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Find video protocols related to scientific articles indexed in Pubmed.
[Feasibility study of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in proposing selection criteria for patients with hepatocellular carcinoma in liver transplantation].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-18-2014
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To explore the feasibility of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in proposing selection criteria for patients with hepatocellular carcinoma (HCC) in liver transplantation.
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Activation of D4 Dopamine Receptor Decreases Angiotensin II Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells.
Hypertension
PUBLISHED: 11-05-2014
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The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal angiotensin type 1 (AT1) receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubule cells from Wistar-Kyoto (WKY) rats, but the D4 receptor regulation of AT1 receptor is aberrant in renal proximal tubule cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time- and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na(+)-K(+) ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na(+)-K(+) ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na(+)-K(+) ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na(+)-K(+) ATPase activity in SHR cells. This was confirmed in vivo; pretreatment with PD128077 for 1 week augmented the antihypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension.
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All-optical wavelength conversion and five-channel multicasting for 20??Gbit/s QPSK signals in a silicon waveguide.
Opt Lett
PUBLISHED: 11-01-2014
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Wavelength conversion and five-channel multicasting for 20??Gbit/s quadrature phase-shift keying signals have been experimentally demonstrated based on four-wave mixing in a silicon waveguide with digital coherent detection. The eye diagrams and constellation diagrams of the converted and multicasting idlers are successfully observed. Moreover, the bit-error rates (BERs) of the generated idlers are measured and the power penalties are all less than 0.7 dB at a BER of 3×10-3.
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[Effect of Feridex-GFP double-labeled BMSC transplant on the damaged liver under the condition of constant magnetic field].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-31-2014
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To evaluate the effect of the bone marrow mesenchymal stem cells (BMSCs) transplant through peripheral vein, portal vein and hepatic artery into liver under the condition of constant magnetic field and to analyze the therapeutic effect on liver function recovery.
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Green facile scalable synthesis of titania/carbon nanocomposites: new use of old dental resins.
ACS Appl Mater Interfaces
PUBLISHED: 10-30-2014
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A green facile scalable method inspired by polymeric dental restorative composite is developed to synthesize TiO2/carbon nanocomposites for manipulation of the intercalation potential of TiO2 as lithium-ion battery anode. Poorly crystallized TiO2 nanoparticles with average sizes of 4-6 nm are homogeneously embedded in carbon matrix with the TiO2 mass content varied between 28 and 65%. Characteristic discharge/charge plateaus of TiO2 are significantly diminished and voltage continues to change along with proceeding discharge/charge process. The tap density, gravimetric and volumetric capacities, and cyclic and rate performance of the TiO2/C composites are effectively improved.
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Association of the plasminogen activator inhibitor-1 (PAI-1) Gene -675 4G/5G and -844 A/G promoter polymorphism with risk of keloid in a Chinese Han population.
Med. Sci. Monit.
PUBLISHED: 10-29-2014
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A keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk.
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[Clinicopathologic features and prognosis of primary bone anaplastic large cell lymphoma].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 10-28-2014
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To study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL).
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The dopamine D1-like receptors regulate the ?1A adrenergic receptor in human renal proximal tubule cells and D1-like dopamine receptor knockout mice.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 10-24-2014
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The homeostatic control of blood pressure hinges upon the delicate balance between pro-hypertensinogenic and anti-hypertensinogenic systems. The D1-like dopamine receptors (D1R and D5R) and the ?1A adrenergic receptor (?1A-AR) are expressed in the renal proximal tubule and engender opposing effects on sodium transport, i.e., natriuresis (via D1R and D5R) or anti-natriuresis (via ?1A-AR). We tested the hypothesis that the D1R/D5R regulates the ?1A-AR. The D1-like dopamine receptors co-immunoprecipitated, co-localized, and co-fractionated with ?1A-AR in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with D1R/D5R agonist fenoldopam resulted in decreased D1R and D5R expression, but increased ?1A-AR abundance in the plasma membrane. Short-term fenoldopam treatment stimulated the translocation of Na(+),K(+)-ATPase from the plasma membrane to the cytosol that was partially reversed by an ?1A-AR agonist, which by itself induced Na(+),K(+)-ATPase translocation from the cytosol to the plasma membrane. The ?1A-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na(+),K(+)-ATPase activity. To determine the interaction among D1R, D5R, and ?1A-AR in vivo, we used phenylephrine and A610603 to decrease Na(+) excretion in several D1-like dopamine receptor knockout mouse strains. Phenylephrine and A61603 treatment resulted in partial reduction of the urinary sodium excretion in wild-type mice and its abolition in Drd1-/-, Drd5(-/-), and Drd1(-/-)/Drd5(-/-) mice. Our results demonstrate the ability of the D1-like dopamine receptors to regulate the expression and activity of ?1A-AR. Elucidating the intricacies of the interaction among these receptors is crucial for a better understanding of the crosstalk between anti- and pro-hypertensive systems.
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[Determination of four phenolic endocrine disruptors in environmental water samples by high performance liquid chromatography-fluorescence detection using dispersive liquid-liquid microextraction coupled with derivatization].
Se Pu
PUBLISHED: 10-02-2014
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To achieve accurate, fast and sensitive detection of phenolic endocrine disruptors in small volume of environmental water samples, a method of dispersive liquid-liquid microextraction (DLLME) coupled with fluorescent derivatization was developed for the determination of bisphenol A, nonylphenol, octylphenol and 4-tert-octylphenol in environmental water samples by high performance liquid chromatography-fluorescence detection (HPLC-FLD). The DLLME and derivatization conditions were investigated, and the optimized DLLME conditions for small volume of environmental water samples (pH 4.0) at room temperature were as follows: 70 microL chloroform as extraction solvent, 400 microL acetonitrile as dispersing solvent, vortex mixing for 3 min, and then high-speed centrifugation for 2 min. Using 2-[2-(7H-dibenzo [a, g] carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEC-Cl) as precolumn derivatization reagent, the stable derivatives of the four phenolic endocrine disruptors were obtained in pH 10.5 Na2CO3-NaHCO3 buffer/acetonitrile at 50 degrees C for 3 min, and then separated within 10 min by HPLC-FLD. The limits of detection (LODs) were in the range of 0.9-1.6 ng/L, and the limits of quantification (LOQs) were in the range of 3.8-7.1 ng/L. This method had perfect linearity, precision and recovery results, and showed obvious advantages and practicality comparing to the previously reported methods. It is a convenient and validated method for the routine analysis of phenolic endocrine disruptors in waste water of paper mill, lake water, domestic wastewater, tap water, etc.
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[Simultaneous determination of seven residual solvents in bovis calculus artifactus by headspace gas chromatography].
Se Pu
PUBLISHED: 09-05-2014
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A headspace gas chromatography (HS-GC) method was developed for the simultaneous determination of seven residual solvents (petroleum ether (60-90 degrees C), acetone, ethyl acetate, methanol, methylene chloride, ethanol and butyl acetate) in bovis calculus artifactus. The DB-WAX capillary column and flame ionization detector (FID) were used for the separation and detection of the residual solvents, and the internal standard method was used for the quantification. The chromatographic conditions, such as equilibrium temperature and equilibrium time, were optimized. Under the optimized conditions, all of the seven residual solvents showed good linear relationships with good correlation coefficients (not less than 0.999 3) in the prescribed concentration range. At three spiked levels, the recoveries for the seven residual solvents were 94.7%-105.2% with the relative standard deviations (RSDs) less than 3.5%. The limits of detection (LODs) of the method were 0.43-5.23 mg/L, and the limits of quantification (LOQs) were 1.25-16.67 mg/L. The method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the seven residual solvents in bovis calculus artifactus.
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[Relationship between genetic polymorphisms of matrix metalloproteinase-2 and -3 and susceptibility to silicosis].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 09-04-2014
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To investigate the relationship between the genetic polymorphisms of matrix metalloproteinase-2 (MMP-2) (-735) and matrix metalloproteinase-3 (MMP-3) (-1171) and the susceptibility to silicosis.
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Nociceptin/orphanin FQ-induced inhibition of delayed rectifier potassium currents by calcium/calmodulin-dependent protein kinase type II.
