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Find video protocols related to scientific articles indexed in Pubmed.
Regioselective Decarboxylative Direct C-H Arylation of Boron Dipyrromethenes (BODIPYs) at 2,6-Positions: A Facile Access to a Diversity-Oriented BODIPY Library.
Org. Lett.
PUBLISHED: 11-18-2014
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A palladium-catalyzed regioselective decarboxylative direct C-H arylation of boron dipyrromethenes (BODIPYs) at the 2,6-positions has been developed as a late-stage approach to rapidly assemble a diversity-oriented BODIPY library. With the complement of this protocol, the direct C-H arylation of BODIPYs becomes regiocontrollable at ?- and ?-positions. A new type of indole-fused BODIPY exhibiting bright red/NIR fluorescence with a large molar extinction coefficient (145?500 M(-1) cm(-1)) and a high quantum yield (71%) has been synthesized for the first time.
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Pd-Catalyzed C-H Carbonylation of (Hetero)arenes with Formates and Intramolecular Dehydrogenative Coupling: A Shortcut to Indolo[3,2-c]coumarins.
Org. Lett.
PUBLISHED: 11-03-2014
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An efficient protocol for the synthesis of (hetero)aryl carboxylic esters has been achieved by Pd-catalyzed C-H carbonylation of (hetero)arenes with aryl formates. A relatively wide range of functional groups can be tolerated in this transformation, and the corresponding esters are obtained in good yields. On this basis, an intramolecular oxidative C-H/C-H coupling has been developed to prepare indolo[3,2-c]coumarins.
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An AIE active Y-shaped diimidazolylbenzene: aggregation and disaggregation for Cd(2+) and Fe(3+) sensing in aqueous solution.
Org. Biomol. Chem.
PUBLISHED: 10-28-2014
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A simple Y-shaped dimb with AIE properties was designed and synthesized. It showed selective fluorescence turn-on toward Cd(2+) ion in MeCN-water (2?:?8, v/v) through aggregation, and also selective fluorescence turn-off toward Fe(3+) ion in MeCN-water (1?:?99, v/v) through disaggregation.
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Radical cascade cyanomethylation of activated alkenes to construct cyano substituted oxindoles.
Chem. Commun. (Camb.)
PUBLISHED: 10-21-2014
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The cyanomethyl radical was easily generated from acetonitrile by using DTBP, which was applied to a cascade alkene addition and cyclization reaction to construct useful oxindole derivatives. This protocol features simple manipulation, cheap reagents and a broad substrate scope. In addition, nitro substituted oxindoles were also synthesized for the first time.
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Three dimensional finite element analysis of a novel osteointegrated dental implant designed to reduce stress peak of cortical bone.
Acta Bioeng Biomech
PUBLISHED: 10-14-2014
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A new type of dental implant was designed as multi-component mainly including inset and abutment between which a gap was introduced to guide the force to transmit from the cancellous bone to cortical bone, with the intention to lower the stress peak at cortical bone. By way of finite element analysis (FEA) associated with advanced computer tomography (CT) and 3D model reconstruction technology to construct precise mandible model, biomechanical aspects of implant were investigated. Compared with traditional implant that created stress dominantly at cortical bone, stress peak at the implant/bone interface in the cervical cortex decreased sharply (about 51%) for the new type of implant. Furthermore, applying varying implant shape and gap dimensions helped to optimize the design of this new implant. Optimization results revealed that: (1) screwed cylindrical implant is superior to tapered, stepped and smooth cylindrical implant in effectively decreasing the stress peak of bone; (2) deepening and widening gap would contribute to the decline of stress peak, but at the cost of break and destruction of the inset; (3) suitable gap size with the depth of 7 mm and width of 0.3 mm would be applicable. This work may provide reference for clinical application of dental implant.
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Inhibition of p70 S6 Kinase (S6K1) Activity by A77 1726 and Its Effect on Cell Proliferation and Cell Cycle Progress.
