OBJECTIVETo study the impact of IFN-gamma on liver fibrosis and its possible mechanism. Thirty healthy male SD rats were randomly divided into two groups: fibrosis model group, IFN-gamma treatment group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After 12-week-treatment, serum hyalurnic acid and TGF-beta1 was examined, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TbetaR- I and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis.

RESULTS(1) Pathological observation of hepatic specimens: histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis (P < 0.05). And the difference between fibrosis model group and IFN-gamma treatment group was significant (P < 0.05). (2) Changes of the hepatic fibrosis index (serum HA and TGF-beta1): the levels of serum HA, TGF-beta1 in fibrosis model group were higher than IFN-gamma treatment groups (P < 0.05). (3) Changes of gene protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR- I and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the three items in model group were higher than normal group (P < 0.01). The difference between model group and IFN-gamma treatment group was significant (P < 0.05);

CONCLUSIONIFN-gamma treatment group had significant results on treating experimental hepatic fibrosis. By the way of inhibiting expressions of TGF-beta1, TbetaR- I, Smad2/3, IFN-gamma treatment group exerted its anti-fibrosis effect.

Animals ; Disease Models, Animal ; Humans ; Interferon-gamma ; therapeutic use ; Liver ; drug effects ; metabolism ; Liver Cirrhosis ; drug therapy ; genetics ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Smad2 Protein ; genetics ; metabolism ; Smad3 Protein ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism

Objective: To observe the changes of liver metabolism in mice exposed to artificial light at night. Methods: Healthy male C57BL/6J mice were randomly divided into the light at night group and the control group, with 8 mice in each group. The daily light/dark cycle was 12/12 hours in the control group, and 24/0 hours in the light at night group for 10 consecutive days. The hepatic metabolite profiles of the two groups of mice were detected by high performance liquid chromatography tandem mass spectrometry. The modelling was assessed by combining principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis ( OPLS-DA ) , The changes of metabolites in the two groups were compared through KEGG database. Results: Compared with the control group, 9 different metabolites were detected in the light at night group, among which the down-regulated metabolites were glycine-betaine, glutathione, tyrosine, betaine, lysine, hypoxanthine, histidine and methionine, and the up-regulated ones were mannose-6-phosphate. The weight analysis of the metabolic pathways showed that the major influences on liver of light at night group were phenylalanine-tyrosine-tryptophan metabolism, tyrosine metabolism, fructose and mannose metabolism, cysteine and methionine metabolism and histidine metabolism. Conclusion The metabolism of various amino acids and sugars in light at night mice is disturbed,and the key differential metabolites are tyrosine, methionine, histidine and mannose-6-phosphate.

OBJECTIVETo investigate if glutamine (Gln) reduces intestinal bacterial translocation in acute hepatic failure (AHF) in rats and its mechanisms.

METHODSAcute hepatic failure model in rat was established by intraperitoneal injection of galatosamine. The rats were randomly divided into 4 groups: the normal control group (A), prevention and treatment group (B), treatment group (C), and model group (D). The rats in groups A and D were fed with normal saline. Two days before intraperitoneal injection, the rats in group B were fed with Gln and those in group C were fed with Gln 24 hours after injection. After 4 days of treatment, the rats were sacrificed and pathological scores of liver were assessed. The percentage of intestinal bacterial transloaction and bacteria in mesenteric lymph nodes (MLN) were measured. The villus height, crypt depth of ileum mucosa were analyzed. The levels of serum diamine oxidase (DAO) were measured.

RESULTSThe liver pathological scores of groups B and C were significantly lower than those of group D. The frequency of the bacteria found in MLN was significantly lower in group B compared with group D. The levels of DAO in blood were significantly lower in groups B and C than that of group D, and the level was significantly lower in group B than in group C. The villus height and crypt depth of the mucosa were significantly greater in group B and group C than in group D, and greater in group B than in group C.

CONCLUSIONThe results of the present study show that Gln can reduce the occurrence of the intestinal bacterial translocation in AHF in rats by improving the function of intestinal barrier.

