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Find video protocols related to scientific articles indexed in Pubmed.
DNA Cleaving "Tandem-Array" Metallopeptides Activated With KHSO5: Towards the Development of Multi-Metallated Bioactive Conjugates and Compounds.
Curr Bioact Compd
PUBLISHED: 11-20-2014
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Amino terminal peptides of the general form Gly-Gly-His have been used to introduce single sites of metal binding and redox activity into a wide range of biomolecules to create bioactive compounds and conjugates capable of substrate oxidation. We report here that Gly-Gly-His-like peptides linked in a tandem fashion can also be generated leading to multi-metal binding arrays. While metal binding by the native Gly-Gly-His motif (typically to Cu(2+), Ni(2+), or Co(2+)) requires a terminal peptide amine ligand, previous work has demonstrated that an ornithine (Orn) residue can be substituted for the terminal Gly residue to allow solid-phase peptide synthesis to continue via the side chain N-?. This strategy thus frees the Orn residue N-? for metal binding and permits placement of a Gly-Gly-His-like metal binding domain at any location within a linear, synthetic peptide chain. As we show here, this strategy also permits the assembly of tandem arrays of metal binding units in linear peptides of the form: NH2-Gly-Gly-His-[(?)-Orn-Gly-His]n-(?)-Orn-Gly-His-CONH2 (where n = 0, 1, and 2). Metal binding titrations of these tandem arrays monitored by UV-vis and ESI-MS indicated that they bind Cu(2+), Ni(2+), or Co(2+) at each available metal binding site. Further, it was found that these systems retained their ability to modify DNA oxidatively and to an extent greater than their parent M(II)•Gly-Gly-His. These findings suggest that the tandem array metallopeptides described here may function with increased efficiency as "next generation" appendages in the design of bioactive compounds and conjugates.
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Microengineered in vitro model of cardiac fibrosis through modulating myofibroblast mechanotransduction.
Biofabrication
PUBLISHED: 11-08-2014
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Cardiac fibrosis greatly impairs normal heart function post infarction and there is no effective anti-fibrotic drug developed at present. The current therapies for cardiac infarction mainly take effect by eliminating occlusion in coronary artery by thrombolysis drugs, vascular stent grafting or heart bypass operation, which are capable to provide sufficient blood flow for intact myocardium yet showed subtle efficacy in ameliorating fibrosis condition. The advances of in vitro cell/tissue models open new avenues for drug assessment due to the low cost, good controllability and availability as well as the convenience for operation as compared to the animal models. To our knowledge, no proper biomimetic in vitro cardiac fibrosis model has been reported yet. Here we engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts, and the fibrogenesis was recapitulated by patterning the substrate rigidity which mimicked the mechanical heterogeneity of myocardium post-infarction. Various biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK) pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility of applying this platform in screening anti-fibrosis drugs.
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Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells.
Mol Med Rep
PUBLISHED: 10-20-2014
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Breast cancer is the most common type of malignancy among females. Previous studies examining breast cancer tissue have demonstrated the presence of stem cells, and have detected octamer?binding protein 4 (Oct4) and Nanog transcription factor expression. In the present study, breast cancer stem cells (CSCs) were isolated and enriched from MDA?MB?231 breast cancer cell lines, and were defined as MDA?MB?231 stem cells using flow cytometry. The expression of Oct4 and Nanog in breast CSCs were detected by quantitative polymerase chain reaction and western blotting. RNA interference (RNAi) was used in order to downregulate the expression of Oct4 and Nanog. Drug resistance and tumor?initiating capability following in vivo injection of MDA?MB?231 stem cells trans-duced with negative RNAi, Oct4 RNAi and Nanog RNAi were compared with that of MDA?MB?231 stem cells without siRNA transfection as a control group. In addition the capability of MDA?MB?231 breast cancer cells to initiate tumor formation in mice was compared with that of MDA?MB?231 stem cells. A paclitaxel inhibition test was also conducted in order to detect resistance of MDA?MB?231 breast cancer stem cells to this treatment. The MDA?MB?231 stem cells were revealed to exhibit elevated percentages of the cluster of differentiation (CD)44+CD24?/low subset, high tumorigenicity and resistance to chemotherapy, all of which are characteristic stem cell properties. In addition, the MDA?MB?231 stem cells were more tumorigenic in vivo. Furthermore, the breast CSCs also expressed high levels of the Oct4 and Nanog transcription factors. Therefore, downregulation of Oct4 or Nanog expression may reduce chemotherapeutic drug resistance and tumorigenicity in breast CSCs. In conclusion, Oct4 and Nanog expression may be a key factor in the development of resistance to chemotherapy and tumor growth of breast CSCs. This finding indicates that Oct4 or Nanog?targeted therapy may be a promising means of overcoming resistance to chemotherapy and inhibiting tumor growth in breast cancer treatment.
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Diastereo- and enantioselective propargylation of benzofuranones catalyzed by pybox-copper complex.
Org. Lett.
PUBLISHED: 10-17-2014
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Diastereo- and enantioselective preparation of 2,2-disubstituted benzofuran-3(2H)-one has been realized by a pybox-copper catalyzed reaction between 2-substituted benzofuran-3(2H)-one and propargyl acetate. The utility of this method was demonstrated by further transformation of the terminal alkyne into a methyl ketone without loss of enantiomeric purity.
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Experimental evaluation of myocardial fibrosis in a rapid atrial pacing model in New Zealand rabbits using quantitative analysis of ultrasonic backscatter.
Med. Sci. Monit.
PUBLISHED: 10-10-2014
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The aim of this study was the establishment of a rapid atrial pacing (RAP)-induced atrial fibrillation (AF) model with electrophotoluminescence and the application of ultrasonic backscatter quantitative analysis of the degree of myocardial fibrosis in New Zealand white rabbits.
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Controlling the Ring Curvature, Solution Assembly, and Reactivity of Gigantic Molybdenum Blue Wheels.
J. Am. Chem. Soc.
PUBLISHED: 09-29-2014
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We describe the synthesis, structure, self-assembly, solution chemistry, and mass spectrometry of two new gigantic decameric molybdenum blue wheels, {Mo200Ce12} (1) and {Mo100Ce6} (2), by building block rearrangement of the tetradecameric {Mo154} framework archetype and control of the architecture's curvature in solution from the addition of Ce(III). The assembly of 1 and 2 could be directed accordingly by adjusting the ionic strength and acidity of the reaction mixture. Alternatively, the dimeric cluster {Mo200Ce12} could be transformed directly to the monomeric species {Mo100Ce6} upon addition of a potassium salt. ESI-ion mobility mass spectra were successfully obtained for both {Mo200Ce12} and {Mo100Ce6}, which is the first report in molybdenum blue chemistry thereby confirming that the gigantic clusters are stable in solution and that ion mobility measurements can be used to characterize nanoscale inorganic molecules.
