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Find video protocols related to scientific articles indexed in Pubmed.
Unusual Dewetting of thin polymer films in liquid media containing a solvent and a non-solvent.
Langmuir
PUBLISHED: 11-18-2014
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We investigate the control of pattern size and kinetics in spontaneous dewetting of thin polymer films (polystyrene) that are stable to thermal annealing by annealing in a poor solvent (acetone)/non-solvent (ethanol or hexane) liquid mixture. Dewetting occurs by the formation and growth of circular holes that coalesce to form droplets. The influence of the nature and the volume fraction of the non-solvents on the contact angle of polymer droplets, number density of holes, and the kinetics of holes formation and growth are studied. Addition of ethanol greatly increases the hole-density and slows down the kinetics substantially, while affecting only a small change in wettability. Hexane addition shows an interesting non-monotonic response in decreasing the hole-density and contact angle in the volume fraction range of 0-0.3, but an opposite effect beyond that. Although the two non-solvents chosen cannot by themselves induce dewetting, their relative affinity to the solid substrate vis-à-vis acetone can strongly influence the observed dewetting scenarios that are not completely understood by the existing theoretical considerations. Hexane, for example, shows great affinity with silicon substrate. In addition to the changes in the wettability by the polar interactions, several other factors need to be considered such as: viscosity and film interfacial tension engendered by the non-solvents and possibility of the formation of adsorbed liquid molecules at the substrate-polymer interface that can modify the interfacial friction and slippage.
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Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: A multicenter, observational study.
Platelets
PUBLISHED: 11-15-2014
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Abstract No effective treatment has been identified for patients of liver cirrhosis (LC) associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to explore the effectiveness and safety of low-dose prednisone or cyclosporine A (CsA) combined with nucleoside analog (NA) in patients with severe thrombocytopenia associated with HBV-related LC. We included 145 consecutive compensated HBV-associated LC patients with severe thrombocytopenia between 1 January 2006 and 31 December 2013. We divided the patients into three groups by treatment strategy, including NA only (n?=?57), NA plus prednisone (n?=?46), and NA plus CsA (n?=?42). We analyzed the platelet counts, bleeding events, liver function, replication of HBV, and outcomes in each group. At all time points during this observation, the platelet counts in prednisone or CsA group were higher than those in the NA only group. There are significant differences in the cumulative rates of bleeding events among the three groups. The platelet counts and treatment were factors associated with bleeding events in multivariate analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates, normal serum alanine transaminase rates, serum alanine transaminase elevated more than two times the baseline rates, and HBeAg seropositive conversion ratio among the groups did not reach statistical significance. The adverse events in our study were, in general, mild and balanced among the three treatment groups. Treatment with low-dose prednisone or CsA plus NA could elevate the platelet counts and reduce the risk of bleeding events in HBV LC with severe thrombocytopenia.
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MeT-DB: a database of transcriptome methylation in mammalian cells.
Nucleic Acids Res.
PUBLISHED: 11-08-2014
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Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/methylation/) is the first comprehensive resource for N6-methyladenosine (m(6)A) in mammalian transcriptome. It includes a database that records publicaly available data sets from methylated RNA immunoprecipitation sequencing (MeRIP-Seq), a recently developed technology for interrogating m(6)A methyltranscriptome. MeT-DB includes ?300k m(6)A methylation sites in 74 MeRIP-Seq samples from 22 different experimental conditions predicted by exomePeak and MACS2 algorithms. To explore this rich information, MeT-DB also provides a genome browser to query and visualize context-specific m(6)A methylation under different conditions. MeT-DB also includes the binding site data of microRNA, splicing factor and RNA binding proteins in the browser window for comparison with m(6)A sites and for exploring the potential functions of m(6)A. Analysis of differential m(6)A methylation and the related differential gene expression under two conditions is also available in the browser. A global perspective of the genome-wide distribution of m(6)A methylation in all the data is provided in circular ideograms, which also act as a navigation portal. The query results and the entire data set can be exported to assist publication and additional analysis.
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The Apelin-APJ Axis Is An Endogenous Counter-injury Mechanism In Experimental Acute Lung Injury.
Chest
PUBLISHED: 11-07-2014
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Although mechanisms and pathways mediating acute respiratory distress syndrome (ARDS) have been extensively studied, less attention has been given to mechanisms and pathways that counteract injury responses. This study uncovered that the apelin-APJ pathway is an endogenous counter-injury mechanism that protects against ARDS.
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Decomposition of RNA methylome reveals co-methylation patterns induced by latent enzymatic regulators of the epitranscriptome.
Mol Biosyst
PUBLISHED: 11-06-2014
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Biochemical modifications to mRNA, especially N6-methyladenosine (m(6)A) and 5-methylcytosine (m(5)C), have been recently shown to be associated with crucial biological functions. Despite the intriguing advancements, little is known so far about the dynamic landscape of RNA methylome across different cell types and how the epitranscriptome is regulated at the system level by enzymes, i.e., RNA methyltransferases and demethylases. To investigate this issue, a meta-analysis of m(6)A MeRIP-Seq datasets collected from 10 different experimental conditions (cell type/tissue or treatment) is performed, and the combinatorial epitranscriptome, which consists of 42?758 m(6)A sites, is extracted and divided into 3 clusters, in which the methylation sites are likely to be hyper- or hypo-methylated simultaneously (or co-methylated), indicating the sharing of a common methylation regulator. Four different clustering approaches are used, including K-means, hierarchical clustering (HC), Bayesian factor regression model (BFRM) and nonnegative matrix factorization (NMF) to unveil the co-methylation patterns. To validate whether the patterns are corresponding to enzymatic regulators, i.e., RNA methyltransferases or demethylases, the target sites of a known m(6)A regulator, fat mass and obesity-associated protein (FTO), are identified from an independent mouse MeRIP-Seq dataset and lifted to human. Our study shows that 3 out of the 4 clustering approaches used can successfully identify a group of methylation sites overlapping with FTO target sites at a significance level of 0.05 (after multiple hypothesis adjustment), among which, the result of NMF is the most significant (p-value 2.81 × 10(-06)). We defined a new approach evaluating the consistency between two clustering results which shows that clustering results of different methods are highly correlated strongly indicating the existence of co-methylation patterns. Consistent with recent studies, a number of cancer and neuronal disease-related bimolecular functions are enriched in the identified clusters, which are biological functions that can be regulated at the epitranscriptional level, indicating the pharmaceutical prospect of RNA N6-methyladenosine-related studies. This result successfully reveals the linkage between the global RNA co-methylation patterns embedded in the epitranscriptomic data under multiple experimental conditions and the latent enzymatic regulators, suggesting a promising direction towards a more comprehensive understanding of the epitranscriptome.
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The Lifespan-Extending Effects of Nymphaea hybrid Root Extract in the Nematode Caenorhabditis elegans.
