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Find video protocols related to scientific articles indexed in Pubmed.
[Cellular and humoral immunity in preterm infants of different gestational ages.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To investigate the characteristics of immune function in newborn infants of different gestational ages.
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[Changes in mitochondria fusion protein-2 hepatic expression in conditions of liver cirrhosis and acute on chronic liver failure].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 11-05-2014
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To determine the differential protein and mRNA expressions of mitochondria fusion protein-2 (Mfn2) in hepatic tissues in conditions of cirrhosis and acute on chronic liver failure using rat model systems,and to determine the correlative effects on production of adenosine triphosphate (ATP) and reactive oxygen species (ROS).
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[Influencing factors for severity of bronchopulmonary dysplasia in preterm infants].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 10-26-2014
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To explore the influencing factors for the severity of bronchopulmonary dysplasia (BPD) in preterm infants.
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Simultaneous targeting of PI3K? and a PI3K?-dependent MEK1/2-Erk1/2 pathway for therapy in pediatric B-cell acute lymphoblastic leukemia.
Oncotarget
PUBLISHED: 10-15-2014
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B cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy diagnosed in children, and blockade of the abnormally activated PI3K? displayed promising outcomes in B cell acute or chronic leukemias, but the mechanisms are not well understood. Here we report a novel PI3K? selective inhibitor X-370, which displays distinct binding mode with p110? and blocks constitutively active or stimulus-induced PI3K? signaling. X-370 significantly inhibited survival of human B cell leukemia cells in vitro, with associated induction of G1 phase arrest and apoptosis. X-370 abrogated both Akt and Erk1/2 signaling via blockade of PDK1 binding to and/or phosphorylation of MEK1/2. Forced expression of a constitutively active MEK1 attenuated the antiproliferative activity of X-370. X-370 preferentially inhibited the survival of primary pediatric B-ALL cells displaying PI3K?-dependent Erk1/2 phosphorylation, while combined inhibition of PI3K? and MEK1/2 displayed enhanced activity. We conclude that PI3K? inhibition led to abrogation of both Akt and Erk1/2 signaling via a novel PI3K-PDK1/MEK1/2-Erk1/2 signaling cascade, which contributed to its efficacy against B-ALL. These findings support the rationale for clinical testing of PI3K? inhibitors in pediatric B-ALL and provide insights needed to optimize the therapeutic strategy.
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Adaptations to Climate-Mediated Selective Pressures in Sheep.
Mol. Biol. Evol.
PUBLISHED: 09-23-2014
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Following domestication, sheep (Ovis aries) have become essential farmed animals across the world through adaptation to a diverse range of environments and varied production systems. Climate-mediated selective pressure has shaped phenotypic variation and has left genetic "footprints" in the genome of breeds raised in different agroecological zones. Unlike numerous studies that have searched for evidence of selection using only population genetics data, here, we conducted an integrated coanalysis of environmental data with single nucleotide polymorphism (SNP) variation. By examining 49,034 SNPs from 32 old, autochthonous sheep breeds that are adapted to a spectrum of different regional climates, we identified 230 SNPs with evidence for selection that is likely due to climate-mediated pressure. Among them, 189 (82%) showed significant correlation (P ? 0.05) between allele frequency and climatic variables in a larger set of native populations from a worldwide range of geographic areas and climates. Gene ontology analysis of genes colocated with significant SNPs identified 17 candidates related to GTPase regulator and peptide receptor activities in the biological processes of energy metabolism and endocrine and autoimmune regulation. We also observed high linkage disequilibrium and significant extended haplotype homozygosity for the core haplotype TBC1D12-CH1 of TBC1D12. The global frequency distribution of the core haplotype and allele OAR22_18929579-A showed an apparent geographic pattern and significant (P ? 0.05) correlations with climatic variation. Our results imply that adaptations to local climates have shaped the spatial distribution of some variants that are candidates to underpin adaptive variation in sheep.
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[Nutritional risk assessment in patients with chronic liver disease].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To use the European Nutritional Risk Screening (NRS)-2002 survey tool to investigate nutritional risk associated to different degrees of liver disease and to assess its ability to identify the nutritional risk of hospitalized patients with chronic liver disease.
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Stromal Interaction Molecule 1 (STIM1) and Orai1 Mediate Histamine-evoked Calcium Entry and Nuclear Factor of Activated T-cells (NFAT) Signaling in Human Umbilical Vein Endothelial Cells.
J. Biol. Chem.
PUBLISHED: 09-04-2014
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Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca(2+) mobilization by releasing Ca(2+) from the endoplasmic reticulum and eliciting Ca(2+) entry across the plasma membrane. Herein, we show that histamine-evoked Ca(2+) entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca(2+) release-activated Ca(2+) (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca(2+) entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca(2+) influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca(2+) mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation.
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Prenatally diagnosed fetal split-hand/foot malformations often accompany a spectrum of anomalies.
J Ultrasound Med
PUBLISHED: 08-27-2014
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The purpose of this series was to identify cases that appeared on sonography to be split-hand/foot malformations (SHFMs) in fetuses and correlate the sonographic findings, including 2-dimensional (2D) and 3-dimensional (3D) sonography, to outcomes. A retrospective review was conducted of sonographic studies from 2002 to 2012 at 2 fetal care centers. Data were collected with respect to the morphologic characteristics of split-hand/foot abnormalities, the utility of 3D sonography, associated anatomic abnormalities, family histories, gestational ages at diagnosis, fetal outcomes, karyotype, and autopsy results. Ten cases were identified with gestational ages ranging from 15 to 29 weeks. Three-dimensional sonography was helpful in defining anatomy in 7 of 9 cases in which it was performed. Bilateral SHFMs were found in 7 cases (3 cases involving both hands and feet, 2 cases isolated to hands, and 2 cases isolated to feet), whereas 3 cases showed unilateral split-hand malformations. Associated anatomic anomalies were present in 6 cases, and 4 of these had recognized syndromes, including 2 with abnormal karyotypes, specifically, del(22q11) and del(7q31). Two cases occurred in the context of a positive family history of SHFM. Three cases were delivered at term, and 7 cases were electively terminated. In conclusion, SHFMs often occur with a broad range of chromosomal abnormalities, single-gene disorders, and other congenital anomalies. Some apparent SHFMs turn out to be other limb anomalies, such as complex syndactyly. Prenatal screening using 2D sonography can identify SHFMs, and 3D sonography often further clarifies them.
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[Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 08-21-2014
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To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants.
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Comparison of oxidation resistance of UHMWPE and POM in H2O2 solution from ReaxFF reactive molecular dynamics simulations.
J Phys Chem B
PUBLISHED: 08-18-2014
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The oxidation mechanism of ultra-high-molecular-weight polyethylene (UHMWPE) and polyoxymethylene (POM) in hydrogen peroxide solution was investigated by molecular dynamics (MD) simulations via reactive force field (ReaxFF) method. MD results from ReaxFF suggested that UHMWPE provided better antioxidation activity at high temperature (>373 K) than its POM counterpart in the same concentration of hydrogen peroxide solution. Furthermore, POM was relatively more susceptible to erosion and swelling because of the infiltration of H2O2 solution. Calculations of the diffusion coefficient at different temperatures permit further understanding of the chemical phenomena involved in the level of oxidation in the course of MD simulations. Results of the simulations are generally consistent with the previous experimental available in literature. The simulations also provide new insights into understanding the mechanism resulting oxidation products among the interested polymers.