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Short and efficient synthesis of fluorinated ?-lactams.
Org. Biomol. Chem.
PUBLISHED: 09-24-2014
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The diastereoselective synthesis of fluorinated ?-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks.
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MANAGEMENT OF ENDOCRINE DISEASE: Effects of telecare intervention for glycemic control in Type 2 Diabetes: A systematic review and meta-analysis of randomized controlled trials.
Eur. J. Endocrinol.
PUBLISHED: 09-18-2014
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Objective: To review published literature on the effects of telecare intervention in patients with Type 2 Diabetes and inadequate glycemic control. Design and methods: A review of randomized controlled trials (RCTs) on telecare intervention in patients with type 2 diabetes, and a search of electronic databases such as The Cochrane Library, PubMed, EBSCO, CINAHL, Science Direct, Journal of Telemedicine and Telecare, and China National Knowledge Infrastructure (CNKI), were conducted from December 8-16, 2013. Two evaluators independently selected and reviewed the eligible studies. Change in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), Body Mass Index (BMI), and body weight were analyzed. Results: An analysis of 18 studies with 3,798 subjects revealed that telecare significantly improved the management of diabetes. Mean HbA1c values reduced by (-0.54; 95% confidence interval [CI], -0.75 to -0.34; P < 0.05), mean FPG levels by (-9.00 mg/dL; 95% CI, -17.36 to -0.64; P = 0.03), and mean PPG levels reduced by (-52.86 mg/dL; 95% CI, -77.13 to -28.58; P < 0.05) than the group receiving standard care. Meta-regression and subgroup analyses showed that study location, sample size, and treatment monitoring techniques were sources of heterogeneity. Conclusions: Patients monitored by telecare showed significant improvement in glycemic control in type 2 diabetes than those monitored by routine follow-up. Significant reduction in HbA1c was associated with Asian populations, small sample size, and telecare, and those with patients with baseline HbA1c greater than 8.0%.
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Estimating radiation absorbed dose of individuals nearby 131I-treated hyperthyroid patients.
Health Phys
PUBLISHED: 09-11-2014
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The purpose of this study was to systematically provide a database for estimating radiation dose of individuals nearby (131)I-treated hyperthyroid patients. External dose rates were measured on 48 hyperthyroid patients using a survey meter in front of patients' thyroid glands. The initial measurement was recorded within 30 min post radioiodine administration at 0.3 m, 0.6 m, 1 m, and 2 m. Follow-up measurements were carried out up to 12 d post radioiodine administration. In addition, ambient dose rates of different locations such as wards, patients' washrooms, medical staffs' workplaces, and corridors were also measured. The Na131I treatment dose administered in this study ranged from 74-555 MBq. Significant positive correlation between dose rate at 1 m and the administered dose was found in this study. The normalized external dose rates at 0.3 m were 0.234 µSv h(-1) MBq(-1) at 0.5 h, 0.325 µSv h(-1) MBq(-1) at 4 h, 0.308 µSv h(-1) MBq(-1) at 6 h, 0.301 µSv h(-1) MBq(-1) at 24 h, 0.259 µSv h(-1) MBq(-1) at 48 h, 0.234 µSv h(-1) MBq(-1) at 72 h, 0.224 µSv h(-1) MBq(-1) at 96 h, 0.186 µSv h(-1) MBq(-1) at 120 h, and 0.158 µSv h(-1) MBq(-1) at 144 h, respectively. With these results, the authors estimated radioactive radiation dose for the public and medical staffs near (131)I-treated hyperthyroid patients. This study is beneficial for radiation safety decision-making.
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Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up.
Crit Care
PUBLISHED: 09-05-2014
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IntroductionPatients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma.MethodsIn this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate in this study and 169 completed 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard antimicrobial therapy (control group). In the control group, patients received antibiotics according to the attending physician; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary endpoint was antibiotic exposure; secondary endpoints were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, numbers of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma.ResultsPCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P <0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P <0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay, clinical, laboratory, spirometry outcomes in both groups. Numbers of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during 12-month follow-up period.ConclusionA PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm.Trial registrationChinese Clinical Trial Register ChiCTR-TRC-12002534. Registered 26 September 2012.
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Reactivity of damaged pyrimidines: DNA cleavage via hemiaminal formation at the C4 positions of the saturated thymine of spore photoproduct and dihydrouridine.
J. Am. Chem. Soc.
PUBLISHED: 09-04-2014
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Described here are mechanistic details of the chemical reactivities of two modified/saturated pyrimidine residues that represent naturally occurring forms of DNA damage: 5-thyminyl-5,6-dihydrothymine, commonly referred to as the "spore photoproduct" (SP), and 5,6-dihydro-2'-deoxyuridine (dHdU), formed via ionizing radiation damage to cytosine under anoxic conditions and also serving as a general model of saturated pyrimidine residues. It is shown that due to the loss of the pyrimidine C5-C6 double bond and consequent loss of ring aromaticity, the C4 position of both these saturated pyrimidines is prone to the formation of a hemiaminal intermediate via water addition. Water addition is facilitated by basic conditions; however, it also occurs at physiological pH at a slower rate. The hemiaminal species so-formed subsequently converts to a ring-opened hydrolysis product through cleavage of the pyrimidine N3-C4 bond. Further decomposition of this ring-opened product above physiological pH leads to DNA strand break formation. Taken together, these results suggest that once the aromaticity of a pyrimidine residue is lost, the C4 position becomes a "hot spot" for the formation of a tetrahedral intermediate, the decay of which triggers a cascade of elimination reactions that can under certain conditions convert a simple nucleobase modification into a DNA strand break.
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3'-Deoxy-3'-[(18)F]-fluorothymidine PET/CT in early determination of prognosis in patients with esophageal squamous cell cancer : Comparison with [(18)F]-FDG PET/CT.
Strahlenther Onkol
PUBLISHED: 08-28-2014
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The purpose of this work was to investigate the prognostic value of response analysis using early 3'-deoxy-3'-[(18)F]-fluorothymidine ((18)F-FLT) PET/CT in esophageal squamous cancer patients and make a comparison with [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/CT.
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[Decreased hypoxic ventilatory chemoresponsiveness and clinical features in patients with narcolepsy cataplexy].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-27-2014
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To explore the relationship between hypoxic responsiveness of the patients with narcolepsy-cataplexy and their clinical features.
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Effect of rosuvastatin on hyperuricemic rats and the protective effect on endothelial dysfunction.
