ABSTRACT
This study aims to explore the efficacy of interferon-α (IFN-α) combined with either entecavir (ETV) or adefovir (ADV) therapy versus IFN-α mono-therapy for chronic hepatitis B (CHB) patients,and to identify the factors associated with treatment outcomes.Totally,159 CHB patients receiving interferon-based treatment for 48 weeks were enrolled in this retrospective study,including IFN-α mono-therapy group (group A,n=44),IFN-α plus ADV group (group B,n=53) and IFN-α plus ETV group (group C,n=62).The primary measures of efficacy assessments were the changes in HBsAg.Cox regression analysis was used to identify the predictors of treatment outcomes.The predictive values of the factors were assessed by ROC analysis.For patients with baseline hepatitis B surface antigen (HBsAg) level ＜1000 IU/mL,the reductions in mean HBsAg levels at week 48 were greater in group C than that in group A (P＜0.05).Higher rate of HBeAg seroconversion was achieved in the combined therapy group than in IFN-α mono-therapy group at week 48 (P＜0.05).Two factors were independently associated with HBeAg seroconversion:baseline HBeAg level ＜2.215 log10 index/mL and △HBeAg (.decline in HBeAg from baseline) ＞0.175 log10 at week 12.In conclusion,interferon-α plus ETV therapy can accelerate HBsAg decline as compared with interferon-α mono-therapy in CHB patients with lower baseline HBsAg levels,and the combination therapy was superior to IFN-α mono-therapy in increasing the rate of HBeAg seroconversion.Baseline HBeAg and △HBeAg at week 12 can independently predict HBeAg seroconversion in patients subject to interferon-based therapy for 48 weeks.
ABSTRACT
Paragonimiasis is an infectious disease caused by Trematodes of the genus Paragonimus that is endemic in Asia, Africa, and South America. Most patients with paragonimiasis are cured by standard praziquantel treatment. However, several cases have been reported to have unsatisfactory responses to the standard praziquantel treatment. To probe the clinical characteristics, possible cause, and management of the paragonimiasis individuals improved by multiple therapies, we present a 12‑year‑old Chinese boy, who was infected with Paragonimus accompanied by arachnoid cyst involvement, as not having typical clinical symptoms, but repeatedly presenting with migrated lesions between the lung and pleura. He responded to treatment with 3 cycles of praziquantel and 1 cycle of albendazole.
ABSTRACT
This study investigated the expression profiles of IL-10 gene in three human hepatoma cell lines including Huh7,HepG2,and HepG2 transfected with a plasmid containing hepatitis B virus (HBV) named HepG2.2.15.RT-PCR analysis demonstrated that IL-10 message RNA was absent in HepG2 and Huh7 cells,whereas it was present in HepG2.2.15 cells,which was consistent with ELISA result.Furthermore,except for lamivudine other antiviral treatments did not significantly decrease the HBV DNA level in HepG2.2.15 cells,while they had different effects on the expression of IL-10 protein,although stimulation by LPS had no significant effect.In addition,except for poly(I:C),the other treatments decreased the expression of IL-10 protein to different degrees,but had no significant effects on the expression of NF-κB and MyD88.Meanwhile,all treatments we used had effect on the expression of STAT1.In conclusion,IL-10 was expressed in HepG2.2.15 cells and STAT1 pathway might be involved in the regulation of IL-10 expression in HepG2.2.15 cells,but it was not the sole pathway,the exact mechanism warrants further study.
ABSTRACT
The clinical significance of a myetoperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS;n=63), the non-HPS group (cirrhotic patients without HPS;n=182), and the control group (healthy subjects without liver disease;n=35). The distribution of the MPO -463 G/A genotype and its relationship with iNOS expression in a typical cell block from as-citic fluid were detected by immunohistochemistry and polymerase chain reaction-restricted fragment length polymorphism analysis (PCR-RFLP). In the HPS group, the partial pressure of oxygen in blood and ascitic fluid was significantly decreased (8.95±1.58 kPa and 6.81±0.95 kPa, respectively;both P<0.01), while the partial pressure of carbon dioxide significantly increased (4.62±0.20 kPa and 5.92±0.45 kPa, respectively;P<0.01). MPO and iNOS levels were significantly increased in the HPS group as compared with the non-HPS group. These increases were even more remarkable in ascitic fluid (41.36±11.62 and 13.23±4.81 μg/L;10.27± 3.2 0 and 4.95±1.12 μg/L) than in blood (16.66±5.24 and 4.87±1.73 μg/L;5.79±2.31 and 2.35±0.84 μg/L). The distribution of the MPO genotypes GG, GA, and AA were 76.2%, 22.2% and 1.6% in the HPS group, and 57.7%, 37.9% and 4.4% in the non-HPS group (P<0.05). The expression of iNOS was significantly higher in patients with the G alleles (G/G and G/A) (61.54%, 48/78) than in patients with A alleles (G/A and A/A) (38.46%, 30/78) (P<0.01). It was suggested that the expression levels of iNOS and MPO were correlated with HPS-induced hypoxemia. The MPO-463 G/A mutation might be a protective factor that prevents the development of HPS. The MPO might be involved in the regulation of iNOS expression. In humans, MPO pathways, the iNOS/NO system, and their interaction might have an impact on the occurrence and development of HPS.