Plant Foods Hum Nutr
PUBLISHED: 11-05-2014
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Nymphaea hybrid, a water lily from the Nymphaeaceae family, has been found to exhibit some in vivo beneficial effects. In the present study we investigated the lifespan-extending effects of Nymphaea hybrid root extract in the nematode Caenorhabditis elegans. We found that Nymphaea hybrid root extract significantly extended the lifespan of C.elegans and improved its locomotion during aging. Moreover, Nymphaea hybrid root extract increased the resistance of C.elegans to both heat stress and oxidative stress. We found that the ability of Nymphaea hybrid root extract to increase lifespan was independent of its antimicrobial effects and was probably associated with its effects on the reproduction of C.elegans. In addition, the lifespan-extending effects of Nymphaea hybrid root extract were found to be dependent on the insulin/IGF signaling pathway. We also found that total flavones of Nymphaea hybrid could increase survival of C.elegans in both normal and adverse conditions, indicating that total flavones comprise the major fractions with lifespan-extending effects. Therefore, Nymphaea hybrid root extract has lifespan-extending effects in C.elegans and could be developed as a functional food.
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Type-1-cytokines synergize with oncogene inhibition to induce tumor growth arrest.
Cancer Immunol Res
PUBLISHED: 10-30-2014
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Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer but responses can be either short-lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explore potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells as previously observed. Instead, we found that the T cell cytokines IFN-? and TNF-? synergized with vemurafenib to induce cell cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma derived cell lines and was restricted to cancers bearing a BRAFV600E-mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the anti-proliferative effects of T cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest have major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer.
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Synthesis of Highly Substituted Imidazolidine-2,4-dione (Hydantoin) through Tf2O-Mediated Dual Activation of Boc-Protected Dipeptidyl Compounds.
Org. Lett.
PUBLISHED: 10-30-2014
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Highly substituted chiral hydantoins were readily synthesized from simple dipeptides in a single step under mild conditions. This reaction proceeded through the dual activation of an amide and a tert-butyloxycarbonyl (Boc) protecting group by Tf2O-pyridine. This method was successfully applied in the preparation of a variety of biologically active compounds, including drug analogs and natural products.
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Cigarette Smoking in Same-Sex and Different-Sex Unions: The Role of Socioeconomic and Psychological Factors.
Popul Res Policy Rev
PUBLISHED: 10-28-2014
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Cigarette smoking has long been a target of public health intervention because it substantially contributes to morbidity and mortality. Individuals in different-sex marriages have lower smoking risk (i.e., prevalence and frequency) than different-sex cohabiters. However, little is known about the smoking risk of individuals in same-sex cohabiting unions. We compare the smoking risk of individuals in different-sex marriages, same-sex cohabiting unions, and different-sex cohabiting unions using pooled cross-sectional data from the 1997-2010 National Health Interview Surveys (N = 168,514). We further examine the role of socioeconomic status (SES) and psychological distress in the relationship between union status and smoking. Estimates from multinomial logistic regression models reveal that same-sex and different-sex cohabiters experience similar smoking risk when compared to one another, and higher smoking risk when compared to the different-sex married. Results suggest that SES and psychological distress factors cannot fully explain smoking differences between the different-sex married and same-sex and different-sex cohabiting groups. Moreover, without same-sex cohabiter's education advantage, same-sex cohabiters would experience even greater smoking risk relative to the different-sex married. Policy recommendations to reduce smoking disparities among same-sex and different-sex cohabiters are discussed.
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[Investigation of Toxoplasma gondii infection in pregnant women in Qingdao area].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 10-28-2014
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To understand the status of Toxoplasma gondii (TOX) infection in pregnant women in Qingdao area.
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A general approach for the development of fluorogenic probes suitable for no-wash imaging of kinases in live cells.
Chem. Commun. (Camb.)
PUBLISHED: 10-27-2014
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A general approach is presented for developing small molecule-based fluorogenic probes suitable for no-wash imaging of endogenous kinases in live cells. Probe 1, including a fluorophore-quencher system, was only "turned on" upon reacting with its target kinase Btk, and disclosed Btk's cellular location in live cells without any washing.
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Accurate Measurement of Magnetic Resonance Imaging Gradient Characteristics.
Materials (Basel)
PUBLISHED: 10-25-2014
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Recently, gradient performance and fidelity has become of increasing interest, as the fidelity of the magnetic resonance (MR) image is somewhat dependent on the fidelity of the gradient system. In particular, for high fidelity non-Cartesian imaging, due to non-fidelity of the gradient system, it becomes necessary to know the actual k-space trajectory as opposed to the requested trajectory. In this work we show that, by considering the gradient system as a linear time-invariant system, the gradient impulse response function (GIRF) can be reliably measured to a relatively high degree of accuracy with a simple setup, using a small phantom and a series of simple experiments. It is shown experimentally that the resulting GIRF is able to predict actual gradient performance with a high degree of accuracy. The method captures not only the frequency response but also gradient timing errors and artifacts due to mechanical vibrations of the gradient system. Some discussion is provided comparing the method presented here with other analogous methods, along with limitations of these methods.
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Combination of 2- and 3-dimensional contrast-enhanced transvaginal sonography for diagnosis of small adnexal masses.
J Ultrasound Med
PUBLISHED: 10-23-2014
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The purpose of this study was to evaluate the efficacy of the combination of 2-dimensional (2D) and 3-dimensional (3D) contrast-enhanced sonography in discriminating between benign and malignant small adnexal masses.
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[Abnormal DNA methylation in CD4? T cells from patients with immune related pancytopenia: a preliminary study].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-22-2014
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To explore the global DNA methylation and the expression of regulatory genes for methylation in CD4? T cells of the patients with immune related pancytopenia (IRP) and explore the role of methylation in the pathogenesis of IRP.
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Chain of rings: a radiographic sign of papillary thyroid cancer.
Acta Clin Belg
PUBLISHED: 10-18-2014
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Papillary thyroid cancer is the most common form of thyroid malignancy in children and adult with frequent metastases to the cervical lymph nodes. We present a case of metastatic papillary thyroid cancer with remarkable imaging findings of consecutive metastatic calcified lymph nodes resembling a chain of rings. While accompanying by a coarsely calcified thyroid mass, possible thyroid cancer should be considered and serve as a guide to warrant further thyroid cancer evaluation.
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Intravenous Anesthetic Propofol Inhibits Multiple Human Cardiac Potassium Channels.
Anesthesiology
PUBLISHED: 10-17-2014
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Propofol is widely used clinically for the induction and maintenance of anesthesia. Clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. The current study investigates the effects of propofol on human cardiac potassium channels.
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Reconstruction of intraoral maxillary defect with buccal fat pad.
J Craniofac Surg
PUBLISHED: 10-17-2014
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: The aim of the study was to evaluate the efficacy of the buccal fat pad (BFP) in the reconstruction of various intraoral maxillary defects as well as the success, anatomy, healing process, merits, demerits, and complications of this technique.
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Activation and Propagation of Tumor-infiltrating Lymphocytes on Clinical-grade Designer Artificial Antigen-presenting Cells for Adoptive Immunotherapy of Melanoma.
J. Immunother.
PUBLISHED: 10-12-2014
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Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) is a therapy for metastatic melanoma with response rates of up to 50%. However, the generation of the TIL transfer product is challenging, requiring pooled allogeneic normal donor peripheral blood mononuclear cells (PBMC) used in vitro as "feeders" to support a rapid-expansion protocol. Here, we optimized a platform to propagate TIL to a clinical scale using K562 cells genetically modified to express costimulatory molecules such as CD86, CD137-ligand, and membrane-bound IL-15 to function as artificial antigen-presenting cells (aAPC) as an alternative to using PBMC feeders.
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[Effects of resting days on live poultry markets in controlling the avian influenza pollution].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 10-09-2014
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To analyze the results of nine-round environmental specimen surveillance programs in five live poultry markets pre-, during and post the 'closing days' and to evaluate the effects of 'closing days' on live poultry markets regarding the control against avian influenza pollution.
