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Find video protocols related to scientific articles indexed in Pubmed.
Advanced Hepatic Fibrosis and Steatosis Are Associated with Persistently Alanine Aminotransferase Elevation in Chronic Hepatitis C Patients Negative for HCV RNA During Pegylated Interferon Plus Ribavirin Therapy.
J. Infect. Dis.
PUBLISHED: 11-13-2014
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?Clinical implications of persistently alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy remain unknown.
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Fibroblast growth factor receptor 1 is a key inhibitor of TGF? signaling in the endothelium.
Sci Signal
PUBLISHED: 09-25-2014
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Abnormal vascular homeostasis can lead to increased proliferation of smooth muscle cells and deposition of extracellular matrix, resulting in neointima formation, which contributes to vascular lumen narrowing, a pathology that underlies diseases including transplant vasculopathy, the recurrence of stenosis, and atherosclerosis. Growth of neointima is in part due to endothelial-to-mesenchymal transition (EndMT), a transforming growth factor-? (TGF?)-driven process, which leads to increased numbers of smooth muscle cells and fibroblasts and deposition of extracellular matrix. We reported that endothelial cell-specific knockout of fibroblast growth factor receptor 1 (FGFR1) led to activation of TGF? signaling and development of EndMT in vitro and in vivo. Furthermore, EndMT in human diseased vasculature correlated with decreased abundance of FGFR1. These findings identify FGFR1 as the key regulator of TGF? signaling and EndMT development.
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An intermolecular C-H functionalization method for the synthesis of 3-hydroxy-2-oxindoles.
Org. Biomol. Chem.
PUBLISHED: 09-24-2014
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An intermolecular C-H functionalization method is developed for the synthesis of 3-hydroxy-2-oxindoles. Rh(iii)-catalyzed N-nitroso-directed C-H addition to ethyl 2-oxoacetate allows subsequent denitrosation-triggered cyclization construction of 3-hydroxy-2-oxindoles. The method features a broad substrate scope and its synthetic utility is demonstrated on the synthesis of target compounds bearing functional groups (hydroxyl, bromo) amenable to further elaboration.
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Anthracene/Phenothiazine ?-Conjugated Sensitizers for Dye-Sensitized Solar Cells using Redox Mediator in Organic and Water-based Solvents.
ChemSusChem
PUBLISHED: 09-18-2014
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Metal-free dyes (MD1 to MD5) containing an anthracene/phenothiazine unit in the spacer have been synthesized. The conversion efficiency (7.13?%) of the dye-sensitized solar cell using MD3 as the sensitizer reached approximately 85?% of the N719-based standard cell (8.47?%). The cell efficiency (8.42?%) of MD3-based dye-sensitized solar cells (DSSCs) with addition of chenodeoxycholic acid is comparable with that of N719-based standard cell. The MD3 water-based DSSCs using a dual-TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl)/iodide electrolyte exhibited very promising cell performance of 4.96?% with an excellent Voc of 0.77?V.
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Cost-effectiveness analysis of an enteral nutrition protocol for children with common gastrointestinal diseases in china: good start but still a long way to go.
JPEN J Parenter Enteral Nutr
PUBLISHED: 09-18-2014
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A standard nutrition screening and enteral nutrition (EN) protocol was implemented in January 2012 in a tertiary children's center in China. The aims of the present study were to evaluate the cost-effectiveness of a standard EN protocol in hospitalized patients.
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Value of interleukin-28B genetic polymorphism on retreatment outcomes of chronic hepatitis C genotype 1 relapsers by peginterferon alfa plus ribavirin.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-11-2014
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Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation.
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Characterization and profiling of phenolic amides from Cortex Lycii by ultra-high performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry.
Anal Bioanal Chem
PUBLISHED: 08-25-2014
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Cortex Lycii, the root bark of Lycium chinense Mill. or Lycium barbarum L., is a frequently used traditional Chinese medicine. Phytochemical studies have shown that phenolic amides are not only characteristic compounds but also abundant ones in this plant. In the present study, an effective method was developed for structural characterization of phenolic amides from Cortex Lycii by ultra-high performance liquid chromatography coupled with linear ion trap Orbitrap tandem mass spectrometry. The fragmentation of 14 compounds including six cinnamic acid amides, six neolignanamides, and two lignanamides were studied systematically for the first time. It was found that, in the positive ion mode, neutral loss of the tyramide moiety (137 Da) or N-(4-aminobutyl)acetamide moiety (130 Da) were characteristic for these compounds. At least 54 phenolic amides were detected in the extract and 48 of them were characterized, among which 14 known compounds were identified unambiguously by comparing the retention time and mass spectra with those of reference compounds, and 34 components were tentatively identified based on the fragmentation patterns, exact mass, UV spectra, as well as retention time. Fifteen compounds were characterized as potential new ones. Additionally, the developed method was applied to analyze eight batches of samples collected from the northwest of China, and it was found that cinnamic acid amides were the main type of phenolic amides in Cortex Lycii. In conclusion, the identification of these chemicals provided essential data for further phytochemical studies, metabolites identification, and the quality control of Cortex Lycii.
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The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo.
Mol Ther Nucleic Acids
PUBLISHED: 08-19-2014
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Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) under current antiviral therapy is a major barrier to eradication of chronic hepatitis B (CHB). Curing CHB will require novel strategies for specific disruption of cccDNA. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target DNA sequence. To examine whether this system can cleave HBV genomes, we designed eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the CRISPR/Cas9 system significantly reduced the production of HBV core and surface proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight screened gRNAs, two effective ones were identified. Interestingly, one gRNA targeting the conserved HBV sequence acted against different genotypes. Using a hydrodynamics-HBV persistence mouse model, we further demonstrated that this system could cleave the intrahepatic HBV genome-containing plasmid and facilitate its clearance in vivo, resulting in reduction of serum surface antigen levels. These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing templates both in vitro and in vivo, indicating its potential in eradicating persistent HBV infection.
