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Find video protocols related to scientific articles indexed in Pubmed.
Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-15-2014
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Sepsis and its associated multiple organ failure are related to high mortality in critical patients. Several studies have reported that gabexate mesilate, a synthetic inhibitor of trypsin-like serine protease, protects tissues/organs against injury in the models of endotoxemia. The aim of this study was to examine whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG). LPS (7.5?mg/kg/h, intravenouly for 4?h) was administered to male adult Wistar rats. Some of the LPS rats received a continuous infusion of gabexate mesilate (10?mg/kg/h, intravenously for 8.5?h) for 30?min before the LPS administration. Variable parameters of hemodynamics, biochemistry, hemostasis and inflammatory response were measured for 6?h after the LPS infusion. TEG variables (R-time, K-time, ?-angle, and maximal amplitude) were also measured. The pretreatment of LPS rats with gabexate mesilate significantly attenuated the lung, liver and kidney dysfunction, consumptive coagulopathy, the increases in serum tumor necrosis factor-?, interleukin-6, plasma thrombin-antithrombin complex and plasminogen activator inhibitor-1, and neutrophils infiltration score in lung, liver and kidney, compared with the LPS alone group. In addition, TEG parameters correlated with tissue and liver injury in the late phase of endotoxemia. In particular, a strong negative correlation between maximal amplitude at 4?h and Ln (lactate dehydrogenase) at 6?h after LPS infusion was noted (r?=?-0.752, P?
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The moderating and mediating roles of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being.
J Health Psychol
PUBLISHED: 11-15-2014
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This study explored the moderating and mediating influences of self-acceptance and tolerance to others in the relationship between mindfulness and subjective well-being. In total, 301 (130 males) university students completed the Five-Facet Mindfulness Questionnaire, Index of Well-being, Self-acceptance Questionnaire, and Tolerance Scale. The results showed that the positive link between mindfulness and subjective well-being was significantly mediated by self-acceptance only. Tolerance played a moderating role. The implications of the results for relevant research and mindfulness training were discussed.
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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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[Differential proteome analysis of carbon tetrachloride-induced mouse liver fibrosis].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 10-28-2014
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To explore the differential proteome pattern in mouse fibrosis liver in comparison to wild type. Mice were fed with carbon tetrachloride or olive oil vehicle for 15 weeks. Mouse livers from both groups were collected and submitted to MS platform for proteome screening. GO (Gene Ontology) biological process and KEGG (Kyoto Enyoolpedia of Genes and Genomes) pathway enrichment analysis were used to analyze differentially expressed proteins. As the results, we identified 17 382 and 20 486 unique peptides in control and carbon tetrachloride-induced groups, respectively. A total of 4 991 proteins (at least 1 unique peptide matched) were identified, of which 2 135 were differentially expressed (> or = 2 fold). In fibrosis mouse liver 1 264 proteins were up regulated and 871 proteins were down regulated. Proteins associated with DNA replication, cell cycle, ECM-receptor interaction, and splicesome were significantly increased in carbon tetrachloride-induced group. Proteins associated with small molecule metabolic process, protein transport, organonitrogen compound metabolic process, and tetrapyrrole biosynthetic processes were down regulated in carbon tetrachloride-induced mouse liver fibrosis tissue. Bioinformatics findings showed that fibrosis was closely related to the regulation of VEGF and T cell receptor signaling pathway, and further suggested that liver fibrosis was a complex signal transduction process that many biological processes such as liver metabolism, inflammation, and immune response are involved. Based this study, we can envision that protection of protein metabolism in liver parenchymal cells and blocking of inflammatory signaling transduction may be beneficial for liver fibrosis therapy.
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[Dynamic response of riverine nitrate flux to net anthropogenic nitrogen inputs in a typical river in Zhejiang Province over the 1980-2010 period].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Based on long-term records of river water quality and discharge and nitrogen sources as well as the LOADEST model, annual riverine NO3(-)-N flux and net anthropogenic nitrogen input (NANI) were both estimated for a typical river catchment (2 474 km2) in Zhejiang Province over the 1980-2010 period. Historical trends in both riverine NO3(-) -N flux and NANI and their dynamic relationships were then fully addressed. Finally, the contributions of annual NANI, retained nitrogen pools, and natural background sources to riverine NO3(-)-N flux were indentified. Results indicated that both riverine NO3(-) -N flux and NANI showed parabolic changing trends with peak value of 5.74 kg x (hm2 x a) for flux and 77.5 kg x (hm2 x a)(-1) for NANI both occurring around 1998. In 1980-2010, net increase of riverine NO3(-) -N flux and NANI was -42% and -77%, respectively. Chemical nitrogen fertilizer application and atmospheric nitrogen deposition, which accounted for -48% and -40% of NANI, respectively, were the major sources of NANI. Although interannual change of riverine NO3(-) -N flux was significantly related to NANI (R2 = 0. 27 * *) as well as the chemical nitrogen fertilizer application amount (R2 = 0.32 * *), it showed higher dependence on the river water discharge (R2 = 0.79 * *) or precipitation (R2 = 0.63 * *), implying that annual riverine NO3(-) -N was not only originated from current year's NANI, but also derived from retained N pools that were ultimately derived from NANI in previous years. A regression model developed by incorporating both NANI and water discharge could account for 94% of the variability of annual NO3(-) -N flux. This model predicted that NO3(-) -N flux could have been reduced by -21% and -30% if the annual NANI and water discharge had been cut by 30%, respectively. Annual NANI, retained nitrogen pools, and natural background sources contributed to -53%, -24%, and -23% of the riverine NO3(-) -N flux, respectively, suggesting that -77% of flux was derived from anthropogenic nitrogen sources. Although observed long-term interannual change of riverine NO3(-) -N flux was dependent on the combined influences of NANI and hydroclimate, a more immediate reduction of riverine NO3(-) -N flux may result from interception strategies than from cutting nitrogen source inputs due to the contribution of retained nitrogen pools.