Neuroreport
PUBLISHED: 08-30-2014
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The neuropeptide nociceptin/orphanin FQ (N/OFQ) has been shown to inhibit delayed rectifier potassium current (IK) in acutely dissociated rat parietal cortical neurons. However, the detailed mechanism of N/OFQ-induced inhibition on IK is not clear. This study is the first to explore an involvement of calcium/calmodulin (CaM)-dependent protein kinase type II (CaMKII) in mediating N/OFQ-induced responses. Utilizing pharmacological inhibitors of CaM and CaMKII, we have investigated the contribution of CaMKII in N/OFQ-induced effects using the whole-cell patch-clamp technique. In whole-cell voltage clamp, W-7 (100??M), an antagonist of CaM, as well as KN-62, an inhibitor of CaMKII activity, attenuated the inhibitory effects of N/OFQ on IK. Activation and inactivation analysis indicated that the kinetics of IK were altered by N/OFQ, with decreased activation and promoted inactivation of IK. W-7 and KN-62 (10??M) partly abolished the activation and inactivation curves shift of IK induced by N/OFQ. These findings show that CaMKII plays a critical role in N/OFQ-induced inhibition of IK in acutely dissociated rat parietal cortical neurons.
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Identification of Lactobacillus from the saliva of adult patients with caries using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
PLoS ONE
PUBLISHED: 08-28-2014
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Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) has been presented as a superior method for the detection of microorganisms in body fluid samples (e.g., blood, saliva, pus, etc.) However, the performance of MALDI-TOF MS in routine identification of caries-related Lactobacillus isolates from saliva of adult patients with caries has not been determined. In the present study, we introduced a new MALDI-TOF MS system for identification of lactobacilli. Saliva samples were collected from 120 subjects with caries. Bacteria were isolated and cultured, and each isolate was identified by both 16S rRNA sequencing and MALDI-TOF MS. The identification results obtained by MALDI-TOF MS were concordant at the genus level with those of conventional 16S rRNA-based sequencing for 88.6% of lactobacilli (62/70) and 95.5% of non-lactobacilli (21/22). Up to 96 results could be obtained in parallel on a single MALDI target, suggesting that this is a reliable high-throughput approach for routine identification of lactobacilli. However, additional reference strains are necessary to increase the sensitivity and specificity of species-level identification.
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Compounding local invariant features and global deformable geometry for medical image registration.
PLoS ONE
PUBLISHED: 08-28-2014
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Using deformable models to register medical images can result in problems of initialization of deformable models and robustness and accuracy of matching of inter-subject anatomical variability. To tackle these problems, a novel model is proposed in this paper by compounding local invariant features and global deformable geometry. This model has four steps. First, a set of highly-repeatable and highly-robust local invariant features, called Key Features Model (KFM), are extracted by an effective matching strategy. Second, local features can be matched more accurately through the KFM for the purpose of initializing a global deformable model. Third, the positional relationship between the KFM and the global deformable model can be used to precisely pinpoint all landmarks after initialization. And fourth, the final pose of the global deformable model is determined by an iterative process with a lower time cost. Through the practical experiments, the paper finds three important conclusions. First, it proves that the KFM can detect the matching feature points well. Second, the precision of landmark locations adjusted by the modeled relationship between KFM and global deformable model is greatly improved. Third, regarding the fitting accuracy and efficiency, by observation from the practical experiments, it is found that the proposed method can improve 6~8% of the fitting accuracy and reduce around 50% of the computational time compared with state-of-the-art methods.
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Theoretical Prediction of a Phase Diagram for Solid Dispersions.
Pharm. Res.
PUBLISHED: 08-28-2014
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To predict the temperature-composition phase diagram of solid dispersions (SDs) through theoretical approaches using cinnarizine-Soluplus(®) SD as a model system and evaluate the predicted results.
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Effect and mechanism of tacrolimus on melanogenesis on A375 human melanoma cells.
Chin. Med. J.
PUBLISHED: 08-19-2014
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Topical tacrolimus has been used for vitiligo as a common treatment option for more than ten years while the underlying mechanism is still uncertain. The aim of this study was to investigate the direct effects of tacrolimus on the melanogenesis and migration on human A375 melanoma cells. The expression of c-KIT mRNA and protein of human A375 cells were also investigated.
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Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells.
Int. J. Oncol.
PUBLISHED: 08-13-2014
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The low efficacy of single-drug chemotherapy forms the basis for combination therapy in esophageal squamous cell carcinoma. SNX-2112, a selective heat shock protein 90 (Hsp90) inhibitor, was recently reported as being effective in combination with cisplatin and paclitaxel. In this study, we investigated the effect of SNX-2112 in combination with 5-fluorouracil (5-FU), another first-line anticancer drug, in esophageal cancer. Unexpectedly, tetrazolium assay revealed that the combination of SNX-2112 with 5-FU exhibited antagonistic effect. Flow cytometry revealed that the SNX-2112 and 5-FU combination greatly decreased the number of G2/M cells compared to SNX-2112-only treatment in Eca?109 cells. This effect might be related to the altered mRNA level of cyclin-related genes including cyclin D1, Chk2 and Cdk4. Further, 5-FU attenuated SNX-2112-induced apoptosis by decreasing poly(ADP-ribose) polymerase (PARP) cleavage and inactivating caspase-3, -8 and -9. Additionally, 5-FU suppressed the SNX-2112-induced decrease of mitochondrial membrane potential. Moreover, 5-FU partly recovered Hsp90 client proteins, including Akt, p-Akt, inhibitor of ?B kinase (IKK)?, extracellular signal-regulated kinase (ERK)1/2, and glycogen synthase kinase (GSK)-3?, which SNX-2112 had downregulated. Taken together, this is the first report that the combination of SNX-2112 with 5-FU exhibited antagonistic effect in esophageal cancer cells by affecting growth inhibition, cell cycle, apoptosis, and Hsp90 client proteins, suggesting that care is required in the clinical application of combined SNX-2112 and 5-FU.
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Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection.
Med. Oncol.
PUBLISHED: 07-21-2014
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Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.
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Synthesis of iodine-containing cyclophosphazenes for using as radiopacifiers in dental composite resin.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 07-19-2014
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In this study, a strategy of using iodine-containing cyclophosphazenes as radiopacifiers for dental composite resin was evaluated. It was hypothesized that cyclophosphazenes bearing both iodine and acrylate group swere able to endow composite resins radiopacity without compromising mechanical properties. The cyclophosphazene compounds were synthesized by subsequently nucleophilic substitution of hexachlorocyclotriphosphazene with hydroxyethyl methacrylate (HEMA) and 4-iodoaniline. Cyclotriphosphazenes containing two different molar ratios of HEMA to 4-iodoaniline (1:5 and 2:4) were obtained, and were identified with (1)H NMR, FT-IR, UV and mass spectroscopy. The iodine-containing cyclophosphazenes were able to dissolve well in bisphenol A glycidyl methacrylate (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA) resin, and were added at two contents (10 or 15%wt. of the resin). The resins were photo-cured and post-thermal treated before characterizations. The resulting composite resins demonstrated the ability of blocking X-ray. And the addition of HEMA-co-iodoaniline substituted cyclotriphosphazenes caused minor adverse effect on the mechanical properties of the resins because the cyclotriphosphazenes could mix well and react with the resins. The presence of rigid phosphazene rings between resin backbones displayed an effective function of decreasing polymerization shrinkage. In summary, soluble and reactive iodine-containing cyclotriphosphazenes demonstrated advantages over traditional heavy metals or metal oxides in being used as additives for producing radiopaque dental resins.
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The alteration of 18F-FDG uptake in bone marrow after treatment with interleukin 11.
Clin Nucl Med
PUBLISHED: 07-19-2014
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Diffuse increased F-FDG in the bone marrow can be seen with colony-stimulating factors. Here, we reported a case of idiopathic cytopenia of undetermined significance treated with interleukin 11. After administration of interleukin 11, both diffuse and focally increased FDG activity in the bone marrow were noted. The focal activity was histologically proven as hyperplastic bone marrow.
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HSV-sr39TK positron emission tomography and suicide gene elimination of human hematopoietic stem cells and their progeny in humanized mice.
Cancer Res.