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Effect of Astragalus polysaccharides on expression of TNF-?, IL-1? and NFATc4 in a rat model of experimental colitis.
Cytokine
PUBLISHED: 08-14-2014
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Astragalus membranaceus is a Chinese medicinal herb and has been shown to improve hapten-induced experimental colitis. One of its major components is polysaccharides. We investigated the effect of Astragalus polysaccharides (APS) on expression of TNF-?, IL-1? and NFATc4 in a rat model of experimental colitis.
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Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility.
Tumour Biol.
PUBLISHED: 07-27-2014
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The objective of this study was to explore the relationship between single-nucleotide polymorphisms (SNPs) of the protein kinase C gamma (PRKCG) gene and osteosarcoma susceptibility in Chinese Han population. A total of 610 cases of osteosarcoma patients and 610 healthy individuals were enrolled in this study. TaqMan method was used to compare genotypes and the allelic distribution frequency of three SNPs (rs454006, rs2242245, and rs8103851) in the PRKGG gene between osteosarcoma patients and healthy individuals. Osteosarcoma patients were grouped according to different clinical parameters (age, gender, pathological types, tumor location, Enneking staging, tumor metastasis and treatment) to compare genotype and allele frequency among different groups as well as to explore the relationship between gene polymorphisms and different clinical parameters. The rs454006 polymorphisms of the PRKCG gene include the CC, CT, and TT genotypes. The differences in genotype frequency and allele frequency between osteosarcoma patients and healthy individuals were significant (both P??0.05). The differences of the rs8103851 genotype frequency and allele frequency in patients with metastatic osteosarcoma and patients without metastasis were significant (both P?
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Rhodium(III)-Catalyzed N-Nitroso-Directed C?H Addition to Ethyl 2-Oxoacetate for Cycloaddition/Fragmentation Synthesis of Indazoles.
Chemistry
PUBLISHED: 07-22-2014
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Rh(III) -catalyzed N-nitroso-directed C?H addition to ethyl 2-oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N-nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful C?H functionalization-based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic-fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.
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Wire-cylinder dielectric barrier discharge induced degradation of aqueous atrazine.
Chemosphere
PUBLISHED: 07-12-2014
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The wire-cylinder dielectric barrier discharge reactor was adopted for removal of aqueous atrazine. The effect of different parameters on the degradation efficiency of atrazine was investigated, and the degradation mechanism of atrazine was studied. The experimental results showed that when the discharge power was 50W and the air flow rate was 140Lh(-1), 93.7% of atrazine was degraded after 18min of discharge time. The concentrations of generated O3 and H2O2 increased with increasing discharge time. The pH decreased from 6.80 to 2.50, 12.7% of TOC was removed after 18min. The concentrations of generated Cl(-) and NO3(-) increased significantly during the degradation process of atrazine, and the decreasing toxicity trend was observed for the treated atrazine solution. The degradation byproducts of atrazine were identified using liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), which might be formed mainly in dechlorination hydroxylation, alkyl oxidation, dechlorination hydroxylation combined with alkyl oxidation and demethylation oxidation reactions.
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Degradation of aqueous 3,4-dichloroaniline by a novel dielectric barrier discharge plasma reactor.
Environ Sci Pollut Res Int
PUBLISHED: 07-03-2014
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Degradation of aqueous 3,4-dichloroaniline (3,4-DCA) was conducted in a novel dielectric barrier discharge (DBD) plasma reactor. The factors affecting the degradation efficiency of 3,4-DCA and the degradation mechanism of 3,4-DCA were investigated. The experimental results indicated that the degradation efficiency of 3,4-DCA increased with increasing input power intensity, and the degradation of 3,4-DCA by the novel DBD plasma reactor fitted pseudo-first-order kinetics. Higher degradation efficiency of 3,4-DCA was observed in acidic conditions. The degradation efficiency of 3,4-DCA, the removal rate of total organic carbon (TOC), and the detected Cl(-) increased dramatically with adding Fe(2+) or Fe(3+). Degradation of 3,4-DCA could be accelerated or inhibited in the presence of H2O2 depending on the dosage. Several degradation intermediates of 3,4-DCA such as 1,2-dichlorobenzene, 2-chloro-1,4-benzoquinone, 3,4-dichlorophenyl isocyanate, 2-chlorohydroquinone, 3,4-dichloronitrobenzene, and 3,4-dichlorophenol were identified by gas chromatography mass spectrometry (GC-MS) analysis. Based on the identification of aromatic intermediates, acetic acid, formic acid, oxalic acid, and Cl(-) released, a possible mineralization pathway of 3,4-DCA was proposed.
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A randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-16-2014
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Albinterferon is a fusion of albumin and interferon alfa-2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-? for the treatment of chronic hepatitis infections.
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Computer-aided method for identification of major flavone/flavonol glycosides by high-performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS/MS).
Anal Bioanal Chem
PUBLISHED: 06-12-2014
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A new computational tool is proposed here for tentatively identifying major (UV quantifiable) flavone/flavonol glycoside peaks of high performance liquid chromatogram (HPLC)-diode array detection (DAD)-tandem mass spectrometry (MS/MS) profiles based on a MATLAB-based script implementing an in-house algorithm. The HPLC-DAD-MS/MS profiles of red onion, Chinese lettuce, carrot leaf, and celery seed extracts were analyzed by the proposed computer-aided screening method for identifying possible flavone/flavonol glycoside peaks from the HPLC-UV and MS total ion current (TIC) chromatograms. The number of identified flavone/flavonol glycoside peaks of the HPLC-UV chromatograms is four, four, six, and nine for red onion, Chinese lettuce, carrot leaf, and celery seed, respectively. These results have been validated by human(s) experts. For the batch processing of nine HPLC-DAD-MS/MS profiles of celery seed extract, the entire script execution time was within 15 s while manual calculation of only one HPLC-DAD-MS/MS profile by a flavonoid expert could take hours. Therefore, this MATLAB-based screening method is able to facilitate the HPLC-DAD-MS/MS analysis of flavone/flavonol glycosides in plants to a large extent.