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Single Dose of Glycoengineered Anti-CD19 Antibody (MEDI551) Disrupts Experimental Autoimmune Encephalomyelitis by Inhibiting Pathogenic Adaptive Immune Responses in the Bone Marrow and Spinal Cord while Preserving Peripheral Regulatory Mechanisms.
J. Immunol.
PUBLISHED: 10-03-2014
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Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.
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Comparison of pre-operation diagnosis of thyroid cancer with fine needle aspiration and core-needle biopsy: a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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The aim of this meta-analysis was to compare sensitivities and specificities of fine needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of thyroid cancer.
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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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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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Multiple variants in UGT1A1 gene are factors to develop indirect hyper-bilirubinemia.
Hepatobiliary Surg Nutr
PUBLISHED: 06-12-2014
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Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATA box upstream of UGT1A1 associated with Gilbert's syndrome. To investigate the role of UGT1A1 in the pathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirect hyper-bilirubinemia for genotypes of promoter [(TA)6TAA6, (TA)7TAA7] and coding region [nucleotide (nt)-211, nt-686, nt-1,091 and nt-1,456] of UGT1A1. Thirty-six of the patients (45.6%) were found to have Gilbert's syndrome with 7/7 genotype; among them, 14 also carried variants at nt-686. Forty-two patients (43.3%) had the 6/7 genotype; among them, 36 patients were found to have one or more variants in the coding region. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert's syndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ?2.5 mg/dL carried the Gilbert's syndrome genotype, while only 23.9% of patients with serum total bilirubin level <2.5 mg/dL carry the same genotype (P=0.0006). Forty-one of the 61 non-Gilbert's patients had one homogenous variants or two or more heterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygous variant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia.
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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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Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis.
J Zhejiang Univ Sci B
PUBLISHED: 06-07-2014
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It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis.
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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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Analyses of factors affecting nickel ferrite nanoparticles synthesis in ultrasound-assisted aqueous solution ball milling.
Ultrason Sonochem
PUBLISHED: 05-28-2014
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Ball milling experiments were conducted with and without ultrasound wave assistance in deionized water using NiCO3·2Ni(OH)2·4H2O as raw materials. In the reaction process of NiFe2O4 prepared by ultrasound-assisted aqueous solution ball milling, some influencing factors including raw materials, ultrasonic frequency, ball to powder ratio and liquid level were changed. Samples were characterized by X-ray diffraction, fluorescence measurements and electroconductivity detections. The results indicate that more hydroxyl radicals and ions can be generated under the coupling effect of ultrasonic and ball milling. The fluorescence measurements and electroconductivity detections also reflect the reaction speed, allowing for optimal parameters to be determined.
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Iron and copper as virulence modulators in human fungal pathogens.
Mol. Microbiol.
PUBLISHED: 05-21-2014
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Fungal pathogens have evolved sophisticated machinery to precisely balance the fine line between acquiring essential metals and defending against metal toxicity. Iron and copper are essential metals for many processes in both fungal pathogens and their mammalian hosts, but reduce viability when present in excess. However, during infection, the host uses these two metals differently. Fe has a long-standing history of influencing virulence in pathogenic fungi, mostly in regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe acquisition pathway of Candida, Cryptococcus and Aspergillus for successful systemic infection. Fe is not free in the host, but is associated with Fe-binding proteins, leading fungi to develop mechanisms to interact with and to acquire Fe from these Fe-bound proteins. Cu is also essential for cell growth and development. Essential Cu-binding proteins include Fe transporters, superoxide dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical roles in fungal survival in the host, recent work has revealed that Cu detoxification is extremely important. Here, we review fungal responses to altered metal conditions presented by the host, contrast the roles of Fe and Cu during infection, and outline the critical roles of fungal metal homeostasis machinery at the host-pathogen axis.
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High-efficiency targeted editing of large viral genomes by RNA-guided nucleases.
PLoS Pathog.
PUBLISHED: 05-01-2014
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A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nuclease system can be introduced into host cells during viral replication. The CRISPR-Cas9 system robustly stimulates targeted double-stranded breaks in the genomes of DNA viruses, where the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways can be exploited to introduce site-specific indels or insert heterologous genes with high frequency. Furthermore, CRISPR-Cas9 can specifically inhibit the replication of the original virus, thereby significantly increasing the abundance of the recombinant virus among progeny virus. As a result, purified recombinant virus can be obtained with only a single round of selection. In this study, we used recombinant adenovirus and type I herpes simplex virus as examples to demonstrate that the CRISPR-Cas9 system is a valuable tool for editing the genomes of large DNA viruses.
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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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Monitor corneal epithelial healing under bandage contact lens using ultrahigh-resolution optical coherence tomography after pterygium surgery.