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Genome-wide linkage disequilibrium in nine-spined stickleback populations.
G3 (Bethesda)
PUBLISHED: 08-12-2014
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Variation in the extent and magnitude of genome-wide linkage disequilibrium (LD) among populations residing in different habitats has seldom been studied in wild vertebrates. We used a total of 109 microsatellite markers to quantify the level and patterns of genome-wide LD in 13 Fennoscandian nine-spined stickleback (Pungitius pungitius) populations from four (viz. marine, lake, pond, and river) different habitat types. In general, high magnitude (D' > 0.5) of LD was found both in freshwater and marine populations, and the magnitude of LD was significantly greater in inland freshwater than in marine populations. Interestingly, three coastal freshwater populations located in close geographic proximity to the marine populations exhibited similar LD patterns and genetic diversity as their marine neighbors. The greater levels of LD in inland freshwater compared with marine and costal freshwater populations can be explained in terms of their contrasting demographic histories: founder events, long-term isolation, small effective sizes, and population bottlenecks are factors likely to have contributed to the high levels of LD in the inland freshwater populations. In general, these findings shed new light on the patterns and extent of variation in genome-wide LD, as well as the ecological and evolutionary factors driving them.
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Ni12P5 nanoparticles as an efficient catalyst for hydrogen generation via electrolysis and photoelectrolysis.
ACS Nano
PUBLISHED: 07-30-2014
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The exploitation of a low-cost catalyst is desirable for hydrogen generation from electrolysis or photoelectrolysis. In this study we have demonstrated that nickel phosphide (Ni12P5) nanoparticles have efficient and stable catalytic activity for the hydrogen evolution reaction. The catalytic performance of Ni12P5 nanoparticles is favorably comparable to those of recently reported efficient nonprecious catalysts. The optimal overpotential required for 20 mA/cm(2) current density is 143 ± 3 mV in acidic solution (H2SO4, 0.5 M). The catalytic activity of Ni12P5 is likely to be correlated with the charged natures of Ni and P. Ni12P5 nanoparticles were introduced to silicon nanowires, and the power conversion efficiency of the resulting composite is larger than that of silicon nanowires decorated with platinum particles. This result demonstrates the promising application potential of metal phosphide in photoelectrochemical hydrogen generation.
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Metal-Free Oxidative Radical Addition of Carbonyl Compounds to ?,?-Diaryl Allylic Alcohols: Synthesis of Highly Functionalized Ketones.
Chemistry
PUBLISHED: 07-18-2014
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A metal-free direct alkylation of simple carbonyl compounds (ketones, esters, and amides) with ?,?-diaryl allylic alcohols is described. The protocol provides facile access to highly functionalized dicarbonyl ketones by a radical addition/1,2-aryl migration cascade. The regioselectivity of the reaction was precisely controlled by the nature of the carbonyl compound.
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Y chromosome haplotype diversity of domestic sheep (Ovis aries) in northern Eurasia.
Anim. Genet.
PUBLISHED: 07-15-2014
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Variation in two SNPs and one microsatellite on the Y chromosome was analyzed in a total of 663 rams representing 59 breeds from a large geographic range in northern Eurasia. SNPA-oY1 showed the highest allele frequency (91.55%) across the breeds, whereas SNPG-oY1 was present in only 56 samples. Combined genotypes established seven haplotypes (H4, H5, H6, H7, H8, H12 and H19). H6 dominated in northern Eurasia, and H8 showed the second-highest frequency. H4, which had been earlier reported to be absent in European breeds, was detected in one European breed (Swiniarka), whereas H7, which had been previously identified to be unique to European breeds, was present in two Chinese breeds (Ninglang Black and Large-tailed Han), one Buryatian (Transbaikal Finewool) and two Russian breeds (North Caucasus Mutton-Wool and Kuibyshev). H12, which had been detected only in Turkish breeds, was also found in Chinese breeds in this work. An overall low level of haplotype diversity (median h = 0.1288) was observed across the breeds with relatively higher median values in breeds from the regions neighboring the Near Eastern domestication center of sheep. H6 is the dominant haplotype in northwestern and eastern China, in which the haplotype distribution could be explained by the historical translocations of the H4 and H8 Y chromosomes to China via the Mongol invasions followed by expansions to northwestern and eastern China. Our findings extend previous results of sheep Y chromosomal genetic variability and indicate probably recent paternal gene flows between sheep breeds from distinct major geographic regions.
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Metal-free oxidative direct C(sp³)-H bond functionalization of ethers with ?,?-diaryl allylic alcohols.
Chem. Commun. (Camb.)
PUBLISHED: 07-15-2014
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A metal-free method for direct C(sp(3))-H bond functionalization of simple ethers with ?,?-diaryl allylic alcohols is described. The established protocol provides facile access to ?-aryl-?-oxyalkylated carbonyl ketones via radical addition and a 1,2-aryl migration cascade process. An application of the product has been demonstrated in the synthesis of a serotonin antagonist.
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Indoor air pollution from solid fuels and peripheral Blood DNA methylation: Findings from a population study in Warsaw, Poland.
Environ. Res.
PUBLISHED: 07-01-2014
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DNA methylation is a potential mechanism linking indoor air pollution to adverse health effects. Fetal and early-life environmental exposures have been associated with altered DNA methylation and play a critical role in progress of diseases in adulthood. We investigated whether exposure to indoor air pollution from solid fuels at different lifetime periods was associated with global DNA methylation and methylation at the IFG2/H19 imprinting control region (ICR) in a population-based sample of non-smoking women from Warsaw, Poland. Global methylation and IFG2/H19 ICR methylation were assessed in peripheral blood DNA from 42 non-smoking women with Luminometric Methylation Assay (LUMA) and quantitative pyrosequencing, respectively. Linear regression models were applied to estimate associations between indoor air pollution and DNA methylation in the blood. Compared to women without exposure, the levels of LUMA methylation for women who had ever exposed to both coal and wood were reduced 6.70% (95% CI: -13.36, -0.04). Using both coal and wood before age 20 was associated with 6.95% decreased LUMA methylation (95% CI: -13.79, -0.11). Further, the negative correlations were more significant with exposure to solid fuels for cooking before age 20. There were no clear associations between indoor solid fuels exposure before age 20 and through the lifetime and IFG2/H19 ICR methylation. Our study of non-smoking women supports the hypothesis that exposure to indoor air pollution from solid fuels, even early-life exposure, has the capacity to modify DNA methylation that can be detected in peripheral blood.
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GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells.
Mol Biosyst
PUBLISHED: 07-01-2014
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Schizophrenia is a debilitating mental disorder. Currently, the lack of disease biomarkers to support objective laboratory tests constitutes a bottleneck in the clinical diagnosis of schizophrenia. Here, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was applied to characterize the metabolic profile of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia. Multivariate statistical analysis was used to visualize group discrimination and to identify differentially expressed metabolites in schizophrenia subjects relative to healthy controls. The multivariate statistical analysis demonstrated that the schizophrenia group was significantly distinguishable from the control group. In total, 18 metabolites responsible for the discrimination between the two groups were identified. These differential metabolites were mainly involved in energy metabolism, oxidative stress and neurotransmitter metabolism. A simplified panel of PBMC metabolites consisting of pyroglutamic acid, sorbitol and tocopherol-? was identified as an effective diagnostic tool, yielding an area under the receiver operating characteristic curve (AUC) of 0.82 in the training samples (45 schizophrenia subjects and 50 healthy controls) and 0.71 in the test samples (24 schizophrenic patients and 35 healthy controls). Taken together, these findings help to develop diagnostic tools for schizophrenia.