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[A clinical trial of ultrasound-guided facet joint block in the lumbar spine to treat facet joint related low back pain].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To determine the feasibility and clinical efficacy of ultrasound-guided facet joint injection and nerve block in lumbar facet joint for the treatment of facet-joint related low back pain.
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Mallory-Denk Body (MDB) formation modulates ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH).
Exp. Mol. Pathol.
PUBLISHED: 10-03-2014
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Promoter CpG island hypermethylation is an important mechanism for inactivating key cellular enzymes that mediate epigenetic processes in hepatitis-related hepatocellular carcinoma (HCC). The ubiquitin-fold modifier 1 (Ufm1) conjugation pathway (Ufmylation) plays an essential role in protein degradation, protein quality control and signal transduction. Previous studies showed that the Ufmylation pathway was downregulated in alcoholic hepatitis (AH), non-alcoholic steatohepatitis (NASH) and in mice fed DDC, resulting in the formation of Mallory-Denk Bodies (MDBs). In this study, we further discovered that betaine, a methyl donor, fed together with DDC significantly prevents the increased expression of Ufmylation in drug-primed mice fed DDC. Betaine significantly prevented transcript silencing of Ufm1, Uba5 and UfSP1 where MDBs developed and also prevented the increased expression of FAT10 and LMP7 caused by DDC re-fed mice. Similar downregulation of Ufmylation was observed in multiple AH and NASH biopsies which had formed MDBs. The DNA methylation levels of Ufm1, Ufc1 and UfSP1 in the promoter CpG region were significantly increased both in AH and NASH patients compared to normal subjects. DNA (cytosine-5-)-methyltransferase 1 (DNMT1) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) mRNA levels were markedly upregulated in AH and NASH patients, implying that the maintenance of Ufmylation methylation might be mediated by DNMT1 and DNMT3B together. These data show that MDB formation results from Ufmylation expression epigenetically in AH and NASH patients. Promoter CpG methylation may be a major mechanism silencing Ufmylation expression.
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[Application of microperimeter in the visual function evaluation].
Fa Yi Xue Za Zhi
PUBLISHED: 10-03-2014
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In condition of direct vision on hindus of eye, microperimeter can quantitatively detect the retinal light sensitivity of macular area, and record real time tracking of the eye, automatically analyze the location and stability of fixation. Microperimeter matches hindus image with micro cyclogram point-to-point, thus it achieves the combination of visual function and structure. The characteristics of microperimeter have good relations with subjective vision, so it can be a new method for the accurate vision evaluation and has application potential to assess the visual function in legal medicine. In this article, we summarize the principle, method and parameters of microperimeter. Also, the applications of microperimeter in vision assessment are focused in order to provide a reference for the assessment of visual function in the legal medicine.
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[Short and mid-term effectiveness of paravertebral adriamycin injection under CT guidance on intractable postherpetic neuralgia].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-02-2014
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To determine the short and mid-term effect of paravertebral adriamycin injection under CT guidance on intractable postherpetic neuralgia (PHN).
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Little Association Between Wellness Policies and School-Reported Nutrition Practices.
Health Promot Pract
PUBLISHED: 09-25-2014
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Background. The Child Nutrition and WIC Reauthorization Act of 2004 mandated written school wellness policies. Little evidence exists to evaluate the impact of such policies. This study assessed the quality (comprehensiveness of topics addressed and strength of wording) of wellness policies and the agreement between written district-level policies and school-reported nutrition policies and practices in 48 low-income Michigan school districts participating in the School Nutrition Advances Kids study. Method. Written wellness policy quality was assessed using the School Wellness Policy Evaluation Tool. School nutrition policies and practices were assessed using the School Environment and Policy Survey. Analysis of variance determined differences in policy quality, and Fisher's exact test examined agreement between written policies and school-reported practices. Results. Written wellness policies contained ambiguous language and addressed few practices, indicating low comprehensiveness and strength. Most districts adopted model wellness policy templates without modification, and the template used was the primary determinant of policy quality. Written wellness policies often did not reflect school-reported nutrition policies and practices. Conclusions. School health advocates should avoid assumptions that written wellness policies accurately reflect school practices. Encouraging policy template customization and stronger, more specific language may enhance wellness policy quality, ensure consistency between policy and practice, and enhance implementation of school nutrition initiatives.
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Potentially optimal body size to adjust tube current for individualized radiation dose control in retrospective ECG-triggered 256-slice CT coronary angiography.
Hellenic J Cardiol
PUBLISHED: 09-23-2014
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We aimed to determine a potentially optimal body size index for adjusting the tube current in retrospective ECG-triggered helical 256-slice CT coronary angiography (CTCA) for individualized radiation dose control.
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Metabolite profiling of anhuienoside C by rat intestinal bacteria using the LC-MS metabolomic approach.
Xenobiotica
PUBLISHED: 09-16-2014
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Abstract 1.?Anhuienoside C (A-C) is the main active component of the saponin exact of "Di Wu", an oral drug for rheumatism treatment in China. In this study, we aimed to elucidate the metabolic pathways of A-C by intestinal bacteria using the metabolomic approach. 2.?Four deglycosylated metabolites (M1, M2, M3 and M4) were identified after A-C (50?µM) was incubated with rat fecal lysate. Chemical structures of these metabolites were determined by high-resolution masses and nuclear magnetic resonance (NMR). 3.?A one-compartment pharmacokinetic model was used to describe the formation of bacterial metabolites at a dose of 10?µM A-C. The results revealed that formation of M1 and M2 was rapid, whereas formation of M3 was rather slow. Further, it was found that the metabolites were generated by successive cleavage of the glycosyl residues. 4.?This is the first report that A-C is subjected to efficient bacterial metabolism in the gut with M1 and M2 as main metabolites. Our study should be helpful for a better understanding of in vivo disposition of oral A-C.
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[Qianlongtong capsule elevates the Smad4 gene expression in prostate stromal cells].
Zhonghua Nan Ke Xue
PUBLISHED: 09-09-2014
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To investigate the effects of the plasma containing Qianlongtong Capsule (QLT)-containing plasma on the expression of the Smad4 gene in prostate stromal cells in vitro and provide some experimental evidence for the treatment of benign prostatic hyperplasia (BPH) with Chinese medicinal compound.
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Increased activity of the complement system in the liver of patients with alcoholic hepatitis.
Exp. Mol. Pathol.
PUBLISHED: 09-08-2014
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Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH.
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Synthesis and spectroscopic properties of novel meso-cyano boron-pyridyl-isoindoline dyes.
Org. Biomol. Chem.
PUBLISHED: 09-08-2014
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meso-Cyano boron-pyridyl-isoindoline dyes with asymmetrical structures were synthesized through a facile two-step reaction. Broad envelopes of intense vibrational bands were observed for the main spectral bands in the absorption and emission spectra. Moderate fluorescence quantum yields were obtained in solution, with significant intensity also observed in film, powder and crystal forms. An analysis of the structure-property relationships was carried out based on X-ray crystallography, optical spectroscopy, and theoretical calculations.
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Unstrained Carbon?Carbon Bond Cleavage.