Eye Contact Lens
PUBLISHED: 04-24-2014
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To monitor corneal epithelial healing under bandage contact lens (BCL) using ultrahigh-resolution optical coherence tomography (UHR-OCT) after pterygium surgery.
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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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Peginterferon ? in the treatment of chronic hepatitis B.
Expert Opin Biol Ther
PUBLISHED: 04-16-2014
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Hepatitis B virus (HBV) infection is a global health problem. Peginterferon ? (PEG-IFN), which includes PEG-IFN ?-2a (Pegasys) and PEG-IFN ?-2b (Peg-Intron), can be used to treat patients with chronic hepatitis B (CHB) infection. A finite duration of PEG-IFN therapy may lead to long-term viral suppression. Clinically, it is important to identify super-responders and null-responders to PEG-IFN due to its substantial side effects.
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Clinical comparison of 2 implantation systems for single-level cervical disk replacement.
Orthopedics
PUBLISHED: 04-01-2014
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The safety and effectiveness of 2 implantation systems for single-segment cervical disk replacement-the Bryan Cervical Disc System (Medtronic Inc, Minneapolis, Minnesota) and the ACCEL system (Medtronic Inc)-have not been clinically compared. A prospective, nonrandomized controlled study in consecutive patients with a minimum 2-year follow-up was performed. Fifty patients with single-level cervical disk degeneration who responded poorly to conservative treatment and underwent Bryan Cervical Disc replacement were involved. Fifty patients were included (24 in group A [Bryan Cervical Disc System] and 26 in group B [ACCEL system]).The patients' visual analog scale scores, Neck Disability Index (NDI) scores, Short Form 36 (SF-36) scores, Odom scores, operative time, blood loss, and complications were compared. Patients' baseline statuses were similar (P>.05). Visual analog scale for neck and arm pain, NDI, and SF-36 were significantly improved postoperatively (P<.05) in both groups, and no clinical differences were found between the groups (P>.05). All Odom scores were better than good. Mean operative time and average blood loss in group A (173±42.5 minutes and 250±159.8 mL, respectively), were both significantly higher than the values in group B (137.5±19.3 minutes and 138.1±86.7 mL, respectively) (P<.05). Complications included intraoperative bleeding, temporary throat discomfort, and slight migration of the prosthesis; there was no significant difference in the total complication rates between the 2 groups (P>.05). The 2 implantation systems displayed equal clinical effectiveness and safety, but the ACCEL system appears to have the advantages of shorter operative time and less blood loss.
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A pilot study of add-on oral hypoglycemic agents in treatment-naïve genotype-1 chronic hepatitis C patients receiving peginterferon alfa-2b plus ribavirin.
J. Formos. Med. Assoc.
PUBLISHED: 03-26-2014
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Insulin resistance (IR) affects sustained virological response (SVR) to peginterferon alfa plus ribavirin (PR) in patients with chronic hepatitis C (CHC). Whether add-on oral hypoglycemic agents (OHAs) to PR improve SVR remains unclear; therefore, we conducted a prospective, randomized pilot trial on 23 consecutive patients with genotype 1 CHC and IR in Taiwan.
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High-throughput absolute quantification of proteins using an improved two-dimensional reversed-phase separation and quantification concatemer (QconCAT) approach.
Anal Bioanal Chem
PUBLISHED: 03-21-2014
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Stable isotope dilution-selective reaction monitoring-mass spectrometry (SID-SRM-MS) has been widely used for the absolute quantitative analysis of proteins. However, when performing the large-scale absolute quantification of proteins from a more complex tissue sample, such as mouse liver, in addition to a high-throughput approach for the preparation and calibration of large amounts of stable-isotope-labelled internal standards, a more powerful separation method prior to SRM analysis is also urgently needed. To address these challenges, a high-throughput absolute quantification strategy based on an improved two-dimensional reversed-phase (2D RP) separation and quantification concatemer (QconCAT) approach is presented in this study. This strategy can be used to perform the simultaneous quantification of hundreds of proteins from mouse liver within one week of total MS measurement time. By using calibrated synthesised peptides from the protein glutathione S-transferase (GST), large amounts of GST-tagged QconCAT internal standards corresponding to hundreds of proteins can be accurately and rapidly quantified. Additionally, using an improved 2D RP separation method, a mixture containing a digested sample and QconCAT standards can be efficiently separated and absolutely quantified. When a maximum gradient of 72 min is employed in the first LC dimension, resulting in 72 fractions, identification and absolute quantification experiments for all fractions can be completed within one week of total MS measurement time. The quantification approach developed here can further extend the dynamic range and increase the analytical sensitivity of SRM analysis of complex tissue samples, thereby helping to increase the coverage of absolute quantification in a whole proteome.
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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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[Inhibitory effect of 2'-hydroxyflavanone on proliferation, invasion and migration of bladder cancer cells in vitro via blocking AKT/STAT3 signaling pathway].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 03-11-2014
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To study the effect of 2'-hydroxyflavanone on proliferation, invasion and migration of bladder cancer cells and its mechanism.
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Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats.
Brain Res.