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Tungsten sulfide enhancing solar-driven hydrogen production from silicon nanowires.
ACS Appl Mater Interfaces
PUBLISHED: 06-16-2014
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Tungsten sulfides, including WS2 (crystalline) and WS3 (amorphous), were introduced to silicon nanowires, and both can promote the photoelectrochemical hydrogen production of silicon nanowires. In addition, more enhancement of energy conversion efficiency can be achieved by the loading of WS3, in comparison with loading of WS2. Polarization curves of WS3 and WS2 suggest that WS3 has higher catalytic activity in the hydrogen evolution reaction than WS2, affording higher energy conversion efficiency in silicon nanowires decorated with WS3. The higher electrocatalytic activity of WS3 correlates with the amorphous structure of WS3 and larger surface area of WS3, which result in more active sites in comparison with crystalline WS2.
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Hypericum japonicum Thunb. ex Murray: phytochemistry, pharmacology, quality control and pharmacokinetics of an important herbal medicine.
Molecules
PUBLISHED: 06-06-2014
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Hypericum japonicum Thunb. ex Murray is mainly distributed throughout Asia, Oceania and North America and is used as an important herbal medicine. H. japonicum contains many valuable secondary metabolites, such as flavonoids, phloroglucinols and xanthones and has hepatoprotective, anti-tumor, antibacterial, antiviral, and antioxidant activities and effects on the cardiovascular system and immunity. Coupled with phytochemical and pharmacological research, a series of analytical methods have been developed to evaluate the quality of H. japonicum based on its bioactive components. A pharmacokinetics study involved the absorption of two main flavonoids of H. japonicum in rats. This review aims to present an up-to-date and comprehensive overview of the phytochemistry, pharmacology, quality control and pharmacokinetics of H. japonicum, which should be useful for the greater development of H. japonicum, especially in the development of new drugs and therapeutics for various diseases.
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Radical phosphinylation of ?,?-diaryl allylic alcohols with concomitant 1,2-aryl migration.
Chem. Commun. (Camb.)
PUBLISHED: 06-05-2014
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A novel radical phosphinylation of ?,?-diaryl allylic alcohols with arylphosphine oxides was described for the direct preparation of ?-aryl-?-phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration. In this reaction, formation of new C(Ar)-C(sp(3)) and C(sp(3))-P bonds was observed.
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Synthesis of 1,4-dihydroquinoline derivatives under transition-metal-free conditions and their diverse applications.
Org. Biomol. Chem.
PUBLISHED: 05-20-2014
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A transition-metal-free process for the synthesis of 1,4-dihydroquinoline derivatives starting from simple enaminones with aldehydes via intermolecular cascade cyclization in a one-pot protocol is developed. This methodology affords a variety of products in moderate to good yields. Particularly, the use of the enaminone fragment in 1,4-dihydroquinoline derivatives 3 as a leaving group for further diverse applications with C-nucleophiles is proved to be feasible.
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Relation of diabetes to coronary artery ectasia: A meta-analysis study.
Anadolu Kardiyol Derg
PUBLISHED: 05-02-2014
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Previous studies have shown a significant negative association between diabetes and abdominal aortic aneurysm. However, the relation of diabetes to coronary artery ectasia (CAE) has not well established. The aim of the current study was to conduct a systemic review for evaluating the relationship between diabetes and CAE.
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Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma.
Diagn Pathol
PUBLISHED: 04-17-2014
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Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence and to give adequate treatment for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the application of miR-143 and miR-215 in the diagnosis of HCC.
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The effects of Ti carbonization on the nucleation and oriented growth of diamond films on cemented carbide.
ACS Appl Mater Interfaces
PUBLISHED: 03-26-2014
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To better understand the influence of carbonization of the Ti interlayer on diamond nucleation and growth, a series of Ti/diamond composite films were deposited on cemented carbide (WC:Co) substrates using a two-step deposition technique. The microstructural properties of the composite films were then characterized by scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy, and their tribological properties were evaluated using a ball-on-disc tester and a metalloscope. The results showed that differences in carbonization for five Ti interlayers of different thicknesses led to variations in the preferred orientations of the TiC layers and in the subsequent nucleation and oriented growth of diamond. This suggests that Ti carbonization significantly influences the nucleation and growth of diamond and subsequently causes variations in the tribological properties of the produced diamond films.
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GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.
Biochem. J.
PUBLISHED: 03-07-2014
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GDF15 (growth/differentiation factor 15), a novel member of the TGF? (transforming growth factor ?) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main ?-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGF?R2 (TGF? receptor 2), not TGF?R1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGF?RII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGF?RII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.
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Biphasic modulation of ?-ENaC expression by lipopolysaccharide in vitro and in vivo.
Mol Med Rep
PUBLISHED: 03-03-2014
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Acute lung injury (ALI) is characterized by pulmonary edema, in which the epithelial sodium channel (ENaC) has a critical role in the clearance of edema ?uid from the alveolar space. Lipopolysaccharide (LPS), frequently employed to induce ALI in experimental animal models, has been reported to regulate ENaC expression and alveolar fluid clearance. The role of LPS in regulating ENaC expression is currently controversial, with increases and decreases reported in ENaC expression in response to LPS treatment, as well as reports that ENaC expression is not affected by LPS induction. The present study aimed to systematically analyze the regulation of ??ENaC expression in LPS models of ALI at different pathological stages in vitro and in vivo. ENaC expression was observed to increase ?8 h after LPS treatment, and to decrease thereafter. This finding may explain the contradictory data regarding ??ENaC expression in response to LPS in the lung. The results of the present study, in combination with those of previous studies, indicate that the modulation of ?-ENaC expression may not be a direct genetic response to LPS exposure, but a general response of the lung to the pathological changes associated with inflammation, hypoxia and endothelial and epithelial damage involved in the development of ALI. The findings of this study may have potential clinical significance for understanding the pathogenesis of ALI and improving patient outcome.
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HSP90 inhibitor AUY922 abrogates up-regulation of RTKs by mTOR inhibitor AZD8055 and potentiates its antiproliferative activity in human breast cancer.
Int. J. Cancer
PUBLISHED: 02-28-2014
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mTOR inhibition led to activation of upstream receptor tyrosine kinases (RTKs) and AKT, which may attenuate the efficacy of mTOR kinase inhibitors. We sought to discover efficient drug combination with mTOR inhibitors by elucidating the survival feedback loops induced by mTOR inhibition in breast cancer. The feedback signaling upon treatment of mTOR inhibitor AZD8055 was determined and the combinatorial activity of AZD8055 and HSP90 inhibitor AUY922 in cell signaling and proliferation were detected. Treatment of breast cancer T47D cells with AZD8055 induced activation of AKT and phosphatidylinositol 3-kinase (PI3K), which was accompanied with increase in expression of multiple upstream proteins including EGFR, HER2, HER3 and IRS-1. Different RTKs were revealed to be responsible for the reactivation of AKT by AZD8055 in different breast cancer cell lines. Down-regulation of these proteins differentially enhanced the antiproliferative activity of AZD8055. AZD8055 and AUY922 displayed synergistic effect against a panel of human breast cancer cells irrespective their genotype, which was associated with enhanced cell cycle arrest and inhibition of DNA synthesis. AUY922 destabilized multiple tested tyrosine kinases and abrogated activation of AKT induced by AZD8055. AZD8055 also inhibited up-regulation of HSP70 and HSP27 upon AUY922 treatment. Cotreatment of these two drugs demonstrated synergistic activity against triple negative MDA-MB-468 xenograft without enhanced toxicity. The combination of AZD8055 and AUY922 demonstrated synergistic activity against various types of breast cancer and established a mechanistic rationale for a combination approach using catalytic mTOR kinase inhibitor and HSP90 inhibitor in the treatment of breast cancer.
