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Find video protocols related to scientific articles indexed in Pubmed.
YM500v2: a small RNA sequencing (smRNA-seq) database for human cancer miRNome research.
Nucleic Acids Res.
PUBLISHED: 11-16-2014
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We previously presented YM500, which is an integrated database for miRNA quantification, isomiR identification, arm switching discovery and novel miRNA prediction from 468 human smRNA-seq datasets. Here in this updated YM500v2 database (http://ngs.ym.edu.tw/ym500/), we focus on the cancer miRNome to make the database more disease-orientated. New miRNA-related algorithms developed after YM500 were included in YM500v2, and, more significantly, more than 8000 cancer-related smRNA-seq datasets (including those of primary tumors, paired normal tissues, PBMC, recurrent tumors, and metastatic tumors) were incorporated into YM500v2. Novel miRNAs (miRNAs not included in the miRBase R21) were not only predicted by three independent algorithms but also cleaned by a new in silico filtration strategy and validated by wetlab data such as Cross-Linked ImmunoPrecipitation sequencing (CLIP-seq) to reduce the false-positive rate. A new function 'Meta-analysis' is additionally provided for allowing users to identify real-time differentially expressed miRNAs and arm-switching events according to customer-defined sample groups and dozens of clinical criteria tidying up by proficient clinicians. Cancer miRNAs identified hold the potential for both basic research and biotech applications.
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Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation.
Circulation
PUBLISHED: 11-01-2014
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-The comparative safety of dabigatran vs. warfarin for treatment of non-valvular atrial fibrillation (AF) in general practice settings has not been established.
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Building carbon-carbon bonds using a biocatalytic methanol condensation cycle.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-29-2014
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Methanol is an important intermediate in the utilization of natural gas for synthesizing other feedstock chemicals. Typically, chemical approaches for building C-C bonds from methanol require high temperature and pressure. Biological conversion of methanol to longer carbon chain compounds is feasible; however, the natural biological pathways for methanol utilization involve carbon dioxide loss or ATP expenditure. Here we demonstrated a biocatalytic pathway, termed the methanol condensation cycle (MCC), by combining the nonoxidative glycolysis with the ribulose monophosphate pathway to convert methanol to higher-chain alcohols or other acetyl-CoA derivatives using enzymatic reactions in a carbon-conserved and ATP-independent system. We investigated the robustness of MCC and identified operational regions. We confirmed that the pathway forms a catalytic cycle through (13)C-carbon labeling. With a cell-free system, we demonstrated the conversion of methanol to ethanol or n-butanol. The high carbon efficiency and low operating temperature are attractive for transforming natural gas-derived methanol to longer-chain liquid fuels and other chemical derivatives.
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Phase I Dose-Escalation Study of Weekly Paclitaxel and Cisplatin Followed by Radical Hysterectomy in Stages IB2 and IIA2 Cervical Cancer.
Am. J. Clin. Oncol.
PUBLISHED: 10-29-2014
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To define the optimal dose of paclitaxel combining cisplatin, as weekly neoadjuvant chemotherapy (NAC) for early-stage bulky squamous cell carcinoma of the uterine cervix.
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HBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B.
Ann Hepatol
PUBLISHED: 10-22-2014
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Introduction. The intrahepatic hepatitis B surface antigens (HBsAg) expression is related to disease progression of chronic hepatitis B. We examined the features of intrahepatic HBsAg expression. Material and methods. A total of 181 patients with e antigen positive chronic hepatitis B were enrolled. Patterns and semi-quantitative measurement of intrahepatic HBsAg expression were analyzed. The association of intrahepatic hepatitis HBsAg expression with clinical, viral, and histological characteristics was evaluated. Results. Higher necroinflammation grade and greater fibrosis stage accompanied with lower serum HBV DNA and HBsAg levels were observed in patients with type II ground glass hepatocytes and 2+/3+ scales of intrahepatic HBsAg expression. Basal core promoter T1762/A1764 mutations were strongly associated with the pattern of type II ground glass hepatocytes expression (P < 0.001) and higher level of HBsAg expression (9.3 ± 8.0% vs. 4.3 ± 5.0%, P = 0.008). In multivariate analysis, basal core promoter mutations (Odds ratio: 6.356, 95% confidence interval: 1.204 ~ 33.356, P = 0.029) was associated with 2+/3+ scale of HBsAg expression. Conclusion. Both pattern and levels of intrahepatic HBsAg expression were associated with severity of liver disease in e antigen positive chronic hepatitis B. Strong relationship between intrahepatic HBsAg expression and basal core promoter 1762/A1764 mutations indicated that HBsAg expression may be the histological manifestation of hepatitis B virus genomic evolution under host immune surveillance.
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Predictors and long-term outcome of seizures in human immuno-deficiency virus (HIV)-negative cryptococcal meningitis.
BMC Neurol
PUBLISHED: 10-06-2014
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Seizures are one of the most important neurologic complications of human immuno-deficiency virus (HIV)-negative cryptococcal meningitis. A better understanding of the risk associated factors can help predict those who will require treatment.
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Tpz1-Ccq1 and Tpz1-Poz1 interactions within fission yeast shelterin modulate Ccq1 Thr93 phosphorylation and telomerase recruitment.
PLoS Genet.