PUBLISHED: 07-18-2014
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Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR-bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173-83. ©2014 AACR.
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Distribution patterns of brominated, chlorinated, and phosphorus flame retardants with particle size in indoor and outdoor dust and implications for human exposure.
Environ. Sci. Technol.
PUBLISHED: 07-17-2014
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Dust samples were collected in Beijing, China, from four different indoor microenvironments (office, hotel, kindergarten, and student dormitory) and one outdoor (road dust) microenvironment. These five composite samples were fractionated into 13 sequential size fractions and an individual fraction of <50 ?m for further analysis. In the fractions of <50 ?m, nine phosphorus flame retardants (?PFRs), four novel brominated flame retardants (?NBFRs), and two Dechlorane Plus isomers (DPs) showed the highest concentrations in hotel dust (124,000 ng g(-1)), dormitory dust (14,200 ng g(-1)), and kindergarten dust (231 ng g(-1)), respectively. Nevertheless, nine polybrominated diphenyl ethers (?PBDEs) were the dominant flame retardants (FRs) (96% of total FRs) in road dust, with the maximum concentration of 23,700 ng g(-1), higher than in any indoor dust. The FR contamination varied strongly among different types of microenvironments, leading to high human exposure to various FRs. Concentrations of FRs did not increase constantly with a particle size decrease. Fractions with a particle size around 900, 100, and 10 ?m could represent peak values, while valley values were commonly detected around fractions with a particle size around 40 ?m. Large differences were found between indoor dust and road dust. In road dust, FRs were mainly enriched in fractions of <50 ?m. The organic content of dust, FR application, and consequent abrasion processes of FR-containing materials might be the determinants of the FR concentrations. Volatilization and abrasion were considered to be important migration pathways for FRs. DPs and BDE-209 were sought to be mainly applied in abrasion-proof materials, while most phosphorus flame retardants (PFRs) were probably added in a large proportion in materials easy to wear.
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Managing agricultural phosphorus for water quality: Lessons from the USA and China.
J Environ Sci (China)
PUBLISHED: 07-14-2014
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The accelerated eutrophication of freshwaters and to a lesser extent some coastal waters is primarily driven by phosphorus (P) inputs. While efforts to identify and limit point source inputs of P to surface waters have seen some success, nonpoint sources remain difficult to identify, target, and remediate. As further improvements in wastewater treatment technologies becomes increasingly costly, attention has focused more on nonpoint source reduction, particularly the role of agriculture. This attention was heightened over the last 10 to 20years by a number of highly visible cases of nutrient-related water quality degradation; including the Lake Taihu, Baltic Sea, Chesapeake Bay, and Gulf of Mexico. Thus, there has been a shift to targeted management of critical sources of P loss. In both the U.S. and China, there has been an intensification of agricultural production systems in certain areas concentrate large amounts of nutrients in excess of local crop and forage needs, which has increased the potential for P loss from these areas. To address this, innovative technologies are emerging that recycle water P back to land as fertilizer. For example, in the watershed of Lake Taihu, China one of the largest surface fresh waters for drinking water supply in China, local governments have encouraged innovation and various technical trials to harvest harmful algal blooms and use them for bio-gas, agricultural fertilizers, and biofuel production. In any country, however, the economics of remediation will remain a key limitation to substantial changes in agricultural production.
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Egr-1 regulates the transcription of NGX6 gene through a Sp1/Egr-1 overlapping site in the promoter.
BMC Mol. Biol.
PUBLISHED: 06-26-2014
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As a novel candidate metastasis suppressor gene, Nasopharyngeal carcinoma-associated gene 6 (NGX6) is involved in cellular growth, cell cycle progression and tumor angiogenesis. Previous studies have shown that NGX6 gene is down-regulated in colorectal cancer (CRC). However, little is known about its transcriptional regulation.
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Comparative effects of SNX-7081 and SNX-2112 on cell cycle, apoptosis and Hsp90 client proteins in human cancer cells.
Oncol. Rep.
PUBLISHED: 06-16-2014
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SNX-2112, a novel 2-aminobenzamide inhibitor of Hsp90, previously showed a broad spectrum of anticancer activity. However, subsequent development has been discontinued due to ocular toxicity as identified in a phase I study. SNX-7081, another closely related Hsp90 inhibitor with a side chain of indole instead of indazole, has recently attracted attention. The aim of the present study was to investigate the anticancer effects of SNX-7081 in eleven cell lines, as well as the mechanisms involved, with SNX-2112 serving as a reference. The cytotoxic effects were determined using an MTT assay and apoptosis was measured using flow cytometry. The results showed that SNX-7081 exerted better inhibitory effects than SNX-2112 in six eighths of the human cancer cell lines, with an average IC50 of 1 µM. The two inhibitors exerted low cytotoxicity in L-02, HDF and MRC5 normal human cells (IC50 >50 µM), and arrested cancer cells at the G2/M phase in a similar manner to normal cells. Compared with SNX-2112, SNX-7081 exhibited more potent effects on cell apoptosis in four sixths of the human cancer cell lines, and was more active in the downregulation of Hsp90 client proteins. In addition, SNX-7081 exhibited a stronger binding affinity to Hsp90 than SNX-2112 in molecular docking experiments. Considering the superior effects against Hsp90 affinity, cell growth, apoptosis, and Hsp90 client proteins in a majority of human cancer cells, the novel SNX-7081 may be a promising alternative to SNX-2112, which merits further evaluation.
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NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer.
Oncol. Rep.
PUBLISHED: 06-04-2014
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quinone oxidoreductase-1 (NQO1) is commonly elevated in various types of human cancers, including pancreatic, breast and thyroid cancer, as well as others. However, little is known concerning the status of NQO1 in small cell lung cancer (SCLC). To investigate the clinicopathological significance of NQO1 expression and evaluate its role as a potential prognostic marker in SCLC, protein and mRNA expression levels of NQO1 were determined in four fresh tissue samples of SCLC and paired adjacent non-cancerous tissues using western blotting and real-time qRT-PCR, respectively, and 115 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of NQO1 protein. The correlation between NQO1 expression and the clinicopathological features of SCLC was evaluated using the Chi-square (?2) and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In regards to the results, levels of NQO1 protein and mRNA were significantly elevated in the four fresh tissue samples of SCLC compared with levels in the paired adjacent non-cancerous tissues, respectively. IHC analysis showed that the rate of strong positive NQO1 protein expression was significantly higher (48.70%) in SCLC when compared with the rate in either adjacent non-cancerous or normal lung tissues (both P<0.001). The rate of strong positive NQO1 protein expression was correlated with large tumor size (P=0.019), late pathologic stage (P=0.001) and the presence of lymph node metastasis (P=0.001). Moreover, high?level expression of NQO1 protein was significantly correlated with lower disease-free survival (P=0.001) and 5-year survival rates (P<0.001) in SCLC patients, particularly early?stage patients (P=0.045 and P=0.033, respectively). Further Cox analysis revealed that NQO1 expression emerged as a significantly independent hazard factor for the 5-year survival rate of patients with SCLC (P=0.042). In conclusion, NQO1 plays an important role in the progression of SCLC, and it may potentially be used as a biomarker and therapeutic target of SCLC.
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Influence of Calcium Hydroxide-loaded Microcapsules on Osteoprotegerin and Receptor Activator of Nuclear Factor Kappa B Ligand Activity.
J Endod
PUBLISHED: 05-27-2014
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Calcium hydroxide (Ca[OH]2) microcapsules were synthesized to allow controlled release of Ca(OH)2. The aim of this study was to evaluate the influence of Ca(OH)2 microcapsules on osteoprotegerin (OPG) activity, receptor activator of nuclear factor kappa B ligand (RANKL) activity, and the OPG/RANKL ratio compared with pure Ca(OH)2 powder and Vitapex (Neo Dental Chemical Products Co Ltd, Tokyo, Japan).
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Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells.
Tumour Biol.