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Micro-evolution of the Hepatitis B Virus Genome in Hepatitis B e-Antigen-Positive Carriers: Comparison of Genotypes B and C at Various Immune Stages.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-12-2014
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Patients with hepatitis B virus (HBV) genotype B infection experience hepatitis B e antigen (HBeAg) seroconversion at an earlier stage than do patients with genotype C infection. Therefore, this study investigated whether the differential phenotypes are related to HBV genomic evolution.
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Plasma adipokines and risk of hepatocellular carcinoma in chronic hepatitis B virus-infected carriers: a prospective study in taiwan.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-03-2014
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Obesity is considered a risk factor for hepatocellular carcinoma (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin, and visfatin levels with HCC.
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Elevated p53 promotes the processing of miR-18a to decrease estrogen receptor-? in female hepatocellular carcinoma.
Int. J. Cancer
PUBLISHED: 05-29-2014
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The estrogen pathway has long been implicated as a tumor protector in female hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Our previous study identified that estrogen receptor alpha (ER?) protein is downregulated in 60% of female HCC cases, via a miR-18a elevation mediated suppression of ER? translation. This study aims to delineate the mechanism underlying the upregulation of miR-18a in female HCC. The analysis of 77 female HCC specimens revealed that miR-18a levels were associated with pre-miR-18a rather than pri-miR-18a levels, suggesting an enhanced processing of pri- to pre-miR-18a. Among a panel of factors involved in microRNA processing, p53 was identified as a novel regulator for miR-18a maturation process. Knockdown of p53 by si-RNA decreased the level of miR-18a, whereas overexpression of either wild-type or mutant p53 increased its level. The association between the elevation of miR-18a and the accumulation of p53, mainly caused by somatic mutations, was confirmed in the clinical specimens of HBV-related female HCC. By analyzing the association with clinicopathological features, activation of this p53/miR-18a pathway mainly occurs in younger or noncirrhosis female HCC patients and associated with a trend of worse overall survival. Therefore, this study demonstrated a novel function of elevated/mutant p53 in regulating the amount of ER? protein through its promoting the biogenesis of miR-18a, which could lead to decrease the tumor-protective function of the estrogen pathway in female hepatocarcinogenesis.
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Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers.
Gut
PUBLISHED: 04-26-2014
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Precore (PC) variant (G1896A) and basal core promoter (BCP) variant (A1762T/G1764A) of HBV are associated with risk of hepatocellular carcinoma in HBV carriers. However, little is known about their impact on the adverse outcomes of hepatitis B e antigen (HBeAg)-negative hepatitis and liver cirrhosis.
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Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial.
Gut
PUBLISHED: 04-22-2014
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Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited.
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Nucleocapsid Phosphorylation and RNA Helicase DDX1 Recruitment Enables Coronavirus Transition from Discontinuous to Continuous Transcription.
Cell Host Microbe
PUBLISHED: 04-19-2014
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Coronaviruses contain a positive-sense single-stranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.
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The docking protein FRS2? is a critical regulator of VEGF receptors signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-02-2014
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Vascular endothelial growth factors (VEGFs) signal via their cognate receptor tyrosine kinases designated VEGFR1-3. We report that the docking protein fibroblast growth factor receptor substrate 2 (FRS2?) plays a critical role in cell signaling via these receptors. In vitro FRS2? regulates VEGF-A and VEGF-C-dependent activation of extracellular signal-regulated receptor kinase signaling and blood and lymphatic endothelial cells migration and proliferation. In vivo endothelial-specific deletion of FRS2? results in the profound impairment of postnatal vascular development and adult angiogenesis, lymphangiogenesis, and arteriogenesis. We conclude that FRS2? is a previously unidentified component of VEGF receptors signaling.
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Anti-viral treatment and cancer control.
Recent Results Cancer Res.
PUBLISHED: 04-02-2014
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Hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV) contribute to about 10-15 % global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infections have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell lymphotropic virus type 1 (HTLV-1) had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA-interference-based therapies for treating HPV-associated cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.
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Antidiabetic effect of Lactobacillus casei CCFM0412 on mice with type 2 diabetes induced by a high-fat diet and streptozotocin.
Nutrition
PUBLISHED: 03-31-2014
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The aim of this study was to evaluate the antidiabetic effects of Lactobacillus casei CCFM0412 on mice with type 2 diabetes induced by a high-fat diet and streptozotocin.
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Lymphedema fat graft: an ideal filler for facial rejuvenation.
Arch Plast Surg
PUBLISHED: 03-17-2014
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Lymphedema is a chronic disorder characterized by lymph stasis in the subcutaneous tissue. Lymphatic fluid contains several components including hyaluronic acid and has many important properties. Over the past few years, significant research has been performed to identify an ideal tissue to implant as a filler. Because of its unique composition, fat harvested from the lymphedema tissue is an interesting topic for investigation and has significant potential for application as a filler, particularly in facial rejuvenation. Over a 36-month period, we treated and assessed 8 patients with lymphedematous limbs who concurrently underwent facial rejuvenation with lymphedema fat (LF). We conducted a pre- and post-operative satisfaction questionnaire survey and a histological assessment of the harvested LF fat. The overall mean general appearance score at an average of 6 months after the procedure was 7.2±0.5, demonstrating great improvement. Patients reported significant improvement in their skin texture with a reading of 8.5±0.7 and an improvement in their self-esteem. This study demonstrates that LF as an ideal autologous injectable filler is clinically applicable and easily available in patients with lymphedema. We recommend the further study and clinical use of this tissue as it exhibits important properties and qualities for future applications and research.
