1) in control group (P=0.013). The serum alanine aminotransferase and aspartate aminotransferase were increased more than 20-fold above the upper limit of normal values, and returned to normal values within 10 days. Compared to the control group, total bilirubin, lactate dehydrogenase, alkaline phosphates, gamma-glutamyltransferase, blood urea nitrogen, creatinine, and white blood cells were increased, while serum cholinesterase was decreased in IH group (P<0.05). The fatality rate of ischemic hepatitis was much higher than that of control group (54.5% vs 16.7%, P=0.041). The main causes of death in IH group were infection, hepatorenal syndrome and hepatic encephalopathy. The patients in IH group lost 200 to 3600 milliliter blood, and hemorrhagic shock occurred in 63.6% (7/11) of IH patients. Therefore the bleeding volume was not correlated with the occurrence rate of ischemic hepatitis. CONCLUSION: Ischemic hepatitis may occur secondary to upper gastrointestinal hemorrhage in hepatitis B related liver cirrhosis. The risk factors of ischemic hepatitis in cirrhositic patients with upper gastrointestinal hemorrhage are young and with hemorrhagic shock, and poor liver function. It is important to use antibiotics in time to improve the prognosis of these patients.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients.

AIM: To study and determine the resting energy expenditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were assessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 +/- 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 +/- 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improvement of liver function, the glucose oxidation rate increased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is significantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These results warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

Progress of research in treatment of hyperlipidemia by monomer or compound recipe of Chinese herbal medicine.

Hyperlipidemia (HLP) is the No.1 risk factor for patients with atherosclerosis (AS) and is directly related to the occurrence of coronary artery disease (CAD) and cerebrovascular disease. Therefore, prevention and treatment of AS is of great importance and of practical significance in controlling the incidence and mortality of CAD. With its peculiar syndrome-dependent therapy, traditional Chinese medicine (TCM) has accumulated abundant practical experiences in this field and good clinical effects have been achieved. Chinese herbal medicine, with its particularly unique advantages and high potentials yet to be tapped, displays its huge strength in HLP prevention and treatment. The progress of studies concerning prevention and treatment of HLP by Chinese herbal medicines, in the form of monomers or compound recipes, is reviewed in this paper.

[Effect of curcumin on the gene expression of low density lipoprotein receptors].

OBJECTIVE: To investigate the molecular mechanisms and effective target points of lipid-lowering drug, Rhizoma Curcumae Longae, and study the effect of curcumin on the expression of low density lipoprotein (LDL) receptors in macrophages in mice. METHODS: Macrophages in mice were treated with curcumin, which was purified from the ethanolly extraction of Rhizoma Curcumae Longae for 24 h. The LDL receptors expressed in the macrophages were determined by enzyme-linked immunosorbent assay (ELISA) and assay of DiI labeled LDL uptake by flow cytometer. RESULTS: It was found for the first time that 10 micromol/L-50 micromol/L curcumin could obviously up-regulate the expression of LDL receptor in macrophages in mice, and a dose-effect relationship was demonstrated. CONCLUSION: One of the lipid-lowering mechanisms of traditional Chinese medicine, Rhizoma Curcumae Longae, was completed by the effect of curcumin through the up-regulation of the expression of LDL receptor.

A peroxisome proliferator response elements regulatory system in xenopus oocytes and its application.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a kind of ligand-activated transcription factors binding to peroxisome proliferator response element (PPRE), a specific recognition site. It is thought to play a critical role in glucose and lipid metabolism and in inflammation control. The aim of this study was to establish a new cellular model for the quick screening of lipid-lowering drugs, which may be effective as PPAR-gamma ligands on the PPRE-mediated pathway regulatory system. METHODS: Two plasmids were constructed: pXOE-PPARgamma, in which the human PPARgamma gene was in the downstream of TFIIIA gene promoter, and pLXRN-PPRE-d2EGFP, in which the enhanced green fluorescent protein (EGFP) gene was subcloned into PPRE. The xenopus oocytes were injected with these two plasmids, and consequently treated with prostaglandin E1, pioglitazone, and different kinds of lipid-lowering drugs. After 3 days, the oocytes were observed under a fluorescence microscope. To confirm the drug action,we injected pXOE-PPARgamma plasmid into the oocytes, which then treated with prostaglandin E1 and Hawthorn flavonoids. The mass of expressed lipoprotein lipase (LPL) in the cells was determined by enzyme labeling linked immunosorbent assay (ELISA). RESULTS: The expression of EGFP was only induced by prostagalandin E1, pioglitazone, Hawthorn flavonoids. A concentration-response relationship was seen between expressed EGFP and Hawthorn flavonoids. The levels of LPL in both Hawthorn flavonoids groups and PPARgamma ligand prostagalandin E1 group injected with pXOE-PPARgamma plasmid increased significantly (< 0.001) compared with controls, and a concentration-response relationship was observed between LPL mass and Hawthorn flavonoids. CONCLUSIONS: It is possible to establish a PPRE regulatory EGFP reporter system in xenopus oocytes to monitor the activity of PPARgamma ligand. Hawthorn flavonoids can increase the expression of gene downsteam of PPRE by effect on the PPRE pathway regulatory system.