PUBLISHED: 10-01-2014
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In both fission yeast and humans, the shelterin complex plays central roles in regulation of telomerase recruitment, protection of telomeres against DNA damage response factors, and formation of heterochromatin at telomeres. While shelterin is essential for limiting activation of the DNA damage checkpoint kinases ATR and ATM at telomeres, these kinases are required for stable maintenance of telomeres. In fission yeast, Rad3ATR and Tel1ATM kinases are redundantly required for telomerase recruitment, since Rad3ATR/Tel1ATM-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 promotes interaction between Ccq1 and the telomerase subunit Est1. However, it remained unclear how protein-protein interactions within the shelterin complex (consisting of Taz1, Rap1, Poz1, Tpz1, Pot1 and Ccq1) contribute to the regulation of Ccq1 Thr93 phosphorylation and telomerase recruitment. In this study, we identify domains and amino acid residues that are critical for mediating Tpz1-Ccq1 and Tpz1-Poz1 interaction within the fission yeast shelterin complex. Using separation of function Tpz1 mutants that maintain Tpz1-Pot1 interaction but specifically disrupt either Tpz1-Ccq1 or Tpz1-Poz1 interaction, we then establish that Tpz1-Ccq1 interaction promotes Ccq1 Thr93 phosphorylation, telomerase recruitment, checkpoint inhibition and telomeric heterochromatin formation. Furthermore, we demonstrate that Tpz1-Poz1 interaction promotes telomere association of Poz1, and loss of Poz1 from telomeres leads to increases in Ccq1 Thr93 phosphorylation and telomerase recruitment, and telomeric heterochromatin formation defect. In addition, our studies establish that Tpz1-Poz1 and Tpz1-Ccq1 interactions redundantly fulfill the essential telomere protection function of the shelterin complex, since simultaneous loss of both interactions caused immediate loss of cell viability for the majority of cells and generation of survivors with circular chromosomes. Based on these findings, we suggest that the negative regulatory function of Tpz1-Poz1 interaction works upstream of Rad3ATR kinase, while Tpz1-Ccq1 interaction works downstream of Rad3ATR kinase to facilitate Ccq1 Thr93 phosphorylation and telomerase recruitment.
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FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells.
Oncotarget
PUBLISHED: 09-20-2014
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Several reports suggest that malignant cells generate phenotypic diversity through fusion with various types of stromal cells within the tumor microenvironment. Mesenchymal stem cell (MSC) is one of the critical components in the tumor microenvironment and a promising fusogenic candidate, but the underlying functions of MSC fusion with malignant cell have not been fully examined. Here, we demonstrate that MSCs fuse spontaneously with lung cancer cells, and the latter is reprogrammed to slow growth and stem-like state. Transcriptome profiles reveal that lung cancer cells are reprogrammed to a more benign state upon MSC fusion. We further identified FOXF1 as a reprogramming mediator that contributes not only to the reprogramming toward stemness but also to the p21-regulated growth suppression in fusion progeny. Collectively, MSC fusion does not enhance the intrinsic malignancy of lung cancer cells. The anti-malignant effects of MSC fusion-induced reprogramming on lung cancer cells were accomplished by complementation of tumorigenic defects, including restoration of p21 function and normal terminal differentiation pathways as well as up-regulation of FOXF1, a putative tumor suppressor. Such fusion process raises the therapeutic potential that MSC fusion can be utilized to reverse cellular phenotypes in cancer.
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The Microtubule-associated Protein EB1 Links AIM2 Inflammasomes with Autophagy-dependent Secretion.
J. Biol. Chem.
PUBLISHED: 08-27-2014
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Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 ? (IL-1?) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1? secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1? secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5'-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1?. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1?.
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Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using electrospinning.
Biomed Eng Online
PUBLISHED: 08-19-2014
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The combination of biliary stent with photodynamic and chemotherapy seemed to be a beneficial palliative treatment of unresectable cholangiocarcinoma. However, by intravenous delivery to the target tumor the distribution of the drug had its limitations and caused serious side effect on non-target organs. Therefore, in this study, we are going to develop a localized eluting stent, named PDT-chemo stent, covered with gemcitabine (GEM) and hematoporphyrin (HP).
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Comparison and validation of International Consensus Diagnostic Criteria for diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese cohort.
BMJ Open
PUBLISHED: 08-18-2014
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The International Consensus Diagnostic Criteria (ICDC) designed to diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The diagnostic performance of ICDC has not been previously evaluated in diffuse-type and focal-type AIP, respectively, in comparison with the revised HISORt and Asian criteria in Taiwan.
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Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions - A Taiwanese Gynecologic Oncology Group (TGOG) study.
Gynecol. Oncol.
PUBLISHED: 08-16-2014
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Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3(+)). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing.
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All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study.
Lancet
PUBLISHED: 08-01-2014
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An unmet need exists for interferon-free and ribavirin-free treatments for chronic hepatitis C virus (HCV) infection. In this study, we assessed all-oral therapy with daclatasvir (NS5A replication complex inhibitor) plus asunaprevir (NS3 protease inhibitor) in patients with genotype 1b infection, including those with high unmet needs or cirrhosis, or both.
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Glucose-regulated protein 58 modulates ?-catenin protein stability in a cervical adenocarcinoma cell line.
BMC Cancer
PUBLISHED: 07-22-2014
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Cervical cancer continues to threaten women's health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown.
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Effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers.
Acta Pharmacol. Sin.
PUBLISHED: 07-10-2014
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Aim:To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans.Methods:Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe(2+)) or calcium carbonate (containing 600 mg of Ca(2+)).Results:Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0-?) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0-? for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0-? by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0-? by 17.8%, Cmax by 14.3%, and Ae by 18.4%.Conclusion:Metal ions, Al(3+), Mg(2+), and Fe(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca(2+) had much weaker effects. To avoid the effects of Al(3+) and Mg(2+)-containing drugs, nemonoxacin should be administered ?2 h before them.
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Aberrant Serum Immunoglobulin G Glycosylation in Chronic Hepatitis B Is Associated With Histological Liver Damage and Reversible by Antiviral Therapy.
J. Infect. Dis.
PUBLISHED: 07-10-2014
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?Aberrant serum immunoglobulin G (IgG) glycosylation and its immunomodulatory effect are rarely addressed in chronic hepatitis B virus (HBV) infection.
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Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus.
J Transl Med
PUBLISHED: 07-07-2014
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BackgroundThis study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).MethodsLeukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.ResultsThe SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p¿<¿0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p¿<¿0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p¿<¿0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p¿<¿0.05).ConclusionsThe disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.
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Intrathymic Tfh/B Cells Interaction Leads to Ectopic GCs Formation and Anti-AChR Antibody Production: Central Role in Triggering MG Occurrence.
Mol. Neurobiol.
