Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy.

Both host and viral factors have been implicated in influencing the response to pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy for hepatitis C virus (HCV) infection. Among the viral factors, sequence heterogeneity within NS5A and core regions has been proposed. This study aimed to clarify the relationship between virological responses to PEG-IFN/RBV therapy and sequence heterogeneity within NS5A, including the IFN/RBV resistance-determining region (IRRDR), the interferon sensitivity-determining region (ISDR) and the core region.

Polymorphisms of hepatitis C virus non-structural protein 5A and core protein and clinical outcome of pegylated-interferon/ribavirin combination therapy.

Objective: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g.

Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy.

Objective: To investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures.

Methods: 31 patients with chronic hepatitis B receiving entecavir (17 responders and 14 partial responders according to the HBV DNA levels at week 48) and 25 patients receiving lamivudine (14 responders and 11 non-responders) as controls were included. An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced.

Analysis of neutralizing antibodies against hepatitis C virus in patients who were treated with pegylated-interferon plus ribavirin.

The role of neutralizing antibodies (NAb) in determining responses to antiviral therapy has not been defined well. By using hepatitis C virus (HCV) cell culture system with the J6/JFH1 strain of HCV genotype 2a, we analyzed NAb responses in patients with chronic hepatitis C who received pegylated-interferon plus ribavirin (PEG-IFN/RBV) antiviral therapy. A total of 65 patients chronically infected with HCV genotype 1b were enrolled in this study.

17β-estradiol inhibits the production of infectious particles of hepatitis C virus.

Persistent infection with hepatitis C virus causes serious liver diseases, such as chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma. The male gender is one of the critical factors in progression of hepatic fibrosis due to chronic HCV infection; thus female hormones may play a role in delaying the progression of hepatic fibrosis. It has also been reported that women are more likely than men to clear HCV in the acute phase of infection.

Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C.

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B.

IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1.

Invasion into adjacent brain parenchyma is the key cause of recurrent human glioblastoma multiforme (GBM). The role of interleukin 6 (IL-6) in the malignant progression of glioma remains undefined. Here, we found that IL-6 promotes the invasion of U87 MG human glioma cells but not in U343 cells.

Characterization of HKI-272 covalent binding to human serum albumin.

The study was initiated as an observation of incomplete extraction recovery of N-(4-(3-chloro-4-(2-pyridinylmethoxy)anilino)-3-cyano-7-ethoxy-6-quinolyl)-4-(dimethylamino)-2-butenamide (HKI-272) from human plasma. The objective of this study was to 1) identify the binding site(s) of HKI-272 to human plasma protein(s); 2) characterize the nature of the binding; and 3) evaluate the potential reversibility of the covalent binding. After incubation of [(14)C]HKI-272 with human plasma, the mixture was directly injected on liquid chromatography/mass spectrometry (LC/MS), and an intact molecular mass of HKI-272 human serum albumin (HSA) adduct was determined to be 66,999 Da, which is 556 Da (molecular mass of HKI-272) larger than the measured molecular mass of HSA (66,443 Da).

Photo-induced transformations of Hg(II) species in the presence of Nitzschia hantzschiana, ferric ion, and humic acid.

Effects of algae Nitzschia hantzschiana, Fe(III) ions, humic acid, and pH on the photochemical reduction of Hg(II) using the irradiation of metal halide lamps (lambda > or = 365 nm, 250 W) were investigated. The photoreduction rate of Hg(II) was found to increase with increasing concentrations of algae, Fe(III) ions, and humic acid. Alteration of pH value affected the photoreduction of Hg(II) in aqueous solution with or without algae.

Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo.

There is growing evidence that the Rho/Rho-kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and proliferation. The aim of this study was to explore the anti-tumor effects of Rho/ROCK inhibitor, fasudil, including the possible mechanisms involved in the suppression of the glioblastoma (GBM) cell line progression in vitro and in vivo. After T98G and U251 cells were treated with various concentrations of fasudil, Y27632, and ROCK siRNA, the effects of ROCK inhibitors on migration, invasion, invasion-related gene expressions, proliferation and apoptosis of cultured tumor cells were examined.

IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines.

Interleukin-6 (IL-6) is a growth and survival factor in human glioblastoma cells and plays an important role in malignant progression. However, its role in glioblastoma invasion is still unknown. This study shows how IL-6 promotes cell invasion and migration in U251 and T98G glioblastoma cell lines.

Characterization of a novel wheat NAC transcription factor gene involved in defense response against stripe rust pathogen infection and abiotic stresses.

Proteins encoded by the NAC gene family constitute one of the largest plant-specific transcription factors, which have been identified to play many important roles in both abiotic and biotic stress adaptation, as well as in plant development regulation. In the current paper, a full-length cDNA sequence of a novel wheat NAC gene, designated as TaNAC4, was isolated using in silico cloning and the reverse transcription PCR (RT-PCR) methods. TaNAC4 sharing high homology with rice OsNAC4 gene was predicted to encode a protein of 308 amino acid residues, which contained a plant-specific NAC domain in the N-terminus.

[Hepatitis C virus NS3/4A with different secondary structures at amino-terminus has different serine protease activities and inhibitory activities on host cell].

Objective: To construct the point mutation plasmids expressing NS3/4A with different secondary structure of the amino-terminal 120 residues of NS3, and to investigate the differences in serine protease and inhibitory effects on host cells between each subgroup.