PUBLISHED: 03-04-2014
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Madecassoside, a triterpenoid derivative isolated from Centella asiatica, exhibits anti-inflammatory and antioxidant activities. We investigated its neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24mg/kg, i.v.) was administered 1h after the start of reperfusion, and neurological deficit score and infarct volume were evaluated 24h later. Neuronal apoptosis was assessed by performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, and pathological brain damage was estimated by performing hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide dismutase activity, reduced glutathione levels, and nitric oxide levels were also determined. mRNA and protein expression of pro-inflammatory cytokines (Interleukin-1?/6, and tumor necrosis factor-?) were measured by real-time RT-PCR and ELISA, respectively; NF-?B p65 expression was determined by western blotting. Madecassoside significantly reduced brain infarct area, resolved neurological deficit, and ameliorated neuronal apoptosis. It also significantly reduced the levels of malondialdehyde and nitric oxide, and augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover, the levels of pro-inflammatory cytokines and NF-?B p65 significantly reduced after madecassoside treatment. These results indicate that madecassoside is neuroprotective and may be useful in reducing the damage caused by stroke.
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On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy.
Antivir. Ther. (Lond.)
PUBLISHED: 02-16-2014
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Serum HBV RNA is detectable during nucleos(t)ide analogue therapy as the consequence of unaffected RNA replicative intermediates or interrupted reverse transcription. We studied the predictive value of serum HBV RNA for initial virologic response during nucleoside analogue therapy.
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Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 01-28-2014
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To determine the intravitreous levels of interleukin-18 (IL-18) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to ascertain their association with PDR activity.
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Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: a nationwide cohort study.
Hepatology
PUBLISHED: 01-13-2014
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The effect of diabetes on cirrhosis, its decompensation, and their time relationship in chronic hepatitis C (CHC) patients remains unclear. We conducted a nation-wide cohort study by using the Taiwanese National Health Insurance Research Database, which is comprised of data from >99% of the entire population. Among having randomly sampled 1 million enrollees, 6,251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in CHC patients who were given the diagnosis in the years 1999-2003, but not in 1997-1998. The cohorts of CHC with new-onset diabetes (n=424) and nondiabetes (n=1,708) were followed up from inception point in diabetes and from year 1999 in the nondiabetes cohort until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. Kaplan-Meier's survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR]=1.53; 95% confidence interval [CI]=1.11-2.11; log-rank test; P<0.001) and decompensated cirrhosis (RR=2.01; 95% CI=1.07-3.79; log-rank test; P<0.001) among patients with new-onset diabetes, as compared to those without. After adjustment for age, gender, CHC treatment, diabetes treatment, hepatocellular carcinoma, comorbidity index, hypertension, hyperlipidemia, and obesity by Cox's proportional hazard model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR]=2.505; 95% CI=1.609-3.897; P<0.001) and its decompensation (HR=3.560; 95% CI=1.526-8.307; P=0.003).
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Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke.
J Neuroinflammation
PUBLISHED: 01-13-2014
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Repetitive hypoxic preconditioning (RHP) creates an anti-inflammatory phenotype that protects from stroke-induced injury for months after a 2-week treatment. The mechanisms underlying long-term tolerance are unknown, though one exposure to hypoxia significantly increased peripheral B cell representation. For this study, we sought to determine if RHP specifically recruited B cells into the protected ischemic hemisphere, and whether RHP could phenotypically alter B cells prior to stroke onset.
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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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Longitudinal effects of metabolic syndrome on Alzheimer and vascular related brain pathology.
Dement Geriatr Cogn Dis Extra
PUBLISHED: 01-01-2014
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This study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)].
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Potential role of cyr61 induced degeneration of human müller cells in diabetic retinopathy.
PLoS ONE
PUBLISHED: 01-01-2014
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The degeneration of Müller cells has been recognized to involve in the pathogenesis of diabetic retinopathy. However, the mechanism is not yet clear. This study is to explore the potential role of Cyr61, a secreted signaling protein in extracellular matrix, in inducing human Müller cell degeneration in diabetic retinopathy (DR). Twenty patients with proliferative diabetic retinopathy (PDR) and twelve non-diabetic patients were recruited for this study. Vitreous fluid was collected during vitrectomy surgery for Cyr61 ELISA. Human Müller cell line MIO-M1 were cultured to be subconfluent, and then treated with glucose (0-20 mM) or Cyr61 (0-300 ng/ml). Cyr61 expression induced by increasing concentrations of glucose was evaluated by RT-qPCR and Western blot. Effects of Cyr61 on Müller cells viability, migration and apoptosis were observed by MTT assay, Transwell assay, and TUNEL assay. Vitreous Cyr61 levels were observed to be 8-fold higher in patients with PDR (3576.92±1574.58 pg/mL), compared with non-diabetic controls (436.14±130.69 pg/mL). Interestingly, the active PDR group was significantly higher than the quiescent PDR group (P<0.01). In retinal Müller cells culture, high glucose significantly and dose-dependently elevated Cyr61 expression at both mRNA and protein levels. Cyr61 at high concentrations dose-dependently inhibited the viability and migration of Müller cells. TUNEL assay further revealed that high concentration of Cyr61 significantly promoted the cell apoptosis. In conclusion, these findings demonstrated for the first time that the expression of Cyr61 was elevated by high glucose in Müller cells, and Cyr61 inhibited cell viability and migration while induced apoptosis, suggesting the potential role of Cyr61 in Müller cell degeneration. The elevated Cyr61 levels in vitreous fluid of PDR patients further support its role in diabetic retinopathy (DR).
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Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus.
PLoS ONE
PUBLISHED: 01-01-2014
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Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed.