ABSTRACT
To better understand the effect of a new split variant of human asialoglycoprotein receptor (ASGPR Hlb) on ASGPR ligands' binding ability, we established a functional cell line which expresses ASGPR. The full lengths of ASGPRH 1 a and H2c fragments from human liver were amplified by reverse transcript PCR (RT-PCR) and inserted into eukaryotic expression vector plRES2EGFP,pCDNA3.1 (Zeo+) respectively. The recombinants were co-transfected into HeLa cells. After selection by using Neocin and Zeocin, a stably transfected cell line was established, which was designated 4-1-6. The transcription and expression of ASGPRHla and H2c in 4-1-6 were confirmed by RT-PCR,Western blotting and immunofluorescence. The endocytosis function of the artificial "ASGPR" on the surface of 4-1-6 was tested by FACS. It was found that the cell line 4-1-6 could bind ASGPR natural ligand molecular asialo-orosomucoid (ASOR). After the eukaryotic plasmid H lb/pCDNA3.1 (neo)was transfected into cell line 4-1-6, Hlb did not down-regulate the ligand binding ability of ASGPR.The eukaryotic expression plasmid Hlb/pcDNA3.1 (neo) and H2c/pcDNA3.1 (neo) were co-transfected transiently into Hela cell. Neither single Hlb nor Hlb and H2c could bind ASOR. In conclusion, a functional cell line of human asialoglycoprotein receptor (ASGPR) which expresses both Hla and H2c stably was established. The new split variant Hlb has no effect on ASGPR binding to ASOR. ASGPRHlb alone can't bind to ASOR, it yet can't form functional complex with ASGPRH2c.
ABSTRACT
Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are believed to play a major role in viral clearance and disease pathogenesis during HBV infection. To clarify the differ-ences in host immune responses between self-limited and chronic HBV infections, we constructed three HLA-A*0201/HBV tetramers with immunodominant epitopes of core18-27, polymerase 575-583 and envelope 335-343, and analyzed the HBV-specific CTLs in peripheral blood mononu-clear cells (PBMCs) from patients infected with HBV. The frequencies and expansion ability of HBV-specific CD8+ T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients. HBV-specific CD8+ T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. In chronic infection, no significant correlation was found either between the frequencies of HBV-specific CD8+ T cells and the viral load, or between the frequencies and the levels of alanine transaminase. Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immuno-therapeutic approaches should be aimed at not only boosting a HBV-specific CD8+T response but also improving its function.
ABSTRACT
The pathogenesis of HBsAg (+)/HBsAb(+) double positive hepatitis B virus infection was investigated by simulating HBsAg/HBsAb coexistence in vitro and establishing HBsAg/HBsAb double positive model in vivo. Eukaryotic expression plasmids PCI-SY, PCI-adw, PCI-adr, PCI-ayw, which ex-pressed S gene product of different serotypes, were constructed and transfected into HepG2 cells. Re-combinant proteins were purified from the transfeeted cells. At the same time, HBsAg mouse antiserum was obtained by immunizing mice with PCI-SY plasmid. HBsAg/HBsAb coexistence was simulated using these antigens and antiserum. Furthermore, the expression plasmids expressing different serotypes of S gene product including PCI-adw, PCI-adr, and PCI-ayw were injected into mice via tail vein.HBsAg and HBsAb in mice sera were tested at the first and 7th day respectively after antigen plasmids injection. Both in vitro simulation and in vivo animal models demonstrated that HBsAg antigen and HBsAb of the same serotypes could not coexist, but HBsAg antigen and HBsAb of different serotype could coexist. HBsAg/HBsAb double positive hepatitis B virus infection could be due to infection of viruses of different serorypes.
ABSTRACT
Human ISG20 gene was cloned and the effect of its anti-HBV was primarily studied. The ISG20 gene was amplified from HeLa cells by RT-PCR and recombinant vector expressing ISG20 was constructed by genetic engineering. The overexpression of ISG20 in HepG2 cells was detected by Western blot and the levels of secretion of HBs antigen and HBe antigen tested by ELISA. The results showed that: (1) Sequence of ISG20 cloned was consistent to that published in Genebank; (2) Recombinant vector expressing ISG20 could be expressed in HepG2 cells by transfection; (3) The overexpression of ISG20 protein could reduce the levels of the secretion of HBs antigen and HBe an-tigen in transfected HepG2 cells. It was suggested that the overexpression of recombinant ISG20 in culture cells could reduce the synthesis of HBV proteins.