Chem Asian J
PUBLISHED: 09-01-2014
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This Focus Review presents recent developments in the cleavage of C?C bonds in organic molecules. Significant progress in C?C activation, including the development of a variety of new synthetic strategies, has contributed to the development of this field over the past few decades. Transition-metal-mediated C?C bond cleavage has been shown to be a quite efficient process and several elegant metal-free methods have also recently been developed. Strained rings have been widely used in C?C cleavage transformations; however, unstrained C?C activation has increasingly caught the attention of organic researchers, which inspired us to clarify the developments in this field.
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The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-30-2014
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Males absent on the first (MOF) is a histone acetyltransferase belongs to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. In mammals, MOF plays critical roles in transcription activation by acetylating histone H4K16, a prevalent mark associated with chromatin decondensation. MOF can also acetylate transcription factor p53 on K120, which is important for activation of pro-apoptotic genes; and TIP5, the largest subunit of NoRC, on K633. However, the role of hMOF in hepatocellular carcinoma remains unknown. Here we find that the expression of hMOF is significantly down-regulated in human hepatocellular carcinoma and cell lines. Furthermore, our survival analysis indicates that low hMOF expression predicts poor overall and disease-free survival. We demonstrate that hMOF knockdown promotes hepatocellular carcinoma growth in vitro and in vivo, while hMOF overexpression reduces hepatocellular carcinoma growth in vitro and in vivo. Mechanically, we show that hMOF regulates the expression of SIRT6 and its downstream genes. In summary, our findings demonstrate that hMOF participates in human hepatocellular carcinoma by targeting SIRT6, and hMOF activators may serve as potential drug candidates for hepatocellular carcinoma therapy.
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Enhancing the electrocatalytic property of hollow structured platinum nanoparticles for methanol oxidation through a hybrid construction.
Sci Rep
PUBLISHED: 08-27-2014
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The integration of different components into a hybrid nanosystem for the utilization of the synergistic effects is an effective way to design the electrocatalysts. Herein, we demonstrate a hybrid strategy to enhance the electrocatalytic property of hollow structured Pt nanoparticles for methanol oxidation reaction. This strategy begins with the preparation of bimetallic Ag-Pt nanoparticles with a core-shell construction. Element sulfur is then added to transform the core-shell Ag-Pt nanostructures into hybrid nanodimers consisting of Ag2S nanocrystals and remaining Pt domains with intact hollow interiors (Ag2S-hPt). Finally, Au is deposited at the surface of the Ag2S domain in each hetero-dimer, resulting in the formation of ternary Ag2S-Au-hPt nanocomposites with solid-state interfaces. The ternary nanocomposites exhibit enhanced electrocatalytic property toward methanol oxidation due to the strong electronic coupling between Pt and other domains in the hybrid particles. The concept might be used toward the design and synthesis of other hetero-nanostructures with technological importance.
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[Memory B (CD5? CD19? CD27?) lymphocyte in patients with immune-related pancytopenia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-26-2014
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To detect memory B lymphocyte (Bm) in peripheral blood (PB) of immune-related pancytopenia (IRP).
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Asymptomatic, mild, and severe influenza A(H7N9) virus infection in humans, Guangzhou, China.
Emerging Infect. Dis.
PUBLISHED: 08-23-2014
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Targeted surveillance for influenza A(H7N9) identified 24 cases of infection with this virus in Guangzhou, China, during April 1, 2013-March 7, 2014. The spectrum of illness ranged from severe pneumonia to asymptomatic infection. Epidemiologic findings for 2 family clusters of infection highlight the importance of rigorous close contact monitoring.
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[Association between serum interleukin-17 level and abnormal cellular immunological status in patients with severe aplastic anemia].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-23-2014
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To explore the role of interleukin-17 (IL-17) in the pathogenesis of severe aplastic anemia (SAA).
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Alcoholic and non-alcoholic steatohepatitis.
Exp. Mol. Pathol.
PUBLISHED: 08-20-2014
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This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes, cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.
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Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway.
Int J Nanomedicine
PUBLISHED: 08-20-2014
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The objective of this study was to prepare and characterize etoposide (VP16)-loaded solid lipid nanoparticles (SLNs) and evaluate their antitumor activity in vitro. VP16-SLNs were prepared using emulsification and low-temperature solidification methods. The physicochemical properties of the VP16-SLNs were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, stability, and in vitro drug-release behavior. In contrast to free VP16, the VP16-SLNs were well dispersed in aqueous medium, showing a narrow size distribution at 30-50 nm, a zeta potential value of -28.4 mV, high drug loading (36.91%), and an ideal drug entrapment efficiency (75.42%). The drug release of VP16-SLNs could last up to 60 hours and exhibited a sustained profile, which made it a promising vehicle for drug delivery. Furthermore, VP16-SLNs could significantly enhance in vitro cytotoxicity against SGC7901 cells compared to the free drug. Furthermore, VP16-SLNs could induce higher apoptotic rates, more significant cell cycle arrest effects, and greater cellular uptake in SGC7901 cells than free VP16. Moreover, results demonstrated that the mechanisms of VP16-SLNs were similar to those claimed for free VP16, including induction of cellular apoptosis by activation of p53, release of cytochrome c, loss of membrane potential, and activation of caspases. Thus, these results suggested that the SLNs might be a promising nanocarrier for VP16 to treat gastric carcinoma.
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[A comparison of 226 Hz and 1 000 Hz tympanometry in diagnosis of infants otitis media effusion].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To provide a clinical reference by comparing the conventional 226 Hz tympanometry with 1000 Hz tympanometry in two groups of young children with otitis media effusion evidenced by CT scan.
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Social relationships play a role in sleep status in Chinese undergraduate students.
Psychiatry Res
PUBLISHED: 08-14-2014
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The purpose of this study was to examine whether social relationships were associated with sleep status in Chinese undergraduate students. A cross-sectional questionnaire survey was conducted in November 2012 at Huzhou Teachers College, China. The questionnaire involved demographic characteristics, personal lifestyle habits, social relationships and Pittsburgh Sleep Quality Index (PSQI). The associations between social relationships and sleep status were analyzed by using regression models after adjustment for potential factors. Poor sleep quality was prevalent among Chinese undergraduate students. Men tended to have better sleep than women. Lower social stress, better management of stress and good social support were correlated with better sleep status, and stress or support from friends, family and classmates were all related with sleep variables. While only weak associations between number of friends and sleep were detected. The results were consistent in men and women. Educators and instructors should be aware of the importance of social relationships as well as healthy sleep in undergraduates.
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Occurrence of antibiotics in the aquatic environment of Jianghan Plain, central China.
Sci. Total Environ.
PUBLISHED: 08-14-2014
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The occurrence of 19 antibiotics (sulfonamide, fluoroquinolone, tetracycline and macrolide) was studied in surface water and groundwater samples collected from Shahu County of Jianghan Plain, central China, in autumn (dry season) and spring (wet season). In autumn, chlorotetracycline, doxycycline and enrofloxacin were the three antibiotics with the highest concentrations and high relevance ratios in all of the water samples. The concentration of chlorotetracycline was greatest in surface water at 122.3 n gL(-1) and was as high as 86.6 ng L(-1) in groundwater, which are among the highest values reported worldwide. In spring, tetracycline was found to be more than 100 ng L(-1) in groundwater and surface water, which also contained high concentrations of ofloxacin (135.1 ng L(-1)), norfloxacin (134.2 ng L(-1)) and erythromycin dehydrate (381.5 ng L(-1)). Most of the SMs were observed at higher detection frequencies in spring than in autumn, which can be ascribed to surface runoff by rain water during the wet season (spring). The average concentrations of compounds in the fluoroquinolone and tetracycline categories were far higher than those in the sulfonamide and macrolide categories, which had concentrations of less than 16 ng L(-1) in groundwater (except erythromycin dehydrate), while macrolides were found in all samples, except erythromycin dehydrate. The main antibiotics present in groundwater were also the dominant compounds found in surface water, with correlation coefficients of 0.93 and 0.97 in autumn and spring, respectively, indicating the potential contamination of groundwater by the infiltration of contaminated surface water.