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Association of alkaline phosphatase with isolated coronary artery ectasia.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 02-24-2014
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It has been shown that alkaline phosphatase (ALP) is a reliable marker for cardiovascular events and mortality. However, there is no data available regarding the association of ALP with isolated coronary artery ectasia (CAE). The aim of the present study was to assess the serum ALP activity in isolated CAE.
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Identification of major and minor QTL for ecologically important morphological traits in three-spined sticklebacks (Gasterosteus aculeatus).
G3 (Bethesda)
PUBLISHED: 02-18-2014
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Quantitative trait locus (QTL) mapping studies of Pacific three-spined sticklebacks (Gasterosteus aculeatus) have uncovered several genomic regions controlling variability in different morphological traits, but QTL studies of Atlantic sticklebacks are lacking. We mapped QTL for 40 morphological traits, including body size, body shape, and body armor, in a F2 full-sib cross between northern European marine and freshwater three-spined sticklebacks. A total of 52 significant QTL were identified at the 5% genome-wide level. One major QTL explaining 74.4% of the total variance in lateral plate number was detected on LG4, whereas several major QTL for centroid size (a proxy for body size), and the lengths of two dorsal spines, pelvic spine, and pelvic girdle were mapped on LG21 with the explained variance ranging from 27.9% to 57.6%. Major QTL for landmark coordinates defining body shape variation also were identified on LG21, with each explaining ?15% of variance in body shape. Multiple QTL for different traits mapped on LG21 overlapped each other, implying pleiotropy and/or tight linkage. Thus, apart from providing confirmatory data to support conclusions born out of earlier QTL studies of Pacific sticklebacks, this study also describes several novel QTL of both major and smaller effect for ecologically important traits. The finding that many major QTL mapped on LG21 suggests that this linkage group might be a hotspot for genetic determinants of ecologically important morphological traits in three-spined sticklebacks.
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The Biomimetic Shark Skin Optimization Design Method for Improving Lubrication Effect of Engineering Surface.
J Tribol
PUBLISHED: 02-17-2014
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Nature has long been an important source of inspiration for mankind to develop artificial ways to mimic the remarkable properties of biological systems. In this work, a new method was explored to fabricate a biomimetic engineering surface comprising both the shark-skin, the shark body denticle, and rib morphology. It can help reduce water resistance and the friction contact area as well as accommodate lubricant. The lubrication theory model was established to predict the effect of geometric parameters of a biomimetic surface on tribological performance. The model has been proved to be feasible to predict tribological performance by the experimental results. The model was then used to investigate the effect of the grid textured surface on frictional performance of different geometries. The investigation was aimed at providing a rule for deriving the design parameters of a biomimetic surface with good lubrication characteristics. Results suggest that: (i) the increase in depression width ratio [Formula: see text] decreases its corresponding coefficient of friction, and (ii) the small coefficient of friction is achievable when [Formula: see text] is beyond 0.45. Superposition of depth ratio ? and angle's couple under the condition of [Formula: see text]?
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Clinical features of coronary artery ectasia in the elderly.
J Geriatr Cardiol
PUBLISHED: 02-08-2014
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To investigate the incidence, imaging and clinical characteristics in elderly patients with coronary artery ectasia (CAE).
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Differential expression of serum miR-126, miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer.
Chin. J. Cancer Res.
PUBLISHED: 02-07-2014
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MicroRNAs (miRNAs) have potential as diagnostic biomarkers in cancer. Evaluation of the association between miRNA expression patterns and early detection of liver metastasis in colorectal cancer (CRC) has not been reported.
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Synthetic lethal therapy for KRAS mutant non-small-cell lung carcinoma with nanoparticle-mediated CDK4 siRNA delivery.
Mol. Ther.
PUBLISHED: 02-05-2014
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The KRAS mutation is present in ~20% of lung cancers and has not yet been effectively targeted for therapy. This mutation is associated with a poor prognosis in non-small-cell lung carcinomas (NSCLCs) and confers resistance to standard anticancer treatment drugs, including epidermal growth factor receptor tyrosine kinase inhibitors. In this study, we exploited a new therapeutic strategy based on the synthetic lethal interaction between cyclin-dependent kinase 4 (CDK4) downregulation and the KRAS mutation to deliver micellar nanoparticles (MNPs) containing small interfering RNA targeting CDK4 (MNPsiCDK4) for treatment in NSCLCs harboring the oncogenic KRAS mutation. Following MNPsiCDK4 administration, CDK4 expression was decreased, accompanied by inhibited cell proliferation, specifically in KRAS mutant NSCLCs. However, this intervention was harmless to normal KRAS wild-type cells, confirming the proposed mechanism of synthetic lethality. Moreover, systemic delivery of MNPsiCDK4 significantly inhibited tumor growth in an A549 NSCLC xenograft murine model, with depressed expression of CDK4 and mutational KRAS status, suggesting the therapeutic promise of MNPsiCDK4 delivery in KRAS mutant NSCLCs via a synthetic lethal interaction between KRAS and CDK4.
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Associations between serum-intact parathyroid hormone, serum 25-hydroxyvitamin D, oral vitamin D analogs and metabolic syndrome in peritoneal dialysis patients: a multi-center cross-sectional study.
Perit Dial Int
PUBLISHED: 02-04-2014
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Although previous studies have suggested associations between serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MS) in the general population, these associations are still uncharacterized in peritoneal dialysis (PD) patients.
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Delivery of antibiotics with polymeric particles.
Adv. Drug Deliv. Rev.
PUBLISHED: 01-29-2014
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Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection.
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2,4-Dihydroxypyrimidine is a potential urinary metabolite biomarker for diagnosing bipolar disorder.
Mol Biosyst
PUBLISHED: 01-24-2014
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Bipolar disorder (BD) is a common and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. Here, we used a gas chromatography-mass spectrometry (GC-MS) based metabonomic method to characterize the urinary metabolic profiling of BD subjects and healthy controls to identify and validate urinary metabolite biomarkers for BD. Multivariate statistical analysis was used to visualize group discrimination and identify differentially expressed urinary metabolites in BD subjects relative to the healthy controls. Multivariate statistical analysis showed that the BD group was significantly distinguishable from the healthy control. Totally, 37 urinary metabolites responsible for discriminating BD subjects from healthy controls were identified. Interestingly, of 37 differential metabolites, 2,4-dihydroxypyrimidine was identified as an effective diagnostic biomarker for BD, yielding an area under the receiver operating characteristic curve (AUC) of 0.889 in the training samples (45 BD subjects and 61 healthy controls) and 0.805 in the test samples (26 BD subjects and 33 healthy controls). Our findings suggest that 2,4-dihydroxypyrimidine is a promising candidate urinary biomarker for BD, which may facilitate development of a urine-based diagnostic test for BD.