PUBLISHED: 06-23-2014
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Myasthenia gravis is a typical acetylcholine receptor (AChR) antibody-mediated autoimmune disease in which thymus frequently presents follicular hyperplasia or thymoma. It is now widely accepted that the thymus is probably the site of AChR autosensitization and autoantibody production. However, the exact mechanism that triggers intrathymic AChR antibody production is still unknown. T follicular helper cells, recently identified responsible for B cell maturation and antibody production in the secondary lymphoid organs, were involved in many autoimmune diseases. Newly studies found T follicular helper (Tfh) cells increased in the peripheral blood of myasthenia gravis (MG). Whether it appears in the thymus of MG and its role in the intrathymic B cells help and autoantibody production is unclear. Therefore, this study aims to determine in more detail whether Tfh/B cell interaction exist in MG thymus and to address its role in the ectopic germinal centers (GCs) formation and AChR antibody production. We observed the frequency of Tfh cells and its associated transcription factor Bcl-6, key cytokine IL-21 enhanced both in the thymocytes and peripheral blood mononuclear cells (PBMCs) of MG patients. In parallel, we also showed increased B cells and autoantibody titers in MG peripheral blood and thymus. Confocal microscope results demonstrated Tfh and B cells co-localized within the ectopic GCs in MG thymus, suggesting putative existence of Tfh/B cells interaction. In vitro studies further showed dynamic behavior of Tfh/B cells interaction and Tfh cells induced autoantibody secretion might through its effector cytokine IL-21. Altogether, our data demonstrated that intrathymic Tfh/B cells interaction played a key role in thymic ectopic GCs formation and anti-AChR antibody production, which might trigger MG occurrence.
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Association of serum IgG N-glycome and transforming growth factor-?1 with hepatitis B virus e antigen seroconversion during entecavir therapy.
Antiviral Res.
PUBLISHED: 06-13-2014
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Aberrant serum IgG N-glycome has been demonstrated in various autoimmune diseases and viral infections. However, the correlation between serum IgG N-glycome and cytokine is unclear. In addition, the clinical relevance of IgG glycosylation and cytokine changes in the treatment outcome of chronic hepatitis B (CHB) has never been assessed. One hundred and three treatment-naive patients with CHB and 101 healthy controls were enrolled in this retrospective cohort study. Serum samples in patients before and after 48weeks of entecavir treatment were collected. In-gel trypsinized serum IgG heavy chain was analyzed using liquid chromatography-tandem mass spectrometry. Selected ion chromatograms corresponding to 10 N-glycoforms on asparagine 297 were individually extracted to calculate the percentage of each glycoforms. Serum cytokine profiles were examined using enzyme-linked immunosorbent assay. Forty-eight weeks of entecavir treatment resulted in decreases in galactose-deficient (total G0) IgG and transforming growth factor (TGF)-?1 levels (both P<0.001) in patients with CHB. The changes in TGF-?1 (?TGF-?1) and IgG total G0 (?total G0) levels during treatment were significantly correlated (r=0.403, P<0.001). Furthermore, higher levels of ?total G0 (P<0.01) and ?TGF-?1 (P<0.001) were found in hepatitis B virus e antigen (HBeAg)-positive patients than in HBeAg-negative patients and were also found in patients with HBeAg seroconversion at week 48. The area under the receiver operating characteristic (ROC) curves for ?total G0 and ?TGF-?1 to discriminate a week-48 HBeAg seroconversion were 0.835 and 0.830, respectively. These results suggested a correlation between serum cytokine and IgG N-glycome and its effect on the outcome of entecavir treatment in patients with CHB.
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Telomere regulation during the cell cycle in fission yeast.
Methods Mol. Biol.
PUBLISHED: 06-08-2014
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The fission yeast Schizosaccharomyces pombe has emerged as a useful model organism to study telomere maintenance mechanisms. In this chapter, we provide detailed protocols for quantitative ChIP and BrdU incorporation analyses to investigate how fission yeast telomeres are regulated during the cell cycle by utilizing cdc25-22 synchronized cell cultures.
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Lineage Tracing Reveals Distinctive Fates for Mesothelial Cells and Submesothelial Fibroblasts during Peritoneal Injury.
J. Am. Soc. Nephrol.
PUBLISHED: 05-24-2014
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Fibrosis of the peritoneal cavity remains a serious, life-threatening problem in the treatment of kidney failure with peritoneal dialysis. The mechanism of fibrosis remains unclear partly because the fibrogenic cells have not been identified with certainty. Recent studies have proposed mesothelial cells to be an important source of myofibroblasts through the epithelial-mesenchymal transition; however, confirmatory studies in vivo are lacking. Here, we show by inducible genetic fate mapping that type I collagen-producing submesothelial fibroblasts are specific progenitors of ?-smooth muscle actin-positive myofibroblasts that accumulate progressively in models of peritoneal fibrosis induced by sodium hypochlorite, hyperglycemic dialysis solutions, or TGF-?1. Similar genetic mapping of Wilms' tumor-1-positive mesothelial cells indicated that peritoneal membrane disruption is repaired and replaced by surviving mesothelial cells in peritoneal injury, and not by submesothelial fibroblasts. Although primary cultures of mesothelial cells or submesothelial fibroblasts each expressed ?-smooth muscle actin under the influence of TGF-?1, only submesothelial fibroblasts expressed ?-smooth muscle actin after induction of peritoneal fibrosis in mice. Furthermore, pharmacologic inhibition of the PDGF receptor, which is expressed by submesothelial fibroblasts but not mesothelial cells, attenuated the peritoneal fibrosis but not the remesothelialization induced by hypochlorite. Thus, our data identify distinctive fates for injured mesothelial cells and submesothelial fibroblasts during peritoneal injury and fibrosis.
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Salivary auto-antibodies as noninvasive diagnostic markers of oral cavity squamous cell carcinoma.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-23-2014
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Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and its incidence is still increasing. Approximately 50% of patients with OSCC die within 5 years after diagnosis, mostly ascribed to the fact that the majority of patients present advanced stages of OSCC at the time of diagnosis.
