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Find video protocols related to scientific articles indexed in Pubmed.
Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells.
Exp. Biol. Med. (Maywood)
PUBLISHED: 11-02-2014
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The epithelial-mesenchymal transition (EMT) of tubular epithelial cells to myofibroblast-like cells plays a substantial role in renal tubulointerstitial fibrosis, which is a common pathological character of end-stage renal disease (ESRD). Fibroblast growth factor-2 (FGF-2) triggers EMT in tubular epithelial cells and increases Bcl-2-associated athanogene 3 (BAG3) expression in neural progenitor and neuroblastoma cells. In addition, a novel role of regulation of EMT has been ascribed to BAG3 recently. These previous reports urged us to study the potential involvement of BAG3 in EMT triggered by FGF-2 in renal tubular epithelial cells. The current study found that FGF-2 induced EMT, simultaneously increased BAG3 expression in human kidney 2 (HK2) cells. Although FGF-2 induced EMT in nontransfected or scramble short hairpin RNA (shRNA) transfected HK2 cells, it was ineffective in BAG3-silenced cells, indicating a favorable role of BAG3 in EMT of tubular cells induced by FGF-2. Knockdown of BAG3 also significantly suppressed motion and invasion of HK2 cells mediated by FGF-2. Furthermore, we confirmed that BAG3 was upregulated in kidney of unilateral ureteral obstruction (UUO) rats, a well-established renal fibrosis model, in which EMT is supposed to exert a substantial influence on renal fibrosis. Importantly, upregulation of BAG3 was limited to tubular epithelial cells. Results of the current study identify BAG3 as a potential player in EMT of tubular epithelial cells, as well as renal fibrosis.
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Unexpected Reconstruction of the ?-Boron (111) Surface.
Phys. Rev. Lett.
PUBLISHED: 10-21-2014
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We report a novel reconstruction of the ?-boron (111) surface, discovered using ab initio evolutionary structure prediction, and show that this unexpected neat structure has a much lower energy than the recently proposed (111)-I_{R,(a)} surface. In this reconstruction, all single interstitial boron atoms bridge neighboring B_{12} icosahedra by polar covalent bonds, and this satisfies the electron counting rule, leading to the reconstruction-induced metal-semiconductor transition. The peculiar charge transfer between the interstitial atoms and the icosahedra plays an important role in stabilizing the surface.
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Cohnella capsici sp. nov., a novel nitrogen-fixing species isolated from Capsicum annuum rhizosphere soil, and emended description of Cohnella plantaginis.
Antonie Van Leeuwenhoek
PUBLISHED: 10-17-2014
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A novel bacterial strain designated YN-59(T) was isolated from Capsicum annuum rhizosphere soil in China. The isolate was found to be aerobic, Gram-positive, rod-shaped and to form ellipsoidal or oval spores positioned centrally in swollen sporangia. On the basis of 16S rRNA gene sequence analysis, the isolated strain YN-59 was determined to be related to members of genus Cohnella. High levels of 16S rRNA gene sequence similarity were found between strain YN-59 and Cohnella plantaginis DSM 25424(T) (98.5 %) and Cohnella ginsengisoli DSM18997(T) (97.3 %); the 16S rRNA gene sequence similarities between strain YN-59 and the other strains recognized members of the genus Cohnella were below 97 %. The DNA-DNA hybridization values of strain YN-59 with C. plantaginis DSM 25424(T) and C. ginsengisoli DSM18997(T) were 44.2 ± 8.4 and 28.8 ± 5.8 %, respectively. The DNA G + C content of strain YN-59(T) was determined to be 59.32 mol %. The major isoprenoid quinone was identified as MK-7 and the predominant fatty acids as anteiso-C15:0 (45.32 %), iso-C16:0 (19.19 %), iso-C15:0 (9.65 %) and C16:0 (8.91 %). The polar lipids of strain YN-59(T) were found to consist of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol; several unidentified phospholipids were also detected. The diagnostic diamino acid in the cell wall was identified as meso-diaminopimelic. On the basis of its phenotypic and genotypic characteristics and levels of DNA-DNA hybridization, strain YN-59(T) is considered to represent a novel species of the genus Cohnella, for which the name Cohnella capsici sp. nov. (type strain YN-59(T) = CGMCC 1.12046(T) = JCM 19168(T)) is proposed.
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Elliptic-symmetry vector optical fields.
Opt Express
PUBLISHED: 10-17-2014
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We present in principle and demonstrate experimentally a new kind of vector fields: elliptic-symmetry vector optical fields. This is a significant development in vector fields, as this breaks the cylindrical symmetry and enriches the family of vector fields. Due to the presence of an additional degrees of freedom, which is the interval between the foci in the elliptic coordinate system, the elliptic-symmetry vector fields are more flexible than the cylindrical vector fields for controlling the spatial structure of polarization and for engineering the focusing fields. The elliptic-symmetry vector fields can find many specific applications from optical trapping to optical machining and so on.
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Notch3 Interactome Analysis Identified WWP2 as a Negative Regulator of Notch3 Signaling in Ovarian Cancer.
PLoS Genet.
PUBLISHED: 10-01-2014
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The Notch3 signaling pathway is thought to play a critical role in cancer development, as evidenced by the Notch3 amplification and rearrangement observed in human cancers. However, the molecular mechanism by which Notch3 signaling contributes to tumorigenesis is largely unknown. In an effort to identify the molecular modulators of the Notch3 signaling pathway, we screened for Notch3-intracellular domain (N3-ICD) interacting proteins using a human proteome microarray. Pathway analysis of the Notch3 interactome demonstrated that ubiquitin C was the molecular hub of the top functional network, suggesting the involvement of ubiquitination in modulating Notch3 signaling. Thereby, we focused on functional characterization of an E3 ubiquitin-protein ligase, WWP2, a top candidate in the Notch3 interactome list. Co-immunoprecipitation experiments showed that WWP2 interacted with N3-ICD but not with intracellular domains from other Notch receptors. Wild-type WWP2 but not ligase-deficient mutant WWP2 increases mono-ubiquitination of the membrane-tethered Notch3 fragment, therefore attenuating Notch3 pathway activity in cancer cells and leading to cell cycle arrest. The mono-ubiquitination by WWP2 may target an endosomal/lysosomal degradation fate for Notch3 as suggested by the fact that the process could be suppressed by the endosomal/lysosomal inhibitor. Analysis of The Cancer Genome Atlas dataset showed that the majority of ovarian carcinomas harbored homozygous or heterozygous deletions in WWP2 locus, and there was an inverse correlation in the expression levels between WWP2 and Notch3 in ovarian carcinomas. Furthermore, ectopic expression of WWP2 decreased tumor development in a mouse xenograft model and suppressed the Notch3-induced phenotypes including increase in cancer stem cell-like cell population and platinum resistance. Taken together, our results provide evidence that WWP2 serves as a tumor suppressor by negatively regulating Notch3 signaling in ovarian cancer.
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Synthesis and biological evaluation of liguzinediol mono- and dual ester prodrugs as promising inotropic agents.
Molecules
PUBLISHED: 09-02-2014
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The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5), monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics.
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Induction of the Unfolded Protein Response by Constitutive G-protein Signaling in Rod Photoreceptor Cells.
J. Biol. Chem.
PUBLISHED: 09-02-2014
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Phototransduction is a G-protein signal transduction cascade that converts photon absorption to a change in current at the plasma membrane. Certain genetic mutations affecting the proteins in the phototransduction cascade cause blinding disorders in humans. Some of these mutations serve as a genetic source of "equivalent light" that activates the cascade, whereas other mutations lead to amplification of the light response. How constitutive phototransduction causes photoreceptor cell death is poorly understood. We showed that persistent G-protein signaling, which occurs in rod arrestin and rhodopsin kinase knock-out mice, caused a rapid and specific induction of the PERK pathway of the unfolded protein response. These changes were not observed in the cGMP-gated channel knock-out rods, an equivalent light condition that mimics light-stimulated channel closure. Thus transducin signaling, but not channel closure, triggers rapid cell death in light damage caused by constitutive phototransduction. Additionally, we show that in the albino light damage model cell death was not associated with increase in global protein ubiquitination or unfolded protein response induction. Taken together, these observations provide novel mechanistic insights into the cell death pathway caused by constitutive phototransduction and identify the unfolded protein response as a potential target for therapeutic intervention.