PUBLISHED: 05-21-2014
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Fatty acid synthase (FAS) is overexpressed in many human cancers including breast cancer and is considered to be a promising target for therapy. Sea buckthorn has long been used to treat a variety of maladies. Here, we investigated the inhibitory effect of sea buckthorn procyanidins (SBPs) isolated from the seeds of sea buckthorn on FAS and FAS overexpressed human breast cancer MDA-MB-231 cells. The FAS activity and FAS inhibition were measured by a spectrophotometer at 340 nm of nicotinamide adenine dinucleotide phosphate (NADPH) absorption. We found that SBP potently inhibited the activity of FAS with a half-inhibitory concentration (IC50) value of 0.087 ?g/ml. 3-4,5-Dimethylthiazol-2-yl-2,3-diphenyl tetrazolium bromide (MTT) assay was used to test the cell viability. SBP reduced MDA-MB-231 cell viability with an IC50 value of 37.5 ?g/ml. Hoechst 33258/propidium iodide dual staining and flow cytometric analysis showed that SBP induced MDA-MB-231 cell apoptosis. SBP inhibited intracellular FAS activity with a dose-dependent manner. In addition, sodium palmitate could rescue the cell apoptosis induced by SBP. These results showed that SBP was a promising FAS inhibitor which could induce the apoptosis of MDA-MB-231 cells via inhibiting FAS. These findings suggested that SBP might be useful for preventing or treating breast cancer.
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Cloning and expression characteristics of the pig Stra8 gene.
Int J Mol Sci
PUBLISHED: 05-19-2014
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Stra8 (Stimulated by Retinoic Acid 8) is considered a meiotic gatekeeper gene. Using reverse transcriptase PCR and rapid amplification of cDNA ends (RACE), the complete sequence of the pig Stra8 gene was cloned. Bioinformatics analyses of this sequence were performed. Using semi-quantitative methods, the expression characteristics of Stra8 in Testis, cauda epididymis, body epididymis, caput epididymis, seminal vesicles, prostate gland, Cowper's gland, heart, liver, spleen, lung, kidney, stomach, hypothalamus, pituitary gland, cerebrum, cerebellum, and hippocampus of adult Meishan boar and sow tissues were examined. The expression pattern in the testis of 2-, 30-, 60-, 90-, and 150-day old Meishan boars were analyzed using real-time PCR. We constructed a eukaryotic expression vector for the Stra8 gene and used it to transfect NIH-3T3 cells and third generation pig spermatogonial stem cells (SSCs) cultured in vitro. Testes weight and sperm count in the cauda epididymis were evaluated at various time points. The results showed that the length of the pig Stra8 gene cDNA was 1444 bp encoding 366 amino acids with one typical helix-loop-helix (HLH) domain. It is testes-specific expression. Expression was first detected in boar testis starting at day 2, and its expression significantly (p<0.05) increased with age and body weight. When NIH-3T3 cells and pig SSCs were transfected with the eukaryotic expression vector EGFP (enhanced green fluorescent protein)-N1-pStra8, it was expressed in the cytoplasm of NIH-3T3 cells. However, in SSCs, Stra8 was expressed predominantly in cytoplasm and few in nucleus. Our data suggest that perhaps Stra8 acts as a transcription factor to initiate meiosis in young boar.
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Effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ADA-deficient mice and rhesus monkeys.
Mol. Ther.
PUBLISHED: 05-11-2014
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Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. Previously, we have shown that transfer of the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and reconstitutes immune function in ADA-deficient mice. In order to translate this approach to ADA-deficient severe combined immune deficiency patients, neonatal ADA-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1-based vector to murine ?-retroviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors had the highest titer and resulted in the highest vector copy number in multiple tissues, particularly liver and lung. In monkeys, HIV-1 or simian immunodeficiency virus vectors resulted in similar biodistribution in most tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30-fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype, but had a similar tissue biodistribution and similar copy number in blood cells. The relative copy numbers achieved in mice and monkeys were similar when adjusted to the administered dose per kg. These results suggest that this approach can be scaled-up to clinical levels for treatment of ADA-deficient severe combined immune deficiency subjects with suboptimal hematopoietic stem cell transplantation options.
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The spectral transmission of non-salticid spider corneas.
J. Exp. Biol.
PUBLISHED: 05-06-2014
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Although many salticid spiders have been shown to have corneas that transmit ultraviolet (UV) light, whether the corneas of non-salticid spiders transmit UV has not been previously investigated. In this study, we determined the spectral corneal transmission properties of 38 species belonging to 13 non-salticid families. We used these data to estimate the T50 transmission cut-off value, the wavelength corresponding to 50% maximal transmission for each species. The corneas of almost all species from the families Deinopidae, Lycosidae, Oxyopidae, Pisauridae, Sparassidae and Thomisidae, all of which have been reported to rely to a substantial extent on vision, transmitted short wavelength light below 400 nm, ranging from 306 to 381 nm. However, species from the families Atypidae and Ctenizidae are not known to rely substantially on vision, and the corneas of these species tended to absorb light of wavelengths below 380 nm, which may not allow UV sensitivity in these spiders. Liphistiidae, the family widely regarded as most basal among spiders, is of particular interest. The species in this family are not known to make substantial use of vision, and yet we found that liphistiid corneas transmitted UV light with a low T50 value (359 nm). T50 values of non-salticid spider corneas also varied with light habitat. Species living in dim environments tended to have UV-opaque corneas, but species inhabiting open areas had UV-transmitting corneas. However, there was no evidence of corneal transmission properties being related to whether a species is diurnal or nocturnal.
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Intraoperative target-controlled infusion anesthesia application using remifentanil hydrochloride with etomidate in patients with severe burn as monitored using Narcotrend.
Burns
PUBLISHED: 04-29-2014
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This study aims to evaluate the feasibility of intraoperative composite target-controlled infusion (TCI) anesthesia application using remifentanil hydrochloride with etomidate in patients with severe burns, as monitored by Narcotrend.
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[Accumulation-associated protein gene and TGF-beta 1 affects the formation of lung cancer-related biological material Staphylococcus epidermidis biofilm].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 04-25-2014
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This study was conducted to evaluate the effects of the accumulation-associated protein (Aap) gene and transform growth factor-beta 1 (TGF-?1) on the biofilm formation of lung cancer-related Staphylococcus epidermidis (SE).
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[Changes of blood pressure and S-100B, neuron specific enolase protein in hypertensive dogs after renal sympathetic denervation].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 04-22-2014
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To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation.
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Phospho-Cdc25 correlates with activating G2/M checkpoint in mouse zygotes fertilized with hydrogen peroxide-treated mouse sperm.
Mol. Cell. Biochem.
PUBLISHED: 04-12-2014
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The presence of oxidative stress in sperm cryopreservation induces sperm DNA damage. Our previous study has discovered that ?H2AX, the DNA-damaged marker, was activated in the early mouse embryos fertilized with hydrogen peroxide (H2O2)-treated sperm. Furthermore, we found that checkpoint proteins ATM and Chk1 were phosphorylated and activated in the early mouse embryos. On the basis of previous researches, we examined the effects of sperm DNA damage on cell cycle arrest in mouse zygotes fertilized with H2O2-treated sperm. Development of fertilized eggs arrested at the PN disappearance stage. At 19 and 24 hours post-insemination (hpi), the percentage of zygotes at the PN disappearance stage was higher in H2O2-treated group compared to the control group. Immunofluorescence staining revealed Phospho-Cdc25C (Ser216) and Phospho-Cdc25B (Ser323) in or surrounding a single pronucleus, following insemination with H2O2-treated sperm. Our study suggests that fertilization with DNA-damaged sperm results in cell cycle arrest mediated by G2/M checkpoint activation in one of the pronuclei in mouse zygotes fertilized with H2O2-treated sperm; Phospho-Cdc25C and Phospho-Cdc25B correlate with activating G2/M checkpoint in zygotes fertilized with H2O2-treated sperm.
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Morphology and quantitative monitoring of gene expression patterns during floral induction and early flower development in Dendrocalamus latiflorus.