Exp Ther Med
PUBLISHED: 08-21-2014
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Endothelial dysfunction plays a key role in the development of cardiovascular diseases, renal injuries and hypertension induced by hyperuricemia. Therapies targeting uric acid (UA) may be beneficial in cardiovascular diseases. In the present study, the effect of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was investigated to determine whether rosuvastatin improves endothelial dysfunction via the endothelial nitric oxide (NO) pathway and delays the pathogenesis of endothelial dysfunction in hyperuricemic rats. A total of 72 Sprague-Dawley rats (age, 8 weeks) were randomly divided into six groups (12 rats per group), including the control, model, 2.5 mg/kg/day rosuvastatin, 5 mg/kg/day rosuvastatin, 10 mg/kg/day rosuvastatin and 53.57 mg/kg/day allopurinol groups. The model, rosuvastatin and allopurinol rats were subjected to hyperuricemia, induced by the administration of yeast extract powder (21 g/kg/day) and oxonic acid potassium salt (200 mg/kg/day). The hyperuricemic rats were treated with 2.5, 5.0 or 10.0 mg/kg/day rosuvastatin orally for six weeks, while rats treated with allopurinol (53.57 mg/kg/day) were used as a positive control. The serum levels of NO and the gene expression levels of endothelial NO synthase in the aortic tissue increased, whereas the serum levels of UA, endothelin-1 and angiotensin II decreased in the hyperuricemic rats treated with rosuvastatin, particularly at a high rosuvastatin dose (10 mg/kg/day). In addition, the curative effect of the 10 mg/kg/day rosuvastatin group was evidently higher compared with the allopurinol group. Therefore, rosuvastatin may be a novel drug candidate for the treatment of hyperuricemia due to its endothelial protective properties.
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Evolution of physiological responses to salt stress in hexaploid wheat.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-29-2014
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Hexaploid bread wheat (Triticum aestivum L., genome BBAADD) is generally more salt tolerant than its tetraploid wheat progenitor (Triticum turgidum L.). However, little is known about the physiological basis of this trait or about the relative contributions of allohexaploidization and subsequent evolutionary genetic changes on the trait development. Here, we compared the salt tolerance of a synthetic allohexaploid wheat (neo-6x) with its tetraploid (T. turgidum; BBAA) and diploid (Aegilops tauschii; DD) parents, as well as a natural hexaploid bread wheat (nat-6x). We studied 92 morphophysiological traits and analyzed homeologous gene expression of a major salt-tolerance gene High-Affinity K(+) Transporter 1;5 (HKT1;5). We observed that under salt stress, neo-6x exhibited higher fitness than both of its parental genotypes due to inheritance of favorable traits like higher germination rate from the 4x parent and the stronger root Na(+) retention capacity from the 2x parent. Moreover, expression of the D-subgenome HKT1;5 homeolog, which is responsible for Na(+) removal from the xylem vessels, showed an immediate transcriptional reprogramming following allohexaploidization, i.e., from constitutive high basal expression in Ae. tauschii (2x) to salt-induced expression in neo-6x. This phenomenon was also witnessed in the nat-6x. An integrated analysis of 92 traits showed that, under salt-stress conditions, neo-6x resembled more closely the 2x than the 4x parent, suggesting that the salt stress induces enhanced expressivity of the D-subgenome homeologs in the synthetic hexaploid wheat. Collectively, the results suggest that condition-dependent functionalization of the subgenomes might have contributed to the wide-ranging adaptability of natural hexaploid wheat.
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Storage of Gold Nanoclusters in Muscle Leads to their Biphasic in Vivo Clearance.
Small
PUBLISHED: 07-25-2014
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Ultrasmall gold nanoclusters (Au NCs) show great potential in biomedical applications. Long-term biodistribution, retention, toxicity, and pharmacokinetics profiles are pre-requisites in their potential clinical applications. Here, the biodistribution, clearance, and toxicity of one widely used Au NC species-glutathione-protected Au NCs or GSH-Au NCs-are systematically investigated over a relatively long period of 90 days in mice. Most of the Au NCs are cleared at 30 days post injection (p.i.) with a major accumulation in liver and kidney. However, it is surprising that an abnormal increase of the Au amount in the heart, liver, spleen, lung, and testis is observed at 60 and 90 days p.i., indicating that the injected Au NCs form a V-shaped time-dependent distribution profile in various organs. Further investigations reveal that Au NCs are steadily accumulating in the muscle in the first 30 days p.i., and the as-stored Au NCs gradually release into the blood in 30-90 days p.i., which induces a re-distribution and re-accumulation of Au NCs in all blood-rich organs. Further hematology and biochemistry studies show that the re-accumulation of Au NCs still causes some liver toxicity at 30 days p.i. The muscle storage and subsequent release may give rise to the potential accumulation and toxicity risk of functional nanomaterials over long periods of time.
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[Investigation of exogenous stimulus effect on the interaction of CdSe/ZnS quantum dots/TiO2 nanocomposites with human serum albumin by resonance light scattering].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 07-11-2014
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The interaction between CdSe/ZnS(quantum dots)/TiO2 nanocomposites and human serum albumin(HSA) was investigated by resonance light scattering (RLS) spectroscopic methods under approximate physiological conditions. Much important information of the interaction between CdSe/ZnS(Quantum Dots)/TiO2 nanocomposites and HSA was obtained by studying comprehensively the Exogenous influence factors of nanocomposites concentration, pH, NaCl concentration, reaction temperature, detection time, coexisting ions, surfactants, sequence of adding to the sample etc. It was showed that the new formation of complex system is likely to enhance the protein hydrophobic cavity and tend to focus the hydrophobic interface in aqueous solution, resulting in strengthening the intensity of resonance light scattering; Also it is very sensitive to the changes in the pH value in the system; The sensitivity of I(RLS) in system can be increased by the appropriate NaCl concentration; The value of IRLS in system would be changed with the change in the concentration of coexisting ions; The value of I(RLS) in system is basically stable when the reaction time reaches 5 min; The value of I(RLS) in system is not exactly the same with a surfactant, and strong electrostatic interaction has occurred between oppositely charged surfactant and nano composites; It is obvious that the value of I(RLS) in complex system is affected by the sequence of adding to sample; It has the incomplete monotonically increasing trend with the changes in temperature. The information is useful for providing theoretical supporting for the mechanism of interaction between nanomaterials and bio-macromolecule, and for understanding the biocompatibility and safety of nano-materials.
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Application of sequential (18)F-FDG PET/CT scans for concurrent chemoradiotherapy of non-surgical squamous cell esophageal carcinoma.
J BUON
PUBLISHED: 06-27-2014
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To explore the values of sequential (18)F-FDG PET/CT scanning in patients with non-surgical esophageal squamous cell carcinoma (ESCC) who received concurrent chemoradiotherapy (CCRT).
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Design and fabrication of memory devices based on nanoscale polyoxometalate clusters.