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Proposal for the creation and optical detection of spin cat states in Bose-Einstein condensates.
Phys. Rev. Lett.
PUBLISHED: 08-26-2014
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We propose a method to create "spin cat states," i.e., macroscopic superpositions of coherent spin states, in Bose-Einstein condensates using the Kerr nonlinearity due to atomic collisions. Based on a detailed study of atom loss, we conclude that cat sizes of hundreds of atoms should be realistic. The existence of the spin cat states can be demonstrated by optical readout. Our analysis also includes the effects of higher-order nonlinearities, atom number fluctuations, and limited readout efficiency.
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The interaction of APEX1 variant with polycyclic aromatic hydrocarbons on increasing chromosome damage and lung cancer risk among male Chinese.
Mol. Carcinog.
PUBLISHED: 08-22-2014
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Polycyclic aromatic hydrocarbons (PAHs) are the most significant contributors to tobacco-induced lung carcinogenesis. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the removal of apurinic/apyrimidinic sites caused by DNA damaging agents. This study aimed to investigate the potential interaction of APEX1 polymorphisms and PAHs on genetic damage and lung cancer risk among male Chinese. We recruited an occupational cohort of 922 male coke oven workers and determined their DNA damage levels by calculating the lymphocytic micronucleus (MN) frequencies. Two well-studied APEX1 polymorphisms (-307A?>?C and Asp148Glu) and their associations with MN frequencies were examined. The impact of MN-related single nucleotide polymorphism (SNP) on lung cancer risk was further investigated in two case-control studies including 1634 male lung cancer patients and 1678 controls. It was shown that, the APEX1 148Glu allele was associated with significantly higher MN frequencies than 148Asp allele, with strongest associations among the highest PAH-exposure workers (P?=?0.008). The APEX1 148Glu allele was also associated with increased lung cancer risk among male smokers, especially among heavy smokers in both case-control studies (odd ratio: 4.40, 95%CI: 3.29-5.72). In addition, APEX1 148Glu variant interacts with smoking in increasing male lung cancer risk, as measured by the attributable proportion due to interaction, which was 0.23 (95%CI: 0.06-0.39). This study showed evidence on interaction between APEX1 148Glu variant and cigarette smoking in increasing lung cancer susceptibility among male Chinese, which may be due to the synergistic effects of APEX1 148Glu and PAHs in increasing chromosome damage levels. The results provide a new insight into gene-interactions in lung carcinogenesis. © 2014 Wiley Periodicals, Inc.
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[Anaplastic lymphoma kinase fusion gene expression, clinical pathological characteristics and prognosis in 95 Chinese patients with non-small cell lung cancer].
Beijing Da Xue Xue Bao
PUBLISHED: 08-19-2014
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To examine the prevalence of anaplastic lymphoma kinase (ALK) fusion gene in Chinese patients with non-small cell lung cancer (NSCLC).
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Fabrication of enrofloxacin imprinted organic-inorganic hybrid mesoporous sorbent from nanomagnetic polyhedral oligomeric silsesquioxanes for the selective extraction of fluoroquinolones in milk samples.
J Chromatogr A
PUBLISHED: 08-16-2014
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This paper reports a nanomagnetic polyhedral oligomeric silsesquioxanes (POSS)-directing strategy toward construction of molecularly imprinted hybrid materials for antibiotic residues determination in milk samples. The imprinted polymeric layer was facilely obtained through the copolymerization of active vinyl groups present on the nanomagnetic POSS (Fe3O4@POSS) surface and functional monomer (methacrylic acid) binding with template (enrofloxacin). Herein, the octavinyl POSS acted as not only the building blocks for hybrid rigid architectures but also the cross-linker for the formation of effective recognition sites during the imprinting process. The molecularly imprinted Fe3O4@POSS nanoparticles (Fe3O4@MI-POSS) demonstrated much higher adsorption capacity and selectivity toward enrofloxacin molecules and its analogs than the non-imprinted Fe3O4@POSS (Fe3O4@NI-POSS) materials. The imprinted particles were applied as a selective sorbent in solid-phase extraction focusing upon sample pretreatment in complex matrices prior to chromatographic analysis. The three FQs (ofloxacin, enrofloxacin, danofloxacin) could be selectively extracted from the biological matrix, while the matrix interferences were effectively eliminated simultaneously under the optimum extraction conditions. A simple, rapid and sensitive method based on the Fe3O4@MI-POSS material combined with HPLC-UV detection was then established for the simultaneous determination of three FQs from milk samples. The average recoveries of the three FQs were in the range of 75.6-108.9%. The relative standard deviations of intra- and inter-day ranging from 2.91 to 8.87% and from 3.6 to 11.5%, respectively. The limits of detections (S/N=3) were between 1.76 and 12.42 ng mL(-1). It demonstrates the effectiveness of trace analysis in complicated biological matrices utilizing magnetic separation in combination with molecularly imprinted solid-phase extraction, the rich chemistry of POSS makes it possible to be an ideal platform for generating molecular imprinted hybrid materials is also exhibited.
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Phase conjugation of vector fields by degenerate four-wave mixing in a Fe-doped LiNbO?.
Opt Lett
PUBLISHED: 08-15-2014
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We propose a method to generate the phase-conjugate wave of the vector field by degenerate four-wave mixing in a c-cut Fe-doped LiNbO3 crystal. We demonstrate experimentally that the phase-conjugate wave of the vector field can be generated. In particular, the phase-conjugate vector field has also the peculiar function of compensating the polarization distortion, as the traditional phase-conjugate scaler field can compensate the phase distortion.
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Fingerprints of topological defects in a metasurface.
Opt Lett
PUBLISHED: 08-15-2014
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Singularity, representing a structurally stable topological defect (TD), plays a pivotal role in various physical systems. Here we theoretically present the fingerprints of TDs and uncover the resulting exotic optical properties in a tailored metasurface system. The presence of the TDs results in coherent perfect absorption, and dramatic optical property transition from slow to superluminal light behavior when the parameters cross the TD. Our investigation provides a new route to explore many phenomena of the TDs, extends the capabilities of metasurface, and offers benefits to develop potential nanophotonic applications based on the design of the metasurface.
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Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle.
Br. J. Nutr.
PUBLISHED: 08-01-2014
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The present study investigated the effects of medium-chain TAG (MCT) on hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). At weaning (mean 21 (SD 1·06) d of age), twenty-four IUGR piglets and twenty-four normal-birth weight (NBW) piglets were selected according to their birth weight (BW; IUGR: mean 0·95 (SD 0·04) kg; NBW: mean 1·58 (SD 0·04) kg) and weight at the time of weaning (IUGR: mean 5·26 (SD 0·15) kg; NBW: mean 6·98 (SD 0·19) kg) and fed either a soyabean oil (SO) diet (containing 5% SO) or a MCT diet (containing 1% SO and 4% MCT) for 28 d. IUGR piglets exhibited poor (P<0·05) growth performance, lower (P<0·05) metabolic efficiency of hepatic glutathione (GSH) redox cycle, and increased (P<0·05) levels of reactive oxygen species, apoptosis and necrosis in hepatocytes compared with NBW piglets. The MCT diet increased (P<0·05) the average daily gain and feed efficiency of piglets during the first 4 weeks after weaning. Furthermore, MCT diet-fed piglets had a higher (P<0·05) GSH:oxidised glutathione ratio and increased (P<0·05) activities of glucose-6-phosphate dehydrogenase (G6PD) and GSH reductase. The expression of G6PD was up-regulated (P<0·05) by the MCT diet irrespective of BW. Moreover, malondialdehyde concentrations in the liver and apoptosis and necrosis levels in hepatocytes were decreased (P<0·05) by the MCT diet irrespective of BW. These results indicate that MCT might have auxiliary therapeutic potential to attenuate hepatic oxidative damage in IUGR offspring during early life, thus leading to an improvement in the metabolic efficiency of the hepatic GSH redox cycle.