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Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B: clinical and mechanistic implications.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-17-2014
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Acute exacerbation (AE) of chronic hepatitis B virus (HBV) infection is common and negatively impacts the clinical outcome. Although upsurge of viral load always precedes or coincides with AE, the underlying immunological mechanisms remain unclear and were investigated.
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Reduced Toll-like receptor 9 expression on peripheral CD14(+) monocytes of chronic hepatitis B patients and its restoration by effective therapy.
Antivir. Ther. (Lond.)
PUBLISHED: 03-14-2014
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Chronic hepatitis B (CHB) patients display Toll-like receptor 9 (TLR9)-dependent defective immune responses. We aimed to study TLR9 expression on CHB patients and its alteration during therapy.
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Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.
World J. Gastroenterol.
PUBLISHED: 02-12-2014
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To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
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A secure RFID authentication protocol adopting error correction code.
ScientificWorldJournal
PUBLISHED: 02-07-2014
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RFID technology has become popular in many applications; however, most of the RFID products lack security related functionality due to the hardware limitation of the low-cost RFID tags. In this paper, we propose a lightweight mutual authentication protocol adopting error correction code for RFID. Besides, we also propose an advanced version of our protocol to provide key updating. Based on the secrecy of shared keys, the reader and the tag can establish a mutual authenticity relationship. Further analysis of the protocol showed that it also satisfies integrity, forward secrecy, anonymity, and untraceability. Compared with other lightweight protocols, the proposed protocol provides stronger resistance to tracing attacks, compromising attacks and replay attacks. We also compare our protocol with previous works in terms of performance.
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Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
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Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is found in HBV or HCV endemic areas, and in specific populations exhibiting a high risk of parenteral viral transmission. Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients. The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations. Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections. Strikingly, approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV. The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined. Furthermore, approximately 30% of dually infected patients lost hepatitis B surface antigen (HBsAg) within 5 years after the start of peginterferon-based therapy, and 40% of them harbored occult HBV infection. The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations. Moreover, the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future, which warrants further clinical trials.
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Hepatitis B surface antigen level complements viral load in predicting viral reactivation in spontaneous HBeAg seroconverters.
J. Gastroenterol. Hepatol.
PUBLISHED: 01-04-2014
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The level of hepatitis B surface antigen (HBsAg) has been shown to complement hepatitis B virus (HBV)-DNA level in predicting disease progression in hepatitis B e antigen (HBeAg)-negative patients, especially those with low viral loads. Whether this finding could be seen in spontaneous HBeAg seroconverters remains unclear.
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Human RAD6 Promotes G1-S Transition and Cell Proliferation through Upregulation of Cyclin D1 Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.
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Overexpression of a Soybean Ariadne-Like Ubiquitin Ligase Gene GmARI1 Enhances Aluminum Tolerance in Arabidopsis.
PLoS ONE
PUBLISHED: 01-01-2014
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Ariadne (ARI) subfamily of RBR (Ring Between Ring fingers) proteins have been found as a group of putative E3 ubiquitin ligases containing RING (Really Interesting New Gene) finger domains in fruitfly, mouse, human and Arabidopsis. Recent studies showed several RING-type E3 ubiquitin ligases play important roles in plant response to abiotic stresses, but the function of ARI in plants is largely unknown. In this study, an ariadne-like E3 ubiquitin ligase gene was isolated from soybean, Glycine max (L.) Merr., and designated as GmARI1. It encodes a predicted protein of 586 amino acids with a RBR supra-domain. Subcellular localization studies using Arabidopsis protoplast cells indicated GmARI protein was located in nucleus. The expression of GmARI1 in soybean roots was induced as early as 2-4 h after simulated stress treatments such as aluminum, which coincided with the fact of aluminum toxicity firstly and mainly acting on plant roots. In vitro ubiquitination assay showed GmARI1 protein has E3 ligase activity. Overexpression of GmARI1 significantly enhanced the aluminum tolerance of transgenic Arabidopsis. These findings suggest that GmARI1 encodes a RBR type E3 ligase, which may play important roles in plant tolerance to aluminum stress.
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Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model.
PLoS ONE
PUBLISHED: 01-01-2014
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Persistent hepatitis B viral (HBV) infection results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). An efficient control of virus infections requires the coordinated actions of both innate and adaptive immune responses. In order to define the role of innate immunity effectors against HBV, viral clearance was studied in a panel of immunodeficient mouse strains by the hydrodynamic injection approach. Our results demonstrate that HBV viral clearance is not changed in IFN-?/? receptor (IFNAR), RIG-I, MDA5, MYD88, NLRP3, ASC, and IL-1R knock-out mice, indicating that these innate immunity effectors are not required for HBV clearance. In contrast, HBV persists in the absence of tumor necrosis factor-alpha (TNF-?) or in mice treated with the soluble TNF receptor blocker, Etanercept. In these mice, there was an increase in PD-1-expressing CD8+ T-cells and an increase of serum HBV DNA, HBV core, and surface antigen expression as well as viral replication within the liver. Furthermore, the induction of TNF-? in clearing HBV is dependent on the HBV core, and TNF blockage eliminated HBV core-induced viral clearance effects. Finally, the intra-hepatic leukocytes (IHLs), but not the hepatocytes, are the cell source responsible for TNF-? production induced by HBcAg. These results provide evidences for TNF-? mediated innate immune mechanisms in HBV clearance and explain the mechanism of HBV reactivation during therapy with TNF blockage agents.