[Effect of curcumin on expression of human low density lipoprotein receptors in Xenopus Laevis oocytes].

OBJECTIVE: To investigate the molecular mechanism of curcumin in reducing blood lipids by establishing gene expression system of human low density lipoprotein receptors (LDL-R) in Xenopus Laevis oocytes (XLO). METHODS: The expression of LDL-R on cytomembrane was determined using immuno-fluorescent, ligand-fluorescent and immune colloidal gold techniques after human LDL-R containing p3.7 LDL plasmid was led into nucleus. And the expression of LDL-R gene in XLO was quantitatively determined by ELISA after being interfered with different concentrations of curcumin. RESULTS: The human LDL-R gene could be expressed on XLO, which could be significantly enhanced by curcumin in a dose-dependent manner. Conclusion One of the paths of curcumin in reducing blood lipids and anti-atherosclerosis was improving LDL-R gene expression and increasing the LDL-cholesterol absorption of cells.

[Impaired non-viral specific immune function of dendritic cell does not interfere with clearance and cytotoxic T lymphocyte response to HBV or HCV].

OBJECTIVE: To investigate the correlation between impaired non-viral specific immune function of dendritic cell (DC) and viral clearance and cytotoxic T lymphocyte (CTL) response to HBV or HCV in patients with HBV and HCV coinfection. METHODS: Twenty-five patients with HBV and HCV coinfection were investigated in this study. In 1994 and 2002, biochemical and virological markers and quantitative serum HBV DNA and HCV RNA levels were detected in these patients. According to the virus clearance status, these patients were divided into 4 groups: 14 patients with both HBV and HCV clearance (Group A), 6 patients with HCV clearance only (Group B), 3 patients with HBV clearance only (Group C), and 2 patients with persistent infection of HBV and HCV (Group D). Phenotypes and immune functions of monocyte-derived DCs were compared between these groups. 51Cr release assay were used to measure CTL response to epitopes derived from HBV, HCV or influenza virus (as positive control) in HLA-A2+ patients. RESULTS: Impaired non-viral specific immune functions of DCs were observed in group B, C and D compared with group A and normal donors (Group N). These impaired functions included CD86 decreasing expression and lower capacity to stimulating allogenic T cells and uptaking antigen. The specific CTL response to HBV- and HCV-derived peptides could be induced in group A (12/12). The specific CTL response to HBV-derived peptides or to HCV-derived peptides could be induced in group C (3/3) or B (5/5), respectively. But the specific CTL response to both of two HBV-derived peptides or two HCV-derived peptides could not be induced in group C (0/3) or B (0/5), respectively. And no CTL response to HBV or HCV-derived peptides could be induced in groups D (0/1) and N (0/4). CONCLUSION: 1. The results suggest that specific CTL response to HBV or HCV play a vital role in the viral clearance. 2. The DCs with impaired non-viral specific immune functions exist in chronic patients with HBV and/or HCV infection, but do not interfere with clearance and CTL response to HBV or HCV. It is reasonable to speculate that impaired functions of DCs result from viral infection.

[Dendritic cells originated from the peripheral blood in chronic hepatitis B patients can induce specific T cell immune response].