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Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 05-23-2014
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Perlecan is a proteoglycan composed of a 470-kDa core protein linked to three heparan sulfate (HS) glycosaminoglycan chains. The intact proteoglycan inhibits the smooth muscle cell (SMC) response to vascular injury. Hspg2(?3/?3) (M?3/?3) mice produce a mutant perlecan lacking the HS side chains. The objective of this study was to determine differences between these two types of perlecan in modifying SMC activities to the arterial injury response, in order to define the specific role of the HS side chains. In vitro proliferative and migratory activities were compared in SMC isolated from M?3/?3 and wild-type mice. Proliferation of M?3/?3 SMC was 1.5× greater than in wild type (P < 0.001), increased by addition of growth factors, and showed a 42% greater migratory response than wild-type cells to PDGF-BB (P < 0.001). In M?3/?3 SMC adhesion to fibronectin, and collagen types I and IV was significantly greater than wild type. Addition of DRL-12582, an inducer of perlecan expression, decreased proliferation and migratory response to PDGF-BB stimulation in wild-type SMC compared with M?3/?3. In an in vivo carotid artery wire injury model, the medial thickness, medial area/lumen ratio, and macrophage infiltration were significantly increased in the M?3/?3 mice, indicating a prominent role of the HS side chain in limiting vascular injury response. Mutant perlecan that lacks HS side chains had a marked reduction in the inhibition of in vitro SMC function and the in vivo arterial response to injury, indicating the critical role of HS side chains in perlecan function in the vessel wall.
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Treatment failure in endometrial carcinoma.
Int. J. Gynecol. Cancer
PUBLISHED: 05-14-2014
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Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer.
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Combining TNFSF15 and ASCA IgA can be used as a predictor for the stenosis/perforating phenotype of Crohn's disease.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-01-2014
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Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.
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The prognostic value of leukocyte apoptosis in patients with severe sepsis at the emergency department.
Clin. Chim. Acta
PUBLISHED: 04-29-2014
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Cell apoptosis in critically ill patients plays a pivotal role in the pathogenesis of sepsis. This study aimed to determine the prognostic value of leukocyte apoptosis in patients with severe sepsis.
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Serum adhesion molecules as outcome predictors in adult severe sepsis patients requiring mechanical ventilation in the emergency department.
Clin. Biochem.
PUBLISHED: 04-21-2014
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Serum adhesion molecules play a pivotal role in the pathogenesis of sepsis syndrome. This study aimed to evaluate the prognostic value of serum adhesion molecules in patients with severe sepsis and mechanical ventilation (MV) at the emergency department.
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miRNome traits analysis on endothelial lineage cells discloses biomarker potential circulating microRNAs which affect progenitor activities.
BMC Genomics
PUBLISHED: 04-08-2014
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Endothelial progenitor cells (EPCs) play a fundamental role in not only blood vessel development but also post-natal vascular repair. Currently EPCs are defined as early and late EPCs based on their biological properties and their time of appearance during in vitro culture. Both EPC types assist angiogenesis and have been linked to ischemia-related disorders, including coronary artery disease (CAD).
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Fertility-preserving treatment in young women with endometrial adenocarcinoma: a long-term cohort study.
Int. J. Gynecol. Cancer
PUBLISHED: 03-01-2014
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Growing evidence suggests that fertility-preserving treatment is feasible for young women with early-stage, low-grade endometrial carcinoma. However, published data on their long-term outcomes and prognostic factors remain scanty. We aimed to investigate the outcomes of young women receiving fertility-preserving treatment.
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Association between oxidative stress and outcome in different subtypes of acute ischemic stroke.
Biomed Res Int
PUBLISHED: 02-27-2014
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This study investigated serum thiobarbituric acid-reactive substances (TBARS) and free thiol levels in different subtypes of acute ischemic stroke (AIS) and evaluated their association with clinical outcomes.
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Carotid Artery Stenting Improves Cerebral Hemodynamics Regardless of the Flow Direction of Ophthalmic Artery.
Angiology
PUBLISHED: 02-27-2014
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We enrolled 221 patients with elective carotid artery stenting (CAS). Patients with contralateral carotid stenosis exceeding 50%, insufficient vertebral artery (VA) flows, or angioplasty at subclavian artery were excluded. All patients underwent serial cerebral ultrasound studies. Of the 116 included patients, the direction of ophthalmic artery (OA) flow was forward in 74 patients while reversed in 42. The reversed flow group had worse ipsilateral stenosis, higher hemoglobin, and cardiac output. After CAS, the reversed flow group had an immediate recovery of ipsilateral internal carotid artery flow volume (FV; P < .0001), time average velocity (TAV) of middle cerebral artery (P = .02), and normalization of OA flow. The forward flow group had gradual decrement in TAV of contralateral anterior cerebral artery (P = .01) and total FV of VA (P = .001). Our results suggest CAS improves cerebral hemodynamics through different ways regardless of the direction of OA flow.
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Elevated serum vascular cell adhesion molecule-1 is associated with septic encephalopathy in adult community-onset severe sepsis patients.
Biomed Res Int
PUBLISHED: 02-26-2014
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Septic encephalopathy (SE) is a common complication of severe sepsis. Increased concentrations of circulating soluble adhesion molecules are reported in septic patients. This study aimed to determine whether serum adhesion molecules are associated with SE.
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The roles of biomarkers of oxidative stress and antioxidant in Alzheimer's disease: a systematic review.
Biomed Res Int
PUBLISHED: 02-25-2014
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Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). This paper aims to examine whether biomarkers of oxidative stress and antioxidants could be useful biomarkers in AD, which might form the bases of future clinical studies.
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The association among antioxidant enzymes, autoantibodies, and disease severity score in systemic lupus erythematosus: comparison of neuropsychiatric and nonneuropsychiatric groups.
Biomed Res Int
PUBLISHED: 02-25-2014
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Antioxidative capacity plays an important role in the severity of systemic lupus erythematosus (SLE), which is characterized by autoantibodies. This study aimed to determine the relationship among autoantibody titers, antioxidative stress reserve, and severity of SLE.