Nature
PUBLISHED: 06-26-2014
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Flash memory devices-that is, non-volatile computer storage media that can be electrically erased and reprogrammed-are vital for portable electronics, but the scaling down of metal-oxide-semiconductor (MOS) flash memory to sizes of below ten nanometres per data cell presents challenges. Molecules have been proposed to replace MOS flash memory, but they suffer from low electrical conductivity, high resistance, low device yield, and finite thermal stability, limiting their integration into current MOS technologies. Although great advances have been made in the pursuit of molecule-based flash memory, there are a number of significant barriers to the realization of devices using conventional MOS technologies. Here we show that core-shell polyoxometalate (POM) molecules can act as candidate storage nodes for MOS flash memory. Realistic, industry-standard device simulations validate our approach at the nanometre scale, where the device performance is determined mainly by the number of molecules in the storage media and not by their position. To exploit the nature of the core-shell POM clusters, we show, at both the molecular and device level, that embedding [(Se(iv)O3)2](4-) as an oxidizable dopant in the cluster core allows the oxidation of the molecule to a [Se(v)2O6](2-) moiety containing a {Se(v)-Se(v)} bond (where curly brackets indicate a moiety, not a molecule) and reveals a new 5+ oxidation state for selenium. This new oxidation state can be observed at the device level, resulting in a new type of memory, which we call 'write-once-erase'. Taken together, these results show that POMs have the potential to be used as a realistic nanoscale flash memory. Also, the configuration of the doped POM core may lead to new types of electrical behaviour. This work suggests a route to the practical integration of configurable molecules in MOS technologies as the lithographic scales approach the molecular limit.
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Syrinx resolution is correlated with the upward shifting of cerebellar tonsil following posterior fossa decompression in pediatric patients with Chiari malformation type I.
Eur Spine J
PUBLISHED: 06-23-2014
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Chiari malformation type I (CMI) is characterized by deformed hindbrain. This study aimed to quantitatively evaluate the alterations in position of hindbrain after Posterior fossa decompression (PFD), and to identify the factors associated with syrinx resolution in pediatric patients with CMI.
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Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis.
Org. Lett.
PUBLISHED: 06-05-2014
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An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed.
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[Positivity analysis of human leukocyte histocompatibility antigen-DQB1*0602 allele in Chinese patients with narcolepsy].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-22-2014
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To explore the association of narcolepsy with human leukocyte histocompatibility antigen (HLA)-DQB1*0602 allele in Chinese narcoleptic patients and examine its relationship with different phenotypes.
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Serine 249 phosphorylation by ATM protein kinase regulates hepatocyte nuclear factor-1? transactivation.
Biochim. Biophys. Acta
PUBLISHED: 05-02-2014
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Hepatocyte nuclear factor-1 alpha (HNF1?) exerts important effects on gene expression in multiple tissues. Several studies have directly or indirectly supported the role of phosphorylation processes in the activity of HNF1?. However, the molecular mechanism of this phosphorylation remains largely unknown. Using microcapillary liquid chromatography MS/MS and biochemical assays, we identified a novel phosphorylation site in HNF1? at Ser249. We also found that the ATM protein kinase phosphorylated HNF1? at Ser249 in vitro in an ATM-dependent manner and that ATM inhibitor KU55933 treatment inhibited phosphorylation of HNF1? at Ser249 in vivo. Coimmunoprecipitation assays confirmed the association between HNF1? and ATM. Moreover, ATM enhanced HNF1? transcriptional activity in a dose-dependent manner, whereas the ATM kinase-inactive mutant did not. The use of KU55933 confirmed our observation. Compared with wild-type HNF1?, a mutation in Ser249 resulted in a pronounced decrease in HNF1? transactivation, whereas no dominant-negative effect was observed. The HNF1?Ser249 mutant also exhibited normal nuclear localization but decreased DNA-binding activity. Accordingly, the functional studies of HNF1?Ser249 mutant revealed a defect in glucose metabolism. Our results suggested that ATM regulates the activity of HNF1? by phosphorylation of serine 249, particularly in glucose metabolism, which provides valuable insights into the undiscovered mechanisms of ATM in the regulation of glucose homeostasis.
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Identification and characterization of a novel phage display-derived peptide with affinity for human brain metastatic breast cancer.
Biotechnol. Lett.
PUBLISHED: 04-29-2014
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A novel peptide, BRBP1 (MYPWTEPSYLSN), was identified using an in vitro phage biopanning strategy against human brain-seeking breast carcinoma cells (231-BR cells).The peptide-phage clone, BRBP1-M13 displaying BRBP1 sequence, specifically bound to 231-BR cells and the binding could be competitively abolished by BRBP1. In vivo distribution studies showed that BRBP1-M13 preferentially homed to the 231-BR tumors. Fluorescently-labeled BRBP1, BRBP1-K(5-TAMRA), preferentially bound to 231-BR cells in a dose-dependent and energy-dependent manner and it was efficiently internalized into the cells after 2 h incubation. Near-infrared fluorophores imaging demonstrated the accumulation of Cy5.5-conjugated BRBP1 peptide in the tumors in vivo. Thus, BRBP1 is a promising peptide binding to human brain metastatic breast cancer and it may be applied to targeted delivery of cytotoxic agents to the intended tumor.
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Cx37 C1019T polymorphism may contribute to the pathogenesis of coronary heart disease.
Genet Test Mol Biomarkers
PUBLISHED: 04-28-2014
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We conducted a meta-analysis of case-control studies to evaluate whether Cx37 C1019T (rs1764391 C>T) polymorphism may be implicated in the pathogenesis of coronary heart disease (CHD).
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[Value of transcutaneous monitoring of CO2 pressure in the diagnosis and treatment of sleep and breathing disorders].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-24-2014
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To evaluate the clinical value of transcutaneous carbon dioxide (TcPCO2) measurement during sleep respiratory monitoring.
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Exploring the symmetry, structure, and self-assembly mechanism of a gigantic seven-fold symmetric {Pd??} wheel.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 04-23-2014
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The symmetry, structure and formation mechanism of the structurally self-complementary {Pd84} = [Pd84O42(PO4)42(CH3CO2)28](70-) wheel is explored. Not only does the symmetry give rise to a non-closest packed structure, the mechanism of the wheel formation is proposed to depend on the delicate balance between reaction conditions. We achieve the resolution of gigantic polyoxopalladate species through electrophoresis and size-exclusion chromatography, the latter has been used in conjunction with electrospray mass spectrometry to probe the formation of the ring, which was found to proceed by the stepwise aggregation of {Pd6}(-) = [Pd6O4(CH3CO2)2(PO4)3Na(6-n)H(n)](-) building blocks. Furthermore, the higher-order assembly of these clusters into hollow blackberry structures of around 50?nm has been observed using dynamic and static light scattering.
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In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration.