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Internal compared with external drainage of pancreatic duct during pancreaticoduodenectomy: a retrospective study.
Chin. J. Cancer Res.
PUBLISHED: 01-22-2014
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To compare internal with external drainage of the pancreatic duct during pancreaticoduodenectomy with regard to the incidence of postoperative pancreatic fistula (POPF) and other complications.
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Association of XRCC1 gene polymorphisms with susceptibility to gastric cancer in Chinese Han population.
J. Pharm. Pharmacol.
PUBLISHED: 01-19-2014
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Gastric cancer is one of the most frequently causing cancer-related deaths worldwide. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene for influencing gastric cancer risk. This study aimed to evaluate the associations between XRCC1 genetic variants and gastric cancer susceptibility in Chinese Han population.
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An analysis of the optimal multiobjective inventory clustering decision with small quantity and great variety inventory by applying a DPSO.
ScientificWorldJournal
PUBLISHED: 01-17-2014
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When an enterprise has thousands of varieties in its inventory, the use of a single management method could not be a feasible approach. A better way to manage this problem would be to categorise inventory items into several clusters according to inventory decisions and to use different management methods for managing different clusters. The present study applies DPSO (dynamic particle swarm optimisation) to a problem of clustering of inventory items. Without the requirement of prior inventory knowledge, inventory items are automatically clustered into near optimal clustering number. The obtained clustering results should satisfy the inventory objective equation, which consists of different objectives such as total cost, backorder rate, demand relevance, and inventory turnover rate. This study integrates the above four objectives into a multiobjective equation, and inputs the actual inventory items of the enterprise into DPSO. In comparison with other clustering methods, the proposed method can consider different objectives and obtain an overall better solution to obtain better convergence results and inventory decisions.
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ScFv-Decorated PEG-PLA-Based Nanoparticles for Enhanced siRNA Delivery to Her2(+) Breast Cancer.
Adv Healthc Mater
PUBLISHED: 01-15-2014
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Patients with Her2-overexpressing (Her2(+) ) breast cancers generally have a poorer prognosis due to the high aggressiveness and chemoresistance of the disease. Small interfering RNA (siRNA) targeting the gene encoding polo-like kinase 1 (Plk1; siPlk1) has emerged as an efficient therapeutic agent for Her2(+) breast cancers. Poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PLA)-based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of siPlk1 to Her2(+) breast cancer, anti-Her2 single-chain variable fragment antibody (ScFvHer2 )-decorated PEG-PLA-based nanoparticles with si Plk1 encapsulation (ScFvHer2 -NPsi Plk1 ) are developed. With the rationally designed conjugation site, ScFvHer2 -NPsiRNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2(+) breast cancer cells. Therefore, ScFvHer2 -NPsi Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2(+) breast cancer cells, when compared with nontargeted NPsi Plk1 . More importantly, ScFvHer2 -NPsiRNA markedly enhances the accumulation of siRNA in Her2(+) breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose-dependent anti-tumor efficacy further demonstrates that ScFvHer2 -decorated PEG-PLA-based nanoparticles with siPlk1 encapsulation can significantly enhance the inhibition of Her2(+) breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFvHer2 -decorated PEG-PLA-based nanoparticles show great potential for targeted RNA interference therapy of Her2(+) breast tumor.
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Morphological evidence for a neurotensinergic periaqueductal gray-rostral ventromedial medulla-spinal dorsal horn descending pathway in rat.
Front Neuroanat
PUBLISHED: 01-01-2014
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Neurotensin (NT) is an endogenous neuropeptide that exerts potent opioid-independent analgesic effects, most likely via the type 2 NT receptor (NTR2). Previous morphological and electrophysiological studies suggested that the NT-NTR2 system is primarily localized in structures that constitute the descending pain control pathway, such as the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal dorsal horn (SDH). However, relevant morphological evidence for this neurotensinergic (NTergic) circuit is lacking. Thus, the aim of the present study was to morphologically elucidate the potential sites and connections in the NT-NTR2 system that are involved in the descending pain control pathway. Based on light and electron microscopy combined with anterograde and retrograde tracing, we found evidence that NTR2-immunoreactive (IR) neurons in the RVM receive NT-IR projections originating from the PAG; express NT, serotonin (5-HT), or both; and send projections that terminate in laminae I and II of the SDH. These results suggest that NTR2 may contribute to pain control by binding to NT in the PAG-RVM-SDH pathway. In conclusion, our data provide morphological evidence for an NTergic PAG-RVM-SDH pathway, implicating novel mechanisms of NT-induced analgesia.
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The associations between the family education and mortality of patients on peritoneal dialysis.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate whether education level of family members predicts all-cause and cardiovascular death and initial-episode peritonitis in patients on peritoneal dialysis (PD).
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Collision tumor of the esophagus: report of a case with mixed squamous cell carcinoma and gastrointestinal stromal tumor.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Esophageal cancer is mainly divided into squamous cell carcinoma and adenocarcinoma. Epidemiologically, the former contributes to 90% of worldwide esophageal cancer cases, while adenocarcinoma contributes to two-thirds of cases in developed countries. Although other rare types and collision with multiple histological types of tumors do occur in the esophagus, it is very rare for a gastrointestinal stromal tumor (GIST) to collide with an epithelial malignant tumor. To date, only three cases have been reported in the literature. The current study reported a 69-year-old male patient with squamous cell carcinoma and GIST in the middle esophagus. There was no merging of tissue components between these tumors. This study together with a literature review indicates that esophageal collision tumors have been increasingly reported in recent years. Histology and immunohistochemistry are needed to make a differential diagnosis. The exact oncogenic mechanism or the interaction of two independent neoplasms still remains to be determined, and further investigation, such as electron microscopy and genetic analysis, may help to elucidate the pathogenesis of the colliding tumors.
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The associations of uric acid, cardiovascular and all-cause mortality in peritoneal dialysis patients.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate whether uric acid (UA) is an independent predictor of cardiovascular (CV) and all-cause mortality in peritoneal dialysis (PD) patients after controlling for recognized CV risk factors.
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DW09849, a selective PI3K inhibitor, Prevents PI3K signaling and preferentially inhibits proliferation of cells containing the oncogenic mutation p110? (H1047R).
J. Pharmacol. Exp. Ther.
PUBLISHED: 12-20-2013
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PI3K? (phosphatidylinositol-3-kinase, ? isoform) plays essential roles in cell metabolism, growth and proliferation and has been validated as a promising anti-cancer target. In an effort to search for new PI3K? selective inhibitors, DW series compounds were designed and synthesized aiming to reduce the off-target effects of their parent compound PIK-75, which was reported to selectively target PI3K?. DW series compounds potently inhibited the kinase activity of PI3K? with little activity against PI3K-related protein kinases (PIKKs) and a panel of 15 tyrosine kinases. Similar to PIK-75, DW series compounds were more potent to inhibit PI3K? among four class I PI3K isoforms, while a representative compound DW09849 displayed distinct binding mode compared to PIK75. Although DW series compounds inhibited proliferation of rhabdomyosarcoma RH30 cells at elevated 50% inhibitory concentrations (IC50s) in comparison with PIK-75, they were more selective than PIK-75 to inhibit PI3K signaling in the cellular context. Particularly, DW09849 significantly and persistently blocked PI3K/Akt signaling in RH30 cells, which consequently arrested RH30 cells in G1 phase. Moreover, DW09849 selectively suppressed the proliferation and clonogenesis of transformed RK3E/HR cells harboring oncogenic mutation of p110? H1047R, as well as a panel of human breast cancer cells containing mutated PI3K?, which is consistent with the result that DW09849 demonstrated preference against H1047R mutated PI3K? in molecular docking stimulation. These results suggest that DW series compounds, especially DW09849, selectively targeting PI3K? with less off-target effects than PIK-75, provide new clues for the design and discovery of new specific PI3K? inhibitors for cancer therapy.