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BAG3 Promoted Starvation-Induced Apoptosis of Thyroid Cancer Cells via Attenuation of Autophagy.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-25-2014
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BAG3 plays a regulatory role in a number of cellular processes. Recent studies have attracted much attention on its role in activation of selective autophagy. In addition, we have very recently reported that BAG3 is implicated in a BECN1-independent autophagy, namely noncanonical autophagy.
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Association of lifestyle factors and suboptimal health status: a cross-sectional study of Chinese students.
BMJ Open
PUBLISHED: 06-22-2014
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Suboptimal health status (SHS) is considered to be an intermediate status between disease and health, and is characterised by a decline in vitality, in physiological function and in the capacity for adaptation. Although the incidence of SHS is high, the underlying causes remain unclear. Lifestyle is one of the most important factors affecting health status; however, the relationship between SHS and lifestyle has not been elucidated.
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Curcumin attenuates D-galactosamine/lipopolysaccharide-induced liver injury and mitochondrial dysfunction in mice.
J. Nutr.
PUBLISHED: 06-04-2014
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Curcumin, a naturally occurring antioxidant, has various beneficial effects in the treatment of human diseases. However, little information regarding the protection it provides against acute liver injury is available. The present study investigated the protective effects of curcumin against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. A total of 40 male Kunming mice were randomly assigned to 5 groups: 1) mice administered saline vehicle injection (control), 2) mice administered 200 mg/kg body weight (BW) curcumin by i.p. injection (CUR), 3) mice administered D-GalN/LPS (700 mg and 5 ?g/kg BW) via i.p. injection (GL), 4) mice administered 200 mg/kg BW curcumin i.p. 1 h before D-GalN/LPS injection (CUR-GL), and 5) mice administered 200 mg/kg BW curcumin i.p. 1 h after D-GalN/LPS injection (GL-CUR). Twenty h after D-GalN/LPS injection, serum alanine aminotransferase activities were 18.5% and 13.5% lower (P < 0.05) and aspartate aminotransferase (AST) activities were 26.6% and 9.6% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. The CUR-GL and GL-CUR groups had 64.4% and 15.0% higher (P < 0.05) mitochondrial membrane potentials, respectively, and the CUR-GL group had a 44.7% lower reactive oxygen species concentration than the GL group (P < 0.05). Mitochondrial manganese superoxide dismutase activities were 111% and 77.9% higher (P < 0.05) and the percentages of necrotic cells were 47.0% and 32.4% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. Liver mRNA levels of sirtuin 1 (Sirt1) were 56.4% lower (P < 0.05) in the CUR-GL group than in the GL group. Moreover, compared with the GL-CUR group, the CUR-GL group had an 18.7% lower serum AST activity, a 31.7% lower mitochondrial malondialdehyde concentration, a 36.0% lower hepatic reactive oxygen species concentration, and a 43.0% higher mitochondrial membrane potential. These results suggested that curcumin protects against D-GalN/LPS-induced liver damage by the enhancing antioxidant defense system, attenuating mitochondrial dysfunction and inhibiting apoptosis. This was especially true for curcumin pretreatment, which highlighted its promise as a preventive treatment for acute liver injury in clinical settings.
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Dual-band unidirectional circular polarizer with opposite handedness filtration using hybridized metamaterial.
Opt Express
PUBLISHED: 05-03-2014
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We theoretically propose a unidirectional dual-band circular polarizer using a subwavelength hybridized metamaterial. By fulfilling the critical requirements of left-/right-handed circular polarizer design at each band, the polarization handedness filtration can be flipped in the same structure at different operation frequency band. The physics behind this exotic performance is further explained by a simple analytical model. Our investigation expands the capabilities of metamaterials in getting intriguing optical properties. The proposed metamaterial polarizer is helpful in effective and fruitful optical polarization manipulation and is highly valuable for the development of nanophotonic devices.
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Urinary Metals and Heart Rate Variability: A Cross-Sectional Study of Urban Adults in Wuhan, China.
Environ. Health Perspect.
PUBLISHED: 04-30-2014
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Epidemiological studies have suggested an association between external estimates of exposure to metals in air particles and altered heart rate variability (HRV). However, studies on the association between internal assessments of metals exposure and HRV are limited.
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A potential target for the treatment of Parkinson's disease: Effect of lateral habenula lesions.
Parkinsonism Relat. Disord.
PUBLISHED: 04-23-2014
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Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that is caused predominantly by the degeneration of the nigrostriatal dopaminergic pathway. Lateral habenula (LHb) has efferent projections that terminate in the substantia nigra pars compacta (SNpc) and electrical stimulation of the LHb effectively suppresses the activity of dopamine-containing neurons in the SNpc. This study was aimed to investigate whether LHb lesions can ameliorate the syndromes of PD via affecting the activities of SNpc neurons in 6-hydroxydopamine (6-OHDA)-induced PD model rats.
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Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma.
Mod. Pathol.
PUBLISHED: 04-17-2014
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Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this study, we used immunohistochemistry to assess the distribution of ALDH1A1 staining in the epithelium of human fallopian tubes, with particular reference to the transition of tubal epithelium to mesothelium (ie, tubal-mesothelial junction), ovarian surface epithelium, as well as putative precursors of ovarian high-grade serous carcinoma, namely, serous tubal intraepithelial carcinoma and 'p53 signatures,' and overt serous carcinoma. Expression of ALDH1A1 was detected in both secretory and ciliated tubal epithelial cells, tubal-mesothelial junctions and ovarian surface epithelium, but was absent in serous tubal intraepithelial carcinoma and p53 signatures. Positive staining in high-grade serous carcinoma, when present, was typically limited to rare tumor cells. In silico analyses of the mRNA expression data set from The Cancer Genome Atlas revealed downregulation of ALDH1A1 transcripts in high-grade serous carcinoma relative to normal tubal epithelium, and no association between ALDH1A1 expression levels and overall survival. Our results do not support ALDH1A1 as a specific marker of stem cells in human fallopian tube and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma.Modern Pathology advance online publication, 12 September 2014; doi:10.1038/modpathol.2014.89.
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Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets.
J. Histochem. Cytochem.
PUBLISHED: 04-07-2014
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Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-? and IFN-? and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment.
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The effect of supercritical carbon dioxide sterilization on the anisotropy of bovine cortical bone.
Cell Tissue Bank
PUBLISHED: 04-05-2014
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Bone allografts are used to replace bone that has been removed or to augment bone tissue in a number of clinical scenarios. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research and debate. Recently, supercritical carbon dioxide (SCCO2) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of these SCCO2 treatments on the anisotropic mechanical properties of cortical bone. Adult bovine cortical cubes were prepared and treated using SCCO2 and a range of common processing additives (ethanol, peracetic acid and hydrogen peroxide). The bone was mechanically tested in uniaxial compression in the axial, radial and tangential orientations. Ultimate stress, strain, elastic modulus, energy and stiffness were evaluated. This study found that SCCO2 treatment without additive did not alter the ultimate stress, stiffness or energy to failure depreciably in any orientation. The addition of sterilants peracetic acid and hydrogen peroxide also preserved mechanical function, with no deleterious effect on stress or stiffness. This study highlights the expediency of SCCO2 treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft.
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Regulation of an antioxidant blend on intestinal redox status and major microbiota in early weaned piglets.
Nutrition
PUBLISHED: 04-05-2014
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According to the "antioxidants network" theory, the present study was conducted to evaluate the regulation of an antioxidant blend on intestinal redox status and major microbiota of early-weaned piglets.
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Recording and reconstruction of vector fields in a Fe-doped LiNbO? crystal.
Opt Lett
PUBLISHED: 04-02-2014
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We propose a flexible method to record and reconstruct vector fields with space-variant polarization distribution in c-cut Fe-doped LiNbO3, based on photorefractive two-wave mixing. To our knowledge, this is the first approach for the reconstruction of vector fields without using the photoinduced anisotropy of the recording material.
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Associations between 25 lung cancer risk-related SNPs and polycyclic aromatic hydrocarbon-induced genetic damage in coke oven workers.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-01-2014
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Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH).