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[Clinical application of optimal designed Upcera super transparent zirconia all-ceramic restorations].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 11-16-2013
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To summarize the clinical application of special designed Upcera ST zirconia all-ceramic restorations in cases with limited occlusal space.
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Cancer prevention in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013.
Lancet Oncol.
PUBLISHED: 11-02-2013
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With economic growth in Asia, cancer has become increasingly prominent as a major health problem. However, discrepancies in infrastructure, economics, and development exist within and between Asian countries. We assess means of primary and secondary prevention for cervical, breast, colorectal, and hepatocellular cancer, and offer recommendations according to resource levels. Primary prevention by health education, lifestyle modification, and avoidance of risk factors should be made available at all resource levels. When resources allow, human papillomavirus and hepatitis B vaccinations should be given to reduce the risk of cervical and hepatocellular cancer, and genetic testing should be offered to detect increased susceptibility to colorectal and breast cancer. Secondary prevention by effective yet affordable screening for precancerous lesions or by early detection of cancer should be offered, followed by appropriate treatment.
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HAF drives the switch of HIF-1? to HIF-2? by activating the NF-?B pathway, leading to malignant behavior of T24 bladder cancer cells.
Int. J. Oncol.
PUBLISHED: 10-07-2013
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Hypoxia is a characteristic feature of solid tumors, leading to malignant behavior. During this process, HIF family members (HIFs) and the NF-?B pathway are activated. In addition, the hypoxia-associated factor (HAF) is reported to participate in the regulation of HIFs. However, the precise relationship among HIFs, HAF and the NF-?B pathway in bladder cancer (BC) remains unknown. In the current investigation, T24 BC cells were exposed to hypoxia, or by plasmid transfection to overexpress HAF or RelA (P65) to demonstrate their roles. The results indicate that hypoxia leads to the elevation of HAF plus activation of the NF-?B pathway, accompanied by the switch of HIF-1? to HIF-2?, resulting in the enhanced ability of malignancy in T24 cells. In order to further demonstrate the significance of this switch, HIF-1? and HIF-2? were co-transfected into T24 cells with HIF-?, respectively. The following results indicate that the T24hif-2?/? cells show enhanced ability of malignancy, accompanied by the maintenance of stem-cell markers, but the T24hif-1?/? cells show higher expression of metabolism-related genes. Boyden assays and wound-healing assays indicate the enhanced ability of malignancy for T24hif-2?/?. Thus, we conclude that on the hypoxic microenvironment, the switching of HIF-1? to HIF-2?, which is driven by HAF through activating the NF-?B pathway, contributes to the malignancy of T24 cells, accompanied by the maintenance of stem-cell markers. This provides us an avenue for understanding the progression of bladder cancer.
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Increased risk of cirrhosis and its decompensation in chronic hepatitis B patients with newly diagnosed diabetes: a nationwide cohort study.
Clin. Infect. Dis.
PUBLISHED: 09-18-2013
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Background.?The impact of diabetes on cirrhosis, its decompensation, and their time relationship in patients with chronic hepatitis B (CHB) remain unclear. Methods.?We conducted a nationwide cohort study by using the Taiwanese National Health Insurance Research Database, which was comprised of data from >99% of the entire population. Among 1 million randomly sampled enrollees, 14 523 adult CHB patients were identified from 1997 to 2009. Diabetes was defined as newly diagnosed in CHB patients who were given the diagnosis in the years 1998-2001 but not in 1996-1997 and with physician visits of at least twice per year. The cohorts of CHB with newly diagnosed diabetes (n = 351) and without diabetes (n = 7886) were followed up from the diagnosis of diabetes and from 2000 in the patients without diabetes until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. Results.?Kaplan-Meier survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR] = 3.43; 95% confidence interval [CI], 2.62-4.49; P < .001, log-rank test) and decompensated cirrhosis (RR = 4.11; 95% CI, 2.95-5.70; P < .001, log-rank test) among patients with newly developed diabetes compared with those without diabetes. After adjustment for age, sex, CHB treatment, hepatocellular carcinoma, and comorbidity index by Cox proportional hazards model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR] = 2.015; 95% CI, 1.393-2.915; P < .001) and its decompensation (HR = 1.792; 95% CI, 1.192-2.695; P = .005). Conclusions.?Patients with CHB who develop diabetes are at an increased risk of liver cirrhosis and its decompensation over time.
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Comparison of cervical disc arthroplasty with anterior cervical discectomy and fusion for the treatment of cervical spondylotic myelopathy.
Acta Orthop Belg
PUBLISHED: 08-10-2013
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The clinical outcome of cervical disc arthroplasty for cervical spondylotic myelopathy (CSM) is still controversial. The authors retrospectively compared the intermediate term clinical outcome of cervical disc arthroplasty and traditional anterior cervical discectomy and fusion (ACDF). Seventy-six cases of single-level CSM with a minimum follow-up of two years were retrospectively analyzed. Thirty-seven patients underwent single-level cervical disc arthroplasty (Bryan disc: 12 cases; Prestige LP disc: 25 cases), while the other 39 patients underwent single-level ACDF. Significant improvement in SF-36 physical/ mental component scores and NDI score was found in both groups (p < 0.05); however, the arthroplasty group had significantly greater score improvement at each follow-up time point (p < 0.05). The JOA score and Nurick grade improved significantly at each time point in both groups (p < 0.05), but there were no significant differences between the groups (p > 0.05). The range of motion (surgical level and C2C7) remained unchanged in the arthroplasty group (p > 0.05), whereas it decreased significantly in the ACDF group (p < 0.05). The arthroplasty group had a lower incidence of complications than the ACDF group. The intermediate outcomes of cervical disc arthroplasty compared favourably to those of ACDF. Arthroplasty avoids complications from spinal fusion by preserving mobility.