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Association of adjuvant antiviral therapy with risk of cancer progression and deaths in patients with hepatitis-B-virus-related hepatocellular carcinoma following curative treatment: a nationwide cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Limited information about tumor status and the time at which antiviral therapy was initiated may have influenced effect estimation in previous research. The aim of this study was to investigate the effect of antiviral therapies on HBV-related HCC progression and deaths in patients receiving curative treatment based on clear clinical-pathological cancer status and the association of start time of adjuvant antiviral therapy initiation and outcomes.
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A procalcitonin-based algorithm to guide antibiotic therapy in secondary peritonitis following emergency surgery: a prospective study with propensity score matching analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Procalcitonin (PCT)-based algorithms have been used to guide antibiotic therapy in several clinical settings. However, evidence supporting PCT-based algorithms for secondary peritonitis after emergency surgery is scanty. In this study, we aimed to investigate whether a PCT-based algorithm could safely reduce antibiotic exposure in this population.
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SC-60, a Dimer-Based Sorafenib Derivative, Shows a Better Anti-Hepatocellular Carcinoma Effect than Sorafenib in a Preclinical Hepatocellular Carcinoma Model.
Mol. Cancer Ther.
PUBLISHED: 11-25-2013
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Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma. Here, we report that SC-60, a dimer-based sorafenib derivative, overcomes the resistance of sorafenib and shows a better anti-hepatocellular carcinoma effect in vitro and in vivo. SC-60 substantially increased SH2 domain-containing phosphatase 1 (SHP-1) phosphatase activity in hepatocellular carcinoma cells and purified SHP-1 proteins, suggesting that SC-60 affects SHP-1 directly. Molecular docking and truncated mutants of SHP-1 further confirmed that SC-60 interferes with the inhibitory N-SH2 domain to relieve the closed catalytic protein tyrosine phosphatase domain of SHP-1. Deletion of N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of SC-60 on SHP-1, p-STAT3, and apoptosis. Importantly, SC-60 exhibited significant survival benefits compared with sorafenib in a hepatocellular carcinoma orthotopic model via targeting the SHP-1/STAT3-related signaling pathway. In summary, dimer derivative of sorafenib, SC-60, is a SHP-1 agonist and may be a potent reagent for hepatocellular carcinoma-targeted therapy. Mol Cancer Ther; 13(1); 1-10. ©2013 AACR.
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Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma.
Gut
PUBLISHED: 11-13-2013
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The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk.
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Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-01-2013
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In kidney collecting duct cells, filamentous actin (F-actin) depolymerization is a critical step in vasopressin-induced trafficking of aquaporin-2 to the apical plasma membrane. However, the molecular components of this response are largely unknown. Using stable isotope-based quantitative protein mass spectrometry and surface biotinylation, we identified 100 proteins that showed significant abundance changes in the apical plasma membrane of mouse cortical collecting duct cells in response to vasopressin. Fourteen of these proteins are involved in actin cytoskeleton regulation, including actin itself, 10 actin-associated proteins, and 3 regulatory proteins. Identified were two integral membrane proteins (Clmn, Nckap1) and one actin-binding protein (Mpp5) that link F-actin to the plasma membrane, five F-actin end-binding proteins (Arpc2, Arpc4, Gsn, Scin, and Capzb) involved in F-actin reorganization, and two actin adaptor proteins (Dbn1, Lasp1) that regulate actin cytoskeleton organization. There were also protease (Capn1), protein kinase (Cdc42bpb), and Rho guanine nucleotide exchange factor 2 (Arhgef2) that mediate signal-induced F-actin changes. Based on these findings, we devised a live-cell imaging method to observe vasopressin-induced F-actin dynamics in polarized mouse cortical collecting duct cells. In response to vasopressin, F-actin gradually disappeared near the center of the apical plasma membrane while consolidating laterally near the tight junction. This F-actin peripheralization was blocked by calcium ion chelation. Vasopressin-induced apical aquaporin-2 trafficking and forskolin-induced water permeability increase were blocked by F-actin disruption. In conclusion, we identified a vasopressin-regulated actin network potentially responsible for vasopressin-induced apical F-actin dynamics that could explain regulation of apical aquaporin-2 trafficking and water permeability increase.
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Re-evaluating transarterial chemoembolization for the treatment of Hepatocellular Carcinoma: Consensus recommendations and review by an International Expert Panel.
Liver Int.
PUBLISHED: 08-29-2013
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Patients with unresectable hepatocellular carcinoma (HCC) usually receive transarterial chemoembolization (TACE) or systemic therapies with intermediate and advanced-stage disease. However, intermediate-stage HCC patients often have unsatisfactory clinical outcomes with repeated TACE and there is considerable uncertainty surrounding the criteria for repeating or stopping TACE treatment. In July 2012, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was re-convened in Shanghai in an attempt to provide a consensus on the practice of TACE, particularly in regard to evaluating TACE failure. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies for intermediate HCC. This review summarizes the evidence discussed at the meeting and provides expert recommendations regarding the use of TACE for unresectable intermediate-stage HCC. A key consensus of the Expert Panel was that the current definitions of TACE failure are not useful in differentiating between situations where TACE is no longer effective in controlling disease locally vs. systemically. By redefining these concepts, it may be possible to provide a clearer indication of when TACE should be repeated and more importantly, when TACE should be discontinued.
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Sorafenib and its derivative SC-49 sensitize hepatocellular carcinoma cells to CS-1008, a humanized anti-TNFRSF10B (DR5) antibody.
Br. J. Pharmacol.
PUBLISHED: 07-03-2013
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Previously, we have shown that sorafenib sensitizes hepatocellular carcinoma (HCC) to apoptosis induced by TNF-related apoptosis-inducing ligand (TNFSF10; TRAIL). Here, we report that sorafenib and SC-49 sensitize HCC cells to CS-1008, a novel anti-human death receptor 5 (TNFRSF10B) antibody.