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MnO(x)-modified ZnAl-LDOs as high-performance adsorbent for the removal of methyl orange.
Dalton Trans
PUBLISHED: 03-15-2014
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MnO(x) modified ZnAl layered double oxides (M-LDO) nanocomposites were prepared through an intercalation/reduction/calcination process. The morphology and crystal structure of M-LDO were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), Thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR) analysis methods. The results confirmed that the manganese oxide nanoparticles were well distributed on the LDO support. Methyl orange (MO) was chosen as a common water-soluble azo dye probe to evaluate the adsorption performance of M-LDO. The effects of MO initial concentration, agitation time, and temperature on MO adsorption were investigated. It was found that adsorption equilibrium data were best represented by the Langmuir and Redlich-Peterson isotherms and the maximum adsorption capacity was 617.28 mg g(-1) obtained from the Langmuir isotherm, which was much larger than some reported adsorbents. Besides, the adsorption process was spontaneous and endothermic in nature and followed a pseudo-second-order kinetic model. The mechanism of the adsorption process was elaborated by an intraparticle diffusion model. Moreover, the regeneration test of M-LDO was carried out and it showed that the used M-LDO was feasible for at least five times. In principle, this adsorbent with a high adsorption capacity and great reutilization performance could be a very promising adsorbent for wastewater treatment.
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Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.
Environ. Health Perspect.
PUBLISHED: 03-13-2014
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Ubiquitous polycyclic aromatic hydrocarbons (PAHs) have been shown to alter gene expression patterns and elevate micronuclei (MN) frequency, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are key gene regulators that may be influenced by PAH exposures and mediate their effects on MN frequency.
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Polycyclic aromatic hydrocarbons-associated microRNAs and their interactions with the environment: influences on oxidative DNA damage and lipid peroxidation in coke oven workers.
Environ. Sci. Technol.
PUBLISHED: 03-12-2014
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We previously identified five polycyclic aromatic hydrocarbons (PAHs)-associated microRNAs (miRNAs) and found they were associated with chromosome damage. As oxidative damage is the common contributory cause of various PAHs-related diseases, we further investigated the influences of these miRNAs and their interactions with environmental factors on oxidative DNA damage and lipid peroxidation. We measured PAHs internal exposure biomarkers [urinary monohydroxy-PAHs (OH-PAHs) and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts], the expression levels of PAHs-associated plasma miRNAs (miR-24-3p, miR-27a-3p, miR-142-5p, miR-28-5p, and miR-150-5p), and urinary biomarkers of oxidative DNA damage [8-hydroxydeoxyguanosine (8-OH-dG)] and lipid peroxidation [8-iso-prostaglandin-F2? (8-iso-PGF2?)] in 365 healthy male coke oven workers. These miRNAs were associated with a dose-response increase in 8-OH-dG (? > 0), and with a dose-response decrease in 8-iso-PGF2? (? < 0), especially in workers with lower PAHs exposure levels, in nonsmokers, and in nondrinkers. These miRNAs interacted antagonistically with ?OH-PAHs and BPDE-Alb adducts (?interaction < 0) and synergistically with drinking status (?interaction > 0) to influence 8-OH-dG, while they interacted synergistically with BPDE-Alb adducts (?interaction > 0) and antagonistically with smoking status (?interaction < 0) to influence 8-iso-PGF2?. Our results suggested that miRNAs and their interactions with environmental factors might be novel mechanisms mediating the effects of PAHs exposure on oxidative DNA damage and lipid peroxidation.
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Risk factors for recurrence of ovarian endometriomas after surgical excision.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 03-10-2014
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Ovarian endometrioma is a common form of endometriosis, which may cause infertility, dysmenorrhea and pelvic pain in women of reproductive age. Although surgery is the treatment of choice for endometriomas, recurrence poses a formidable frustration. This study investigated potential risk factors of endometriomas recurrence, aiming to better understand its pathogenesis. A total of 307 patients with endometriomas were followed up for an average of 28.6 months and the 1-, 2- and 3-year cumulative recurrence rate was 9.5%, 21.9%, and 29.2%, respectively. Twenty-one potential risk factors for endometriomas recurrence were evaluated using Cox's proportional hazards models. Total revised American Fertility Society (rAFS) score was significantly associated with higher recurrence (OR=1.858, 95% CI=1.122-3.075, P=0.016), as well as younger age at surgery (OR=0.953, 95% CI=0.915-0.992, P=0.020). Semiradical surgical treatment was defined as surgical removal of cyst plus hysterectomy with preservation of bilateral or unilateral ovary, and was a significant factor that was associated with lower recurrence than the conservative surgery (OR=0.318, 95% CI=0.107-0.951, P=0.040). Postoperative pregnancy was favorable factors for disease recurrence (OR=0.217, 95% CI=0.102-0.460, P=0.000). The results suggest that endometrioma recurrence is inversely associated with age at surgery and postoperative pregnancy, and may correlate with total rAFS score and conservative surgery method.
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Twist2, the key Twist isoform related to prognosis, promotes invasion of cervical cancer by inducing epithelial-mesenchymal transition and blocking senescence.
Hum. Pathol.
PUBLISHED: 02-17-2014
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In response to tumor development, cells initially undergo invasion and metastasis followed by epithelial-mesenchymal transition (EMT, a process by which cells acquire motility) and overriding senescence (an endogenous defense mechanism against tumor progression). Oncogenic activation of Twist1 and Twist2 is essential for EMT and senescence; however, little is known about the specific contributions of Twist1 versus Twist2 to prognosis, metastasis, and the mechanism underlying cervical carcinoma. Here, we investigated the similarities and differences between Twist1 and Twist2 in assessing prognosis and promoting invasion and metastasis of cervical carcinoma as well as their roles in the underlying molecular mechanisms. By monitoring the survival of 144 clinical cervical cancer patients, we demonstrated that Twist2 shows more effective predictive performance compared with Twist1 and is more closely correlated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Compared with Twist1, Twist2 more strongly promotes invasivity and motility by inducing EMT and overriding senescence. Differences between Twist1 and Twist2 in regulating senescence and the cell cycle might be due to their individual roles in regulating the cyclin D1/cyclin dependent kinase 4 (Cdk4) pathway. Overall, our data indicate that Twist2 is the key Twist isoform coupling aberrant signals from EMT to senescence and is an important candidate biomarker for cervical cancer prognosis.
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Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood.
Ann. Rheum. Dis.
PUBLISHED: 02-14-2014
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Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance.
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Galectin-3 contributes to cisplatin-induced myeloid derived suppressor cells (MDSCs) recruitment in Lewis lung cancer-bearing mice.
Mol. Biol. Rep.
PUBLISHED: 02-13-2014
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Recently the recruitment/migration of myeloid derived suppressor cells (MDSCs) to tumor microenvironment after chemotherapy has attracted much attention. To determine the detailed mechanism for the responses of MDSCs to these chemotherapies, we investigated the changes of galectin-3 and MDSCs in response to cisplatin(0.4 mg/kg, 4 mg/kg) treatment both in vivo and ex vivo. In the process of cisplatin, we assessed levels of galectin-3 and MDSCs in the Lewis lung cancer (LLC) bearing mice using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), immunofluorence and flow cytometry (FCM). The expression and changes of galectin-3 in the LLC cell line were detected by western blot, immunofluorence and ELISA. The ligand for galectin-3 on MDSCs and the chemotaxis of galectin-3 to MDSCs were confirmed using FCM and transwell. Parallel increased level of galectin-3 with the number of MDSCs in vivo was detected after cisplatin treatment. LLC cells expressed galectin-3 and cisplatin increased galectin-3 level in the culture medium. Furthermore, MDSCs were detected to express CD98, the ligand of galectin-3, and could be recruited by galectin-3. Our results suggested that the elevated expression of gelectin-3 in LLC tumor cells may contribute to the migration of MDSCs to the tumor microenvironment in response to cisplatin.
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Light field shaping by tailoring both phase and polarization.