J Ethnopharmacol
PUBLISHED: 04-06-2014
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Salvia miltiorrhiza Bunge (Labiatae sp. plant, Chinese name Danshen) and Panax notoginseng (Burk.) F. H. Chen (Araliaceae plant, Chinese name Sanqi) have a long history in treating coronary heart disease, cerebrovascular disease and inner ear disorders in traditional Chinese medicine. To provide a rational basis for the use of these herbs in clinical practice, we investigated the in vivo distribution and pharmacokinetics of marker agents in Danshen and Sanqi via intravenous and inner ear administration and explored the potential interactions of these agents in compound prescription.
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Step-by-step covalent modification of Cr-templated Anderson-type polyoxometalates.
Dalton Trans
PUBLISHED: 04-04-2014
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A series of tripodal alcohols substituted Anderson-type polyoxometalates (POMs) including mono-substituted (compounds and ), asymmetrical bi-substituted (compound ), and symmetrical bi-substituted ones (compounds and ) have been synthesized under hydrothermal conditions using a pre-designed step-by-step strategy, and compounds , and have been fully characterized by single-crystal X-ray diffraction, ESI-MS, and elemental analysis.
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Occurrence, sources, and potential human health risks of polycyclic aromatic hydrocarbons in agricultural soils of the coal production area surrounding Xinzhou, China.
Ecotoxicol. Environ. Saf.
PUBLISHED: 04-02-2014
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A comprehensive investigation of the levels, distribution patterns, and sources of polycyclic aromatic hydrocarbons (PAHs) in agricultural soils of the coal production area surrounding Xinzhou, China, was conducted, and the potential human health risks associated with the levels observed were addressed. A total of 247 samples collected from agricultural soils from the area were analyzed for sixteen PAHs, including highly carcinogenic isomers. The PAH concentrations had a range of n.d. to 782ngg(-1), with a mean value of 202ngg(-1). The two-three ring PAHs were the dominant species, making up 60 percent of total PAHs. Compared with the pollution levels and carcinogenic potential risks reported in other studies, the soil PAH concentrations in the study area were in the low to intermediate range. A positive matrix factorization model indicates that coal/biomass combustion, coal and oil combustion, and coke ovens are the primary PAH sources, accounting for 33 percent, 26 percent, and 24 percent of total PAHs, respectively. The benzo[a]pyrene equivalent (BaPeq) concentrations had a range of n.d. to 476ngg(-1) for PAH7c, with a mean value of 34ngg(-1). The BaPeq concentrations of PAH7c accounted for more than 99 percent of the ?PAH16, which suggests that seven PAHs were major carcinogenic contributors of ?PAH16. According to the Canadian Soil Quality Guidelines, only six of the soil samples had concentrations above the safe BaPeq value of 600ngg(-1); the elevated concentrations observed at these sites can be attributed to coal combustion and industrial activities. Exposure to these soils through direct contact probably poses a significant risk to human health as a result of the carcinogenic effects of PAHs.
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CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer.
Clin. Chim. Acta
PUBLISHED: 03-28-2014
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To determine whether the combination of tumor markers (CA72-4, CA125, CA19-9 and CEA) could increase the sensitivity and accuracy for in the diagnosis of gastric cancer (GC).
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Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers.
Cell. Physiol. Biochem.
PUBLISHED: 03-20-2014
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Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS.
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Polyoxometalate clusters integrated into peptide chains and as inorganic amino acids: solution- and solid-phase approaches.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-12-2014
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General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution-phase approach, pre-synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid-phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain "inorganic" amino acids.
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Pre-treatment metabolic tumor volume and total lesion glycolysis are useful prognostic factors for esophageal squamous cell cancer patients.
Asian Pac. J. Cancer Prev.
PUBLISHED: 03-11-2014
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To study application of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with 18F-FDG PET/CT for predicting prognosis of esophageal squamous cell cancer (ESC) patients.
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Time-resolved assembly of cluster-in-cluster {Ag??}-in-{W??} polyoxometalates under supramolecular control.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-02-2014
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We report the time-resolved supramolecular assembly of a series of nanoscale polyoxometalate clusters (from the same one-pot reaction) of the form: [H(10+m)Ag18Cl(Te3W38O134)2]n, where n=1 and m=0 for compound 1 (after 4?days), n=2 and m=3 for compound 2 (after 10?days), and n=? and m=5 for compound 3 (after 14?days). The reaction is based upon the self-organization of two {Te3W38} units around a single chloride template and the formation of a {Ag12} cluster, giving a {Ag12}-in-{W76} cluster-in-cluster in compound 1, which further aggregates to cluster compounds 2 and 3 by supramolecular Ag-POM interactions. The proposed mechanism for the formation of the clusters has been studied by ESI-MS. Further, control experiments demonstrate the crucial role that TeO3(2-), Cl(-), and Ag(+) play in the self-assembly of compounds 1-3.
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A robust automated markerless registration framework for neurosurgery navigation.
Int J Med Robot
PUBLISHED: 02-26-2014
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The registration of a pre-operative image with the intra-operative patient is a crucial aspect for the success of navigation in neurosurgery.
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?-Radiolysis of ionic liquid irradiated with helium ion beam and the influence of radiolytic products on Dy3+ extraction.
Dalton Trans
PUBLISHED: 02-20-2014
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Helium ion (He(+)) beam produced by a heavy ion linear accelerator was used to simulate ?-rays for studying the radiation effect on 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid ([C4mim][NTf2]). The water-soluble radiolytic products of [C4mim][NTf2] under He(+) beam irradiation were analysed, and it was found that they were similar to those by ?-ray irradiation, but their amount was much less than that by ?-ray irradiation, which was attributed to the recombination of [C4mim][NTf2] radical cations in track by high linear energy transfer (LET) radiations of the He(+) beam. The extracting behaviour of Dy(3+) using irradiated [C4mim][NTf2] in combination with alkylated bis-triazinyl-pyridine (CA-BTP) was assessed, and found that the influence of He(+) beam on the extraction was less than that of ?-ray irradiation. In addition, radiolytic products have a different influence on Dy(3+) extraction at different doses; Dy(3+) partitioning decreases at 50 kGy due to the protonation of CA-BTP and the inhibition of cation exchange mechanism by radiation-formed hydrogen ions. The abnormal increase of Dy(3+) partitioning at 100 kGy is mainly attributed to the precipitation formed between Dy(3+) and radiolytic products (F(-) and SO3(2-)).
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Degradation of 1,4-dioxane in water with heat- and Fe(2+)-activated persulfate oxidation.