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Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production.
J. Hepatol.
PUBLISHED: 02-24-2014
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Hepatitis C virus (HCV) infection leads to glucose abnormality. HCV depends on lipid droplets (LDs) and very-low density lipoproteins for assembly/releasing; however, the components and locations for this process remain unidentified. Apolipoprotein J (ApoJ), upregulated by glucose, functions as Golgi chaperone of secreted proteins and resides abundantly in very-low density lipoproteins. This study investigates the interplay between glucose, ApoJ and HCV virion production.
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A dual tyrosine kinase inhibitor lapatinib suppresses overexpression of matrix metallopeptidase 1 (MMP1) in endometrial cancer.
J. Mol. Med.
PUBLISHED: 02-07-2014
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Endometrial cancers have been recently molecularly characterized; amplifications of human epidermal growth factor receptor 2 (HER2) were seen in 25 % of the serous-like tumors, and mutations in the PI(3)K/AKT pathways were seen in 93 % of endometrioid tumors. These new findings about endometrial cancer suggest a potential for targeted therapy with lapatinib, a dual inhibitor of epidermal growth factor receptor and HER2 tyrosine kinases. However, the clinical efficacy of lapatinib in phase II clinical trials for the treatment of endometrial cancers was only minimal. In this study, we investigated the signaling changes induced by lapatinib in endometrial cancer, which may improve its therapeutic efficacy in molecularly selected patient groups. We identified one of the final molecular targets of lapatinib to be interstitial collagenase, matrix metallopeptidase 1 (MMP1). Lapatinib suppresses MMP1 through EGFR and HER2, and their downstream ERK and AKT signaling pathways. We also found that the activating protein-1 binding site of MMP1 promoter is required for its transcriptional activation, which may be unique for endometrial cancers. Our results also showed that forced expression of active ERK or active AKT mutants rescued MMP1 expression from lapatinib suppression, further suggesting the importance of molecular selection to find appropriate patients with endometrial cancer for future clinical trials with any targeted therapies.
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Angiopoietin-2-induced arterial stiffness in CKD.
J. Am. Soc. Nephrol.
PUBLISHED: 02-07-2014
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The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C(low) macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-?1 in aortic endothelial cells and Ly6C(low) macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD.
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Chinese adolescents' attitudes toward sexual relationships and premarital sex: implications for promoting sexual health.
J Sch Nurs
PUBLISHED: 02-06-2014
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This study was designed to explore Taiwanese school students' attitudes toward sexual relationships and premarital sex. This was an exploratory descriptive, qualitative study. Focus groups (N = 8) were conducted with 47 adolescents from three high schools in Taiwan. Transcripts were transcribed and thematically analyzed using Atlas V 5.0. Adolescent attitudes toward sexual relationships and premarital sexual behavior comprise the following three dimensions: (1) external incentives, (2) the developmental process, and (3) internal control. External incentives include the normalization of sexual behavior between peers, the desire to feel included in a group, parental influence, and media influence. The developmental process includes imagining the sexual experience and onset of sexual activity. Internal control includes the fear of pregnancy, the fear of parental rejection, and the fear of being judged. These findings can provide a reference for designing future sex education curricula and counseling programs for adolescents.
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The association between autoantibodies and peripheral neuropathy in lupus nephritis.
Biomed Res Int
PUBLISHED: 02-04-2014
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The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy.
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The association between serological biomarkers and primary Sjogren's syndrome associated with peripheral polyneuropathy.
Biomed Res Int
PUBLISHED: 02-04-2014
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The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy of Sjogren's syndrome (SJS) patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating autoantibodies levels in SJS patients with peripheral neuropathy.
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Efficacy of entecavir in chronic hepatitis B patients with persistently normal alanine aminotransferase: randomized, double-blind, placebo-controlled study.
Antivir. Ther. (Lond.)
PUBLISHED: 01-27-2014
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It is still inconclusive whether chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT) should receive nucleos(t)ides analogues. This study is to evaluate the efficacy of entecavir in improving liver histology in CHB patients with PNALT.
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Coexisting diseases of moyamoya vasculopathy.
J Stroke Cerebrovasc Dis
PUBLISHED: 01-25-2014
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Several coexisting diseases have been reported in patients with moyamoya vasculopathy (MMV), but studies of quasi-moyamoya disease (quasi-MMD) are rare. This study aims to investigate the frequency of known coexisting diseases in patients with quasi-MMD and to compare quasi-MMD with moyamoya disease (MMD).
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A multi-digit tactile motion stimulator.
J. Neurosci. Methods
PUBLISHED: 01-20-2014
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One of the hallmarks of haptic exploration is that it typically involves movement between skin and object. Explored objects may contact multiple digits simultaneously so information about motion must be integrated across digits, a process about which little is known.
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Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA.
Gastroenterology
PUBLISHED: 01-15-2014
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Little is known about the benefit of antiviral therapy for hepatitis B e antigen (HBeAg)-positive patients with high viral load and normal levels of alanine aminotransferase. We evaluated the effects of single and combination therapies in immune-tolerant patients with chronic hepatitis B.
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Uterine-sparing surgery for adenomyosis and/or adenomyoma.
Taiwan J Obstet Gynecol
PUBLISHED: 01-09-2014
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Adenomyosis of the uterus is defined as the presence of endometrial tissue, including glands and stroma, situated at least 2.5 mm below the endometrial-myometrial junction and widely distributed within the myometrium layer of the uterus. There is no consensus on the appropriate treatment for symptomatic uterine adenomyosis in women who want to preserve their uterus, partly because adenomyosis is somewhat enigmatic in diagnosis and owing to its clinical significance. Hysterectomy, through either exploratory laparotomy or minimally invasive procedures, is a definite treatment for uterine adenomyosis, once the women have completed childbirth or do not require future fertility. However, many women with a uterine pathology still have a strong desire to preserve the uterus, for which conservative and uterine-sparing procedures are increasingly used, and with which fertility preservation or quality-of-life improvement can be achieved. Although medical management can be effective, similar to the management of uterine fibroids (myoma), its effect is often transient and rapid regrowth of adenomyosis and relapse of symptoms and signs always occur once the treatment is stopped. Therefore, other strategies should be selected. Conservative and uterine-sparing surgery might be one of the most familiar procedures of these uterine-sparing procedures. In this article, the latest knowledge and research evidence on uterine-sparing surgery for uterine adenomyosis are reviewed.