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Pregnancy-related systemic lupus erythematosus: clinical features, outcome and risk factors of disease flares--a case control study.
PLoS ONE
PUBLISHED: 08-13-2014
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To investigate the clinical features, outcome, and risk factors of disease flares in patients with pregnancy-related lupus (PRL).
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Comparison of the effect of 'metabolically healthy but obese' and 'metabolically abnormal but not obese' phenotypes on development of diabetes and cardiovascular disease in Chinese.
Endocrine
PUBLISHED: 08-11-2014
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The present study was designed to determine the prevalence of 'metabolically healthy but obese' (MHO) and 'metabolically abnormal but not obese' (MANO) phenotypes in Chinese population, and to investigate the association of these two phenotypes with the risk of diabetes and cardiovascular disease (CVD). A total of 2,764 subjects aged 30-90 were followed up over a mean period of 43.80 ± 11.25 months. The metabolic syndrome was defined according to the joint committee for developing Chinese guidelines on prevention and treatment of dyslipidemia in adults. Subjects with body fat percentage (BF %) >25 % for men or BF % >35 % for women were defined as being obese. The proportion of MHO and MANO phenotypes were 22.9, 7.6 % in men, and 26.2, 6.0 % in women, respectively. The MANO phenotype was associated with increased risk for diabetes both in men [hazard ratios (HR): 4.44 (1.21-16.26)] and women [HR: 8.68 (2.87-24.96)] after adjustment of age, serum total cholesterol (TC), triglycerides (TG), and family history of diabetes. This association held for CVD in women [HR: 2.87 (1.44-5.73)], but not in men after adjustment of age, serum TC, TG, and family history of CVD. No association was observed between the MHO phenotype and incident diabetes or CVD. MHO and MANO phenotypes are common in Chinese population. Metabolic risk factors appeared to play a more important role in the development of diabetes and CVD than body fat alone.
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Alloy Cu?Pt nanoframes through the structure evolution in Cu-Pt nanoparticles with a core-shell construction.
Sci Rep
PUBLISHED: 07-31-2014
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Noble metal nanoparticles with hollow interiors and customizable shell compositions have immense potential for catalysis. Herein, we present an unique structure transformation phenomenon for the fabrication of alloy Cu?Pt nanoframes with polyhedral morphology. This strategy starts with the preparation of polyhedral Cu-Pt nanoparticles with a core-shell construction upon the anisotropic growth of Pt on multiply twinned Cu seed particles, which are subsequently transformed into alloy Cu?Pt nanoframes due to the Kirkendall effect between the Cu core and Pt shell. The as-prepared alloy Cu?Pt nanoframes possess the rhombic dodecahedral morphology of their core-shell parents after the structural evolution. In particular, the resulting alloy Cu?Pt nanoframes are more effective for oxygen reduction reaction but ineffective for methanol oxidation reaction in comparison with their original Cu-Pt core-shell precursors.
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Ultrasound promoted catalytic liquid-phase dehydrogenation of isopropanol for Isopropanol-Acetone-Hydrogen chemical heat pump.
Ultrason Sonochem
PUBLISHED: 07-28-2014
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The apparent kinetic of the ultrasound assisted liquid-phase dehydrogenation of isopropanol over Raney nickel catalyst was determined in the temperature range of 346-353K. Comparison of the effects of ultrasound and mechanical agitation on the isopropanol dehydrogenation was investigated. The ultrasound assisted dehydrogenation rate was significantly improved when relatively high power density was used. Moreover, the Isopropanol-Acetone-Hydrogen chemical heat pump (IAH-CHP) with ultrasound irradiation, in which the endothermic reaction is exposure to ultrasound, was proposed. A mathematical model was established to evaluate its energy performance in term of the coefficient of performance (COP) and the exergy efficiency, into which the apparent kinetic obtained in this work was incorporated. The operating performances between IAH-CHP with ultrasound and mechanical agitation were compared. The results indicated that the superiority of the IAH-CHP system with ultrasound was present even if more than 50% of the power of the ultrasound equipment was lost.
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Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk of Parkinson's disease: the impact of ethnicity and onset age.
Neurol. Sci.
PUBLISHED: 07-23-2014
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The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of this gene has been studied for the association with the disease extensively among worldwide populations, but the results were inconsistent and controversial. Here, to estimate the association between UCHL1 S18Y polymorphism and risk of PD in general population, we conducted a systematic meta-analysis by combining all available case-control subjects in Asian, European, and American populations, with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for UCHL1 S18Y polymorphism and PD were calculated using the Mantel-Haenszel method with a fixed- or random-effects model. Subgroup analysis was also performed in different onset age-matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95 % CI 1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95 % CI 1.005-1.157; p = 0.035). When stratifying for ethnicity, none association were observed in subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed that the polymorphism was not associated with the risk of PD. In conclusion, our meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with susceptibility to PD, and more studies are needed to confirm our conclusion.
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Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein.
Arch. Toxicol.
PUBLISHED: 07-22-2014
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Perfluoroalkyl acids (PFAAs) are highly persistent and bioaccumulative, resulting in their broad distribution in humans and the environment. The liver is an important target for PFAAs, but the mechanisms behind PFAAs interaction with hepatocyte proteins remain poorly understood. We characterized the binding of PFAAs to human liver fatty acid-binding protein (hL-FABP) and identified critical structural features in their interaction. The binding interaction of PFAAs with hL-FABP was determined by fluorescence displacement and isothermal titration calorimetry (ITC) assay. Molecular simulation was conducted to define interactions at the binding sites. ITC measurement revealed that PFOA/PFNA displayed a moderate affinity for hL-FABP at a 1:1 molar ratio, a weak binding affinity for PFHxS and no binding for PFHxA. Moreover, the interaction was mainly mediated by electrostatic attraction and hydrogen bonding. Substitution of Asn111 with Asp caused loss of binding affinity to PFAA, indicating its crucial role for the initial PFAA binding to the outer binding site. Substitution of Arg122 with Gly caused only one molecule of PFAA to bind to hL-FABP. Molecular simulation showed that substitution of Arg122 increased the volume of the outer binding pocket, making it impossible to form intensive hydrophobic stacking and hydrogen bonds with PFOA, and highlighting its crucial role in the binding process. The binding affinity of PFAAs increased significantly with their carbon number. Arg122 and Asn111 played a pivotal role in these interactions. Our findings may help understand the distribution pattern, bioaccumulation, elimination, and toxicity of PFAAs in humans.
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Determination of the total mass of antioxidant substances and antioxidant capacity per unit mass in serum using redox titration.