Int J Mol Sci
PUBLISHED: 03-26-2014
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The mechanism of floral transition in bamboo remains unclear. Dendrocalamus latiflorus (Bambusease, Bambusoideae, Poaceae) is an economically and ecologically important clumping bamboo in tropical and subtropical areas. We evaluated morphological characteristics and gene expression profiling to study floral induction and early flower development in D. latiflorus. The detailed morphological studies on vegetative buds and floral organography were completed using paraffin sectioning and scanning electron microscopy. The 3 mm floral buds commence the development of stamen primordia and pistil primordium. Furthermore, homologs of floral transition-related genes, including AP1, TFL1, RFL, PpMADS1, PpMADS2, SPL9, FT, ID1, FCA, and EMF2, were detected and quantified by reverse transcriptase PCR and real-time PCR in vegetative and floral buds, respectively. Distinct expression profiles of ten putative floral initiation homologues that corresponded to the developmental stages defined by bud length were obtained and genes were characterized. Six of the genes (including DlTFL1, DlRFL, DlMADS2, DlID1, DlFCA, DlEMF2) showed statistically significant changes in expression during floral transition. DlAP1 demonstrated a sustained downward trend and could serve as a good molecular marker during floral transition in D. latiflorus. The combined analysis provided key candidate markers to track the transition from the vegetative to reproductive phase.
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Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer.
Mol. Cancer Res.
PUBLISHED: 03-25-2014
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Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways that have shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor protein phosphatase 2A (PP2A). Here, the endogenous inhibitors of PP2A, SET (also known as I2PP2A) and cancerous inhibitor of PP2A (CIP2A), were shown to be overexpressed in human pancreatic cancer, contributing to decreased PP2A activity and overexpression and stabilization of the oncoprotein c-Myc, a key PP2A target. Knockdown of SET or CIP2A increases PP2A activity, increases c-Myc degradation, and decreases the tumorigenic potential of pancreatic cancer cell lines both in vitro and in vivo. Moreover, treatment with a novel SET inhibitor, OP449, pharmacologically recapitulates the phenotypes and significantly reduces proliferation and tumorigenic potential of several pancreatic cancer cell lines, with an accompanying attenuation of cell growth and survival signaling. Furthermore, primary cells from patients with pancreatic cancer were sensitive to OP449 treatment, indicating that PP2A-regulated pathways are highly relevant to this deadly disease.
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Genetic characterization of a novel duck-origin picornavirus with six 2A proteins.
J. Gen. Virol.
PUBLISHED: 03-21-2014
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A novel virus was detected from diseased ducks and completely determined. The virus was shown to have a picornavirus-like genome layout. Interestingly, the genome contained a total of up to six 2As, including four 2As (2A1-2A4) each having an NPGP motif, an AIG1-like 2A5, and a parechovirus-like 2A6. The 5'UTR was predicted to possess a hepacivirus/pestivirus-like internal ribosome entry site (IRES). However, the subdomain IIIe consisted of a 3 nt stem and five unpaired bases, distinct from those found in all other HP-like IRESs. The virus was most closely related to duck hepatitis A virus, with amino acid identities of 37.7?%, 39?% and 43.7?% in the P1, P2 and P3 regions, respectively. Based on these investigations, together with phylogenetic analyses, the virus could be considered as the founding member of a novel picornavirus genus that we tentatively named 'Aalivirus', with 'Aalivirus A' as the type species.
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Epithelial-mesenchymal transition and apoptosis of renal tubular epithelial cells are associated with disease progression in patients with IgA nephropathy.
Mol Med Rep
PUBLISHED: 03-19-2014
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The aim of the present study was to examine the effects of epithelial-mesenchymal transition (EMT) and apoptosis of renal tubular epithelial cells on the prognosis of immunoglobulin A (IgA) nephropathy. Renal biopsy tissues from 74 cases of IgA nephropathy were divided into a mild mesangial proliferation group (27 cases), a focal hyperplasia group (28 cases) and a proliferative sclerosis group (19 cases). The blood pressure, serum creatinine and 24 h urinary protein excretion of all patients were detected. To define EMT, ?-smooth muscle actin (?-SMA), vimentin and collagen fibers were assessed. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The blood pressure, serum creatinine and 24 h urinary protein excretion of patients with IgA nephropathy altered with increasing pathological grade. All clinical indices of patients in the proliferative sclerosis group were higher than those of the other two groups, and the 24 h urinary protein excretion of the focal hyperplasia group was statistically higher than that of the mild mesangial proliferation group. The expression of tubular interstitial ?-SMA, vimentin and collagen fibers increased with the pathological grade and was closely correlated with clinical indices, including collagen fibers and 24 h urinary protein excretion. TUNEL-positive cells increased with the exacerbation of pathological changes. The EMT and apoptosis of renal tubular epithelial cells reflected the clinical severity of IgA nephropathy. ?-SMA, vimentin and the apoptotic index may be used as important markers for evaluating the prognosis of IgA nephropathy.
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Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-07-2014
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Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.
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Complete genome sequence of a novel calicivirus from a goose.
Arch. Virol.
PUBLISHED: 02-23-2014
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A novel goose calicivirus (GoCV) was sequenced. The 8013-nt-long genome was organized into two open reading frames that were in the same frame and separated by 3 nucleotides. This feature is similar to what has been observed in turkey calicivirus (TuCV). Comparison of GoCV with other caliciviruses showed that it shared the highest amino acid sequence identities of 62, 38, and 52% in the nonstructural protein, VP1, and VP2, respectively, with TuCV. Phylogenetic analysis based on the amino acid sequences of nonstructural protein and VP1 demonstrated that GoCV was most closely related to but distinct from TuCV. Thus, GoCV was identified as a novel member in the proposed genus Nacovirus.
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Isoflurane inhibits occludin expression via up-regulation of hypoxia-inducible factor 1?.
Brain Res.
PUBLISHED: 02-19-2014
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The blood-brain barrier (BBB) is a functional structure which regulates and restricts the transfer of circulating molecules and immune cells into the central nervous system. The barrier is formed by the presence of tight junctions (TJ) between the specialized brain endothelial cells. The volatile anesthetic isoflurane may affect the permeability of the BBB. Previous studies have proven that isoflurane alters hypoxia-inducible factor-1? (HIF-1?) expression, which may affect the TJ proteins; however, the mechanism of how TJ proteins are affected by isoflurane is still unclear. Primary human brain vascular endothelial cells (HBVEC) were exposed to isoflurane at various concentrations (0-2.5%) and different time periods (0-6 h). The cell viability, occludin expression, paracellular permeability, VEGF expression, TGF-?3 expression and occludin protein endocytosis were quantified. Isoflurane treatment induced a time- and concentration-dependent decrease in occludin mRNA and protein levels in HBVEC. This effect was partially abrogated by silencing the HIF-1? expression. Isoflurane could activate HIF-1?, and the overexpression HIF-1? up-regulated the level of VEGF and TGF-?3, VEGF decreased the expression of occludin and TGF-?3 accelerated the endocytosis of occludin. RNA interference targeting HIF-1? reduced both VEGF and TGF-?3 expression after isoflurane treatment.
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Novel monodisperse molecularly imprinted shell for estradiol based on surface imprinted hollow vinyl-SiO? particles.
Talanta
PUBLISHED: 02-14-2014
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A novel monodisperse molecularly imprinted shell was prepared based on surface imprinted hollow vinyl-SiO2 particles and applied to selective recognition and adsorption of estradiol (E2). This method was carried out by introducing vinyltriethoxysilane to the surface of polystyrene (PS) spheres by a simple one-step modification, followed by dissolution to remove the PS cores, and then by copolymerization of functional monomers via surface imprinted on the hollow vinyl-SiO2 particles to prepare uniform E2-imprinted shells. Two interesting characteristics were found: first, the obtained hollow molecularly imprinted polymer shells (H-MIPs) had highly monodispersity, uniform spherical shape with a shell thickness of about 40 nm; and then, the method was simple, easy to operate by directing coating of a uniform shell on hollow particles via surface imprinting. The resultant H-MIPs demonstrated improvements in imprinting factor and binding kinetics, owing to the high selectivity to template molecules, surface imprinting technique and hollow porous structure. Furthermore, satisfactory recoveries of 97.0 and 94.8% with respective precisions of 2.5 and 2.7% were achieved by one-step extraction when H-MIPs were used for the preconcentration and selective separation of estradiol in milk samples at two spiked levels. The simple, effective H-MIPs based strategy provided new insights into the formation of various functionalized coating layers on different kinds of support materials with versatile potential applications.
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Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets.
Am. J. Pathol.