Neoplasia
PUBLISHED: 10-01-2014
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Leflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid arthritis. It inhibits the activity of protein tyrosine kinases and dihydroorotate dehydrogenase, a rate-limiting enzyme in the pyrimidine nucleotide synthesis pathway. Here, we report that A77 1726, the active metabolite of leflunomide, inhibited the phosphorylation of ribosomal protein S6 and two other substrates of S6K1, insulin receptor substrate-1 and carbamoyl phosphate synthetase 2, in an A375 melanoma cell line. A77 1726 increased the phosphorylation of AKT, p70 S6 (S6K1), ERK1/2, and MEK through the feedback activation of the IGF-1 receptor-mediated signaling pathway. In vitro kinase assay revealed that leflunomide and A77 1726 inhibited S6K1 activity with IC50 values of approximately 55 and 80 ?M, respectively. Exogenous uridine partially blocked A77 1726-induced inhibition of A375 cell proliferation. S6K1 knockdown led to the inhibition of A375 cell proliferation but did not potentiate the antiproliferative effect of A77 1726. A77 1726 stimulated bromodeoxyuridine incorporation in A375 cells but arrested the cell cycle in the S phase, which was reversed by addition of exogenous uridine or by MAP kinase pathway inhibitors but not by rapamycin and LY294002 (a phosphoinositide 3-kinase inhibitor). These observations suggest that A77 1726 accelerates cell cycle entry into the S phase through MAP kinase activation and that pyrimidine nucleotide depletion halts the completion of the cell cycle. Our study identified a novel molecular target of A77 1726 and showed that the inhibition of S6K1 activity was in part responsible for its antiproliferative activity. Our study also provides a novel mechanistic insight into A77 1726-induced cell cycle arrest in the S phase.
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Synthesis and biological evaluation of novel millepachine derivatives as a new class of tubulin polymerization inhibitors.
J. Med. Chem.
PUBLISHED: 09-29-2014
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Twenty-one novel derivatives of millepachine were synthesized and evaluated for their in vitro antiproliferative activity. Among them, 8 exhibited the most potent activity, with IC50 values of 8-27 nM against panel of cancer cell lines and retained full activity in multidrug resistant cancer cells. Treated cells were arrested in G2/M phase and resulted in cellular apoptosis. Microtubule dynamics confirmed 8 was a novel tubulin polymerization inhibitor by binding at the colchicine site. 8 also exhibited antivascular activity because it concentration dependently reduced the cell migration and disrupted capillary like tube formation in HUVEC cells. Furthermore, the hydrochloride salt of 8 (8·HCl) significantly improved the bioavailability up to 47% while retaining the antiproliferative activity. Importantly, 8·HCl significantly inhibited tumor growths in four xenograft models including resistance tumor-cell-bearing mice models without causing significant loss of body weight, suggesting that 8 is a promising new orally anticancer agent to be developed.
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Versatile palladium-catalyzed C-H olefination of (hetero)arenes at room temperature.
Chem. Commun. (Camb.)
PUBLISHED: 09-27-2014
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The room-temperature oxidative C-H/C-H cross-couplings between (hetero)arenes and alkenes, coumarins or quinones have been reported by using a highly electrophilic palladium species [Pd(TFA)2], generated in situ from Pd(OAc)2 and TFA, as the catalyst and cheap (NH4)2S2O8 as the oxidant under air.
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Cu-catalysed oxidative C-H/C-H coupling polymerisation of benzodiimidazoles: an efficient approach to regioregular polybenzodiimidazoles for blue-emitting materials.
Chem. Commun. (Camb.)
PUBLISHED: 09-25-2014
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The Cu-catalysed oxidative C-H/C-H coupling reaction of azoles has been used for the first time to develop polymerisation, which provides an efficient method for the preparation of polybenzodiimidazoles. These polymers exhibit high molecular weights, regioregularity, blue-emitting performance and thermal stability.
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Applications of absorption spectroscopy using quantum cascade lasers.
Appl Spectrosc
PUBLISHED: 09-21-2014
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Infrared laser absorption spectroscopy (LAS) is a promising modern technique for sensing trace gases with high sensitivity, selectivity, and high time resolution. Mid-infrared quantum cascade lasers, operating in a pulsed or continuous wave mode, have potential as spectroscopic sources because of their narrow linewidths, single mode operation, tunability, high output power, reliability, low power consumption, and compactness. This paper reviews some important developments in modern laser absorption spectroscopy based on the use of quantum cascade laser (QCL) sources. Among the various laser spectroscopic methods, this review is focused on selected absorption spectroscopy applications of QCLs, with particular emphasis on molecular spectroscopy, industrial process control, combustion diagnostics, and medical breath analysis.
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T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT.
Blood
PUBLISHED: 09-11-2014
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We developed an approach of T-cell-replete haploidentical hematopoietic stem cell transplantation (HSCT) with low-dose anti-T-lymphocyte globulin and prospectively compared outcomes of all contemporaneous T-cell-replete HSCT performed at our center using matched sibling donors (MSDs), unrelated donors (URDs), and haploidentical related donors (HRDs). From 2008 to 2013, 90 patients underwent MSD-HSCT, 116 underwent URD-HSCT, and 99 underwent HRD-HSCT. HRDs were associated with higher incidences of grades 2 to 4 (42.4%) and severe acute graft-versus-host disease (17.2%) and nonrelapse mortality (30.5%), compared with MSDs (15.6%, 5.6%, and 4.7%, respectively; P < .05), but were similar to URDs, even fully 10/10 HLA-matched URDs. For high-risk patients, a superior graft-versus-leukemia effect was observed in HRD-HSCT, with 5-year relapse rates of 15.4% in HRD-HSCT, 28.2% in URD-HSCT (P = .07), and 49.9% in MSD-HSCT (P = .002). Furthermore, 5-year disease-free survival rates were not significantly different for patients undergoing transplantation using 3 types of donors, with 63.6%, 58.4%, and 58.3% for MSD, URD, and HRD transplantation, respectively (P = .574). Our data indicate that outcomes after HSCT from suitably matched URDs and HRDs with low-dose anti-T-lymphocyte globulin are similar and that HRD improves outcomes of patients with high-risk leukemia. This trial was registered at www.chictr.org (Chinese Clinical Trial Registry) as #ChiCTR-OCH-12002490.