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Fabrication of large perfusable macroporous cell-laden hydrogel scaffolds using microbial transglutaminase.
Acta Biomater
PUBLISHED: 05-21-2013
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In this study, we developed a method to fabricate large, perfusable, macroporous, cell-laden hydrogels. This method is suitable for efficient cell seeding, and can maintain sufficient oxygen delivery and mass transfer. We first loaded three types of testing cells (including NIH 3T3, ADSC and Huh7) into gelatin hydrogel filaments, then cross-linked the cell-laden gelatin hydrogel filaments using microbial transglutaminase (mTGase). In situ cross-linking by mTGase was found to be non-cytotoxic and prevented the scattering of the cells after delivery. The gelatin hydrogel constructs kept the carried cells viable; also, the porosity and permeability were adequate for a perfusion system. Cell proliferation was better under perfusion culture than under static culture. When human umbilical vein endothelial cells were seeded into the constructs, we demonstrated that they stably formed an even coverage on the surface of the hydrogel filaments, serving as a preliminary microvasculature network. We concluded that this method provides a viable solution for cell seeding, oxygen delivery, and mass transfer in large three-dimensional (3-D) tissue engineering. Furthermore, it has the potential for being a workhorse in studies involving 3-D cell cultures and tissue engineering.
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Reduction of HBV replication prolongs the early immunological response to IFN? therapy.
J. Hepatol.
PUBLISHED: 05-17-2013
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The interaction between HBV replication and immune modulatory effects mediated by IFN? therapy is not well understood. We characterized the impact of HBV DNA replication on the early IFN?-induced immunomodulatory mechanisms.
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Treatment of patients with dual hepatitis C and B by peginterferon ? and ribavirin reduced risk of hepatocellular carcinoma and mortality.
Gut
PUBLISHED: 05-15-2013
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OBJECTIVE: Whether peginterferon ? and ribavirin combination therapy reduces risk of hepatocellular carcinoma (HCC) or improves survival in patients dual-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) is unknown. Since it is ethically impossible to conduct a randomised trial to learn the long-term efficacy, we rely upon the large database to explore the effectiveness of combination therapy among dual-infected patients. DESIGN: Data for this population-based retrospective cohort study were obtained from the treatment programme, Cancer Registry, National Health Insurance and death certification. We examined the risk of HCC, mortality and adverse events in 1096 treated and 18 988 untreated HCV-HBV dually-infected patients. Outcomes were analysed using the bias corrected inverse probability weighting (IPW) by propensity scores. Outcomes of HCV-HBV dually-infected and HCV mono-infected patients receiving the same treatment were compared using new user design with IPW estimators to adjust for confounding. RESULTS: After adjustment, combination therapy significantly reduced the risk of HCC (HR 0.76, 95% CI 0.59 to 0.97), liver-related mortality (HR 0.47, 95% CI 0.37 to 0.6) and all-cause mortality (HR 0.42, 95% CI 0.34 to 0.52). Nevertheless, the underlying HBV infection was still a risk factor for HCC and mortality after treatment. Treatment was associated with an increase in the incidence of thyroid dysfunction (HR 1.9, p<0.001) and mood disorders (HR 1.81, p=0.005). CONCLUSIONS: This is the first evidence showing that combination therapy decreased the risk of HCC and improved survival in HCV-HBV dually-infected patients despite a slight increase in the incidence of thyroid and mood disorders.
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Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers.
J. Infect. Dis.
PUBLISHED: 05-08-2013
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The serum hepatitis B virus (HBV) surface antigen (HBsAg) level can predict hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients with an HBV DNA level of <2000 IU/mL. However, little is known regarding how well the combination of both viral biomarkers stratifies HCC risk.
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Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up.
Hepatology
PUBLISHED: 04-26-2013
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Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared with HCV-monoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5-year follow-up study. Patients with active HCV genotype 1, both HBV-coinfected (n = 97) and HBV-monoinfected (n = 110), underwent 48-week combination therapy with peginterferon alfa-2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV-coinfected (n = 64) and monoinfected (n = 50) patients underwent 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow-up; 264 (89.5%) patients agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 ± 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV-coinfected patients and one HCV genotype 2/3-monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group. Conclusion: Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;).
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Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy.
Antivir. Ther. (Lond.)
PUBLISHED: 04-23-2013
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Toll-like receptor (TLR)3 gene variants may correlate with clinical significance of chronic viral infections including HBV. We aimed to investigate the expression of TLR3 in peripheral blood mononuclear cells (PBMCs) and liver cells of chronic hepatitis B (CHB) patients and its response to pegylated interferon or nucleoside analogue therapy.
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Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-23-2013
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MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, ?-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.
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Eltrombopag Increases Platelet Numbers in Thrombocytopenic Patients With HCV Infection and Cirrhosis, Allowing for Effective Antiviral Therapy.
Gastroenterology
PUBLISHED: 04-18-2013
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Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.
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Focal Nodular Hyperplasia and Hepatocellular Adenoma around the World Viewed through the Scope of the Immunopathological Classification.
Int J Hepatol
PUBLISHED: 04-14-2013
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Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors. The risk of bleeding and malignant transformation of HCA are strong arguments to differentiate HCA from FNH. Despite great progress that has been made in the differential radiological diagnosis of the 2 types of nodules, liver biopsy is sometimes necessary to separate the 2 entities. Identification of HCA subtypes using immunohistochemical techniques, namely, HNF1A-inactivated HCA (35-40%), inflammatory HCA (IHCA), and beta-catenin-mutated inflammatory HCA (b-IHCA) (50-55%), beta-catenin-activated HCA (5-10%), and unclassified HCA (10%) has greatly improved the diagnostic accuracy of benign hepatocellular nodules. If HCA malignant transformation occurs in all HCA subgroups, the risk is by far the highest in the ? -catenin-mutated subgroups (b-HCA, b-IHCA). In the coming decade the management of HCA will be more dependent on the identification of HCA subtypes, particularly for smaller nodules (<5?cm) in terms of imaging, follow-up, and resection.