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Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels.
Pancreatology
PUBLISHED: 01-07-2014
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To distinguish autoimmune pancreatitis (AIP), especially focal type, from pancreatic cancer, is a greatest challenge for clinician. The aim of the study is to compare the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of combined serum IgG4 and CA19-9 levels to differentiate AIP from pancreatic cancer by HISORt, Asian and international consensus diagnostic criteria.
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Hydrogen induced redox mechanism in amorphous carbon resistive random access memory.
Nanoscale Res Lett
PUBLISHED: 01-06-2014
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We investigated the bipolar resistive switching characteristics of the resistive random access memory (RRAM) device with amorphous carbon layer. Applying a forming voltage, the amorphous carbon layer was carbonized to form a conjugation double bond conductive filament. We proposed a hydrogen redox model to clarify the resistive switch mechanism of high/low resistance states (HRS/LRS) in carbon RRAM. The electrical conduction mechanism of LRS is attributed to conductive sp2 carbon filament with conjugation double bonds by dehydrogenation, while the electrical conduction of HRS resulted from the formation of insulating sp3-type carbon filament through hydrogenation process.
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Statin therapy reduces oxidized low density lipoprotein level, a risk factor for stroke outcome.
Crit Care
PUBLISHED: 01-06-2014
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Statins are reported to have anti-inflammatory and anti-oxidative effects aside from cholesterol-lowering effects. This study aimed to evaluate the effects of statin therapy on oxidized LDL (Ox-LDL) and the clinical outcome of patients with acute ischemic stroke (AIS).
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Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma.
World J. Gastroenterol.
PUBLISHED: 01-05-2014
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To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC).
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Screening and early detection of pancreatic cancer in high risk population.
World J. Gastroenterol.
PUBLISHED: 01-05-2014
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Pancreatic cancer is a serious growing health issue in developed countries. For patients diagnosed with pancreatic cancer, the five year survival rate is below 5%. One major important reason leads to the poor survival rate is lack of early detection of pancreatic cancer. Over 80% of the patients are diagnosed in advanced disease stages. Screening for pancreatic cancer is a desirable option for high risk individuals to allow early detection and treatment of curable pancreatic neoplasms at a pre-invasive stage. This article highlights the need, endpoint, population, method, diagnostic yield, and the problems of current screening programs.
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YAP/TEAD Co-Activator Regulated Pluripotency and Chemoresistance in Ovarian Cancer Initiated Cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs) and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC) through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.
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5-Lipoxygenase activating protein (FLAP) dependent leukotriene biosynthesis inhibition (MK591) attenuates Lipid A endotoxin-induced inflammation.
PLoS ONE
PUBLISHED: 01-01-2014
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The Lipid A moiety of endotoxin potently activates TLR-4 dependent host innate immune responses. We demonstrate that Lipid-A mediated leukotriene biosynthesis regulates pathogen-associated molecular patterns (PAMP)-dependent macrophage activation. Stimulation of murine macrophages (RAW264.7) with E. coli 0111:B4 endotoxin (LPS) or Kdo2-lipid A (Lipid A) induced inflammation and Lipid A was sufficient to induce TLR-4 mediated macrophage inflammation and rapid ERK activation. The contribution of leukotriene biosynthesis was evaluated with a 5-lipoxygenase activating protein (FLAP) inhibitor, MK591. MK591 pre-treatment not only enhanced but also sustained ERK activation for up to 4 hours after LPS and Lipid A stimulation while inhibiting cell proliferation and enhancing cellular apoptosis. Leukotriene biosynthesis inhibition attenuated inflammation induced by either whole LPS or the Lipid A fraction. These responses were regulated by inhibition of the key biosynthesis enzymes for the proinflammatory eicosanoids, 5-lipoxygenase (5-LO), and cyclooxygenase-2 (COX-2) quantified by immunoblotting. Inhibition of leukotriene biosynthesis differentially regulated TLR-2 and TLR-4 cell surface expression assessed by flow cytometry, suggesting a close mechanistic association between TLR expression and 5-LO associated eicosanoid activity in activated macrophages. Furthermore, MK591 pre-treatment enhanced ERK activation and inhibited cell proliferation after LPS or Lipid A stimulation. These effects were regulated in part by increased apoptosis and modulation of cell surface TLR expression. Together, these data clarify the mechanistic association between 5-lipoxygenase activating protein-mediated leukotriene biosynthesis and 5-LO dependent eicosanoid metabolites in mediating the TLR-dependent inflammatory response after endotoxin exposure typical of bacterial sepsis.
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Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response.
PLoS ONE
PUBLISHED: 01-01-2014
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The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR).
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Contribution of endothelial injury and inflammation in early phase to vein graft failure: the causal factors impact on the development of intimal hyperplasia in murine models.
PLoS ONE
PUBLISHED: 01-01-2014
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Autologous veins are preferred conduits in by-pass surgery. However, long-term results are hampered by limited patency due to intimal hyperplasia. Although mechanisms involved in development of intimal hyperplasia have been established, the role of inflammatory processes is still unclear. Here, we studied leukocyte recruitment and intimal hyperplasia in inferior vena cava grafts transferred to abdominal aorta in mice.
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Impact of coexisting coronary artery disease on the occurrence of cerebral ischemic lesions after carotid stenting.
PLoS ONE
PUBLISHED: 01-01-2014
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Coronary artery disease (CAD) may coexist with extracranial carotid artery stenosis (ECAS), but the influence of CAD on procedure-related complications after carotid artery stenting (CAS) has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning.