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[Effects of autologous plasma and gentamicin on immunophenotype and viability of cytokine-induced killer cells].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 09-10-2014
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Objective To investigate the effects of treatment with different volumes of autologous plasma and gentamicin on immunophenotype and viability of cytokine-induced killer (CIK) cells in vitro. Methods Flow cytometry (FCM) was used to analyze the effects of autologous plasma and gentamicin on different immunocyte subtypes of CIK cells. The cell count method and MTT assay were used to detect the cytotoxicity of such pretreated CIK cells on HeLa cells. Results No significance was found in the relative amount of immunocyte subtypes CD3(+), CD56(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD56(+), CD4(+)CD25(+) between autologous plasma and control groups. Compared with control group, CD3(+), CD56(+), CD3(+)CD8(+), CD3(+)CD56(+) cells of gentamicin group were significantly down-regulated by 1.4, 1.7, 1.4 and 2.5 folds (P<0.05), respectively. Furthermore, the cytotoxicity of CIK cells in gentamicin and control goups on HeLa cells were 43.0% and 90.0%, respectively, with a statistically significant difference (P<0.05). Conclusion Autologous plasma has little effect on different subtypes of CIK cells. On the contrary, gentamicin can cause a decrease in the number of CD3(+), CD56(+), CD3(+)CD8(+), CD3(+)CD56(+) cells with some cytotoxicity.
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Can we early diagnose metabolic syndrome using brachial-ankle pulse wave velocity in community population?
Chin. Med. J.
PUBLISHED: 09-06-2014
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The prevalence of metabolic syndrome (MetS) increased recently and there was still not a screening index to predict MetS. The aim of this study was to estimate whether brachial-ankle pulse wave velocity (baPWV), a novel marker for systemic arterial stiffness, could predict MetS in Chinese community population.
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NdhO, a subunit of NADPH dehydrogenase, destabilizes medium size complex of the enzyme in Synechocystis sp. strain PCC 6803.
J. Biol. Chem.
PUBLISHED: 08-08-2014
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Two mutants that grew faster than the wild-type (WT) strain under high light conditions were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in ssl1690 encoding NdhO. Deletion of ndhO increased the activity of NADPH dehydrogenase (NDH-1)-dependent cyclic electron transport around photosystem I (NDH-CET), while overexpression decreased the activity. Although deletion and overexpression of ndhO did not have significant effects on the amount of other subunits such as NdhH, NdhI, NdhK, and NdhM in the cells, the amount of these subunits in the medium size NDH-1 (NDH-1M) complex was higher in the ndhO-deletion mutant and much lower in the overexpression strain than in the WT. NdhO strongly interacts with NdhI and NdhK but not with other subunits. NdhI interacts with NdhK and the interaction was blocked by NdhO. The blocking may destabilize the NDH-1M complex and repress the NDH-CET activity. When cells were transferred from growth light to high light, the amounts of NdhI and NdhK increased without significant change in the amount of NdhO, thus decreasing the relative amount of NdhO. This might have decreased the blocking, thereby stabilizing the NDH-1M complex and increasing the NDH-CET activity under high light conditions.
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Overexpression of the Survivin gene in SGC7901 cell resistance to cisplatin.
Oncol Lett
PUBLISHED: 08-07-2014
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The aim of the present study was to investigate the mechanism of SGC7901 cell resistance to cisplatin (CDDP). SGC7901/CDDP cells were established by the long-term continuous exposure of SGC7901 cells to CDDP in stepwise concentration increments. The morphologies of the SGC7901/CDDP and SGC7901 cells were observed by microscopy. The expression levels of Survivin mRNA and protein in the SGC7901/CDDP and SGC7901 cells were examined by reverse transcription polymerase chain reaction and western blotting respectively. The results revealed morphological differences between the SGC7901 and SGC7901/CDDP cells. The expression levels of Survivin mRNA and protein were significantly higher in the SGC7901/CDDP cells than in the SGC7901 cells. Therefore, high expression levels of the Survivin gene may explain SGC7901 cell resistance to CDDP.