Bioinorg Chem Appl
PUBLISHED: 07-20-2014
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Objective. Total antioxidant capacity in serum is determined by the total mass of antioxidant substances and the antioxidant capacity per unit mass (average activity). The purpose of this study was to develop a method to determine the mass of antioxidant substances and average activity in human serum. Methods. Specimens of serum were collected from 100 subjects each from two different age groups: over 75 years old and 20-40 years old. The test serum was diluted into a series of concentrations, following which standard oxidation agents (KMnO4 for potassium permanganate method and I2 for iodimetry) were added to each concentration of serum, and the absorbance of the mixture (optical density, OD) was measured. The OD value and logarithm of dilution factor (lgT) at the end of the titration were obtained, from which the lgT could be considered as mass of antioxidant substances (M). Total antioxidant capacity (Ta) was calculated with the equation Ta = 100/(OD1 + 2 ? OD2 + 2 ? OD3 + 2 ? OD4 + OD5), and average activity (A) was calculated as A = Ta/M. Results. The potassium permanganate method generated similar results to the iodimetric method. Compared with the younger group, total antioxidant capacity in the over-75-year age group was found to be significantly reduced, along with a decrease in the mass of antioxidant substances and average activity levels in human serum. Conclusions. The approach described in this paper is suitable for determining the average activity and mass of antioxidant substances in human serum.
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Application of an LC-MS/MS method to the pharmacokinetics of TM-2, a potential antitumour agent, in rats.
Drug Test Anal
PUBLISHED: 07-14-2014
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TM-2 is a novel semi-synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of TM-2 in rat plasma. The biological samples were extracted with methyl tert-butyl ether and separated on a C18 column (50?mm?×?2.1?mm, 1.7?µm) using a mobile phase consisting of acetonitrile and 2?mM ammonium acetate. The standard curves were linear over the range 5-1000?ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from -1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM-2 to rats. The pharmacokinetics of TM-2 in rats were characterized by a large volume of distribution and a long half-life of elimination after single dose (4, 8, and 16?mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM-2. Copyright © 2014 John Wiley & Sons, Ltd.
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Immunohistochemical detection of the BRAF V600E mutation in melanoma patients with monoclonal antibody VE1.
Pathol. Int.
PUBLISHED: 07-08-2014
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A novel mutation-specific monoclonal antibody VE1 was generated to detect BRAF V600E mutation with immunohistochemistry. This study aims to investigate the sensitivity and specificity of immunohistochemistry compared with conventional Sanger sequencing and to evaluate whether IHC would become the routine screening method of BRAF V600E mutation. A total of 84 cases of melanoma lesion specimens were selected to make the tissue microarray and to perform IHC with VE1 antibody. Simultaneously Sanger sequencing was applied to test and verify. VE1 has a high specificity (100%) and sensitivity (72.2%), and the concordance between the two techniques is excellent (93.8% cases coherent and kappa?=?0.801). As a rapid, cost-effective method, IHC may become the routine diagnostic means for the detection of BRAF V600E mutation of malignant melanomas in the near future, and the recommended detection process is initial immunohistochemical staining for positive cases, followed by molecular techniques for negative or ambiguous cases.
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Rhodococcus kronopolitis sp. nov., a novel actinobacterium isolated from a millipede (Kronopolites svenhedind Verhoeff).
Antonie Van Leeuwenhoek
PUBLISHED: 07-08-2014
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A novel actinobacterium, designated strain NEAU-ML12(T), was isolated from a millipede (Kronopolites svenhedind Verhoeff), which was collected from Fenghuang Mountain in Wuchang, Heilongjiang Province, north China. The strain was characterized using a polyphasic approach. Strain NEAU-ML12(T) was found to have morphological and chemotaxonomic characteristics typical of the members of the genus Rhodococcus. 16S rRNA gene sequence similarity analysis showed that the strain NEAU-ML12(T) belongs to the genus Rhodococcus, and was most closely related to Rhodococcus tukisamuensis Mb8(T) (98.9 %) and Rhodococcus koreensis DNP505(T) (97.7 %). Phylogenetic analysis based on 16S rRNA gene sequences also demonstrated that strain NEAU-ML12(T) should be classified in the genus Rhodococcus, forming a distinct clade with R. tukisamuensis Mb8(T) supported by a 99 % bootstrap value. However, the DNA-DNA relatedness between strain NEAU-ML12(T) and R. tukisamuensis Mb8(T) was found to be 41.9 ± 0.7 %. Furthermore, strain NEAU-ML12(T) could also be differentiated from R. tukisamuensis Mb8(T) and other closely related strains (R. koreensis DNP505(T) and Rhodococcus maanshanensis M712(T)) by morphological and physiological characteristics. Therefore, it is proposed that strain NEAU-ML12(T) represents a novel species of the genus Rhodococcus, for which the name Rhodococcus kronopolitis sp. nov. is proposed. The type strain is NEAU-ML12(T) (=CGMCC 4.7145(T) = DSM 46702(T)).
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Band Gap Tunable Zn2SnO4 Nanocubes through Thermal Effect and Their Outstanding Ultraviolet Light Photoresponse.
Sci Rep
PUBLISHED: 07-02-2014
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This work presents a method for synthesis of high-yield, uniform and band gap tunable Zn2SnO4 nanocubes. These nanocubes can be further self-assembled into a series of novel nanofilms with tunable optical band gaps from 3.54 to 3.18?eV by simply increasing the heat treatment temperature. The Zn2SnO4 nanocube-nanofilm based device has been successfully fabricated and presents obviously higher photocurrent, larger photocurrent to dark current ratio than the previously reported individual nanostructure-based UV-light photodetectors, and could be used in high performance photodetectors, solar cells, and electrode materials for Li-ion battery.
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XAGE-1b expression is associated with the diagnosis and early recurrence of hepatocellular carcinoma.
Mol Clin Oncol
PUBLISHED: 06-26-2014
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XAGE-1b is a 470 bp transcript of the XAGE-1 gene, which belongs to the cancer-testis antigens that exhibit a restricted pattern of expression in normal tissues. Recently, the expression of XAGE-1b has been shown to be frequent in patients with hepatocellular carcinoma (HCC). However, the underlying mechanism is not fully understood. To investigate the role of XAGE-1b in HCC diagnosis and postoperative evaluation, the expression level of XAGE-1b was first examined in the tissue and peripheral blood of HCC patients and controls by using quantitative polymerase chain reaction. Subsequently, the associations between XAGE-1b and the clinical variables were assessed using ?(2) or Kaplan-Meier tests. The data showed that HCC tissues had increased XAGE-1b expression when compared to paired non-tumorous tissues. The blood samples from the HCC patients showed upregulated XAGE-1b mRNA, as compared to non-HCC patients. The patients with portal vein tumor thrombus or higher tumor-node metastasis stages (II~IV) were more likely to have increased levels of XAGE-1b mRNA. Furthermore, the 1-year recurrence rate of the patients with a high level of XAGE-1b mRNA was significantly greater compared to the patients with a low level. All these findings indicate that XAGE-1b is associated with the aggressive biological behavior of HCC cells and it may be a potential biomarker for HCC diagnosis and prognosis.
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Monitoring Plasmodium vivax chloroquine sensitivity along China-Myanmar border of Yunnan Province, China during 2008-2013.
Malar. J.
PUBLISHED: 06-26-2014
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Plasmodium vivax is the most widespread of the malaria parasites infecting human hosts. In malaria-eliminating settings, both imported and local malaria predominantly occurs in border areas, and most of them are P. vivax. Chloroquine (CQ) is the first-line drug for P. vivax treatment in China. To understand CQ sensitivity in P. vivax, in vivo monitoring of CQ resistance was conducted along the China-Myanmar border from 2008 to 2013.