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Surface scattering mechanisms of tantalum nitride thin film resistor.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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In this letter, we utilize an electrical analysis method to develop a TaN thin film resistor with a stricter spec and near-zero temperature coefficient of resistance (TCR) for car-used electronic applications. Simultaneously, we also propose a physical mechanism mode to explain the origin of near-zero TCR for the TaN thin film resistor (TFR). Through current fitting, the carrier conduction mechanism of the TaN TFR changes from hopping to surface scattering and finally to ohmic conduction for different TaN TFRs with different TaN microstructures. Experimental data of current-voltage measurement under successive increasing temperature confirm the conduction mechanism transition. A model of TaN grain boundary isolation ability is eventually proposed to influence the carrier transport in the TaN thin film resistor, which causes different current conduction mechanisms.
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YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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YAP is a key component of the Hippo signaling pathway and plays a critical role in the development and progression of multiple cancer types, including ovarian cancer. However, the effects of YAP on ovarian cancer development in vivo and its downstream effectors remain uncertain. In this study we found that strong YAP expression was associated with poor ovarian cancer patient survival. Specifically, we showed for the first time that high YAP expression levels were positively correlated with TEAD4 gene expression, and their co-expression was a prognostic marker for poor ovarian cancer survival. Hyperactivation of YAP by mutating its five inhibitory phosphorylation sites (YAP-5SA) increased ovarian cancer cell proliferation, resistance to chemotherapeutic drugs, cell migration, and anchorage-independent growth. In contrast, expression of a dominant negative YAP mutant reversed these phenotypes in ovarian cancer cells both in vitro and in vivo. Our results suggested that YAP caused these effects by promoting an epithelial-to-mesenchymal transition. Thus, YAP promotes ovarian cancer cell growth and tumorigenesis both in vitro and in vivo. Further, high YAP and TEAD4 expression is a prognostic marker for ovarian cancer progression and a potential target for ovarian cancer treatment.
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Microvascular pericytes in healthy and diseased kidneys.
Int J Nephrol Renovasc Dis
PUBLISHED: 01-01-2014
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Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte-myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the reduced erythropoietin production occurring during pericyte-myofibroblast transition may be promising for the development of new treatment strategies for anemia in chronic kidney disease.
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Integrated One Diode-One Resistor Architecture in Nanopillar SiOx Resistive Switching Memory by Nanosphere Lithography.
Nano Lett.
PUBLISHED: 12-30-2013
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We report on a highly compact, one diode-one resistor (1D-1R) nanopillar device architecture for SiOx-based ReRAM fabricated using nanosphere lithography (NSL). The intrinsic SiOx-based resistive switching element and Si diode are self-aligned on an epitaxial silicon wafer using NSL and a deep-Si-etch process without conventional photolithography. AC-pulse response in 50 ns regime, multibit operation, and good reliability are demonstrated. The NSL process provides a fast and economical approach to large-scale patterning of high-density 1D-1R ReRAM with good potential for use in future applications.
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DriverDB: an exome sequencing database for cancer driver gene identification.
Nucleic Acids Res.
PUBLISHED: 11-07-2013
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Exome sequencing (exome-seq) has aided in the discovery of a huge amount of mutations in cancers, yet challenges remain in converting oncogenomics data into information that is interpretable and accessible for clinical care. We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification. We provide two points of view, Cancer and Gene, to help researchers to visualize the relationships between cancers and driver genes/mutations. The Cancer section summarizes the calculated results of driver genes by eight computational methods for a specific cancer type/dataset and provides three levels of biological interpretation for realization of the relationships between driver genes. The Gene section is designed to visualize the mutation information of a driver gene in five different aspects. Moreover, a Meta-Analysis function is provided so researchers may identify driver genes in customer-defined samples. The novel driver genes/mutations identified hold potential for both basic research and biotech applications.
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Fission yeast shelterin regulates DNA polymerases and Rad3(ATR) kinase to limit telomere extension.
PLoS Genet.
PUBLISHED: 11-01-2013
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Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR)/Tel1(ATM)-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT)), DNA polymerases, Replication Protein A (RPA) complex, Rad3(ATR)-Rad26(ATRIP) checkpoint kinase complex, Tel1(ATM) kinase, shelterin subunits (Tpz1, Ccq1 and Poz1) and Stn1. We further investigated how telomere shortening, caused by trt1? or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Pol?) and lagging (Pol?) strand DNA polymerases at telomeres to modulate Rad3(ATR) association, Ccq1 Thr93 phosphorylation and telomerase recruitment.
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Relationships between ophthalmic artery flow direction and cognitive performance in patients with unilateral carotid artery stenosis.
J. Neurol. Sci.
PUBLISHED: 09-12-2013
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Cerebral hypoperfusion is responsible for cognitive impairment in patients with severe carotid artery stenosis (CAS). The manifestation of reversed ophthalmic artery flow (ROAF) is not uncommon in patients with CAS, suggesting a state of intensified cerebral hypoperfusion. This study aimed to examine whether the presence of ROAF can exacerbate cognitive impairment in patients with severe unilateral CAS.
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Space electric field concentrated effect for Zr:SiO2 RRAM devices using porous SiO2 buffer layer.
Nanoscale Res Lett
PUBLISHED: 08-22-2013
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To improve the operation current lowing of the Zr:SiO2 RRAM devices, a space electric field concentrated effect established by the porous SiO2 buffer layer was investigated and found in this study. The resistive switching properties of the low-resistance state (LRS) and high-resistance state (HRS) in resistive random access memory (RRAM) devices for the single-layer Zr:SiO2 and bilayer Zr:SiO2/porous SiO2 thin films were analyzed and discussed. In addition, the original space charge limited current (SCLC) conduction mechanism in LRS and HRS of the RRAM devices using bilayer Zr:SiO2/porous SiO2 thin films was found. Finally, a space electric field concentrated effect in the bilayer Zr:SiO2/porous SiO2 RRAM devices was also explained and verified by the COMSOL Multiphysics simulation model.
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High performance of graphene oxide-doped silicon oxide-based resistance random access memory.