Appl Opt
PUBLISHED: 02-12-2014
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We propose a method to generate a vectorial focal field with reconfigurable distributions for both the intensity and polarization state. The three-dimensional focal volume was configured by modulating the phase and polarization of the incident light. The incident light yielding the desired field was determined based on an iterative scheme involving vectorial diffraction calculations and fast Fourier transforms. Optical experiments on vectorial field shaping were performed to validate the feasibility of our method. This method may have applications in optical tweezers, such as for realizing the optical manipulation of particles via polarization modulation in addition to phase control.
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A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population.
BMC Med Genomics
PUBLISHED: 02-05-2014
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Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited.
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Gene expression signatures of primary and metastatic uterine leiomyosarcoma.
Hum. Pathol.
PUBLISHED: 02-04-2014
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Leiomyosarcoma (LMS) is the most common uterine sarcoma. Although the disease is relatively rare, it is responsible for considerable mortality due to frequent metastasis and chemoresistance. The molecular events related to LMS metastasis are unknown to date. The present study compared the global gene expression patterns of primary uterine LMSs and LMS metastases. Gene expression profiles of 13 primary and 15 metastatic uterine LMSs were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. To identify differently expressed genes between primary and metastatic tumors, we performed one-way analysis of variance with Benjamini-Hochberg correction. This led to identification of 203 unique probes that were significantly differentially expressed in the 2 tumor groups by greater than 1.58-fold with P < .01, of which 94 and 109 were overexpressed in primary and metastatic LMSs, respectively. Genes overexpressed in primary uterine LMSs included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS, and TSPAN7. Genes overexpressed in LMS metastases included TNNT1, FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2, and AGT. Quantitative real-time PCR confirmed significant anatomical site-related differences in FOLR3, OSTN, and NLGN4X levels; and immunohistochemistry showed significant differences in TDO2 expression. Gene expression profiling differentiates primary uterine LMSs from LMS metastases. The molecular signatures unique to primary and metastatic LMSs may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery.
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Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases.
Cell
PUBLISHED: 01-26-2014
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Inherited mtDNA diseases transmit maternally and cause severe phenotypes. Currently, there is no effective therapy or genetic screens for these diseases; however, nuclear genome transfer between patients' and healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, we perform polar body transfer to prevent the transmission of mtDNA variants. We compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and first and second polar body transfer, in mice. Reconstructed embryos support normal fertilization and produce live offspring. Importantly, genetic analysis confirms that the F1 generation from polar body transfer possesses minimal donor mtDNA carryover compared to the F1 generation from other procedures. Moreover, the mtDNA genotype remains stable in F2 progeny after polar body transfer. Our preclinical model demonstrates polar body transfer has great potential to prevent inherited mtDNA diseases.
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Yanshu spraying agent, a traditional Chinese medicine, relieves chronic pharyngitis in animals by anti-inflammatory and antibacterial effects.
Exp Ther Med
PUBLISHED: 01-21-2014
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Chronic pharyngitis is chronic inflammation that is often caused by repeated occurrences of acute pharyngitis or upper respiratory tract infections, including Streptococcus and Staphylococcus. The present study aimed to investigate the effects of Yanshu spraying agent (Yanshu) in relieving chronic pharyngitis, as well as the possible underlying mechanisms. The results revealed that Yanshu inhibited chronic inflammation in ammonia-induced chronic pharyngitis in rabbits and cotton pellet-induced granuloma tissue formation in rats. Yanshu also demonstrated antibacterial effects on Streptococcus and Staphylococcus in vitro. Yanshu did not exhibit any effects on the immune system, including the spleen and thymus indexes, immunocyte count and monocyte-macrophage function, when compared with the effects of dexamethasone. Therefore, the results of the present study indicate that Yanshu may relieve chronic pharyngitis via its anti-inflammatory and antibacterial activities.
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Effect of zinc-bearing zeolite clinoptilolite on growth performance, nutrient retention, digestive enzyme activities, and intestinal function of broiler chickens.
Biol Trace Elem Res
PUBLISHED: 01-20-2014
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This study was conducted to investigate the effect of zinc-bearing zeolite clinoptilolite (Zn-ZCP) on performance, growth performance, nutrient retention, digestive enzyme activities, and intestinal function in broiler chickens. A total of 180 1-day-old Arbor Acres chickens were randomly divided into three groups with six replicates of ten birds for a 21-day feeding period. Birds were fed a basal corn-soybean meal diet (29.1 mg of Zn per kilogram of diet) without supplemental zinc (control) or the same diet supplemented with 80 mg/kg zinc from ZnSO4 or Zn-ZCP. Zn-ZCP and ZnSO4 treatments had lower feed: gain ratio than that of control group (P < 0.05). Addition of Zn-ZCP increased (P < 0.05) the apparent retention of organic matter and ether extract during 14-17 days, and increased (P < 0.05) pancreatic lipase activity at 14 and 21 days as well as amylase activity at 21 days. Addition of Zn-ZCP increased the villus heights and villus height to crypt depth ratio at the duodenal (P < 0.05) and jejunal (P < 0.05) of broilers at 14 days. Broilers fed the diet supplemented with 80 mg/kg Zn from Zn-ZCP had higher villus heights and villus height to crypt depth ratio of duodenum (P < 0.05) and jejunum (P < 0.05) than those fed with control diet on day 21. Zn-ZCP treatment increased (P < 0.05) IgG and sIgA concentrations in jejunum at 21 days. The results indicated that Zn-ZCP supplementation which might have modified the release of Zn further down in the intestinal tract with the controlled-release characteristic, modulated digestive enzyme activities and intestinal structure and function, increased nutrient retention, and improved feed efficiency.
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Observation of the interference effect in vibrationally resolved electron momentum spectroscopy of H2.
Phys. Rev. Lett.
PUBLISHED: 01-14-2014
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We report the first measurement on vibrationally resolved electron momentum spectroscopy of H2 by using a high-resolution (e, 2e) spectrometer. The vibrational-specific experimental momentum profiles have been obtained and shown to be in agreement with calculations of (e, 2e) ionization cross sections taking into account the vibrational wave functions. Distinct deviations from Franck-Condon predictions have been observed in vibrational ratios of cross sections, which can readily be ascribed to the Young-type two-center interference. Unlike previous (e, 2e) work, the present observation of an interference effect does not rely on the comparison with the one-center atomic cross section.
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The ?-alanyl-monoamine synthase ebony is regulated by schizophrenia susceptibility gene dysbindin in Drosophila.
Sci China Life Sci
PUBLISHED: 01-09-2014
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The Drosophila homolog of schizophrenia susceptibility gene dysbindin (Ddysb) affects a range of behaviors through regulation of multiple neurotransmitter signals, including dopamine activity. To gain insights into mechanisms underlying Ddysb-dependent regulation of dopamine signal, we investigated interaction between Ddysb and Ebony, the Drosophila ?-alanyl-monoamine synthase involved in dopamine recycling. We found that Ddysb was capable of regulating expression of Ebony in a bi-directional manner and its subcellular distribution. Such regulation is confined to glial cells. The expression level of ebony and its accumulation in glial soma depend positively on Ddysb activity, whereas its distribution in glial processes is bound to be reduced in response to any alterations of Ddysb from the normal control level, either an increase or decrease. An optimal binding ratio between Dysb and Ebony might contribute to such non-linear effects. Thus, Ddysb-dependent regulation of Ebony could be one of the mechanisms that mediate dopamine signal.
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Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical cancer.
Front Med
PUBLISHED: 01-08-2014
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Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA-IIA, and SCC IIB-IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated ?-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.
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Twist2 contributes to cisplatin-resistance of ovarian cancer through the AKT/GSK-3? signaling pathway.