Animals ; Bacterial Physiological Phenomena ; Bacterial Translocation ; Glutamine ; metabolism ; Intestines ; metabolism ; microbiology ; Liver Failure, Acute ; complications ; microbiology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Hepatitis B ; prevention & control ; transmission ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Thymidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo investigate the influence of the individual genotype differences of DC-SIGN and DC-SIGNR on the mother-to-neonate intrauterine infection of HBV.

METHODSThe genotypes of the gene DC-SIGN and DC-SIGNR in the pregnant women with HBV positive were detected by PCR and agarose gel electrophoresis. The significant difference of gene diversity of DC-SIGN and DC-SIGNR was analyzed by chi-square test.

RESULTS(1) All of 29 cases in intrauterine infection group were 7/7 DC-SIGN genotype. In the non-intrauterine infection group, 7/5 genotype were observed in 2 of 54 cases, and the other 52 cases were 7/7 genotype. The two groups was no significant difference (P = 0.54). (2) 29 cases of intrauterine infection group was observed 4 genotypes of DC-SIGNR such as 7/7, 7/5, 9/7 and 6/5, the genotype frequencies were 0.3793, 0.3448, 0.2414 and 0.0345 respectively. 54 cases of non-intrauterine infection group was found 6 genotypes such as 7/7, 7/5, 9/5, 9/7, 7/6 and 6/5, genotype frequencies were 0.5186, 0.1481, 0.0926, 0.1852, 0.0370 and 0.0185 respectively. The distribution of 7/5 genotype in the intrauterine infection group (29 cases) and the non-intrauterine infection group (54 cases) was statistically significant (P = 0.038) , and no significant difference was found in other genotypes between the two groups (P > 0.05).

CONCLUSIONThe gene DC-SIGN showed relatively little variation in the pregnant women infected with HBV. On the countrary, there were multiple genotypes of the gene DC-SIGNR in these women, and the genotype "7/5" of DC-SIGNR might be one of the susceptibility genes associated with intrauterine infection.

Cell Adhesion Molecules ; genetics ; metabolism ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Hepatitis B ; genetics ; transmission ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Lectins, C-Type ; genetics ; metabolism ; Male ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications, Infectious ; genetics ; virology ; Receptors, Cell Surface ; genetics ; metabolism

OBJECTIVE: To investigate the effect of prostaglandin E1 (PGE1) on the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in experimental liver fibrosis rats. METHODS: The liver fibrosis model was established by carbon tetrachloride. Rats were divided into a control group and PGE1-treated group. The pathological changes of the liver tissue from the two groups, the semi-quantitative analysis of hepatitic activity in HE stain sections, the pathological image quantitative analysis of the fibrosis degree, TIMP-1 positive cells, and the content of collagen were synthetically analysed. RESULTS: The mark changes of liver pathology in HE stain sections were that the degree of hepatitic activity in the PGE1-treated group was obviously lower than that in the control group (P < 0.05). The fibrosis degree, TIMP-1 positive cells and the collagenous fibers decreased in the PGE1-treated group (P <0.05). CONCLUSION PGE1 has an anti-hepatofibrosis effect in the experimental rats, the inflammation of liver is light, and the proliferation of collagenous fibers can be restrained, whose mechanism is probably associated with the suppression of TIMP-1 expression caused by PGE1.
Alprostadil ; pharmacology ; Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

OBJECTIVE: To establish a liver metastasis model of nude mice in colon cancer so as to determine the function of NGX6. METHODS: The cells of Group HT-29, pcDNA3.1(+)/HT-29, and pcDNA3.1(+)/NGX6/HT-29 were implanted into the spleen of nude mice, respectively. Everyday we measured the weight of the nude mice and observed their ingestion, movement and mental status. The nude mice were killed after 45 days, and the effect of NGX6 on the malignant behavior of HT-29 was assessed by this experiment. RESULTS: In contrast to the other two groups, the metastasis in the liver and xenograft tumor in the spleen of pcDNA3.1(+)/NGX6/HT-29 group was significantly reduced (P<0.01). CONCLUSION The metastasis of HT-29 colon cancer cell line was significantly inhibited by NGX6 gene. This model of liver metastasis in the nude mice is a proper model to determine the anti-metastasis mechanism of NGX6 gene.
Animals ; Colonic Neoplasms ; genetics ; pathology ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic ; HT29 Cells ; Humans ; Liver Neoplasms ; pathology ; secondary ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Splenic Neoplasms ; pathology ; Transfection ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo investigate the clinical features of thyroid disease occurring in response to antiviral therapy in patients with chronic hepatitis C (CHC).