OBJECTIVE: To study whether dendritic cells (DCs) derived from the peripheral blood in chronic hepatitis B patients can induce specific T cell immune response. METHODS: (1)The subjects were divided into 3 groups: chronic hepatitis B group (CHB), acute hepatitis B group (AHB), and normal donor group (ND). The peripheral blood mononuclear cells (PBMCs) isolated from those subjects were stimulated with HBcAg 18 to 27 CTL epitope peptide, and intracellular cytokine staining (ICCS) was used for detecting IFN-gamma, IL-2 and TNF-alpha produced by CD8+ T cell. (2) DCs generated from PBMCs were pulsed with HBcAg 18 to 27 CTL epitope peptide, then were cocultured with autologous lymphocytes for 10 days to induce antigen-specific T cell, which was assessed by ICCS and cytotoxic assay. RESULTS: (1) The memory effect of the PBMCs from AHB group to HBcAg 18 to 27 CTL epitope peptide was stronger than that from CHB or ND group (t=2.508-3.305, P<0.05). (2)After lymphocytes were cocultured with DC treated with HBcAg 18 to 27 CTL epitope peptide, antigen-specific T cell effect was induced. And the killing rates were (57.0+/-23.0)%, (49.5+/-20.2)%, (21.8+/-12.9)% at the effector/target of 30:1, 10:1, 3:1, which were higher than that in control group. CONCLUSIONS: The memory T cells against HBV antigen lacks in CHB patients. DCs from CHB patients pulsed with HBcAg 18 to 27 epitope peptide can induce HBV antigen-specific T cell, which can kill specific target cells and produce cytokines involved in virus clearance.

Spontaneous viral clearance after 6-21 years of hepatitis B and C viruses coinfection in high HBV endemic area.

AIM: To investigate the clinical and virological course of coinfection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China. METHODS: We enrolled 40 patients with chronic HBV and HCV coinfection (Group BC), 16 patients with chronic HBV infection (Group B) and 31 patients with chronic HCV infection (Group C). They infected HBV and/or HCV during 1982 to 1989. Sera of all the 87 patients were collected in 1994 and 2002 respectively. We detected biochemical and virologic markers and serum HBV DNA and HCV RNA levels of all the patients. B-type ultrasound detection was performed in some patients. RESULTS: In Group BC, 67.5 % of the patients cleared HBsAg, and 92.5 % of the patients cleared HBeAg. The clearance rate of HBV DNA was 87.5 %. There was no significant difference of HBV clearance between Group BC and Group B. In Group BC, 85.7 % of males and 47.4 % of females cleared HBV, and males were easier to clear HBV (chi(2)=6.686, P=0.010). Such a tendency was also found in Group B. The clearance rate of HCV RNA in Group BC was 87.5 %, significantly higher than that in Group C (chi(2)=22.963, P<0.001). Less than 40 % of the patients in all groups had elevated liver enzyme values. The highest value of alanine aminotransferase (ALT) was 218 u/L (normal range for ALT is 0-40 u/L). In most patients the ultrasonogram presentations changed mildly. CONCLUSION: The clinical manifestations of patients with HBV/HCV coinfection are mild and occult. High clearance rate of HBV and easy to clear HBV in male patients are the characteristics of HBV infection in adults in China. HBV can inhibit HCV replication, but no evidence has been found in our data that HCV suppresses HBV replication.

[Clinical and virological course of dual infection by hepatitis B and C viruses in China].

OBJECTIVE: To investigate the clinical and virological course of dual infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China. METHODS: We enrolled 40 patients with chronic HBV and HCV dual infection (Group BC), 16 patients with chronic single HBV infection (Group B) and 31 patients with chronic single HCV infection (Group C). They infected HBV and/or HCV during 1982 to 1989. The sera of all the 87 patients were collected in 1994 and 2002 respectively. We detected biochemical and virologic markers and quantitative serum HCV DNA and HCV RNA levels of all the patients. The B-type ultrasound detecting was performed in some patients. RESULTS: In Group BC, 67.5% of the patients have cleared HBsAg, and 92.5% of the patients have cleared HBeAg. The clearance rate of HBV DNA was 87.5%. There was no significant difference of HBV clearance between Group BC and Group B. In Group BC, the clearance rate of HBV-RNA was 87.5%, significantly higher than those in Group C. Less than 40% of the patients in all groups have elevated liver enzyme values. The highest value of alanine aminotransferase (ALT) was 218 u/L (normal range for ALT 0 - 40 u/L). In most patients the ultrasonogram presentations were changed mildly. CONCLUSION: The clinical presentation of patients with HBV/HCV coinfection seemed mild and occult. High clearance of HBV, easy to clear HBV in male patient was the characteristics of infection by HBV in adult time in China. HBV could inhibit HCV replication, but no evidence could be found in our data that HCV could suppress HBV replication.