Oncol Lett
PUBLISHED: 01-03-2014
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Cisplatin is regularly used in the treatment of ovarian cancer. However, the drug only provides a modest survival advantage, primarily due to chemoresistance and the upregulation of antiapoptotic machineries in ovarian cancer cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in ovarian cancer cells may improve the therapeutic outcomes. Twist basic helix-loop-helix transcription factor 2 (Twist2) is a novel zinc finger transcription factor that has been indicated to be an important inducer of epithelial-mesenchymal transition, which has been shown to be involved in various phases of tumorigenicity and progression. However, whether Twist2 suppression increases the chemosensitivity of ovarian cancer cells to chemotherapeutic agents remains unclear. In the present study, Twist2 expression was found to differ between human ovarian cisplatin-sensitive cancer cell line, OV2008, and the resistant variant, C13K cells. Twist2 plasmids or RNA interference were then utilized to alter Twist2 expression in OV2008 or C13K cells, respectively, to further assess apoptosis, cell viability and cell growth, as well as a possible mechanism. The results of the present study indicated that Twist2 plays a crucial role in the chemoresistance of ovarian cancer. In addition, the downregulation of Twist2 expression may facilitate apoptosis and recover the sensitivity of chemoresistant ovarian cancer through the protein kinase B/glycogen synthase kinase-3? pathway. Therefore, Twist2 depletion may be a promising approach to ovarian cancer therapy.
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Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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To investigated the influence of H. pylori on TLR4 and TLR9 in gastric mucosa during gastric carcinogenesis.
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Evaluation of antioxidant activities of ampelopsin and its protective effect in lipopolysaccharide-induced oxidative stress piglets.
PLoS ONE
PUBLISHED: 01-01-2014
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The aim of this study was to investigate the antioxidant potential of ampelopsin (APS) by using various methods in vitro, as well as to determine effects of APS on LPS-induced oxidative stress in piglets. The results showed that APS exhibited excellent free radical scavenging by DPPH, ABTS, O2•-, H2O2 and ferric reducing antioxidant power. Ampelopsin also protected pig erythrocytes against AAPH-induced apoptosis and hemolysis, decreased total superoxide dismutase activity, and increased lipid peroxidation. Furthermore the results demonstrated that APS enhanced the total antioxidant capacity and decreased the malondialdehyde and protein carbonyl contents in LPS-treated piglets. The results of the present investigation suggest that APS possesses a strong antioxidant activity and alleviates LPS-induced oxidative stress, possibly due to its ability to prevent reactive oxygen species.
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The co-stimulatory effects of MyD88-dependent Toll-like receptor signaling on activation of murine ?? T cells.
PLoS ONE
PUBLISHED: 01-01-2014
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?? T cells express several different toll-like receptor (TLR)s. The role of MyD88- dependent TLR signaling in TCR activation of murine ?? T cells is incompletely defined. Here, we report that Pam3CSK4 (PAM, TLR2 agonist) and CL097 (TLR7 agonist), but not lipopolysaccharide (TLR4 agonist), increased CD69 expression and Th1-type cytokine production upon anti-CD3 stimulation of ?? T cells from young adult mice (6-to 10-week-old). However, these agonists alone did not induce ?? T cell activation. Additionally, we noted that neither PAM nor CL097 synergized with anti-CD3 in inducing CD69 expression on ?? T cells of aged mice (21-to 22-month-old). Compared to young ?? T cells, PAM and CL097 increased Th-1 type cytokine production with a lower magnitude from anti-CD3- stimulated, aged ?? T cells. V?1+ and V?4+ cells are two subpopulations of splenic ?? T cells. PAM had similar effects in anti-CD3-activated control and V?4+ subset- depleted ?? T cells; whereas CL097 induced more IFN-? production from V?4+ subset-depleted ?? T cells than from the control group. Finally, we studied the role of MyD88-dependent TLRs in ?? T cell activation during West Nile virus (WNV) infection. ?? T cell, in particular, V?1+ subset expansion was significantly reduced in both MyD88- and TLR7- deficient mice. Treatment with TLR7 agonist induced more V?1+ cell expansion in wild-type mice during WNV infection. In summary, these results suggest that MyD88-dependent TLRs provide co-stimulatory signals during TCR activation of ?? T cells and these have differential effects on distinct subsets.
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Proteomics analysis of normal and senescent NG108-15 cells: GRP78 plays a negative role in cisplatin-induced senescence in the NG108-15 cell line.
PLoS ONE
PUBLISHED: 01-01-2014
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Accelerated senescence (ACS) leading to proliferative arrest is a physiological mechanism of the DNA damage response that occurs during tumor therapy. Our experiment was designed to detect unknown genes that may play important roles in cisplatin-induced senescence and to illustrate the related senescence mechanism. Using 2-dimension electrophoresis (2-DE), we identified 5 protein spots with different expression levels in the normal and senescent NG108-15 cells. According to MALDI-TOF MS analysis, the 5 proteins were determined to be peptidylprolyl isomerase A (PPIA), peroxiredoxin 1 (PRX1), glutathione S-transferase mu 1 (GSTM1), vimentin (VIM) and glucose-regulated protein 78 (GRP78). Then, we investigated how cisplatin-induced senescence was mediated by GRP78 in the NG108-15 cells. Knockdown of GRP78 significantly increased P53 expression in NG108-15 cells. Additionally, 2-deoxy-D-glucose (2DG)-induced GRP78 overexpression protected the NG108-15 cells from cisplatin-induced senescence, which was accompanied by the obvious suppression of P53 and p-CDC2 expression. Inhibition of Ca2+ release from endoplasmic reticulum (ER) stores was also found to be associated with the anti-senescence effect of 2DG-induced GRP78 overexpression. In conclusion, we found 5 proteins that were differentially expressed in normal NG108-15 cells and senescent NG108-15 cells. GRP78 plays an important role in cisplatin-induced senescence in NG108-15 cells, mainly through its regulation of P53 expression and ER calcium efflux.
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[Association between genetic polymorphisms in pre-miR-146a and pre-miR-196a2 and genetic damage levels among coke oven workers].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 11-20-2013
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To investigate the association of rs2910164 G > C polymorphism and rs11614913 T > C polymorphism in pre-miR-146a and pre-miR-196a2 with genetic damage levels in coke oven workers.
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Online least squares one-class support vector machines-based abnormal visual event detection.
Sensors (Basel)
PUBLISHED: 10-30-2013
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The abnormal event detection problem is an important subject in real-time video surveillance. In this paper, we propose a novel online one-class classification algorithm, online least squares one-class support vector machine (online LS-OC-SVM), combined with its sparsified version (sparse online LS-OC-SVM). LS-OC-SVM extracts a hyperplane as an optimal description of training objects in a regularized least squares sense. The online LS-OC-SVM learns a training set with a limited number of samples to provide a basic normal model, then updates the model through remaining data. In the sparse online scheme, the model complexity is controlled by the coherence criterion. The online LS-OC-SVM is adopted to handle the abnormal event detection problem. Each frame of the video is characterized by the covariance matrix descriptor encoding the moving information, then is classified into a normal or an abnormal frame. Experiments are conducted, on a two-dimensional synthetic distribution dataset and a benchmark video surveillance dataset, to demonstrate the promising results of the proposed online LS-OC-SVM method.
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Vector optical fields with bipolar symmetry of linear polarization.
Opt Lett
PUBLISHED: 10-10-2013
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We focus on a new kind of vector optical field with bipolar symmetry of linear polarization instead of cylindrical and elliptical symmetries, enriching members of family of vector optical fields. We design theoretically and generate experimentally the demanded vector optical fields and then explore some novel tightly focusing properties. The geometric configurations of states of polarization provide additional degrees of freedom assisting in engineering the field distribution at the focus to the specific applications such as lithography, optical trapping, and material processing.
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Sharper focal spot generated by 4? tight focusing of higher-order Laguerre-Gaussian radially polarized beam.
Opt Lett
PUBLISHED: 10-02-2013
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The focal electric fields for a 4? high numerical aperture (NA) focusing system with both the doughnut and higher-order Laguerre-Gaussian (LG) radially polarized (RP) beams are investigated in the case of NA=1, and the full width at half-maximum values of the focal spots are calculated. Compared with the single-lens high NA focusing configuration, a sharper spot, whose size is reduced efficiently in the transverse as well as the axial direction, can be formed. Such size reduction is attributed to not only the destruction interference of the longitudinal component caused by the ? phase shift between any two adjacent rings of the incident higher-order LG RP beam coming from one particular direction but also the perfect destruction interference of the radial component formed by the two counter-propagating incident beams.
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Genome-wide association study on serum alkaline phosphatase levels in a Chinese population.