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Thymic neuroendocrine tumors (paraganglioma and carcinoid tumors): a comparative immunohistochemical study of 46 cases.
Hum. Pathol.
PUBLISHED: 06-23-2014
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Twenty-two paragangliomas from different anatomical sites and 24 thymic neuroendocrine carcinomas (carcinoid tumors) were analyzed for traditional and novel immunohistochemical markers. In the paraganglioma group, there were 8 men and 14 women between the ages of 23 and 79 years (mean, 46 years). Their symptoms depended on the location of the tumor and included neck swelling and Horner syndrome for neck tumors, whereas abdominal and chest pain was present in tumors of the abdomen and mediastinum, respectively. One patient had Carney triad. In the carcinoid group, the patients were 20 men and 4 women between the ages of 25 and 78 years (mean, 48 years). These patients were symptomatic with chest pain, shortness of breath, and dyspnea. One patient presented with multiple endocrine neoplasia syndrome. Complete surgical resection was accomplished in all patients. The 46 neuroendocrine tumors were evaluated for GATA-3, pancytokeratin, thryoid transcription factor 1 (TTF-1), napsin A, chromogranin A, and synaptophysin. All paragangliomas were universally positive for chromogranin A and synaptophysin, but negative for pancytokeratin, TTF-1, and napsin A. GATA-3 was expressed in 12 (55%) of 22 tumors. The thymic neuroendocrine carcinomas (carcinoid tumors) were universally positive for pancytokeratin, but negative for GATA-3 and napsin A. Chromogranin A and synaptophysin were expressed in 92% and 88% of cases, respectively, and TTF-1 in 4 (17%) of 24 cases. Based on these results, we recommend that the workup of neuroendocrine tumors should include not only the conventional neuroendocrine markers and pancytokeratin but also other markers such as GATA-3 and TTF-1 in order to arrive at a better interpretation.
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LIM mineralization protein-1 suppresses TNF-? induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression.
J. Orthop. Res.
PUBLISHED: 06-18-2014
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Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF-? induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LV-shLMP-1 aggravated TNF-? mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-? induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-?B inhibition. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Geldanamycin mediates the apoptosis of gastric carcinoma cells through inhibition of EphA2 protein expression.
Oncol. Rep.
PUBLISHED: 06-04-2014
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The aim of the present study was to investigate the role of EphA2 in the carcinogenesis and progression of gastric carcinoma. Moreover, we aimed to determine the effect of geldanamycin (GA), an inhibitor of Hsp90, on the proliferation and apoptosis of human gastric carcinoma cells. Gastric carcinoma tissues, paired adjacent mucosa and paired normal mucosa were obtained from resected surgical specimens of gastric carcinoma, and EphA2 mRNA and protein levels were assessed by RT-PCR, immunohistochemistry and western blot analysis. FCM was used to detect cell cycle distribution and apoptosis. MGC803 cell proliferation and apoptosis were assessed by MTT and FCM, respectively. We found that EphA2 protein was increased in the carcinogenesis of gastric epithelial cells. Proliferation index (PI) was significantly upregulated following an increase in EphA2 expression in gastric carcinoma compared with dysplasia and normal samples, and was notably correlated with grade and lymph node metastasis. Knockdown of EphA2 increased the apoptosis rate and decreased the PI of MGC803 cells, which overexpressed the EphA2 protein. GA inhibited the cell proliferation of MGC803 cells in a dose- and time-dependent manner and induced cell apoptosis. In addition, GA decreased the EphA2 protein expression in MGC803 cells. Overexpression of EphA2 inhibited cell growth, blocked cells in the G0/G1 stage and increased cell apoptosis induced by GA in MGC803 cells. However, knockdown of EphA2 in MGC803 cells increased the apoptosis ratio induced by GA. In conclusion, EphA2 overexpression is an important characteristic in the carcinogenesis of gastric epithelial cells, followed by an increase in apoptosis and cell cycle arrest. Knockdown of EphA2 blocked MGC803 cell proliferation and induced cell apoptosis. In conclusion GA inhibits MGC803 cell proliferation and induces cell apoptosis by upregulating expression of EphA2.
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Development of andrographolide loaded PLGA microspheres: Optimization, characterization and in vitro-in vivo correlation.
Int J Pharm
PUBLISHED: 05-25-2014
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The purpose of this study was to develop a sustained-release drug delivery system based on the injectable PLGA microspheres loaded with andrographolide. The andrographolide loaded PLGA microspheres were prepared by emulsion solvent evaporation method with optimization of formulation using response surface methodology (RSM). Physicochemical characterization, in vitro release behavior and in vivo pharmacokinetics of the optimized formulation were then evaluated. The percent absorbed in vivo was determined by deconvolution using the Loo-Riegelman method, and then the in vitro-in vivo correlation (IVIVC) was established. Results showed that the microspheres were spherical with a smooth surface. Average particle size, entrapment efficiency and drug loading were found to be 53.18±2.11?m, 75.79±3.02% and 47.06±2.18%, respectively. In vitro release study showed a low initial burst release followed by a prolonged release up to 9 days and the release kinetics followed the Korsmeyer-Peppas model. After a single intramuscular injection, the microspheres maintained relatively high plasma concentration of andrographolide over one week. A good linear relationship was observed between the in vitro and in vivo release behavior (R(2)=0.9951). These results suggest the PLGA microspheres could be developed as a potential delivery system for andrographolide with high drug loading capacity and sustained drug release.
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Basic fibroblast growth factor promotes stem Leydig cell development and inhibits LH-stimulated androgen production by regulating microRNA expression.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 05-13-2014
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Leydig cells are the primary source of testosterone in the testes, and their steroidogenic function is strictly controlled by the hypothalamus-pituitary-gonad axis. Emerging evidence has indicated that fibroblast growth factors play a role in regulating stem Leydig cell development and steroidogenesis, but little is known about the regulatory mechanism. Using a seminiferous tubule culture system, we demonstrated that basic fibroblast growth factor (bFGF) can promote stem Leydig cell proliferation and commitment toward differentiation in testosterone-producing Leydig cells. However, these promoting effects decreased with an increase in the bFGF dose. Previous studies have reported that bFGF inhibits luteinizing hormone (LH)-stimulated androgen production by downregulating the mRNA expression of steroidogenic genes in immature Leydig cells. However, the expression levels of 677 microRNAs did not change significantly during the LH-mediated process of testosterone synthesis. Five microRNAs (miR-29a, -29c, -142-3p, -451 and -335) were identified, and their expression in immature Leydig cells was regulated simultaneously by bFGF and LH. These results suggested that the inhibition of LH-stimulated androgen production may be modulated by a change in bFGF-mediated microRNA expression, which further impacts the signaling pathway of testosterone biosynthesis and steroidogenic gene expression.
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QSAR studies of bioconcentration factors of polychlorinated biphenyls (PCBs) using DFT, PCS and CoMFA.