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[HSV-1 based vector mediated IL-1R? gene for knee osteoarthritis in rabbits].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 07-06-2013
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To investigate the effect and mechanism of herpes simplex virus type 1 (HSV-1) based vector mediated interlukin-1 receptor antagonist (IL-1R?) gene for knee osteoarthritis in rabbits.
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Is prophylactic somatostatin effective to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis or hyperamylasemia? A randomized, placebo-controlled pilot trial.
Chin. Med. J.
PUBLISHED: 07-05-2013
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Effects of prophylactic somatostatin on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and hyperamylasemia remain inconclusive. This study aimed to examine whether high-dose, long-term continuous infusion of somatostatin can reduce the incidence of PEP and post-ERCP hyperamylasemia.
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Treatment of Cytomegalovirus infection after renal transplantation: experience from a single center in China.
Ann. Transplant.
PUBLISHED: 06-25-2013
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We compared the efficacy and safety of 2 different treatments of CMV infection, including asymptomatic CMV replication and CMV disease.
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Consolidation therapy for HBeAg-positive Asian chronic hepatitis B patients receiving lamivudine treatment: a multicentre study.
J. Antimicrob. Chemother.
PUBLISHED: 06-24-2013
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For hepatitis B e antigen (HBeAg)-positive patients, continuing therapy (consolidation) for 6-12 months before cessation of nucleos(t)ide analogues (NAs) was recommended. This study aimed to investigate whether a longer period of lamivudine consolidation therapy leads to better outcomes and the clinical factors associated with response.
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Elevated CNS inflammation in patients with preclinical Alzheimers disease.
J. Cereb. Blood Flow Metab.
PUBLISHED: 06-06-2013
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Alzheimers disease (AD) is a progressive, neurodegenerative disease that may involve inflammatory responses in the central nervous system (CNS). Our objective was to determine whether patients with amnestic mild cognitive impairment (aMCI), a preclinical stage of AD, have inflammatory characteristics similar to patients with multiple sclerosis (MS), a known CNS inflammatory disease. The frequency of lymphocytes and levels of pro-inflammatory cytokines in the cerebrospinal fluid of aMCI patients was comparable to MS patients or patients at high risk to develop MS. Thus, brain inflammation occurs early at the preclinical stage of AD and may have an important role in pathology.
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Structure of the Chlamydia trachomatis immunodominant antigen Pgp3.
J. Biol. Chem.
PUBLISHED: 05-23-2013
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Chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. Left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. Here we present the structure of the secreted C. trachomatis protein Pgp3, an immunodominant antigen and putative virulence factor. The ?84-kDa Pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular N- and C-terminal assemblies connected by a triple-helical coiled-coil. The C-terminal domains possess folds similar to members of the TNF family of cytokines. The closest Pgp3 C-terminal domain structural homologs include a lectin from Burkholderia cenocepacia, the C1q component of complement, and a portion of the Bacillus anthracis spore surface protein BclA, all of which play roles in bioadhesion. The N-terminal domain consists of a concatenation of structural motifs typically found in trimeric viral proteins. The central parallel triple-helical coiled-coil contains an unusual alternating pattern of apolar and polar residue pairs that generate a rare right-handed superhelical twist. The unique architecture of Pgp3 provides the basis for understanding its role in chlamydial pathogenesis and serves as the platform for its optimization as a potential vaccine antigen candidate.
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A novel technique of modified continuous blanket suture for amniotic membrane fixation in severe ocular surface diseases.
JAMA Ophthalmol
PUBLISHED: 05-18-2013
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The purpose of this article is to demonstrate a novel technique using modified continuous blanket suture (MCBS) to fix the amniotic membrane (AM) in different severe ocular surface disease lesions. The MCBS techniques were used to fix the AMs of 5 representative patients with different ocular surface lesions related to severe ocular surface diseases. In all cases, stable adherence of the AM was maintained until the epithelialization of the ocular surface was completed. No early detachment, dissolution, or dislocation of the AM patch was observed. During follow-up, all patients acquired a smooth and acceptable ocular surface without any persistent epithelial defect, infection, or ulceration. The MCBS method achieved good AM fixation on the ocular surface in cases of severe ocular surface lesions and could prevent the early detachment of the AM and promote the epithelialization of the ocular surface.
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A fast workflow for identification and quantification of proteomes.