Environ Sci Pollut Res Int
PUBLISHED: 02-19-2014
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This research investigated the 1,4-dioxane (1,4-D) degradation efficiency and rate during persulfate oxidation at different temperatures, with and without Fe(2+) addition, also considering the effect of pH and persulfate concentration on the oxidation of 1,4-D. Degradation pathways for 1,4-D have also been proposed based on the decomposition intermediates and by-products. The results indicate that 1,4-D was completely degraded with heat-activated persulfate oxidation within 3-80 h. The kinetics of the 1,4-D degradation process fitted well to a pseudo-first-order reaction model. Temperature was identified as the most important factor influencing the 1,4-D degradation rate during the oxidation process. As the temperature increased from 40 to 60 °C, the degradation rate improved significantly. At 40 °C, the addition of Fe(2+) also increased the 1,4-D degradation rate. Interestingly, at 50 and 60 °C, the 1,4-D degradation rate decreased slightly with the addition of Fe(2+). This reduced degradation rate may be attributed to the rapid conversion of Fe(2+) to Fe(3+) and the production of an Fe(OH)3 precipitate which limited the ultimate oxidizing capability of persulfate with Fe(2+) under higher temperatures. Higher persulfate concentrations led to higher 1,4-D degradation rates, but pH adjustment had no significant effect on the 1,4-D degradation rate. The identification of intermediates and by-products in the aqueous and gas phases showed that acetaldehyde, acetic acid, glycolaldehyde, glycolic acid, carbon dioxide, and hydrogen ion were generated during the persulfate oxidation process. A carbon balance analysis showed that 96 and 93% of the carbon from the 1,4-D degradation were recovered as by-products with and without Fe(2+) addition, respectively. Overall, persulfate oxidation of 1,4-D is promising as an economical and highly efficient technology for treatment of 1,4-D-contaminated water.
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Assembly and core transformation properties of two tetrahedral clusters: [Fe(III)13P8W60O227(OH)15(H2O)2]30- and [Fe(III)13P8W60O224(OH)12(PO4)4]33-.
Dalton Trans
PUBLISHED: 02-12-2014
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Two nanosized 2.6 nm Fe(III) substituted polyoxotungstates [Fe(III)13P8W60O227(OH)15(H2O)2](30-) (1) and [Fe(III)13P8W60O224(OH)12(PO4)4](33-) (2) are presented herein. Both clusters are synthesized from the reactions of trilacunary polyoxotungstate precursor [?-P2W15O56](12-) and FeCl3 under strict pH control at atmospheric pressure. The compounds are fully characterised in the solid state (FTIR and single-crystal XRD, elemental and thermogravimetric analyses), solution (cyclic voltammetry and UV-Vis spectroscopy) and in the gas phase (ESI-MS). An {Fe(III)13} core is present in both clusters which can be described as Archimedean solids (truncated tetrahedron, 1; elongated cuboctahedron, 2). 1 shows iron delivery properties coupled to a K(+)-triggered transformation of the {Fe13} core to a {K?Fe12} core in solution. Cyclic voltammetry shows the presence of independent W- and Fe-centred redox processes that support the stability of the clusters in solution. ESI-MS analyses confirm further the stability of 1 and 2 in the gas phase.
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Process and outcome for international reliability in sleep scoring.
Sleep Breath
PUBLISHED: 02-03-2014
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The aim was to evaluate the inter-rater reliability in scoring sleep stages in two sleep labs in Berlin Germany and Beijing China.
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Solid-phase synthesis of amidine-substituted phenylbenzimidazoles and incorporation of this DNA binding and recognition motif into amino acid and peptide conjugates.
Amino Acids
PUBLISHED: 01-31-2014
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Amidine-substituted phenylbenzimidazoles are well-established DNA-binding structural motifs that have contributed to the development of diverse classes of DNA-targeted agents; this ring system not only assists in increasing the overall DNA affinity of an agent, but can also influence its site selectivity. Seeking a means to conveniently exploit these attributes, a protocol for the on-resin synthesis of amino acid- and peptide-phenylbenzimidazole-amidine conjugates was developed to facilitate installation of phenylbenzimidazole-amidines into peptide chains during the course of standard solid-phase syntheses. Building from a resin-bound amino acid or peptide on Rink amide resin, 4-formyl benzoic acid was coupled to the resin-bound free amine followed by introduction of 3,4-diamino-N'-hydroxybenzimidamide (in the presence of 1,4-benzoquinone) to construct the benzimidazole heterocycle. Finally, the resin-bound N'-hydroxybenzimidamide functionality was reduced to an amidine via 1 M SnCl2·2H2O in DMF prior to resin cleavage to release final product. This procedure permits the straightforward synthesis of amino acids or peptides that are N-terminally capped by a phenylbenzimidazole-amidine ring system. Employing this protocol, a series of amino acid-phenylbenzimidazole-amidine (Xaa-R) conjugates was synthesized as well as dipeptide conjugates of the general form Xaa-Gly-R (where R is the phenylbenzimidazole-amidine and Xaa is any amino acid).
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[Changes in T lymphocyte subsets in preterm infants with intrauterine growth retardation].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 01-28-2014
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To study changes in T lymphocyte subsets in preterm infants with intrauterine growth retardation (IUGR).
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Anatomical and functional volume concordance between FDG PET, and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 01-25-2014
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To evaluate the concordance among (18)F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR.
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Towards imaging electron density inside metal-organic framework structures.
Chem. Commun. (Camb.)
PUBLISHED: 01-17-2014
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Herein, we present electron density maps of three MOFs with different guests or post-synthetic modifications produced using single crystal X-ray data from laboratory diffractometers. Analysis of the electron density maps reveals possible differences inside the pores indicating that this approach may be used to explore frameworks using inexpensively gained X-ray data.
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Formation, self-assembly and transformation of a transient selenotungstate building block into clusters, chains and macrocycles.
Chem. Commun. (Camb.)
PUBLISHED: 01-15-2014
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The one-pot syntheses of a series of dimeric and trimeric selenotungstates based on the [Se2W12O46](12-) unit are presented alongside the structure of the tetrameric [Se8W48O176](32-) wheel. Mass spectrometry has probed the stability of these clusters whilst their electronic structure has been contrasted to their known phosphotungstate analogues.
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Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-13-2014
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The human heart's failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite the myocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling.
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Molecular cloning, expression and functional analysis of B-cell activating factor (BAFF) in yellow grouper, Epinephelus awoara.
Mol. Immunol.
PUBLISHED: 01-08-2014
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B cell activating factor (BAFF), a ligand belonging to the tumor necrosis factor (TNF) family is critical to B cell survival, proliferation, maturation and immunoglobulin secretion. In this study, the yellow grouper (Epinephelus awoara) BAFF (designated EaBAFF) gene was cloned using RT-PCR and RACE (rapid amplification of cDNA ends) techniques. The full-length EaBAFF was 1442bp and contained an open reading frame of 780bp encoding a putative protein of 259 amino acids. Amino acids sequence comparison indicated that EaBAFF possessed the TNF signature. The soluble BAFF (EasBAFF) had been cloned into pET28a. SDS-PAGE and Western blotting analysis confirmed that the soluble fusion protein His-EasBAFF was efficiently expressed in Escherichia coli BL21 (DE3). In vitro, the WST-8 assay indicated that EasBAFF was not only able to promote the survival/proliferation of yellow grouper splenic lymphocytes but also able to promote the survival/proliferation of mouse splenic B cells. Our findings may provide valuable information for research into the immune system of E. awoara and EasBAFF may serve as a potential immunologic factor for enhancing immunological efficacy in fish.