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[Effect of inorganic amendments on the stabilization of heavy metals in contaminated soils].
Huan Jing Ke Xue
PUBLISHED: 12-03-2013
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Effects of single and mixed inorganic amendments on the stabilization of heavy metals in contaminated soils were investigated. Significant synergistic effects on the stabilization of Zn and Cu were observed with the mixed inorganic amendments of KH2PO4 and Ca(OH)2 in the laboratory test. In the field test, the stabilization ratios of Zn, Cu and Cd were 41.8%, 28.2% and 48.4%, respectively, with the dosage of 0.5 kg x m(-2). The growth of peanut was inhibited by the addition of the inorganic amendments. Meanwhile, the uptake of heavy metals was reduced in peanut.
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Transcriptome Profiling Identifies Differentially Expressed Genes in Postnatal Developing Pituitary Gland of Miniature Pig.
DNA Res.
PUBLISHED: 11-26-2013
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In recent years, Tibetan pig and Bama pig are popularly used as animal models for medical researches. However, little genomic information is available for the two breeds, particularly regarding gene expression pattern at the whole-transcriptome level. In this study, we characterized the pituitary transcriptome profile along their postnatal developmental stages within and between the two breeds in order to illustrate the differential dynamics and functions of differentially expressed genes. We obtained a total of ?300 million 80-bp paired-end reads, detected 15 715 previously annotated genes. Most of the genes (90.33%) were shared between the two breeds with the main functions in metabolic process. Four hormone genes (GH, PRL, LHB, and FSHB) were detected in all samples with extremely high levels of expression. Functional differences between the three developmental stages (infancy, puberty and adulthood) in each breed were dominantly presented by the gene expressions at the first stage. That is, Bama pig was over-represented in the genes involved in the cellular process, while Tibetan pig was over-represented in the genes represented by the reproductive process. The identified SNPs indicated that the divergence between the miniature pig breeds and the large pig (Duroc) were greater than that between the two miniature pig breeds. This study substantially expands our knowledge concerning the genes transcribed in the pig pituitary gland and provides an overview of pituitary transcriptome dynamics throughout the period of postnatal development.
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[Establishment of a rabbit model of cardiopulmonary bypass in acute cerebral embolism phase].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 11-26-2013
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To establish a stable and feasible rabbit model of cardiopulmonary bypass (CPB) in acute cerebral embolism phase for studying the effects of CPB on brain tissues and the timing of surgical intervention of acute cerebral embolism.
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Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial.
Chin. Med. J.
PUBLISHED: 11-19-2013
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A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.
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Differential anticancer drug delivery with a nanogel sensitive to bacteria-accumulated tumor artificial environment.
ACS Nano
PUBLISHED: 11-18-2013
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Differential anticancer drug delivery that selectively releases a drug within a tumor represents an ideal cancer therapy strategy. Herein, we report differential drug delivery to the tumor through the fabrication of a special bacteria-accumulated tumor environment that responds to bacteria-sensitive triple-layered nanogel (TLN). We demonstrate that the attenuated bacteria SBY1 selectively accumulated in tumors and were rapidly cleared from normal tissues after intravenous administration, leading to a unique bacteria-accumulated tumor environment. Subsequent administrated doxorubicin-loaded TLN (TLND) was thus selectively degraded in the bacteria-accumulated tumor environment after its accumulation in tumors, triggering differential doxorubicin release and selectively killing tumor cells. This concept can be extended and improved by using other factors secreted by bacteria or materials to fabricate a unique tumor environment for differential drug delivery, showing potential applications in drug delivery.
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[Research on methane concentration monitoring system based on electro-optical modulation interference].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-29-2013
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Gas monitoring for methane concentration has been applied in many areas, while the vast majority of methods were based on the chemical reaction. There is a low security and poor stability shortcomings. In contrast, it is of high stability and strong anti-interference ability to monitor methane concentration using optical interferometry for quantitative analysis. As the system static interference limits the spectrcum resolution, we designed the electro-optical modulation interference system to further improve the detection accuracy for methane concentration. In the interferometer system, a variable refractive index crystal LiNbO3 was used for electro-optical modulation, and the static optical path length scan range was increased to improve the spectrum resolution. Both sides of the crystal were loaded with opposite phase modulated signal, so that it does not change the improved spectrum resolution interferometer size. By derivation of refractive index modulation as a function of optical path difference, the simulation found that the resolution was increased by nearly an order of magnitude than interference system spectrum resolution of the same size. The experiments used the SGT-3-type acousto-optical modulator and the 1 650 nm infrared lasers to detect different concentrations of methane gas. The experimental results show that the method is better than the traditional pyroelectric method in terms of accuracy and stability, and more suitable for application in the mine complex environment.
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Vitamin D status and the risk of pancreatic cancer: a meta-analysis.
Chin. Med. J.
PUBLISHED: 09-17-2013
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Vitamin D status in relation to pancreatic cancer risks is still inconsistent. This study was performed to evaluate the association between vitamin D status and risk of pancreatic cancer using a meta-analysis approach.
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New clerodane diterpenoid glycosides from the aerial parts of Nannoglottis carpesioides.
Fitoterapia
PUBLISHED: 09-11-2013
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Three new clerodane diterpenoid glycosides with l-arabinose (1-3), together with ten known compounds including phytol-type diterpenes; cycloartane-type, ursane-type, and oleanane-type triterpenes, were isolated from the aerial parts of Nannoglottis carpesioides which a Chinese endemic genus. The structures of the new compounds 1-3 were identified based on chemical and spectroscopic studies, including one- and two-dimensional NMR, HRESIMS, UV, and IR results. Their absolute configurations were determined by the application of theory calculations of optical rotation, which were compared with the experimental data. New aglycone 1a and l-arabinose were obtained by acid hydrolysis of 1 and GC-MS analysis. The cytotoxicities of some isolated compounds against a panel of human cancer cell lines were evaluated by the MTT assay. Clerodane diterpenoides are the characteristic chemical constituents and may be used as chemical markers of the genus Nannoglottis.
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Systematic chemical profiling of Citrus grandis Tomentosa by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 08-25-2013
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Citrus grandis Tomentosa, as the original plant of the traditional Chinese medicine "Huajuhong", has been used as antitussive and expectorant in clinic for thousands of years. The fruit epicarp and whole fruit of this plant were both literarily recorded and commonly used. In the present study, an ultra-fast liquid chromatography coupled with diode-array detection and quadrupole/time-of-flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) based chemical profiling method was developed for rapid holistic quality evaluation of C. grandis Tomentosa, which laid basis for chemical comparison of two medicinal parts. As a result, forty-eight constituents, mainly belonging to flavonoids and coumarins, were unambiguously identified by comparison with reference standards and/or tentatively characterized by elucidating UV spectra, quasi-molecular ions and fragment ions referring to information available in literature. Both of the epicarp and whole fruit samples were rich in flavonoids and coumarins, but major flavonoids contents in whole fruit were significantly higher than in epicarp (P<0.5). The proposed method could be useful in quality control and standardization of C. grandis Tomentosa raw materials and its products. Results obtained in this study will provide a basis for quality assessment and further study in vivo.