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Clinical and virological features of occult hepatitis B in patients with HBsAg seroclearance post-treatment or spontaneously.
Liver Int.
PUBLISHED: 04-09-2013
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Occult hepatitis B virus (HBV) infection (OHB) may exist in patients experiencing hepatitis B surface antigen (HBsAg) seroclearance.
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Report from a Viral Hepatitis Policy Forum on implementing the WHO Framework for Global Action on viral hepatitis in North Asia.
J. Hepatol.
PUBLISHED: 04-04-2013
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The World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop.
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Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy.
J. Gastroenterol.
PUBLISHED: 03-20-2013
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BACKGROUND: Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy. METHODS: Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998-1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially. RESULTS: There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12-22.00, P = 0.035). CONCLUSIONS: The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.
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Liver sinusoidal endothelial cell lectin inhibits CTL-dependent virus clearance in mouse models of viral hepatitis.
J. Immunol.
PUBLISHED: 03-13-2013
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Liver sinusoidal endothelial cell lectin (LSECtin) was recently reported to suppress intrahepatic T cell immunity and to limit immune-mediated liver injury. However, its role in the outcome and pathogenesis of viral infection has not yet been elucidated. Using a mouse model infected with a hepatotropic adenovirus, we found that the absence of LSECtin led to a higher frequency of intrahepatic effector CTLs. These cells produced higher levels of antiviral cytokines and cytotoxic factors and exhibited an increased expression of the transcription factors T-bet and Runx3. This phenotype observed in the LSECtin-knockout cells mediated a more efficient virus-specific cytotoxicity compared with that of wild-type cells. As a consequence, LSECtin deficiency significantly accelerated liver adenovirus clearance. In contrast, LSECtin upregulation in the liver delayed viral clearance; this delayed clearance was accompanied by the downregulation of the antiviral activity of CTLs. We further constructed an immunocompetent mouse model of acute hepatitis B viral infection to demonstrate that LSECtin significantly delayed the clearance of hepatitis B virus from blood and infected hepatocytes by limiting the frequency of hepatitis B virus-specific IFN-?-producing cells. Consistent with this function, LSECtin was upregulated in the liver of mouse models of viral hepatitis. Taken together, our results suggest that LSECtin may facilitate the reduction of liver inflammation at the cost of delaying virus clearance and that this effect might be hijacked by the virus as an escape mechanism.
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Immunocompetent nontransgenic mouse models for studying hepatitis B virus immune responses.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-10-2013
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Although the chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV-specific immune responses that cannot eliminate or clear the infected hepatocytes efficiently, many issues remained unsettled. It is thus crucial to have a suitable laboratory animal to study the immunopathogenesis of HBV infection and the mechanisms of HBV persistence. To meet the requirement of a mouse model resembling natural chronic HBV infection in human, there are several approaches in the development of mouse animal model by using hydrodynamic-based transfection of HBV DNA, delivery of adenovirus or adeno-associated viral vectors containing HBV DNA for studying HBV immune responses. These immunocompetent nontransgenic mouse animal models will provide new approaches to investigate the mechanisms of immune pathogenesis in HBV infection.
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Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol.
Syst Rev
PUBLISHED: 03-06-2013
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Diagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria.
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Discovery of novel src homology region 2 domain-containing phosphatase 1 agonists from sorafenib for the treatment of hepatocellular carcinoma.
Hepatology
PUBLISHED: 03-04-2013
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Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma (HCC). Here, we report that Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1) is a major target of sorafenib and generates a series of sorafenib derivatives to search for potent SHP-1 agonists that may act as better anti-HCC agents than sorafenib. Sorafenib increases SHP-1 activity by direct interaction and impairs the association between the N-SH2 domain and the catalytic protein tyrosine phosphatase domain of SHP-1. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of sorafenib on SHP-1, phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and apoptosis, suggesting that sorafenib may affect SHP-1 by triggering a conformational switch relieving its autoinhibition. Molecular docking of SHP-1/sorafenib complex confirmed our findings in HCC cells. Furthermore, novel sorafenib derivatives SC-43 and SC-40 displayed more potent anti-HCC activity than sorafenib, as measured by enhanced SHP-1 activity, inhibition of p-STAT3, and induction of apoptosis. SC-43 induced substantial apoptosis in sorafenib-resistant cells and showed better survival benefits than sorafenib in orthotopic HCC tumors. Conclusion: In this study, we identified SHP-1 as a major target of sorafenib. SC-43 and SC-40, potent SHP-1 agonists, showed better anti-HCC effects than sorafenib in vitro and in vivo. Further clinical investigation is warranted. (Hepatology 2014;58:190-201).
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Recurrent acute pancreatitis and massive hemorrhagic ascites secondary to a duodenal duplication in a child: a case report.
J Med Case Rep
PUBLISHED: 02-12-2013
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Duodenal duplication is a rare congenital malformation and has been reported as a rare cause of recurrent acute pancreatitis. Hemorrhagic ascites has been reported in only one case of duodenal duplication.
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Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention.
J. Hepatol.
PUBLISHED: 02-11-2013
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Immunoprophylaxis reduces but does not completely eradicate hepatitis B virus (HBV) transmission. This prospective study aims at assessing the rate and risk factors of maternally transmitted HBV infection.
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A mutation of the Col2a1 gene (G1170S) alters the transgenic murine phenotype and cartilage matrix homeostasis.