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Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation.
PLoS ONE
PUBLISHED: 01-01-2014
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Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPK?2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice.
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Megakaryocytic differentiation of K562 cells induced by PMA reduced the activity of respiratory chain complex IV.
PLoS ONE
PUBLISHED: 01-01-2014
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Mitochondria are involved in the regulation of cell differentiation processes, but its function changes and molecular mechanisms are not yet clear. In this study, we found that mitochondrial functions changed obviously when K562 cells were induced to megakaryocytic differentiation by phorbol 12-myristate 13-acetate (PMA). During the cell differentiation, the reactive oxygen species (ROS) level was increased, mitochondrial membrane potential declined and respiratory chain complex IV activity was decreased. Treatment with specific inhibitor of mitochondrial respiratory chain complex IV led to a significant inhibition in mitochondrial membrane potential and reduction of PMA-induced cell differentiation. However, treatment with cyclosporine A, a stabilization reagent of mitochondrial membrane potential, did not improve the down-regulation of mitochondrial respiratory chain complex IV induced by PMA. Furthermore, we found that the level of the complex IV core subunit COX3 and mitochondrial transport-related proteins Tim9 and Tim10 were decreased during the differentiation of K562 cells induced by PMA, suggesting an important role of these factors in mitochondrial functional changes. Our results suggest that changes in mitochondrial functions are involved in the PMA-induced K562 cell differentiation process, and the maintenance of the steady-state of mitochondrial functions plays a critical role in the regulation of cell differentiation.
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Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.
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Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.
Nat Commun
PUBLISHED: 01-01-2014
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The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.
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Procalcitonin guided antibiotic therapy of acute exacerbations of asthma: a randomized controlled trial.
BMC Infect. Dis.
PUBLISHED: 12-09-2013
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This randomized controlled trial aimed to evaluate whether the serum procalcitonin (PCT) level can be utilized to guide the use of antibiotics in the treatment of acute exacerbations of asthma.
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[Daytime hypercapnia in patients with obstructive sleep apnea hypopnea syndrome].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 11-23-2013
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To evaluate the incidence and factors related to daytime CO2 retention (PaCO2 ? 45 mm Hg, 1 mm Hg = 0.133 kPa) in Chinese patients with obstructive sleep apnea hypopnea syndrome.
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[Value of cerebral spinal fluid measurement of hypocretin-1 in the diagnosis of Chinese patients with narcolepsy].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-31-2013
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To evaluate the diagnostic value of cerebral spinal fluid (CSF) measurement of hypocretin-1 (hcrt-1) in Chinese patients with narcolepsy.
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Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.
PLoS Genet.
PUBLISHED: 10-01-2013
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Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.
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A redox-triggered structural rearrangement in an iodate-templated polyoxotungstate cluster cage.
Chem. Commun. (Camb.)
PUBLISHED: 09-12-2013
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The new tungstatoiodate, ?-[H5W18O59(IO3)](6-), containing I(V)O3(-) within a {W18O54} metal oxide framework has been prepared and shown by X-ray crystallography and mass spectrometry to be derived from the fully oxidised [H3W18O56(IO6)](6-) by two-electron reduction accompanied by a redox-triggered structural rearrangement where three I-O covalent bonds are broken.
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Enantioselective intermolecular formal [3 + 3] cycloaddition of 2,3-disubstituted indoles with acrolein.
Org. Lett.
PUBLISHED: 08-15-2013
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An expedient enantioselective synthesis of highly substituted hydrocarbazoles has been realized by an organocatalyzed formal [3 + 3] cycloaddition between acrolein and 2,3-disubstituted indoles. Tricyclic hydrocarbazoles were obtained from a broad range of 2,3-disubstituted indoles and acrolein in good to excellent yields and excellent enantioselectivites.
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Exploring the assembly of supramolecular polyoxometalate triangular morphologies with Johnson solid cores: [(Mn(II)(H2O)3)2(K?{?-GeW10Mn(II)2O38}3)]19-.
Inorg Chem
PUBLISHED: 07-26-2013
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A new polyoxometalate (POM) cluster compound is presented which incorporates a trimeric assembly of Keggin-type germanotungstate fragments trapping a Johnson-type solid {Mn8} core. The mixed K-Li salt of the polyanion [(Mn(II)(H2O)3)2(K?{?-GeW10Mn(II)2O38}3)](19-) was characterized in the solid state and solution. The correlation of the assembly processes and the observed architecture of the "trinity" family of POMs is discussed.
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Quick and selective synthesis of Li6[?-P2W18O62]·28H2O soluble in various organic solvents.
Dalton Trans
PUBLISHED: 07-08-2013
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Herein we report the synthesis of ?-Dawson type POM, Li6[?-P2W18O62]·28H2O, directly from the use of Li2WO4 as the tungstate source. The salt obtained was soluble not only in water but also in a range of polar and non-polar organic solvents, such as benzene.
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Multimeric immobilization of alcohol oxidase on electrospun fibers for valid tests of alcoholic saliva.
J. Biotechnol.
PUBLISHED: 06-18-2013
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An accurate quantitation of ethanol is of great importance in clinical and forensic analyses. In the current study, alcohol oxidase (AOX) from Pichia pastoris, a multimeric enzyme consisting of eight identical subunits, was immobilized on electrospun polystyrene-co-maleic anhydride (PSMA) fibers for valid tests of alcoholic saliva. Branched polyethyleneimine (PEI) was grafted on PSMA fibers with a density of 0.15 nmol/cm(2) as tethers to allow multipoint covalent binding of enzyme molecules through glutaraldehyde activation, and the secondary and tertiary amino groups of PEI could intensify the interactions with AOX subunits to stabilize the quaternary structure. PSMA-PEI-AOX fibers were less sensitive than free AOX to the incubation temperature and pH, and indicated no detectable subunit release from the immobilized AOX after boiling in the presence of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol. Color strips were established on PSMA-PEI-AOX fibrous mats dyed with indigo Carmine after incubation into ethanol solutions of different concentrations. The color fading ratio remained no significant change after repeat tests for 9 cycles after immersion in 0.2 and 0.8 mg/mL of alcoholic saliva. It was indicated that multipoint immobilization of the multimeric enzyme was essential to improve the enzyme stability by stabilizing both the quaternary structure of the enzyme and the structure of each individual subunit.
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Removal of PCDD/Fs from contaminated sediment and released effluent gas by charcoal in a proposed cost-effective thermal treatment process.