Mol. Cell Proteomics
PUBLISHED: 05-13-2013
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The current in-depth proteomics makes use of long chromatography gradient to get access to more peptides for protein identification, resulting in covering of as many as 8000 mammalian gene products in 3 days of mass spectrometer running time. Here we report a fast sequencing (Fast-seq) workflow of the use of dual reverse phase high performance liquid chromatography - mass spectrometry (HPLC-MS) with a short gradient to achieve the same proteome coverage in 0.5 day. We adapted this workflow to a quantitative version (Fast quantification, Fast-quan) that was compatible to large-scale protein quantification. We subjected two identical samples to the Fast-quan workflow, which allowed us to systematically evaluate different parameters that impact the sensitivity and accuracy of the workflow. Using the statistics of significant test, we unraveled the existence of substantial falsely quantified differential proteins and estimated correlation of false quantification rate and parameters that are applied in label-free quantification. We optimized the setting of parameters that may substantially minimize the rate of falsely quantified differential proteins, and further applied them on a real biological process. With improved efficiency and throughput, we expect that the Fast-seq/Fast-quan workflow, allowing pair wise comparison of two proteomes in 1 day may make MS available to the masses and impact biomedical research in a positive way.
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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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Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries.
J Bone Joint Surg Am
PUBLISHED: 05-03-2013
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There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair.
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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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Approximating the baseline hazard function by taylor series for interval-censored time-to-event data.
J Biopharm Stat
PUBLISHED: 04-25-2013
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In many oncology clinical trials, time-to-event data are generated from scanning for cancer within a specific interval, resulting in interval censoring along with complete-time and right-left-censored time-to-event data. A common practice in analyzing data from this type of trial is to impute the interval-censored event time using the midpoint or right endpoint (i.e., the first observed time) of the interval so that well-known statistical methods developed for right-censored time-to-event data, such as Cox regression, may be used for the requisite analyses. This may introduce bias and lead to erroneous conclusions. In this paper, a Taylor series is proposed to approximate the log baseline hazard function in Cox proportional hazards regression to mitigate the bias arising from analyzing the imputed time-to-event data. With this formulation, the likelihood ratio test can be used to select an appropriate order for this Taylor series approximation and maximum likelihood techniques used to estimate model parameters and provide statistical inference, for example, on treatment effect. The application of this novel method is demonstrated by a simulation study and application to data from a breast cancer clinical trial.
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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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Novel bacterial groups dominate in a thermophilic methanogenic hexadecane-degrading consortium.
FEMS Microbiol. Ecol.
PUBLISHED: 04-17-2013
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A methanogenic hexadecane-degrading consortium designated SK originating from the Shengli oil field was cultured at 55 °C. The structure and dynamics of the microbial community during successive transfers were examined using terminal restriction fragment length polymorphism (T-RFLP) fingerprinting and sequencing of 16S rRNA gene fragments. The archaeal community was mainly composed of hydrogenotrophic methanogens affiliated with Methanothermobacter crinale and acetoclastic methanogens related to Methanosaeta thermophila. Over four-fifths of the bacterial clones in the hexadecane-degrading subcultures exhibited < 90% similarity to sequences of known type strains, and clones were mainly grouped into unclassified bacteria (66.3-66.7%), Firmicutes (9.6-10.6%), Thermotogae (7.0-7.7%), and Nitrospira (5.3-5.8%). The dominant operating taxonomic unit (OTU) (41.3-43.0% of all clones) representing terminal restriction fragment (T-RF) 125 bp exhibited only 82.6% sequence similarity to Thermotoga maritime and clustered in a monophyletic, deep-branching lineage (designated Shengli cluster). Two other OTUs (T-RFs 66 and 67 bp) were assigned to uncultured members of the candidate phylum OP8 and Firmicutes, respectively. These novel bacterial assemblages are likely to be involved in the process of hexadecane degradation because of their high abundance in the enrichments. These result substantially expand the knowledge of the extent of bacterial diversity associated with the anaerobic degradation of alkanes under thermophilic conditions.
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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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Proteome-wide profiling of activated transcription factors with a concatenated tandem array of transcription factor response elements.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-03-2013
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Transcription factors (TFs) are families of proteins that bind to specific DNA sequences, or TF response elements (TFREs), and function as regulators of many cellular processes. Because of the low abundance of TFs, direct quantitative measurement of TFs on a proteome scale remains a challenge. In this study, we report the development of an affinity reagent that permits identification of endogenous TFs at the proteome scale. The affinity reagent is composed of a synthetic DNA containing a concatenated tandem array of the consensus TFREs (catTFRE) for the majority of TF families. By using catTFRE to enrich TFs from cells, we were able to identify as many as 400 TFs from a single cell line and a total of 878 TFs from 11 cell types, covering more than 50% of the gene products that code for the DNA-binding TFs in the genome. We further demonstrated that catTFRE pull-downs could quantitatively measure proteome-wide changes in DNA binding activity of TFs in response to exogenous stimulation by using a label-free MS-based quantification approach. Applying catTFRE on the evaluation of drug effects, we described a panoramic view of TF activations and provided candidates for the elucidation of molecular mechanisms of drug actions. We anticipate that the catTFRE affinity strategy will find widespread applications in biomedical research.
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Proteomic analysis of coregulators bound to ER? on DNA and nucleosomes reveals coregulator dynamics.
Mol. Cell
PUBLISHED: 04-02-2013
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Chromatin immunoprecipitation studies have mapped protein occupancies at many genomic loci. However, a detailed picture of the complexity of coregulators (CoRs) bound to a defined enhancer along with a transcription factor is missing. To address this, we used biotin-DNA pull-down assays coupled with mass spectrometry-immunoblotting to identify at least 17 CoRs from nuclear extracts bound to 17?-estradiol (E2)-liganded estrogen receptor-? on estrogen response elements (EREs). Unexpectedly, these complexes initially are biochemically stable and contain certain atypical corepressors. Addition of ATP dynamically converts these complexes to an "activated" state by phosphorylation events, primarily mediated by DNA-dependent protein kinase. Importantly, a "natural" ERE-containing enhancer and nucleosomal EREs recruit similar complexes. We further discovered the mechanism whereby H3K4me3 stimulates ER?-mediated transcription as compared with unmodified nucleosomes. H3K4me3 templates promote specific CoR dynamics in the presence of ATP and AcCoA, as manifested by CBP/p300 and SRC-3 dismissal and SAGA and TFIID stabilization/recruitment.