PUBLISHED: 01-27-2014
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Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 ?g elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients.
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Hürthle cell neoplasms diagnosed by fine needle aspiration are not associated with an increased risk of malignancy.
Acta Cytol.
PUBLISHED: 01-23-2014
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The aim of this study is to determine the risk of neoplasm and malignancy in thyroid fine needle aspiration (FNA) diagnosed as atypia of undetermined significance with Hürthle cell change (AUS-H) or Hürthle cell neoplasm (HCN).
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Precursor T-cell lymphoblastic lymphoma extensively involving the mediastinum, pleura and pericardium: A case report.
Mol Clin Oncol
PUBLISHED: 01-16-2014
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Precursor T-cell lymphoblastic lymphoma (T-LBL) is a rare type of malignant lymphoma, with clinical manifestations including diaphragmatic lymph node enlargement, accompanied by local oppression and/or systemic lymphoma symptoms. However, extensive involvement of the mediastinum, pleura and pericardium is rare in T-LBL cases. This is the case report of a T-LBL extensively involving the mediastinum, pleura and pericardium in a 54-year-old woman. The patient complained of anhelation, chest tightness and tiredness for ~3 months. A computed tomography (CT) scan of the chest revealed a diffuse mass of soft tissue density involving the mediastinum, pleura and pericardium. Several thoracocenteses indicated inflammatory changes and cytological examination of the pleural fluid and pleural biopsy under CT guidance identified no heterotypic cells. As (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging revealed a diffused moderate FDG uptake (maximum standard uptake value of 4) by the mediastinum, pleura and cardiac sac, we diagnosed a malignant lymphoma. We subsequently successfully performed needle biopsy under PET/CT guidance according to the PET/CT images and the diagnosis of T-LBL was pathologically confirmed.
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A ratiometric fluorescent chemosensor for Al³? in aqueous solution based on aggregation-induced emission and its application in live-cell imaging.
Anal. Chim. Acta
PUBLISHED: 01-16-2014
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A ratiometric fluorescent chemosensor 1 was developed for the detection of Al(3+) in aqueous solution based on aggregation-induced emmision (AIE). The chemosensor showed the fluorescence of its aggregated state and Al(3+)-chelated soluble state in the absence and in the presence of Al(3+), respectively, and resulted in a fluorescence ratio (I461/I537) response to Al(3+) in neutral aqueous solution at a detection limit as low as 0.29 ?mol L(-1). The method was also highly selective to Al(3+) over other physiological relevant metal ions investigated in this study. Taking advantage of its AIE characteristics, the chemosensor was successfully applied on test papers for simple and rapid detection of Al(3+). Moreover, the application of 1 for the imaging of Al(3+) in living cells by ratiometric fluorescence changes was also achieved.
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Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia.
BMC Complement Altern Med
PUBLISHED: 01-13-2014
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Panax Notoginseng Saponins (PNS) is the major class of active constituents of notoginseng, a natural product extensively used as a therapeutic agent in China. Tumor when accompanied by cardiovascular disorders poses a greater challenge for clinical management given the paradoxical involvement of angiogenesis, therefore gaining increased research attention. This study aim to investigate effects of PNS and its activity components in the mouse model of tumor complicated with myocardial ischemia.
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The expression of a novel anti-inflammatory cytokine IL-35 and its possible significance in childhood asthma.
Immunol. Lett.
PUBLISHED: 01-07-2014
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Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine and has been shown to play an important role in maintaining immune homeostasis. However, the effect of IL-35 on human asthma remains unclear. The present study is to investigate the expression and significance of IL-35 in childhood asthma. Forty-one asthmatic children and forty-two healthy controls were recruited in Qilu Children's Hospital of Shandong University. Serum total immunoglobulin E level was measured by radioimmunosorbent test. Peripheral blood eosinophils were counted using BC-5800 Automatic Blood Cell Analyzer. IL-35 mRNA in peripheral blood mononuclear cells was detected by quantitative real-time polymerase chain reaction. Serum IL-35, IL-4 and interferon-? levels were measured using enzyme-linked immunosorbent assay. The correlations among the above indexes were also analyzed using Pearson's method. Our results showed that serum total IgE, eosinophil count and serum IL-4 were significantly increased in asthmatic children compared with control children, and serum IFN-? level in asthmatic patients was obviously lower than that in healthy controls. We also found that there was an obviously positive correlation between serum IgE and IL-4 levels in asthmatic patients. In addition, significantly negative correlation was found between serum total IgE and IFN-? levels. More importantly, we found that the expression of IL-35 mRNA and protein was both down-regulated in asthmatic children, and serum IL-35 level was inversely related to serum IL-4 level. Moreover, significantly positive correlation was also found between serum IL-35 and IFN-? levels. The results suggest that the decreased expression of IL-35 could be involved in the pathogenesis of childhood asthma.
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Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction.
Int. J. Mol. Med.
PUBLISHED: 01-02-2014
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Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)??1, tumor necrosis factor (TNF)-?, interleukin (IL)-1? and nuclear factor (NF)-?B. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.
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Indolent T-lymphblastic proliferation: report of a case involving the upper aerodigestive tract.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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T-lymphoblastic lymphoma (T-LBP) is a high-grade malignant lymphoma, which possesses the characteristic of high metastasis and high mortality without treatment. We are presenting a special T-lymphoblastic proliferation involving in the oropharynx, nasopharynx, sinus and trachea in a patient with local involved about 15-years without systemic dissemination. The immunophenotype of this case was similar to T-LBP. The proliferous cells were positive for terminal deoxynucleotidyl transferase (TdT), CD3, and appeared co-expression CD4 and CD8. No clonal rearrangements of TCR? and/or TCR? gene were detected. Indolent T-lymphoblastic proliferations rarely occurred or unusually could not be diagnosed, combing with the relevant literature and clinically indolent manifestation, we interpreted this case as indolent T-lymphoblastic proliferation (iT-LBPs). So far, the mechanism of the T-lymphoblastic proliferations is still uncertain and requires further study.
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High expression of oncoprotein DEK predicts poor prognosis of small cell lung cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Oncoprotein DEK plays an important role in cancer tumorigenesis. To explore the clinical implication of DEK expression on prognostic evaluation in small cell lung cancer (SCLC), 130 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of DEK protein. The correlation between DEK expression and clinicopathological features of SCLC was evaluated using the Chi-square and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. IHC analysis demonstrated that DEK protein staining was strongly positive and significantly higher (44.62%) in SCLC compared with either adjacent non-tumor or normal lung tissues (P < 0.001 for both). DEK expression correlated with large tumor size (P = 0.025) and late pathologic stage (P = 0.005). Moreover, it correlated with low disease-free (P = 0.004) and 5-year (P = 0.005) survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with high level DEK expression were significantly lower than those with low level DEK expression (P = 0.006 and P = 0.001, respectively). Furthermore, Cox analysis revealed that DEK expression emerged as a significant independent hazard factor for the overall survival rate of patients with SCLC (HR: 1.594, 95% CI: 1.087-2.336, P = 0.017). In conclusion, DEK plays an important role in the progression of SCLC. DEK may potentially be used as an independent biomarker for the prognostic evaluation of SCLC.
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Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes.
Oncoimmunology
PUBLISHED: 01-01-2014
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Targeting immune inhibitory receptors has brought excitement, innovation and hope to cancer patients. Our recent work revealed the immunological effects of blocking the CTLA4 and PD-1 immune checkpoints on T cell receptor usage among peripheral blood cells, and further uncovers how the expansion of the T cell repertoire matches the immunotoxicity profile of the therapy.
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Expression of G protein-coupled estrogen receptor in irritable bowel syndrome and its clinical significance.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Estrogen is suggested to participate in pathogenesis of irritable bowel syndrome (IBS), but expression of G protein-coupled estrogen receptor (GPER) in the colon of IBS patients has never been investigated. The aim of this study was to investigate the expression of GPER and classical estrogen receptors in the colon of IBS patients and healthy controls.
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Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients.