Chemosphere
PUBLISHED: 06-09-2013
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A novel cost-effective thermal treatment technology has been proposed for the removal of PCDD/Fs from contaminated sediment and released effluent gas using charcoal as both an adsorbent and a thermal source. When a reactor was used for thermal treatment, the PCDD/Fs removal efficiency exceeded 98% from the sediment at the three different air superficial velocities employed in this study. The total PCDD/F international toxic equivalent (I-TEQ) contents, both in the treated sediments and effluent gas, were below the Japanese emission standard limit. Analysis of the PCDD/F contents in different fractions showed that large quantities of PCDDs but not PCDFs were evaporated from the sediment and adsorbed in the moist sediment column. This difference was attributed to the formation of PCDDs from pentachlorophenol (PCP) during the cooling process following the thermal treatment process in the reactor. This proposed thermal process provides a promising alternative to the conventional methods.
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Study on incompatibility of traditional chinese medicine: evidence from formula network, chemical space, and metabolism room.
Evid Based Complement Alternat Med
PUBLISHED: 06-07-2013
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A traditional Chinese medicine (TCM) formula network including 362 TCM formulas was built by using complex network methodologies. The properties of this network were analyzed including network diameter, average distance, clustering coefficient, and average degree. Meanwhile, we built a TCM chemical space and a TCM metabolism room under the theory of chemical space. The properties of chemical space and metabolism room were calculated and analyzed. The properties of the medicine pairs in "eighteen antagonisms and nineteen mutual inhibitors," an ancient rule for TCM incompatibility, were studied based on the TCM formula network, chemical space, and metabolism room. The results showed that the properties of these incompatible medicine pairs are different from those of the other TCM based on the analysis of the TCM formula network, chemical space, and metabolism room. The lines of evidence derived from our work demonstrated that the ancient rule of TCM incompatibility, "eighteen antagonisms and nineteen mutual inhibitors," is probably scientifically based.
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Source identification and health risk assessment of metals in urban soils around the Tanggu chemical industrial district, Tianjin, China.
Sci. Total Environ.
PUBLISHED: 06-07-2013
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We conducted an investigation to identify the sources of metals in urban surface soils, and to assess the associated human health risks, around the Tanggu chemical industrial district, Tianjin, China. The metal concentrations and spatial distributions in 70 soil samples from the study area were determined. Pollution sources were identified using multivariate statistical analysis. They mainly attributed Cu, Pb, and Zn pollution to vehicular traffic and industrial discharges, Cd pollution to industrial activities and anthropogenic waste including industrial discharges, sewage sludge, and municipal solid waste, As and Hg pollution to coal combustion and point source emissions from the chemical industry, and Cr and Ni pollution to the soil parent material. Soil properties, particularly the organic matter content, were found to be important factors in the distribution and composition of metals. A health risk assessment showed that samples from the northwestern and southeastern parts of the study area may pose significant health risks to the population.
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Assembly of thiometalate-based {Mo16 } and {Mo36 } composite clusters combining [Mo2O2S2 ](2+) cations and selenite anions.
Adv. Mater. Weinheim
PUBLISHED: 06-05-2013
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A new family of thiometalate-based composite molecular materials is synthesized and characterized. 1.6 and 1.9 nm-sized clusters are observed in the gas phase utilizing high-resolution ESI-MS. The diversity of the selenite anions as an inorganic ligand is demonstrated by the isolation of the highest nuclearity selenium-based oxothiometalate materials reported so far. The observed proton conductivity of the selenite based oxothiometalate species renders them as promising alternative materials for fuel-cell applications.
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Naphthoxanthenyl, a New Stable Phenalenyl Type Radical Stabilized by Electronic Effects.
Org. Lett.
PUBLISHED: 06-03-2013
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Naphthoxanthenyl 1 is a new stable phenalenyl-type radical. Electrochemical studies indicate that 1 has two reversible redox processes that occur on comparatively short time scales. Crystals containing 1 can be grown by electrocrystallization, suggesting that they are conductive.
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[Utility of portable monitoring device with airflow, oxygen saturation and respiratory effort in the diagnosis of sleep apnea hypopnea syndrome].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-11-2013
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To validate the values of monitoring airflow, oxygen saturation and respiratory effort in the diagnosis of sleep apnea-hypopnea syndrome (SAHS).
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Electrically driven ultraviolet random lasing from an n-MgZnO/i-ZnO/SiO2/p-Si asymmetric double heterojunction.
Nanoscale
PUBLISHED: 05-02-2013
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Electrically pumped lasing action has been realized in ZnO from an n-MgZnO/i-ZnO/SiO2/p-Si asymmetric double heterostructure, an ultralow threshold of 3.9 mA was obtained. The mechanism of the laser is associated with the in-plane random resonator cavities formed in the ZnO films and the elaborate hollow-shaped SiO2 cladding pattern, which prevent the lateral diffusion of injection current and ultimately lower the threshold current of the laser diode. In addition, a waveguide mechanism due to different refractive indices of three epilayers enhances the guided optical field on the ZnO side, resulting in an improved light extraction efficiency.
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Synthesis and characterisation of a lanthanide-capped dodecavanadate cage.
Chem. Commun. (Camb.)
PUBLISHED: 03-19-2013
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The synthesis of a series of discrete lanthanide-capped polyoxovanadate cages is presented along with magnetic and electrochemical measurements which reveal a redox active dodecavanadate cluster with potential as a new functional building unit in polyoxovanadate chemistry.
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Metabonomics Combined with UPLC-MS Chemical Profile for Discovery of Antidepressant Ingredients of a Traditional Chinese Medicines Formula, Chaihu-Shu-Gan-San.
Evid Based Complement Alternat Med
PUBLISHED: 02-15-2013
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This study proposed a new strategy for uncovering the active chemical constituents of a traditional Chinese medicines (TCMs) formula, Chaihu-Shu-Gan-San (CSGS). Metabonomics and chemical profile were integrated in combination with the multivariate statistical analysis (MVA) to discover the chemical constituents which contribute to the antidepressant effect of CSGS. Based upon the difference between CSGS and QZ (CSGS without Zhi-Qiao) extracts in the chemical profiles and the regulations of metabolic disturbances induced by CUMS, synephrine, naringin, hesperidin, and neohesperidin were recognized as the active constituents of CSGS from Zhi-qiao responsible for those missing regulations of CSGS when Zhi-Qiao was subtracted from the whole formula. They participated in the regulations of the deviated metabolites 2-4, 10-14, and 22-25, involved in metabolic pathways of ketone bodies synthesis, phenylalanine, tyrosine and tryptophan biosynthesis, valine, aspartate, glutamate metabolism, and glycolysis/gluconeogenesis. Furthermore, the assay of MAO-A activity confirmed the potential antidepressant effect of naringin and its active sites on the MAO-A was inferred by molecular docking study. The integration of metabonomics and chemical profile was proved to be a useful strategy for uncovering what the active chemical constituents in TCM formula are and how they make contributions for the efficacy of the formula.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.