BMC Genomics
PUBLISHED: 09-24-2013
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Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated.
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Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels.
Cell Biochem. Biophys.
PUBLISHED: 09-11-2013
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Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby canine kidney (MDCK) cells. We found that bumetanide and furosemide dose-dependently enhanced cytoplasmic GTTR fluorescence by ~60 %. This enhancement was suppressed by La(3+), a non-selective cation channel (NSCC) blocker, and by K(+) channel blockers Ba(2+) and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl(-) channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (V r) ~-80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba(2+) or clotrimazole, and absent in elevated [Ca(2+)]i, but was not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA, or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca(2+). Ba(2+) and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current V r near -85 mV, and reduced GTTR uptake by ~20 %. La(3+) alone hyperpolarized the cells by ~-14 mV, reduced the I/V slope with a net current V r near -10 mV, and inhibited GTTR uptake by ~50 %. In the presence of La(3+), bumetanide-caused negligible change in potential or I/V. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases the cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating intracellular Ca(2+) and thus facilitating activation of the intermediate conductance Ca(2+)-activated K(+) channels.
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[Relationship between health-promoting lifestyle and sub-health status in the employees of an enterprise].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-03-2013
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To study the relationship between sub-health status and the health-promoting lifestyle of employees.
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Mesostructured nanomagnetic polyhedral oligomeric silsesquioxanes (POSS) incorporated with dithiol organic anchors for multiple pollutants capturing in wastewater.
ACS Appl Mater Interfaces
PUBLISHED: 08-15-2013
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A functionalizable organosiliceous hybrid magnetic material was facilely constructed by surface polymerization of octavinyl polyhedral oligomeric silsesquioxane (POSS) on the Fe3O4 nanoparticles. The resultant Fe3O4@POSS was identified as a mesoporous architecture with an average particle diameter of 20 nm and high specific surface area up to 653.59 m(2) g(-1). After it was tethered with an organic chain containing dithiol via thiol-ene addition reaction, the ultimate material (Fe3O4@POSS-SH) still have moderate specific area (224.20 m(2) g(-1)) with almost identical porous morphology. It turns out to be a convenient, efficient single adsorbent for simultaneous elimination of inorganic heavy metal ions and organic dyes in simulate multicomponent wastewater at ambient temperature. The Fe3O4@POSS-SH nanoparticles can be readily withdrawn from aqueous solutions within a few seconds under moderate magnetic field and exhibit good stability in strong acid and alkaline aqueous matrices. Contaminants-loaded Fe3O4@POSS-SH can be easily regenerated with either methanol-acetic acid (for organic dyes) or hydrochloric acid (for heavy metal ions) under ultrasonication. The renewed one keeps appreciable adsorption capability toward both heavy metal ions and organic dyes, the removal rate for any of the pollutants exceeds 92% to simulate wastewater with multiple pollutants after repeated use for 5 cycles. Beyond the environmental remediation function, thanks to the pendant vinyl groups, the Fe3O4@POSS derived materials rationally integrating distinct or versatile functions could be envisaged and consequently a wide variety of applications may emerge.
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[Androgen receptor silencing by shRNA inhibits human prostate cancer xenograft growth in nude mice].
Beijing Da Xue Xue Bao
PUBLISHED: 08-14-2013
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To investigate the inhibitory effect of silencing androgen receptor (AR) gene by AR short-hairpin RNA (shRNA) on the growth of human prostate cancer xenograft in nude mice.
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Methionine improves the performance and breast muscle growth of broilers with lower hatching weight by altering the expression of genes associated with the insulin-like growth factor-I signalling pathway.
Br. J. Nutr.
PUBLISHED: 08-06-2013
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The present study aimed to investigate the responses of broilers with different hatching weights (HW) to dietary methionine (Met). A total of 192 1-d-old Arbor Acres broiler chicks with different HW (heavy: 48·3 (sem 0·1) g and light: 41·7 (sem 0·1) g) were allocated to a 2 (HW) × 2 (Met) factorial arrangement with six replicates of eight chicks. Control starter (1-21 d) and finisher (22-42 d) diets contained 0·50 and 0·43 % Met, respectively. Corresponding values for a high-Met treatment were 0·60 and 0·53 %. Light chicks had poorer (P< 0·05) growth performance and breast muscle weight and lower (P< 0·05) insulin-like growth factor-I (IGF-I) concentration and mRNA level in breast muscle than heavy chicks when both were fed the control diets. High-Met diets improved performance and promoted breast muscle growth and IGF-I concentration in light chicks (P< 0·05). Increased IGF-I and target of rapamycin (TOR) mRNA levels as well as decreased eIF4E-binding protein 1 (4EBP1), atrogin-1 and forkhead box O 4 (FOXO4) mRNA levels were induced by high-Met diets in light chicks (P< 0·05). In conclusion, the Met requirement of broilers might depend on their HW and Met levels used in the control diets in the present study were adequate for heavy chicks but inadequate for light chicks, resulting in poorer performance and breast muscle growth, which were improved by increasing dietary Met supply presumably through alterations in IGF-I synthesis and gene expression of the TOR/4EBP1 and FOXO4/atrogin-1 pathway.
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Anti-inflammatory Effect of Acetylpuerarin on Eicosanoid Signaling Pathway in Primary Rat Astrocytes.
J. Mol. Neurosci.
PUBLISHED: 07-26-2013
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Astrocytes activation has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including bacterial infections, cerebral ischemia, and Parkinsons diseases. Acetylpuerarin is a newly modified isoflavone based on puerarin that has neuroprotective and antioxidant effects. In this study, we investigated the anti-inflammatory action of acetylpuerarin in regulating the eicosanoids generation and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced production of arachidonic acid (AA) metabolites in primary rat astrocytes. The results showed that acetylpuerarin concentration dependently inhibited the LPS-induced production of AA metabolites such as prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), and acetylpuerarin significantly attenuated the expression and immunoreactivity of group V secretory phospholipase A2 (sPLA2) protein induced by LPS in astrocytes. Furthermore, in astrocytes pretreated with acetylpuerarin, the time course of phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and of cytosolic PLA2 alpha (cPLA2?) and expression of transcription factors, nuclear factor kappa B (NF-?B), was markedly truncated. Acetylpuerarin concentration dependently abolished the LPS-induced expressions of AA-metabolizing enzymes including cyclooxygenase-2 (COX-2) and lipooxygenase-5 (LOX-5). This study indicates that acetylpuerarin inhibited LPS-induced AA-metabolizing enzymes and AA metabolites in astrocytes via downregulation expression of group V sPLA2 and phosphorylation of ERK1/2, cPLA2?, and NF-?B. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of acetylpuerarin.
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Role of natural killer and Gamma-delta T cells in West Nile virus infection.
Viruses
PUBLISHED: 07-25-2013
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Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV), a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection.
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Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.
Fitoterapia
PUBLISHED: 07-25-2013
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Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-? (TNF-?) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-?, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-? in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect.
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MicroRNAs in regulation of pluripotency and somatic cell reprogramming: small molecule with big impact.
RNA Biol
PUBLISHED: 07-23-2013
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MicroRNAs (miRNAs), a group of small non-coding RNAs, have emerged as significant modulators in the establishment and generation of pluripotency, a developmental process that consists of complex cell-fate arrangements. The finding of embryonic stem cell (ESC) cycle-specific miRNAs reveals an important regulation scheme of pluripotency. Subsequent studies showed the ESC-enriched or ESC-depleted miRNAs can regulate induced pluripotent stem cells(iPSC). Moreover, miRNA profiling of iPSC and ESC may distinguish them from one another and facilitate the complex of regulatory network. The accumulative effects of miRNA action enable using miRNA alone to generate iPSCs. Despite the robustness of iPSC studies, further investigations are needed since miRNA may have more impact on induced pluripotency, and the roles of miRNAs in somatic cell nuclear transfer (SCNT), another approach toward cellular reprogramming, remains unclear. This point-of-view article will discuss miRNAs and their impact on the normal and induced pluripotency, as well as bring new insights on somatic cell reprogramming.
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Vector optical fields with polarization distributions similar to electric and magnetic field lines.