Chemosphere
PUBLISHED: 05-13-2014
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The bioconcentration factors (BCFs) of 58 polychlorinated biphenyls (PCBs) were modeled by quantitative structure-activity relationship (QSAR) using density functional theory (DFT), the position of Cl substitution (PCS) and comparative molecular field analysis (CoMFA) methods. All the models were robust and predictive, and especially, the best CoMFA model was significant with a correlation coefficient (R(2)) of 0.926, a cross-validation correlation coefficient (Q(2)) of 0.821 and a root mean square error estimated (RMSE) of 0.235. The results indicate that the electrostatic descriptors play a more significant role in BCFs of PCBs. Additionally, a test set was used to compare the predictive ability of our models to others, and results show that our CoMFA model present the lowest RMSE. Thus, the models obtain in this work can be used to predict the BCFs of remaining 152 PCBs without available experimental values.
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Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells.
BMC Biol.
PUBLISHED: 05-11-2014
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BackgroundEmerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cell (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated.ResultsWe demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers and enhanced the neuroectodermal specification once neural differentiation was initiated, thereby leading to more NPC generation. Similarly, the transcriptome analysis showed that HDACi increased the expression levels of ectodermal markers and triggered the NPC differentiation related pathways, while decreased the expression levels of endodermal and mesodermal markers. Furthermore, we documented that HDAC3 but not HDAC1 or HDAC2 was the critical regulator participating in NPC differentiation, and knockdown of HDAC3¿s cofactor SMRT exhibited a similar effect as HDAC3 on NPC generation.ConclusionsOur study reveals that HDACs, especially HDAC3, negatively regulate the differentiation of hPSCs towards NPCs at an earlier stage of neural differentiation. Moreover, HDAC3 might function by forming a repressor complex with its cofactor SMRT during this process. Thus our findings uncover an important epigenetic mechanism of HDAC3 in the differentiation of hPSCs towards NPCs.
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Damage of hippocampal neurons in rats with chronic alcoholism.
Neural Regen Res
PUBLISHED: 05-10-2014
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Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear membrane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.
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Influence of scan duration on the estimation of pharmacokinetic parameters for breast lesions: a study based on CAIPIRINHA-Dixon-TWIST-VIBE technique.
Eur Radiol
PUBLISHED: 05-09-2014
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To evaluate the influence of scan duration on pharmacokinetic parameters and their performance in differentiating benign from malignant breast lesions.
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Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile.
Nature
PUBLISHED: 05-04-2014
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The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7?-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.
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The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages.
Int J Pharm
PUBLISHED: 04-03-2014
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Endomorphins, although they have high analgesic activity and few undesirable side effects, are not in clinical use because of the blood-brain barrier (BBB). One promising solution is to use cell-penetrating peptides (CPPs). CPPs have the ability to translocate cell membranes and have been successfully applied for delivery of therapeutic molecules across the BBB. However, little is known about the transport efficiency of different conjugation strategies between cargo and CPPs. In this study, endomorphin-1 (EM-1) was conjugated with SynB3, an efficient CPP-carrier, via amide, maleimide and disulfide linkages. The delivery efficiency of three linkers was compared in terms of pharmacodynamics and in vitro metabolic stability. Near-infrared fluorescent and fluorescent microscopy experiments were applied to detect the brain uptake and distribution of CPP delivery qualitatively and quantitatively. After the most successful linkage was screened out, the further mechanisms were discussed. We concluded that compared with the other two linkages, the disulfide bond was the most efficient linkage to deliver EM-1 across the BBB and confirmed that it could be reduced at physiological conditions in the brain and release its active form. These findings indicate that for those who need to release a free drug in the brain and maintain activity, a disulfide bond might be the most efficient linkage across the BBB.
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Cassava genome from a wild ancestor to cultivated varieties.
Nat Commun
PUBLISHED: 03-20-2014
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Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.
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Characterization of in vitro metabolites of TM-2, a potential antitumor drug, in rat, dog and human liver microsomes using liquid chromatography/tandem mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 02-18-2014
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TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-?-diacetoxy-2-?-benzoyloxy-5-?,20-epoxy-1,13-?-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semi-synthetic taxane derivative. Our previous study demonstrated that it is a promising taxane derivative. The in vitro comparative metabolic profile of a drug between animals and humans is a key issue that should be investigated at early stages of drug development to better select drug candidates. In this study, the in vitro metabolic pathways of TM-2 in rat, dog and human liver microsomes were established and compared.
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TNF-like ligand 1A is associated with the pathogenesis of psoriasis vulgaris and contributes to IL-17 production in PBMCs.
Arch. Dermatol. Res.
PUBLISHED: 01-28-2014
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TNF-like ligand 1A (TL1A), a newly identified member of the TNF superfamily, has been proved as an important mediator of inflammation and critically involved in the pathogenesis of rheumatoid arthritis and several other autoimmune diseases. The aim of our study was to determine the possible role of TL1A in the pathogenesis of psoriasis. In this study, serum levels of TL1A in patients with psoriasis vulgaris (PV) and atopic dermatitis (AD) were detected by enzyme-linked immunosorbent assay (ELISA). Then, peripheral blood mononuclear cells (PBMCs) from patients with PV were isolated, the mRNA expression of TL1A was measured by real-time quantitative PCR. The effects of TL1A on the production of T cell cytokines, such as IL-17, IFN-?, IL-4 and IL-10 in PBMCs were determined. We demonstrated that serum TL1A levels were significantly elevated in patients with PV but not in patients with AD. Besides, the high serum TL1A levels in patients with PV decreased after treatment. PBMCs derived from psoriatic patients showed significantly increased TL1A mRNA levels. Soluble TL1A synergized with IL-23 to stimulate PBMCs from patients with PV to produce IL-17. Taken together, these findings strongly suggest that TL1A may play a role in the pathogenesis of PV.
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Specific growth inhibition of ErbB2?expressing human breast cancer cells by genetically modified NK?92 cells.
Oncol. Rep.
PUBLISHED: 01-13-2014
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The natural killer cell line NK?92 shows great cytotoxicity against various types of cancer. Several types of solid tumor cells, however, can effectively resist NK-mediated lysis by interaction of major histocompatibility complex (MHC) molecules with NK cell inhibitory receptors. To generate a eukaryotic expression vector encoding chimeric antigen receptor scFv anti-erbB2-CD28-? and to investigate the expression and action of this chimeric antigen receptor in cancer cells both in vitro and in vivo, NK?92 cells were genetically modified with an scFv anti-erbB2-CD28-? chimeric recep-tor by optimized electro-poration using the Amaxa Nucleofector system. The expression of the chimeric receptor was evaluated by RT-PCR and immunofluorescence. The ability of the genetically modified NK?92 cells to induce cell death in tumor targets was assessed in vitro and in vivo. The transduced NK?92-anti-erbB2 scFv-CD28-? cells expressing high levels of the fusion protein on the cell surface were analyzed by fluorescence-activated cell-sorting (FACS) analysis. These cells specifically enhanced the cell death of the erbB2?expressing human breast cancer cell lines MDA-MB-453 and SKBr3. Furthermore, adoptive transfer of genetically modified NK?92 cells specifically reduced tumor size and lung metastasis of nude mice bearing established MDA-MB-453 cells, and significantly enhanced the survival period of these mice. The genetically modified NK?92 cells significantly enhanced the killing of erbB2?expressing cancer and may be a novel therapeutic strategy for erbB2?expressing cancer cells.
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Clinical outcome of small hepatocellular carcinoma after different treatments: a meta-analysis.
World J. Gastroenterol.
PUBLISHED: 01-04-2014
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To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).
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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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