J. Formos. Med. Assoc.
PUBLISHED: 02-10-2013
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Genomic studies have revealed that there is a significant association between a point mutation of the human Col2A1 gene (G1170S) and several hip disorders. The purpose of the study was to explore the phenotype and altered cartilage matrix homeostasis of transgenic mice carrying this mutated Col2a1 gene.
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Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced hepatitis B e antigen seroconversion.
Hepatology
PUBLISHED: 02-07-2013
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Precore (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations of the hepatitis B virus (HBV) genome often emerge in chronic hepatitis B (CHB) patients. Their roles in hepatitis B e antigen (HBeAg) seroconversion induced by interferon (IFN) therapy remain controversial, partly because quantitative analysis for these mutants is lacking. This study aimed to develop a new assay to accurately quantify the PC and BCP mutant percentages and correlate their dynamic changes with IFN-induced HBeAg seroconversion in HBeAg-positive CHB patients. The PC and BCP mutant percentages were analyzed by polymerase chain reaction (PCR)-pyrosequencing. Our results showed that this quantitative assay for PC and BCP mutants achieved high accuracy (R(2) > 0.99) within a range between 10% and 90% mutants. We examined dynamic changes of the PC and BCP mutant percentages following IFN treatment in 203 HBeAg-positive CHB patients. By multiple logistic regression analysis, we found that the chance of HBeAg seroconversion increased by 2.2% (odds ratio [OR] = 1.022, 95% confidence interval [CI]: 1.009-1.034, P = 0.001) and 2.3% (OR = 1.023, 95% CI: 1.010-1.037, P = 0.001) per 1% increase of the pretreatment PC and BCP mutant percentages, respectively, after adjustment for other predictors. However, only the pretreatment PC mutation percentage was significantly associated with HBeAg seroconversion with HBV DNA < 2,000 IU/mL (OR = 1.030, 95% CI: 1.014-1.047, P < 0.001). Furthermore, the mutant percentage of PC, but not BCP, in patients achieving HBeAg seroclearance with HBV DNA < 20,000 IU/mL increased significantly during IFN treatment (P = 0.039). Interestingly, patients with HBeAg seroconversion who had a high PC mutant percentage at the end of IFN treatment tended to exhibit high viremia after seroconversion. Conclusion: Quantitative analysis of PC and BCP mutants can predict IFN-induced HBeAg seroconversion and demonstrate their distinct evolution patterns during HBeAg seroconversion. (HEPATOLOGY 2013).
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Effect of parenteral selenium supplementation in critically ill patients: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-25-2013
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It is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes.
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Application of massively parallel sequencing to genetic diagnosis in multiplex families with idiopathic sensorineural hearing impairment.
PLoS ONE
PUBLISHED: 01-21-2013
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Despite the clinical utility of genetic diagnosis to address idiopathic sensorineural hearing impairment (SNHI), the current strategy for screening mutations via Sanger sequencing suffers from the limitation that only a limited number of DNA fragments associated with common deafness mutations can be genotyped. Consequently, a definitive genetic diagnosis cannot be achieved in many families with discernible family history. To investigate the diagnostic utility of massively parallel sequencing (MPS), we applied the MPS technique to 12 multiplex families with idiopathic SNHI in which common deafness mutations had previously been ruled out. NimbleGen sequence capture array was designed to target all protein coding sequences (CDSs) and 100 bp of the flanking sequence of 80 common deafness genes. We performed MPS on the Illumina HiSeq2000, and applied BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV for bioinformatics analyses. Initial data filtering with allele frequencies (<5% in the 1000 Genomes Project and 5400 NHLBI exomes) and PolyPhen2/SIFT scores (>0.95) prioritized 5 indels (insertions/deletions) and 36 missense variants in the 12 multiplex families. After further validation by Sanger sequencing, segregation pattern, and evolutionary conservation of amino acid residues, we identified 4 variants in 4 different genes, which might lead to SNHI in 4 families compatible with autosomal dominant inheritance. These included GJB2 p.R75Q, MYO7A p.T381M, KCNQ4 p.S680F, and MYH9 p.E1256K. Among them, KCNQ4 p.S680F and MYH9 p.E1256K were novel. In conclusion, MPS allows genetic diagnosis in multiplex families with idiopathic SNHI by detecting mutations in relatively uncommon deafness genes.
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Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC).
Liver Int.
PUBLISHED: 01-18-2013
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Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.
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Long-term follow-up of children with postnatal immunoprophylaxis failure who were infected with hepatitis B virus surface antigen gene mutant.
J. Infect. Dis.
PUBLISHED: 01-08-2013
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The long-term evolution and outcomes of infection with a hepatitis B virus (HBV) surface antigen (HBsAg) gene mutant (hereafter, "HBsAg-mutant HBV") among immunized children remain unclear.
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One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor.
Cell Biosci
PUBLISHED: 01-07-2013
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Following the successful cloning of receptor for SARS coronavirus a few years ago, Dr. Wenhui Li and colleagues raised attention again by publishing a possible receptor for hepatitis B virus in eLife. We will briefly review the significance of this finding and the future prospects of hepatitis B research.
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IL-21R gene polymorphisms and serum IL-21 levels predict virological response to interferon-based therapy in Asian chronic hepatitis C patients.
Antivir. Ther. (Lond.)
PUBLISHED: 01-07-2013
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IL-21R polymorphisms have been identified as potential predictors of virological outcomes in Western chronic hepatitis C (CHC) patients receiving interferon-based treatment. We aimed to examine the associations of IL-21R genotypes and serum IL-21 levels with virological responses to interferon-based treatment in Asian CHC patients.
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Longitudinal change of HBsAg in HBeAg-negative patients with genotype B or C infection.
PLoS ONE
PUBLISHED: 01-03-2013
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Quantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.