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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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[Bivariate statistical model for calculating phosphorus input loads to the river from point and nonpoint sources].
Huan Jing Ke Xue
PUBLISHED: 03-16-2013
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Based on the hydrological difference between the point source (PS) and nonpoint source (NPS) pollution processes and the major influencing mechanism of in-stream retention processes, a bivariate statistical model was developed for relating river phosphorus load to river water flow rate and temperature. Using the calibrated and validated four model coefficients from in-stream monitoring data, monthly phosphorus input loads to the river from PS and NPS can be easily determined by the model. Compared to current hydrologica methods, this model takes the in-stream retention process and the upstream inflow term into consideration; thus it improves the knowledge on phosphorus pollution processes and can meet the requirements of both the district-based and watershed-based wate quality management patterns. Using this model, total phosphorus (TP) input load to the Changle River in Zhejiang Province was calculated. Results indicated that annual total TP input load was (54.6 +/- 11.9) t x a(-1) in 2004-2009, with upstream water inflow, PS and NPS contributing to 5% +/- 1%, 12% +/- 3% and 83% +/- 3%, respectively. The cumulative NPS TP input load during the high flow periods (i. e. , June, July, August and September) in summer accounted for 50% +/- 9% of the annual amount, increasing the alga blooming risk in downstream water bodies. Annual in-stream TP retention load was (4.5 +/- 0.1) t x a(-1) and occupied 9% +/- 2% of the total input load. The cumulative in-stream TP retention load during the summer periods (i. e. , June-September) accounted for 55% +/- 2% of the annual amount, indicating that in-stream retention function plays an important role in seasonal TP transport and transformation processes. This bivariate statistical model only requires commonly available in-stream monitoring data (i. e. , river phosphorus load, water flow rate and temperature) with no requirement of special software knowledge; thus it offers researchers an managers with a cost-effective tool for quantifying TP pollution processes in both district and watershed scales.
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A new insight into the impact of different proteases on SILAC quantitative proteome of the mouse liver.
Proteomics
PUBLISHED: 03-12-2013
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In this study, we examined the use of multiple proteases (trypsin, LysC, tandem LysC/trypsin) on both protein identification and quantification in the Lys-labeled SILAC mouse liver. Our results show that trypsin and tandem LysC/trypsin digestion are superior to LysC in peptides and protein identification while LysC shows advantages in quantification of Lys-labeled proteins. Combination of experimental results from different proteases (LysC and trypsin) enabled a significant increase in the number of identified protein and protein can be quantified. Thus, taking advantage of the complementation of different protease should be a good strategy to improve both qualitative and quantitative proteomics research.
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A systematic review of vascular endothelial growth factor expression as a biomarker of prognosis in patients with osteosarcoma.
Tumour Biol.
PUBLISHED: 02-20-2013
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Vascular endothelial growth factor (VEGF) plays an important role in the tumor angiogenesis, and its expression has been supposed to be a biomarker of prognosis in patients with osteosarcoma. There are many studies assessing the prognostic role of VEGF expression in osteosarcoma, and no consistent outcomes are reported. To provide a comprehensive assessment of the prognostic role of VEGF expression, we performed a systematic review and meta-analysis of published studies. We assessed the effect of VEGF expression on the overall survival rate and the disease-free survival rate by calculating the pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI). Finally, 12 studies with a total of 559 osteosarcoma patients were included into the systematic review and meta-analysis. Compared with osteosarcoma patients with low or negative VEGF expression, patients with high VEGF expression were obviously associated with lower disease-free survival (OR=0.25, 95 %CI 0.11-0.58, P=0.001, I (2)?=56.4 %). In addition, patients with high VEGF expression were obviously associated with lower overall survival (OR=0.22, 95 %CI 0.13-0.35, P<0.001, I (2)?=0.0 %). Therefore, the findings from this systematic review suggest that VEGF expression is an effective biomarker of prognosis in patients with osteosarcoma.
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Preparation of magnesium ferrite nanoparticles by ultrasonic wave-assisted aqueous solution ball milling.
Ultrason Sonochem
PUBLISHED: 02-11-2013
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Magnesium ferrite, MgFe2O4 nanoparticles with high saturation magnetization were successfully synthesized using ultrasonic wave-assisted ball milling. In this study, the raw materials were 4MgCO3·Mg(OH)2·5H2O and Fe2O3 powders and the grinding media was stainless steel ball. The average particle diameter of the product MgFe2O4 powders was 20 nm and the saturation magnetization of them reached 54.8 emu/g. The different results of aqueous solution ball milling with and without ultrasonic wave revealed that it was the coupling effect of ultrasonic wave and mechanical force that played an important role during the synthesis of MgFe2O4. In addition, the effect of the frequency of the ultrasonic wave on the ball milling process was investigated.
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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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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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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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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.