Opt Express
PUBLISHED: 07-12-2013
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We present, design and generate a new kind of vector optical fields with linear polarization distributions modeling to electric and magnetic field lines. The geometric configurations of "electric charges" and "magnetic charges" can engineer the spatial structure and symmetry of polarizations of vector optical field, providing additional degrees of freedom assisting in controlling the field symmetry at the focus and allowing engineering of the field distribution at the focus to the specific applications.
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Scanning tunneling microscopy investigation of self-assembled poly(3-hexylthiophene) monolayer.
J Chem Phys
PUBLISHED: 07-05-2013
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Poly(3-hexylthiophene) (P3HT) monolayer has been investigated by scanning tunneling microscopy (STM). The monolayer was dominated by three kinds of ordered structure (I, II, and III), where the thiophene main chains lied parallel to one another, but high resolution STM images revealed that the arrangement of the hexyl side chains was different. In structure I, the hexyl side chains tilted at ~60° with respect to the main chain, and the interchain distance (distance between two parallel neighboring backbones) was ~1.41 nm. In structure II, the interchain distance was significantly larger at ~1.52 nm, and the hexyl side chains were liquid-like. Structure III exhibited similar interchain distance as structure II, but the hexyl side chains were perpendicular to the main chain and were interdigitated. In addition to these ordered domains, individual poly(3-hexylthiophene) chains in various special configurations were observed, and their unfolding into more stable structures was tracked by dynamic STM, which provides evidence that P3HT is a relatively flexible polymer.
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Association of STAT4 gene polymorphism with increased susceptibility of rheumatoid arthritis in a northern Chinese Han subpopulation.
Int J Rheum Dis
PUBLISHED: 06-19-2013
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Several studies have reported STAT4 polymorphism is strongly associated with increased susceptibility to rheumatoid arthritis (RA). However, a study from China showed no association between STAT4 and RA susceptibility in a Chinese Han subpopulation. Since the northern Hans are known to be genetically different from the southern Hans, the aim of this study was to investigate the association of STAT4 polymorphism with RA in a large cohort of a northern Chinese Han subpopulation.
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Effects of clinoptilolite on growth performance and antioxidant status in broilers.
Biol Trace Elem Res
PUBLISHED: 06-04-2013
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The objective of this study was to compare the effects of natural clinoptilolite and modified clinoptilolite on growth performance and antioxidant capacity in broiler chicks. Two hundred forty 1-day-old commercial Arbor Acres broilers were randomly distributed into three treatments, each of which had eight replicates. Each replicate contains 10 chicks. Control (CON) group fed with the basal diets, natural clinoptilolite (NCLI) group fed basal diets with 2 % natural clinoptilolite, and modified clinoptilolite (MCLI) group fed basal diets with 2 % modified clinoptilolite for 42 days. The results showed that the 2 % supplementation of natural clinoptilolite and modified clinoptilolite had no adverse effect on growth performance of broilers at 42 days of age. Relative weights of organs were not influenced by dietary treatments at 21 and 42 days. The activity of total nitric oxide synthase was significantly (P < 0.05) decreased in MCLI group than CON group at 21 days of age. At 21 and 42 days, the activities of glutathione peroxidase, catalase, total superoxide dismutase, total antioxidant capacity (T-AOC) were significantly (P < 0.05) increased in NCLI and MCLI groups than the CON group while there was no difference in T-AOC between CON and NCLI groups. The malondialdehyde content was significantly (P < 0.05) decreased in NCLI and MCLI groups than the CON group. It was concluded that the addition of 2 % natural clinoptilolite and modified clinoptilolite to diet can improve antioxidant capacity in broilers, although their effects on growth performance was negligible.
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Neuroprotective effect of hydroxysafflor yellow A on 6-hydroxydopamine-induced Parkinsons disease in rats.
Eur. J. Pharmacol.
PUBLISHED: 06-03-2013
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Parkinsons disease (PD) is a progressive neurodegenerative disorder affecting predominantly the dopaminergic mesotelencephalic system. Enormous progress has been made in the treatment of PD. Our previous study has shown that hydroxysafflor yellow A (HSYA) could attenuate the neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. In the present work, we examined whether HSYA had the neuroprotective effect on dopaminergic neurons of substantia nigra in a rat model of PD. Adult Sprague-Dawley rats were unilaterally injected with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The PD rats were treated with HSYA (2 or 8 mg/kg) via caudal vein injection daily for 4 weeks. Rotational tests showed that HSYA significantly attenuated apomorphine-induced turns in 6-OHDA-induced PD rats. HSYA treatment resulted in a significant protection against the loss of tyrosine hydroxylase-positive cells. Our data showed that HSYA also increased the levels of dopamine and its metabolites, glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor in striatum of PD rats. In conclusion, these results supported a role for HSYA in preserving dopamine neuron integrity and motor function in a rodent model of PD, and implied a potential neuroprotective role for HSYA in this disease.
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A hamster-derived West Nile virus isolate induces persistent renal infection in mice.
PLoS Negl Trop Dis
PUBLISHED: 06-01-2013
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West Nile virus (WNV) can persist long term in the brain and kidney tissues of humans, non-human primates, and hamsters. In this study, mice were infected with WNV strain H8912, previously cultured from the urine of a persistently infected hamster, to determine its pathogenesis in a murine host.
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Assessment of free radicals scavenging activity of seven natural pigments and protective effects in AAPH-challenged chicken erythrocytes.
Food Chem
PUBLISHED: 05-04-2013
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The purpose of this study was to compare the antioxidant capacities of seven natural pigments including the fat-soluble pigments curcumin, lycopene, lutein and ?-carotene and water-soluble pigments--betalain, capsanthin and cyanidin-3-rutinoside relative to a commonly-used synthetic food antioxidant BHA. The antioxidant capacities of seven pigments and BHA were evaluated based on their ability to quench several free radicals, including DPPH, ABTS, O2(·-), H2O2 as well as using FRAP assay. Specifically, curcumin and cyanidin-3-rutinoside, which showed the highest antioxidant capacities, were further investigated using a chicken erythrocyte model. After separating pretreatments of the two pigments, AAPH was added to the erythrocyte-pigment medium to induce oxidative stress. Then the attenuation effects of the two pigments on AAPH-induced oxidative damage in chicken erythrocytes were assessed. It was found that both curcumin and cyanidin-3-rutinoside significantly attenuated apoptosis and hemolysis, decreased MDA content, and increased T-SOD activity in a time- and dose- dependent manner.
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Imputation-based association analyses identify new lung cancer susceptibility variants in CDK6 and SH3RF1 and their interactions with smoking in Chinese populations.
Carcinogenesis
PUBLISHED: 05-03-2013
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Cell cycle regulation, apoptosis, oxidative stress and inflammation response play critical roles in the development of smoking-induced lung cancer. However, it is still not well known whether their genetic variants are associated with lung cancer susceptibility. In this study, we performed imputation-based association analyses to investigate the influence of common genetic variants in these pathways and their interactions with smoking on lung cancer susceptibility. We first selected 24 042 unvalidated genetic variants in 798 genes from the imputed dataset of the previous lung cancer genome-wide association study in 2331 cases and 3077 controls, and then conducted additional two-stage validations in 4133 cases and 4522 controls. We found a genome-wide significant (P < 5.0 × 10(-8)) association for rs2282987 in CDK6 at 7q21.2 [odds ratio (OR) = 1.18, combined P add = 2.27 × 10(-9)] and a consistent association for rs2706748 in SH3RF1 at 4q32.3 (OR = 1.17, combined P add = 5.10 × 10(-6)). Interaction analyses showed that rs2282987 and rs2706748 interacted with both smoking status (P interaction were 1.04 × 10(-2) and 3.03 × 10(-2), respectively) and smoking history (P interaction were 1.21 × 10(-2) and 5.21 × 10(-2), respectively) to contribute to lung cancer susceptibility in subjects aged 51-60 years. These results further underscore the contribution of genetic variants involved in pathways of cell cycle regulation and apoptosis to lung cancer susceptibility, and highlight gene-environment interactions in lung cancer etiology, especially in subjects aged 51-60 years.
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