J Immunother Cancer
PUBLISHED: 01-01-2014
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Immunotherapeutic approaches, such as dendritic cell (DC) vaccination, have emerged as promising strategies in the treatment of glioblastoma. Despite their promise, however, the absence of objective biomarkers and/or immunological monitoring techniques to assess the clinical efficacy of immunotherapy still remains a primary limitation. To address this, we sought to identify a functional biomarker for anti-tumor immune responsiveness associated with extended survival in glioblastoma patients undergoing DC vaccination.
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Dopamine D3 receptor inhibits the ubiquitin-specific peptidase 48 to promote NHE3 degradation.
FASEB J.
PUBLISHED: 12-05-2013
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The dopamine D3 receptor (D3R) is crucial in the regulation of blood pressure and sodium balance, in that Drd3 gene ablation in mice results in hypertension and failure to excrete a dietary salt load. The mechanism responsible for the renal sodium retention in these mice is largely unknown. We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin-specific peptidase 48 (USP48), thereby promoting Na(+)-H(+) exchanger (NHE)-3 degradation. We found that stimulation with the D3R-specific agonist PD128907 (1 ?M, 30 min) promoted the interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (-35±6%, vs. vehicle), resulting in increased ubiquitinylated NHE3 (+140±10%); and decreased NHE3 expression (-50±9%) in human renal proximal tubule cells (hRPTCs). USP48 silencing decreased NHE3s half-life (USP48 siRNA t1/2=6.1 h vs. vehicle t1/2=12.9 h), whereas overexpression of USP48 increased NHE3 half-life (t1/2=21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation. USP48 accounted for ?30% of the total deubiquitinylating activity in these cells. Extending our studies in vivo, we found that pharmacologic blockade of D3R via the D3R-specific antagonist GR103691 (1 ?g/kg/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310±15%, vs. vehicle), whereas an innovative kidney-restricted Usp48 silencing via siRNA (3 ?g/d, 7 d) increased ubiquitinylated NHE3 (+250±30%, vs. controls), decreased total NHE3 (-23±2%), and lowered blood pressure (-24±2 mm Hg), compared with that in control mice that received either the vehicle or nonsilencing siRNA. Our data demonstrate a crucial role for the dynamic interaction between D3R and USP48 in the regulation of NHE3 expression and function.-Armando, I., Villar, V. A. M., Jones J. E., Lee, H., Wang, X., Asico L. D., Yu, P., Yang, J., Escano, C. S. Jr, Pascua-Crusan, A. M., Felder, R. A., Jose, P. A. Dopamine D3 receptor inhibits the ubiquitin-specific peptidase 48 to promote NHE3 degradation.
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Testing the quality of images for permanent magnet desktop MRI systems using specially designed phantoms.
Phys Med Biol
PUBLISHED: 11-22-2013
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Our aim was to measure the performance of desktop magnetic resonance imaging (MRI) systems using specially designed phantoms, by testing imaging parameters and analysing the imaging quality. We designed multifunction phantoms with diameters of 18 and 60 mm for desktop MRI scanners in accordance with the American Association of Physicists in Medicine (AAPM) report no. 28. We scanned the phantoms with three permanent magnet 0.5 T desktop MRI systems, measured the MRI image parameters, and analysed imaging quality by comparing the data with the AAPM criteria and Chinese national standards. Image parameters included: resonance frequency, high contrast spatial resolution, low contrast object detectability, slice thickness, geometrical distortion, signal-to-noise ratio (SNR), and image uniformity. The image parameters of three desktop MRI machines could be measured using our specially designed phantoms, and most parameters were in line with MRI quality control criterion, including: resonance frequency, high contrast spatial resolution, low contrast object detectability, slice thickness, geometrical distortion, image uniformity and slice position accuracy. However, SNR was significantly lower than in some references. The imaging test and quality control are necessary for desktop MRI systems, and should be performed with the applicable phantom and corresponding standards.
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The ex vivo and in vivo biological performances of graphene oxide and the impact of surfactant on graphene oxides biocompatibility.
J Environ Sci (China)
PUBLISHED: 11-14-2013
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Graphene oxide (GO) displays promising properties for biomedical applications including drug delivery and cancer therapeutics. However, GO exposure also raises safety concerns such as potential side effects on health. Here, the biological effects of GO suspended in phosphate buffered saline (PBS) with or without 1% nonionic surfactant Tween 80 were investigated. Based on the ex vivo experiments, Tween 80 significantly affected the interaction between GO and peripheral blood from mice. GO suspension in PBS tended to provoke the aggregation of diluted blood cells, which could be prevented by the addition of Tween 80. After intravenous administration, GO suspension with or without 1% Tween 80 was quickly eliminated by the mononuclear phagocyte system. Nevertheless, GO suspension without Tween 80 showed greater accumulation in lungs than that containing 1% Tween 80. In contrast, less GO was found in livers for GO suspension compared to Tween 80 assisted GO suspension. Organs including hearts, livers, lungs, spleens, kidneys, brains, and testes did not reveal histological alterations. The indexes of peripheral blood showed no change upon GO exposure. Our results together demonstrated that Tween 80 could greatly alter GOs biological performance and determine the pattern of its biodistribution in mice.
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Facile Creation of 3-Substituted-3-Hydroxy-2-Oxindoles by Arginine-Catalyzed Aldol Reactions of ?,?-Unsaturated Ketones with Isatins.
Molecules
PUBLISHED: 10-14-2013
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An efficient approach for the synthesis of 3-substituted-3-hydroxy-2-oxindoles has been achieved via an aldol reaction of ?,?-unsaturated ketones and isatins using arginine as an organocatalyst. A range of 3-substituted-3-hydroxy-2-oxindoles were obtained in moderate to high (up to 99%) yields. These 3-substituted-3-hydroxy-2-oxindoles with an additional enone moiety provide an opportunity for further elaboration of the products and for potentially interesting biological activities. In addition, the formation of 3-substituted-3-hydroxy-2-oxindole 3a was con?rmed by X-ray crystallography. The possible reaction mechanism reveals that the reaction proceeds via a double action process.
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Pre-clinical demonstration of lentiviral vector mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency.
Mol. Ther.
PUBLISHED: 10-11-2013
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Gene transfer into autologous hematopoietic stem cells by ?-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA) deficient-SCID. However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy, we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1? promoter (LV-EFS-ADA). In ADA-/- mice, LV-EFS-ADA displayed high efficiency gene transfer and sufficient ADA expression to rescue ADA-/- mice from their lethal phenotype with good thymic and peripheral T and B cell reconstitution. Human ADA-deficient CD34+ cells transduced with 1-5x10(7) TU/ml had 1-3 vector copies/cell and expressed 1-2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV-EFS-ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV-EFS-ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, whilst reducing the potential for vector mediated insertional mutagenesis.Molecular Therapy (2013); doi:10.1038/mt.2013.265.
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pH-Induced Conformational Change and Dimerization of DNA Chains Investigated by Analytical Ultracentrifugation.
J Phys Chem B
PUBLISHED: 09-24-2013
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pH-induced conformational change of i-motif DNA has been studied by analytical ultracentrifugation. As pH increases, the hydrodynamic radius of individual DNA chains in aqueous solutions prepared by being heat-treated suddenly increases while the molar mass is constant, indicating that the conformation changes from an i-motif to a random coil. When DNA concentrations are higher than 1.0 ?M, relatively stable dimers are formed as pH sharply decreases from 7.5 to 4.5. Moreover, the weight percentage of the dimers increases with the initial DNA concentration. The study can help to understand the functions of the telomeres containing repeated cytosine-rich sequences and to develop DNA-based devices.
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Fine Needle Aspiration of Oncocytic Variants of Pancreatic Neuroendocrine Tumor: A Report of Three Misdiagnosed Cases.
Acta Cytol.