Nanoscale Res Lett
PUBLISHED: 08-22-2013
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In this letter, a double active layer (Zr:SiOx/C:SiOx) resistive switching memory device with outstanding performance is presented. Through current fitting, hopping conduction mechanism is found in both high-resistance state (HRS) and low-resistance state (LRS) of double active layer RRAM devices. By analyzing Raman and FTIR spectra, we observed that graphene oxide exists in C:SiOx layer. Compared with single Zr:SiOx layer structure, Zr:SiOx/C:SiOx structure has superior performance, including low operating current, improved uniformity in both set and reset processes, and satisfactory endurance characteristics, all of which are attributed to the double-layer structure and the existence of graphene oxide flakes formed by the sputter process.
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Early growth response 1 is an early signal inducing Cav3.2 T-type calcium channels during cardiac hypertrophy.
Cardiovasc. Res.
PUBLISHED: 08-08-2013
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The Cav3.2 T-channel plays a pivotal role in inducing calcineurin/nuclear factor of activated T cell (NFAT) signalling during cardiac hypertrophy. Because calcineurin/NFAT signalling is induced early after pressure overload, we hypothesized that Cav3.2 is induced by an early signal. Our aim is to investigate when and how Cav3.2 is induced during cardiac hypertrophy.
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Clinicopathologic parameters and immunohistochemical study of endometrial stromal sarcomas.
Int. J. Gynecol. Pathol.
PUBLISHED: 07-31-2013
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We aimed to investigate the clinicopathologic features, immunohistochemical studies, and prognosis in patients with endometrial stromal sarcoma (ESS). Clinical information was reviewed retrospectively for cases of ESS (1985-2009). A histologic review and immunohistochemical staining for the estrogen receptor, progesterone receptor, c-Kit, CD-10, Ki-67, and m-TOR were performed. Sixty-one patients (median age, 44 y; range, 22-71) were eligible for analysis (1988 International Federation of Gynecology and Obstetrics Stage I, 43; Stage II, 2; Stage III, 11; Sage IV, 4; unstaged, 1). The median follow-up period for survivors was 73 mo. Of those, the patients who underwent an adnexectomy and a pelvic lymphadenectomy, 15% and 13%, respectively, revealed metastasis. There were 20 relapses/persistence, including 13 (65%) in the pelvis and abdomen and 7 (35%) in distant sites. Eight patients died from ESS at a median duration of 14.5 mo (range, 2-50 mo) after relapse. Five- and 10-yr cancer-specific survival (CSS) rates were 88% and 85%, respectively; and 5- and 10-yr progression-free survival rates were 69% and 57%, respectively. Stage, residual disease, and high proliferative index of Ki-67 were significant prognostic factors for both progression-free survival and CSS in a univariate analysis, in addition to mitotic index for CSS. Multivariate analysis selected only residual disease as an independent variable for progression-free survival and stage and residual disease for CSS. Our results support using clinical Stage I, no residual disease, low proliferative index of Ki-67, and estrogen receptor/progesterone receptor overexpression as potential biomarkers to select patients with ESS for fertility-preservation surgery (5 such patients were alive and free).
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Quantitative phosphoproteomic study of pressure-overloaded mouse heart reveals dynamin-related protein 1 as a modulator of cardiac hypertrophy.
Mol. Cell Proteomics
PUBLISHED: 07-23-2013
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Pressure-overload stress to the heart causes pathological cardiac hypertrophy, which increases the risk of cardiac morbidity and mortality. However, the detailed signaling pathways induced by pressure overload remain unclear. Here we used phosphoproteomics to delineate signaling pathways in the myocardium responding to acute pressure overload and chronic hypertrophy in mice. Myocardial samples at 4 time points (10, 30, 60 min and 2 weeks) after transverse aortic banding (TAB) in mice underwent quantitative phosphoproteomics assay. Temporal phosphoproteomics profiles showed 360 phosphorylation sites with significant regulation after TAB. Multiple mechanical stress sensors were activated after acute pressure overload. Gene ontology analysis revealed differential phosphorylation between hearts with acute pressure overload and chronic hypertrophy. Most interestingly, analysis of the cardiac hypertrophy pathway revealed phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (DRP1) by prohypertrophic kinases. Phosphorylation of DRP1 S622 was confirmed in TAB-treated mouse hearts and phenylephrine (PE)-treated rat neonatal cardiomyocytes. TAB-treated mouse hearts showed phosphorylation-mediated mitochondrial translocation of DRP1. Inhibition of DRP1 with the small-molecule inhibitor mdivi-1 reduced the TAB-induced hypertrophic responses. Mdivi-1 also prevented PE-induced hypertrophic growth and oxygen consumption in rat neonatal cardiomyocytes. We reveal the signaling responses of the heart to pressure stress in vivo and in vitro. DRP1 may be important in the development of cardiac hypertrophy.
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The chromatin modification by SUMO-2/3 but not SUMO-1 prevents the epigenetic activation of key immune-related genes during Kaposis sarcoma associated herpesvirus reactivation.
BMC Genomics
PUBLISHED: 07-15-2013
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SUMOylation, as part of the epigenetic regulation of transcription, has been intensively studied in lower eukaryotes that contain only a single SUMO protein; however, the functions of SUMOylation during mammalian epigenetic transcriptional regulation are largely uncharacterized. Mammals express three major SUMO paralogues: SUMO-1, SUMO-2, and SUMO-3 (normally referred to as SUMO-1 and SUMO-2/3). Herpesviruses, including Kaposis sarcoma associated herpesvirus (KSHV), seem to have evolved mechanisms that directly or indirectly modulate the SUMO machinery in order to evade host immune surveillance, thus advancing their survival. Interestingly, KSHV encodes a SUMO E3 ligase, K-bZIP, with specificity toward SUMO-2/3 and is an excellent model for investigating the global functional differences between SUMO paralogues.
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The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus.
J Transl Med
PUBLISHED: 07-05-2013
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Both apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE.
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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.

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

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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.