METHODSEighty-two patients diagnosed with CHC were recruited for study from our hospital between 2009 and 2010. All patients were given a 48-week course of antiviral combination therapy with pegylated-interferon (Peg-IFN; 180 mug qw ih) and ribavirin (RBV; 15 mg/kg bw). Patient sera was collected prior to treatment (baseline), at treatment weeks 24 and 48, and post-treatment week 24, and used to detect changes in levels of thyroid function markers, thyroid-specific and other autoantibodies, complement factors, and immunoglobulins (Igs). Differential expression of biomarkers was assessed between patients who developed thyroid disorder and those who did not.

RESULTSAt treatment week 48, 13.4% (11/82) of cases developed hypothyroidism, 3.7% (3/82) developed hyperthyroidism, 20.7% (17/82) tested positive for thyroglobulin antibody, and 22.0% (18/82) tested positive for thyroid peroxidase antibody. The patients who did not develop thyroid disease had significantly higher post-treatment levels (vs. baseline) of IgG (14.84 +/- 2.61 vs. 12.95 +/- 3.32 g/L, F = 10.458, P = 0.002) and C4 (0.26 +/- 0.09 vs. 0.22 +/- 0.08 g/L, F = 6.835, P = 0.011) and significantly lower IgM (0.86 +/- 0.48 vs. 1.00 +/- 0.42 g/L, F = 9.106, P = 0.003). The patients who developed thyroid disease showed no significant differences in the baseline and post-treatment levels of IgG, C4, or IgM. When the two groups of patients who did or did not develop thyroid disease were compared, there was no difference in the amount of patients who achieved sustained virological response.

CONCLUSIONAntiviral-induced thyroid disease in patients with refractory hepatitis C manifests as clinically-detectable abnormalities in serum levels of thyroid autoantibody and markers of hypothyroidism. Levels of other autoantibodies and Igs do not correlate with the development of thyroid disease in these patients, and thyroid disease does not appear to affect the efficacy of Peg-IFN + RBV antiviral therapy.

Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Ribavirin ; therapeutic use ; Thyroid Diseases ; chemically induced

Aged ; Biopsy, Needle ; methods ; Coal Mining ; Humans ; Lung ; pathology ; Lung Neoplasms ; complications ; diagnosis ; Middle Aged ; Pneumoconiosis ; complications

Canine adenovirus type 2 (CAV-2) has been proposed as a vector for recombinant vaccine. Alternatively, it may be an attractive tool for gene transfer due to lack of pre-existing immunity in humans. In this study, a transfer vector based on CAV-2, in which the 1381bp fragment of the E3 region was deleted, and a linker containing the Not I, Cla I, Fse I restriction enzyme sites were cloned into the deleted region. The recombinant CAV-2 genome was released from the plasmids enzyme digestion and transfected into MDCK cells by lipofectamine to obtain the recombinant virus. No significant difference in morphology, hemagglutination and replication between the recombinant and the wide type CAV-2 was found. These results indicated that this recombinant virus CAV-2-deltaE3 (NF) may be an efficient vector for gene transfer and the capacity of the vector for inserted foreign gene was up to 3.3kb.
Adenoviruses, Canine ; genetics ; ultrastructure ; Animals ; Binding Sites ; genetics ; Cell Line ; Cloning, Molecular ; DNA Restriction Enzymes ; metabolism ; DNA, Viral ; chemistry ; genetics ; Dogs ; virology ; Genetic Vectors ; genetics ; Humans ; Lipids ; chemistry ; Microscopy, Electron ; Transfection ; methods ; Virus Replication ; genetics