Methods: The point mutation plasmids were constructed, which expressed NS3/4A with the corresponding secondary structures of subgroup, and were named as A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, and B2-2, with the backbone of M-H05-5 (A1-1). Western blot was performed to detect the expression of NS3/4A and the difference in in cis and in trans NS3 serine protease activity between each subgroup.

[Construction of pSG5/NS5A5BdeltaC and its expression in Huh7 cells].

Aim: To construct the plasmid pSG5/NS5A5BdeltaC, and to investigate its expression in Huh7 cells.

Methods: The plasmidpTM1-NS2NS5A5BdeltaC was taken as the template. The primers were designed according to the characteristics of the sequence and endoenzyme cleavage sites in HCV NS5A5BdeltaC and vector pTM1, pSG5.

Characterization of a pathogenesis-related thaumatin-like protein gene TaPR5 from wheat induced by stripe rust fungus.

Pathogenesis-related (PR) proteins, induced in plants in response to various biotic and abiotic stresses, have been assumed to play a role in plant defense system. Proteins of the PR5 family, also named thaumatin-like proteins (TLPs), have been detected in numerous plant species. In this research, a novel PR5 gene, designated as TaPR5, was isolated and characterized from wheat leaves (cv.

A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis.

Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal cancer. However, our mechanistic understanding of the link between inflammation and tumorigenesis in the colon is limited. Here we established a novel mouse model of colitis-associated cancer by genetically inactivating signal transducer and activator of transcription 3 (Stat3) in macrophages, with partial deletion in other myeloid and lymphoid cells.

The hepatitis C virus core protein contains a BH3 domain that regulates apoptosis through specific interaction with human Mcl-1.

The hepatitis C virus (HCV) core protein is known to modulate apoptosis and contribute to viral replication and pathogenesis. In this study, we have identified a Bcl-2 homology 3 (BH3) domain in the core protein that is essential for its proapoptotic property. Coimmunoprecipitation experiments showed that the core protein interacts specifically with the human myeloid cell factor 1 (Mcl-1), a prosurvival member of the Bcl-2 family, but not with other prosurvival members (Bcl-X(L) and Bcl-w).

[Relationship between IL-10 promoter gene polymorphisms and the susceptibility to endometriosis].

The purpose of this study was to investigate the relationship between IL-10 promoter gene polymorphism and the susceptibility to endometriosis (EMs) in Chinese population. Amplification refractory mutation system polymerase chain reactions (ARMS-PCR) and DNA sequencing were performed to detect polymorphism of -1082G/A site and PCR-RFLP was used to determine the genotypes in -819T/C and -592A/C sites. One hundred and nineteen Chinese women with different stage EMs and 120 controls were employed in this study.

HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters.

Background/aims: Persistent infection with hepatitis C virus (HCV) causes extrahepatic diseases, including diabetes. We investigated the possible effect(s) of HCV replication on cellular glucose uptake and expression of the facilitative glucose transporter (GLUT) 2 and 1.

Methods: We used Huh-7.

Efficient production of infectious hepatitis C virus with adaptive mutations in cultured hepatoma cells.

Robust production of infectious hepatitis C virus (HCV) in cell culture was realized by using the JFH1 strain and the homologous chimeric J6/JFH1 strain in Huh-7.5 cells, a highly HCV-permissive subclone of Huh-7 cells. In this study, we aimed to establish a more efficient HCV-production system and to gain some insight into the adaptation mechanisms of efficient HCV production.

[Application of endovascular covered stent for treating vertebral dissecting aneurysm and carotid-cavernous fistula].

Objective: To investigate the therapeutic effects of endovascular covered stent on vertebral dissecting aneurysm and carotid-cavernous fistula (CCF).

Methods: From March 2006 to May 2007, Jostent coronary stent grafts were used to treat 4 patients with vertebral dissecting aneurysm and 3 patients with CCF. The patients of vertebral dissecting aneurysm were male and 37- 57-years-old, the lesion was located on the left vertebral artery in 3 patients and on the right vertebral artery in 1 patient, with the primary symptoms of sudden headache and vomiting; CT scan demonstrated subarachnoid hemorrhage; and the medical history varied from 2 days to 10 years.

Photo-induced transformations of mercury(II) species in the presence of algae, Chlorella vulgaris.

The effects of algae (i.e., Chlorella vulgaris), Fe(III), humic substances, and pH on the photoreduction of Hg(II) under the irradiation of metal halide lamps (lambda>or=365 nm, 250 W) were investigated in this paper.

Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway.

We previously reported that cells harboring the hepatitis C virus (HCV) RNA replicon as well as those expressing HCV NS3/4A exhibited increased sensitivity to suboptimal doses of apoptotic stimuli to undergo mitochondrion-mediated apoptosis (Y. Nomura-Takigawa, et al., J.

[Association between susceptibility of endometriosis and the gene polymorphism of tumor necrosis factor].

Objective: To evaluate the association between the susceptibility of endometriosis (EMS) and the gene polymorphism of tumor necrosis factor (TNF) in Chinese Han population.

Methods: Peripheral blood samples were collected from 76 EMS patients and 87 normal controls. PCR-RFLP was used to detect the single base change polymorphism in both TNFalpha gene and TNFbeta gene.

Evaluation of the efficacy of a danazol-loaded intrauterine contraceptive device on adenomyosis in an ICR mouse model.

Background: Danazol, a synthetic steroid with antigonadotrophic properties, has been widely used for the treatment of endometriosis and adenomyosis. However, the local application of danazol to the uterus to treat adenomyosis is controversial. The objective of this study is to develop an effective treatment for adenomyosis using danazol via intrauterine contraceptive device (IUCD) delivery.