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Improved Early Postresuscitation EEG Activity for Animals Treated with Hypothermia Predicted 96?hr Neurological Outcome and Survival in a Rat Model of Cardiac Arrest.
Biomed Res Int
PUBLISHED: 08-13-2013
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Purpose. To investigate the effect of hypothermia on 96?hr neurological outcome and survival by quantitatively characterizing early postresuscitation EEG in a rat model of cardiac arrest. Materials and Methods. In twenty male Sprague-Dawley rats, cardiac arrest was induced through high frequency transesophageal cardiac pacing. Cardiopulmonary resuscitation was initiated after 5?mins untreated arrest. Immediately after resuscitation, animals were randomized to either 2?hrs of hypothermia (N = 10) or normothermia (N = 10). EEG, ECG, aortic pressure, and core temperature were continuously recorded for 6?hrs. Neurological outcome was evaluated daily during the 96?hrs postresuscitation period. Results. No differences in the baseline measurements and resuscitation outcome were observed between groups. However, 96?hr neurological deficit score (204 ± 255 versus 500 ± 0, P = 0.005) and survival (6/10 versus 0/10, P = 0.011) were significantly better in the hypothermic group. Quantitative analysis of early postresuscitation EEG revealed that burst frequency and spectrum entropy were greatly improved in the hypothermic group and correlated with 96?hr neurological outcome and survival. Conclusion. The improved burst frequency during burst suppression period and preserved spectrum entropy after restoration of continuous background EEG activity for animals treated with hypothermia predicted favorable neurological outcome and survival in this rat model of cardiac arrest.
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Serum microRNA-21 levels are related to tumor size in gastric cancer patients but cannot predict prognosis.
Oncol Lett
PUBLISHED: 07-17-2013
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In patients with gastric cancer (GC), circulating microRNA-21 (miR-21) is overexpressed and may serve as a diagnostic biomarker. In the present study, it was hypothesized that the serum miR-21 expression levels were associated with prognosis in the patients with GC. The expression levels of serum miR-21 were measured using quantitative polymerase chain reaction (qPCR) assays in 103 GC patients. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between serum miR-21 expression levels and prognosis in the patients. The correlation between the serum miR-21 levels and the clinicopathological factors of the patients was also analyzed. Survival curves were not significantly different between the groups exhibiting high and low levels of serum miR-21 expression. High levels of miR-21 in the serum were associated with an increased tumor size and an advanced pT stage. These findings suggest that serum miR-21 could be exploited as a practical biomarker for monitoring tumor burden in patients with GC.
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Ethyl 4-(2-eth-oxy-2-oxoeth-yl)-3-oxo-4,13-di-aza-penta-cyclo-[11.8.0.0(2,11).0(5,10).0(14,19)]henicosa-1,5(10),6,8,11,14(19),15,17,20-nona-ene-12-carboxyl-ate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 07-01-2013
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In the title compound, C26H22N2O5, the system consisting of five fused rings, being essentially planar with an r.m.s. deviation from the least-squares plane of 0.049?(3)?Å, makes a dihedral angle of 58.72?(12)° with the plane of the ethyl carboxyl-ate group immediately attached to it, and a dihedral angle of 89.48?(14)° with the plane of the ethyl carboxyl-ate group attached via the -CH2- bridge. Bond lengths indicate ?-delocalization over the whole penta-cyclic system. The mol-ecular conformation is stabilized by a weak intra-molecular C-H?O hydrogen bond. In the crystal, mol-ecules form stacks along the b-axis direction, neighboring mol-ecules within each stack being related by inversion and the shortest distance between the centroids of the pyridine rings within the stack being 3.667?(2)?Å.
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Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.
Pediatr Blood Cancer
PUBLISHED: 06-28-2013
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This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China.
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Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status.
Cancer Causes Control
PUBLISHED: 06-28-2013
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Physical activity both before and after breast cancer diagnosis has been associated with improved survival. However, it is not clear whether this association differs by molecular features of the tumor or by recency of the physical activity to the time of diagnosis.
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Systematic combination screening reveals synergism between rapamycin and sunitinib against human lung cancer.
Cancer Lett.
PUBLISHED: 06-04-2013
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Mammalian target of rapamycin (mTOR) acts as a hub integrating signals from nutrient availability and growth factors and plays central roles in regulating protein synthesis and cell growth, which has been validated as a promising target for cancer therapy. Rapamycin and its analogues have emerged as the first generation of mTOR inhibitors, but their efficacy is modest in clinical settings. Combinatorial use of rapamycin with other drugs is a promising strategy to improve its anticancer activity. Here we developed an unbiased systematic binary screening platform aiming to discover new remedy for rapamycin-based cancer therapy. We found that sunitinib emerged as one of the clinically available anticancer drugs screened that displayed significant synergy with rapamycin in NSCLC cells. Combination of rapamycin with sunitinib resulted in enhanced cell cycle arrest in G1 phase, which was accompanied with enhanced suppression of mTOR signaling and disruption of the negative feedback loop that activate AKT upon mTORC1 inhibition. Furthermore, sunitinib and rapamycin displayed synergistic activity against tube formation by human microvessel endothelial cells as well as outgrowth of endothelial tubes and microvessels both in vitro and in vivo, which is associated with down-regulation of VEGF secretion and HIF1? expression. Our study demonstrated that new combinatorial regimen could be identified via systematic drug combination screening and established a mechanistic rationale for a combination approach using rapalogs and sunitinib in the treatment of human NSCLC.
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Evaluation of pluronic nanosuspensions loading a novel insoluble anticancer drug both in vitro and in vivo.
Int J Pharm
PUBLISHED: 05-23-2013
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To improve the solubility, stability and the antitumor activity of a novel anticancer drug, 3-(4-bromopheny l)-2-(ethyl-sulfonyl)-6-methylquinoxaline1,4-dioxide (Q39), a poloxamer nanosuspension was developed by precipitation combined with high pressure homogenization in present study. In vitro characterizations of Q39 nanosuspension (Q39/NS), including particle size, polydispersity index (PI), morphology, crystalline, saturation solubility, stability and releases were evaluated. BABL/c nude mice bearing HepG2 cells were used as in vivo tumor models to evaluate the anti-tumor activity of Q39/NS after intravenous administration. The particle size and PI for Poloxamer188 nanosuspension (P188/NS) were (304±3) nm, and (0.123±0.005) respectively, and it was (307±5) nm and (0.120±0.007) for Poloxamer85 nanosuspension (P85/NS) correspondingly. The morphology of P188/NS was spherical shape while elliptoid shape for P85/NS. The crystalline of Q39/NS did not change as shown by the X-ray diffraction analysis. The stability of Q39/NS improved compared with the solution. The solubility of Q39 in P188/NS was 7.3 times higher than the original solubility, while it was 6 times for P85/NS. Sustained release as shown from the in vitro release test, together with the tumor-targeting as shown from in vivo NS distribution, may contribute to the enhanced in vivo antitumor activity of Q39/NS.