PUBLISHED: 09-23-2013
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Objectives: An oncocytic variant of pancreatic neuroendocrine tumors (PanNET) is exceedingly rare. Here we report cytomorphological features of the oncocytic variant of PanNET and discuss how to avoid diagnostic pitfalls. Study Design: A computerized search of our laboratory information system was performed over an 18-year period to identify all cytology and surgical pathology cases where a diagnosis of PanNET was made or considered in the differential diagnosis. Three cases of the oncocytic variant of PanNET were identified. Results: Endoscopic ultrasound-guided fine needle aspiration (FNA) smears showed cohesive clusters of large atypical cells with abundant eosinophilic granular cytoplasm, anisonucleosis, nuclear enlargement and overlapping, prominent nucleoli, and a relatively smooth nuclear membrane. Nuclei were round to oval with finely granular chromatin. Additional features included rare isolated cells and glandular formation. Some of these morphological features, such as anisonucleosis, nuclear enlargement, and overlapping, prominent nucleoli, are also commonly seen in the pancreatic adenocarcinoma. All these cases were misclassified by FNA as adenocarcinoma (2 cases) or suspicious for carcinoma (1 case) and were histologically confirmed to be oncocytic variants of PanNET. Conclusions: Useful salient features of the oncocytic variant of PanNET include abundant eosinophilic granular cytoplasm, finely granular chromatin, and relatively smooth nuclear membrane. The awareness of this variant will help to avoid misdiagnosis. © 2013 S. Karger AG, Basel.
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Kruppel-like factor 2 regulates dendritic cell activation in patients with acute coronary syndrome.
Cell. Physiol. Biochem.
PUBLISHED: 09-01-2013
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Dendritic cells (DCs) activation is important in atherosclerosis and coronary heart disease, but the mechanisms regulating activation of dendritic cells remain largely unclear. The aim of this study was to evaluate the effect of transcription factor Kruppel-like factor 2 (KLF2) in the proinflammatory activation of DCs in acute coronary syndrome.
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[miR-126 inhibits colon cancer proliferation and invasion through targeting IRS1, SLC7A5 and TOM1 gene].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 08-29-2013
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To explore the expression pattern and function of miR-126 in human colon cancer and the underlying mechanisms.
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Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1.
Mol. Cancer
PUBLISHED: 08-27-2013
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Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues.
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Could microwave induced catalytic oxidation (MICO) process over CoFe2O4 effectively eliminate brilliant green in aqueous solution?
J. Hazard. Mater.
PUBLISHED: 08-11-2013
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In this study, we adopted the chemical co-precipitation (CP) method and sol-gel method followed by calcination at temperatures of 100-900°C for 12h to synthesize CoFe2O4 materials, which were further characterized by TEM, XRD and XPS techniques. The properties of CoFe2O4 materials were evaluated in a microwave (MW) induced catalytic oxidation (MICO) process for the elimination of brilliant green (BG). The results showed that: (1) the removal rates of BG gradually decreased over a series of CoFe2O4 materials prepared by CP method and calcinated with 100-700°C (except 900°C) for 12h within three reuse cycles; for comparison, no removal of BG was obtained over CoFe2O4 synthesized by sol-gel method and CoFe2O4-900 (CP); (2) no hydroxyl radicals were captured with salicylic acid used as molecular probe in the MICO process; (3) MW irradiation enhanced the release of residual NaOH within the microstructure of CoFe2O4 and further discolored BG, because BG is sensitive to pH; (4) granular activated carbon (GAC), an excellent MW-absorbing material possessing higher dielectric loss tangent compared to that of a series of CoFe2O4 materials, could not remove BG in suspensions at a higher efficiency, even if the loading amount was 20gL(-1). Accordingly, MICO process over CoFe2O4 materials and GAC could not effectively eliminate BG in suspensions.
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A protective role of heme-regulated eIF2? kinase in cadmium-induced toxicity in erythroid cells.
Food Chem. Toxicol.
PUBLISHED: 08-09-2013
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Although a number of studies have demonstrated that cadmium (Cd) can incur damage to mature red cells, the potential injuries of Cd to erythroid progenitor cells have not been investigated thus far. Heme-regulated eIF2? kinase (Hri) is essential for translational regulation and survival of erythroid precursors in the setting of iron deficiency. Hri has been demonstrated to activate Atf4 signaling in reducing oxidative stress and in promoting erythroid differentiation during stress erythropoiesis. Here, we demonstrated that Cd significantly provoked cell death and suppressed erythroid differentiation of erythroid progenitor cells. Importantly, our results established a crucial role of Hri in ameliorating Cd-induced impairment to erythropoiesis. Upon Cd treatment, Hri-eIF2?P-Atf4 signaling was activated to protect cells from cell death and differentiation attenuation in Wt fetal liver erythroblasts; in contrast, Hri(-/-) erythroblasts suffered from enhanced oxidative stress, as evidenced by increased levels of reactive oxygen species (ROS) and consequentially elevated apoptosis. As for Cd administration in vivo, impaired erythropoiesis in bone marrow and dramatic extramedullary erythropoiesis in spleen were observed in Hri(-/-) mice. Taken together, our combined data highlighted a crucial role of Hri in protecting survival and differentiation of erythroid progenitor cells upon Cd treatment.
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Galactose-decorated reduction-sensitive degradable chimaeric polymersomes as a multifunctional nanocarrier to efficiently chaperone apoptotic proteins into hepatoma cells.
Biomacromolecules
PUBLISHED: 07-16-2013
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Hepatoma-targeting reduction-sensitive chimaeric biodegradable polymersomes were designed and developed based on galactose-poly(ethylene glycol)-poly(?-caprolactone) (Gal-PEG-PCL), PEG-PCL-poly(2-(diethylamino)ethyl methacrylate) (PEG-PCL-PDEA, asymmetric), and PEG-SS-PCL for facile loading and triggered intracellular delivery of proteins. The chimaeric polymersomes formed from PEG-PCL-PDEA and PEG-SS-PCL had a monodisperse distribution with average sizes ranging from 95.5 to 199.2 nm depending on PEG-SS-PCL contents. Notably, these polymersomes displayed decent loading of bovine serum albumin (BSA), ovalbumin (OVA), and cytochrome C (CC) proteins likely due to presence of electrostatic and hydrogen bonding interactions between proteins and PDEA block located in the interior of polymersomes. The in vitro release studies showed that protein release was largely accelerated under a reductive condition containing 10 mM dithiothreitol (DTT). For example, ca. 77.2 and 22.1% of FITC-BSA were released from CP(SS50) (chimaeric polymersomes containing 50 wt % PEG-SS-PCL) at 37 °C in 12 h in the presence and absence of 10 mM DTT, respectively. Confocal microscopy showed that FITC-CC-loaded Gal-decorated CP(SS40) could efficiently deliver and release FITC-CC into HepG2 cells following 24 h treatment, in contrast to little or negligible fluorescence detected in HepG2 cells treated with FITC-CC-loaded nontargeting polymersomes or free CC. MTT assays revealed that CC-loaded Gal-decorated CP(SS40) exhibited apparent targetability and pronounced antitumor activity to HepG2 cells, in which cell viabilities decreased from 81.9, 60.6, 49.5, 42.2 to 31.5% with increasing Gal-PEG-PCL contents from 0, 10, 20, 30 to 40 wt %. Most remarkably, granzyme B-loaded Gal-decorated chimaeric polymersomes effectively caused apoptosis of HepG2 cells with a markedly low half-maximal inhibitory concentration (IC(50)) of 2.7 nM. These reduction-responsive chimaeric biodegradable polymersomes offer a multifunctional platform for efficient intracellular protein delivery.
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Abundance and community structure of ammonia-oxidizing microorganisms in reservoir sediment and adjacent soils.
Appl. Microbiol. Biotechnol.
PUBLISHED: 07-06-2013
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Ammonia oxidation is an important process for global nitrogen cycling. Both ammonia-oxidizing bacteria (AOB) and archaea (AOA) can be the important players in nitrification process. However, their relative contribution to nitrification remains controversial. This study investigated the abundance and community structure of AOA and AOB in sediment of Miyun Reservoir and adjacent soils. Quantitative PCR assays indicated that the highest AOA abundance occurred in unplanted riparian soil, followed by reservoir sediment, reed-planted riparian soil and agricultural soil. The AOB community size in agricultural soil was much larger than that in the other habitats. Large variations in the structures of AOA and AOB were also observed among the different habitats. The abundance of Nitrosospira-like AOB species were detected in the agricultural soil and reservoir sediment. Pearsons correlation analysis showed the AOB diversity had positive significant correlations with pH and total nitrogen, while the AOA diversity might be negatively affected by nitrate nitrogen and ammonia nitrogen. This work could add new insights towards nitrification in aquatic and terrestrial ecosystems.
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