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In vivo synthesis of calcium oxalate whiskers on CoCrMo alloy surfaces via biomineralization.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 04-28-2013
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Surface treatments using bio-technology are valuable and fascinating in the sense that such treatments are natural and yield good biocompatibility. Calcium oxalate whiskers for biomedical applications were successfully synthesized on the CoCrMo alloy surfaces implanted in Aloe leaves which consist of many active bio-chemical elements. The effect of surface wettability and surface morphology on the formation of whiskers was investigated using four differently treated CoCrMo surfaces: (i) smoothly polished surface, (ii) electrochemical etched surface, (ii) textured surface with dimples, and (iv) parallel orientated-grooved surface. Results showed that the formed whiskers had a length ranging between 100 ?m and 600 ?m, and a diameter in the range of 2 ?m to 5 ?m. Electrochemically etched surfaces had better wettability and were favorably for growing whiskers. Surface morphology with (i) dimple textures or (ii) parallel grooves facilitated the effective control of the size and amount of the grown whiskers.
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Decursin inhibited proliferation and angiogenesis of endothelial cells to suppress diabetic retinopathy via VEGFR2.
Mol. Cell. Endocrinol.
PUBLISHED: 04-26-2013
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Diabetes induces pathologic proliferation and angiogenesis in the retina that leads to catastrophic loss of vision. Decursin is a novel therapeutic that targets the vascular endothelial growth factor (VEGF) receptor (VEGFR) with putative anti-proliferative and anti-angiogenic activities. Thereby we utilized human retinal microvascular endothelial cells (HRMEC) and human umbilical vein endothelial cells (HUVEC) under conditions of excess glucose to explore dose-dependent responses of decursin on markers of migration, angiogenesis, and proliferation. Decursin dose-dependently inhibited tube formation, VEGFR-2 expression, along with relative metabolic activity and 5-bromo-2-deoxy-uridine (BrdU) activity in both cell lines. We then correlated our findings to the streptozotocin-induced rat model of diabetes. Following three months of decursin treatment VEGFR-2 expression was significantly inhibited. Our data would suggest that decursin may be a potent anti-angiogenic and anti-proliferative agent targeting the VEGFR-2 signaling pathway, which significantly inhibits diabetic retinal neovascularization.
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A pharmacological model reveals biased dependency on PI3K isoforms for tumor cell growth.
Acta Pharmacol. Sin.
PUBLISHED: 04-19-2013
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To identify the contribution of individual isoform (?, ?, ?, ?) of class I PI3Ks to tumor cell growth for proper use of PI3K inhibitors in cancer therapy.
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Potassium map from ChangE-2 constraints the impact of Crisium and Orientale basin on the Moon.
Sci Rep
PUBLISHED: 03-25-2013
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KREEP materials were thought to be last crystallized at the lunar crust and mantle boundary. Impact cratering and volcanism are mainly responsible for their distributions on the lunar surface. Therefore, observation of global KREEP materials and investigation of distributions in the areas of large basins are of critical importance to understand the geologic history of the Moon. Here we report the new global potassium distribution on the Moon detected by ChangE-2 Gamma-ray Spectrometer. We found that our new measurements are in general agreement with previous observation. A new finding and an important difference is that relatively higher K abundances in the Mare Crisium and Mare Orientale than their surrounding rims were detected for the first time. In light of our observations in these two areas, we propose that Crisium and Orientale basin-forming impact events may have penetrated to the lower crust and excavate the deeper materials to the lunar surface.
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The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells.
Biomaterials
PUBLISHED: 03-19-2013
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The interaction of nanocarriers with cells including their transcellular behavior is vital not only for a drug delivery system, but also for the safety of nanomaterials. In an attempt to clarify how the structures of polymers impact the transport mechanisms of their nanocarriers in epithelial cells, three amphiphilic polymers (PEEP-PCL, PEG-PCL and PEG-DSPE) with different hydrophilic or hydrophobic blocks were synthesized or chosen to form different micelle systems here. The endocytosis, exocytosis, intracellular colocalization, paracellular permeability and transcytosis of these micelle systems were compared using Förster resonance energy transfer analysis, real-time confocal images, colocalization assay, transepithelial electrical resistance study, and so on. All micelle systems were found intact during the studies with cells. The endocytosis and exocytosis studies with undifferentiated MDCK cells and the transcytosis study with differentiated MDCK monolayers all indicated the fact that PEG-DSPE micelles achieved the most and fastest transport, followed by PEG-PCL and PEEP-PCL in order. These might be because DSPE has higher hydrophobicity than PCL while PEG has lower hydrophilicity than PEEP. Different in hydrophilic or hydrophobic structures, all kinds of micelles demonstrated similar pathways during endocytosis and exocytosis, both caveolae- and clathrin-mediated but with difference in degree. The colocalization studies revealed different behaviors in intracellular trafficking among the three polymer micelles, suggesting the decisive role of hydrophilic shells on this process. Finally, all micelle systems did not impact the paracellular permeability of test cell monolayer. In conclusion, the hydrophilic and hydrophobic structures of test micelles could influence their transport ability, intracellular trafficking and the transport level under each pathway in MDCK cells.
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Meta-analysis of randomized controlled trials on the efficacy and safety of intracoronary administration of tirofiban for no-reflow phenomenon.
BMC Cardiovasc Disord
PUBLISHED: 03-11-2013
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Currently, there is still a lack of an optimal treatment for no-reflow phenomenon (NR). The aim of this simple meta-analysis was to evaluate the efficacy and safety of intracoronary (IC) administration of tirofiban compared with other conventional drugs during percutaneous coronary intervention (PCI) for NR.
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Airborne microbial composition in a high-throughput poultry slaughtering facility.
J. Food Prot.
PUBLISHED: 03-07-2013
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A high-throughput chicken slaughtering facility in Beijing was systematically investigated for numbers of airborne microorganisms. Samples were assessed for counts of aerobic bacteria, Staphylococcus aureus, total coliforms, Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Bacillus cereus, and Salmonella. During a 4-month period (September to December 2011), samples were collected for 10 min three times daily (preproduction, production, and postproduction). Samples were collected for three consecutive days of each month with an FA-1 sampler from six sampling sites: receiving-hanging, soaking-scalding and defeathering, evisceration, precooling, subdividing, and packing. Humidity, temperature, wind velocity, and airborne particulates also were recorded at each sampling site and time. The highest counts of microorganisms were recorded in the initial stages of processing, i.e., the receiving-hanging and defeathering areas, with a definite decline toward the evisceration, prechilling, subdividing, and packing areas; the prechilling area had the lowest microbial counts of 2.4 × 10(3) CFU/m(3). Mean total coliforms counts ranged from 8.4 × 10(3) to 140 CFU/m(3). Maximum E. coli counts were 6.1 × 10(3) CFU/m(3) in the soaking-scalding and defeathering area. B. cereus, P. aeruginosa, and S. aureus represented only a small proportion of the microbial population (1,900 to 20 CFU/m(3)). L. monocytogenes and Salmonella were rarely detected in evisceration, precooling, subdividing, and packing areas. Our study identified the levels of bioaerosols that may affect chicken product quality. This finding could be useful for improved control of microbial contamination to ensure product quality.
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