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siRNA-Mediated Suppression of Synuclein ? Inhibits MDA-MB-231 Cell Migration and Proliferation by Downregulating the Phosphorylation of AKT and ERK.
J Breast Cancer
PUBLISHED: 07-25-2014
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Synuclein-? (SNCG), which was initially identified as breast cancer specific gene 1, is highly expressed in advanced breast cancers, but not in normal or benign breast tissue. This study aimed to evaluate the effects of SNCG siRNA-treatment on breast cancer cells and elucidate the associated mechanisms.
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Use of the Wilkinson Catalyst for the ortho-C?H Heteroarylation of Aromatic Amines: Facile Access to Highly Extended ?-Conjugated Heteroacenes for Organic Semiconductors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 06-21-2014
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An unprecedented catalytic system composed of the Wilkinson catalyst [Rh(PPh3 )3 Cl] and CF3 COOH enabled the highly regioselective cross-coupling of aromatic amines with a variety of heteroarenes through dual C?H bond cleavage. This protocol provided a facile and rapid route from readily available substrates to (2-aminophenyl)heteroaryl compounds, which may be conveniently transformed into highly extended ?-conjugated heteroacenes. The experimental studies and calculations showed that thianaphtheno[3,2-b]indoles have large HOMO-LUMO energy gaps and low-lying HOMO levels, and could therefore potentially be high-performance organic semiconductors. Herein we report the first use of a rhodium(I) catalyst for oxidative C?H/C?H coupling reactions. The current innovative catalyst system is much less expensive than [RhCp*Cl2 ]2 /AgSbF6 and could open the door for the application of this approach to other types of C?H activation processes.
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Development of two molecular approaches for differentiation of clinically relevant yeast species closely related to Candida guilliermondii and Candida famata.
J. Clin. Microbiol.
PUBLISHED: 06-20-2014
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The emerging pathogens Candida palmioleophila, Candida fermentati, and Debaryomyces nepalensis are often misidentified as Candida guilliermondii or Candida famata in the clinical laboratory. Due to the significant differences in antifungal susceptibilities and epidemiologies among these closely related species, a lot of studies have focused on the identification of these emerging yeast species in clinical specimens. Nevertheless, limited tools are currently available for their discrimination. Here, two new molecular approaches were established to distinguish these closely related species. The first approach differentiates these species by use of restriction fragment length polymorphism analysis of partial internal transcribed spacer 2 (ITS2) and large subunit ribosomal DNA with the enzymes BsaHI and XbaI in a double digestion. The second method involves a multiplex PCR based on the intron size differences of RPL18, a gene coding for a protein component of the large (60S) ribosomal subunit, and species-specific amplification. These two methods worked well in differentiation of these closely related yeast species and have the potential to serve as effective molecular tools suitable for laboratory diagnoses and epidemiological studies.
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Few-cycle optical rogue waves: complex modified Korteweg-de Vries equation.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 06-18-2014
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In this paper, we consider the complex modified Korteweg-de Vries (mKdV) equation as a model of few-cycle optical pulses. Using the Lax pair, we construct a generalized Darboux transformation and systematically generate the first-, second-, and third-order rogue wave solutions and analyze the nature of evolution of higher-order rogue waves in detail. Based on detailed numerical and analytical investigations, we classify the higher-order rogue waves with respect to their intrinsic structure, namely, fundamental pattern, triangular pattern, and ring pattern. We also present several new patterns of the rogue wave according to the standard and nonstandard decomposition. The results of this paper explain the generalization of higher-order rogue waves in terms of rational solutions. We apply the contour line method to obtain the analytical formulas of the length and width of the first-order rogue wave of the complex mKdV and the nonlinear Schrödinger equations. In nonlinear optics, the higher-order rogue wave solutions found here will be very useful to generate high-power few-cycle optical pulses which will be applicable in the area of ultrashort pulse technology.
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Copper-mediated tandem oxidative C(sp2)-H/C(sp)-H alkynylation and annulation of arenes with terminal alkynes.
Org. Lett.
PUBLISHED: 05-23-2014
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The copper-mediated tandem oxidative C(sp(2))-H/C(sp)-H cross-coupling and intramolecular annulation of arenes with terminal alkynes has been developed, which offers a highly efficient approach to the 3-methyleneisoindolin-1-one scaffold. In this oxidative coupling process, Cu(OAc)2 acts as both the promoter and the terminal oxidant. This protocol features a wide substrate scope; high functional group tolerance; exclusive chemo-, regio-, and stereoselectivity; and simple, easily available, and inexpensive reaction system. The transformation has demonstrated for the first time that Cu(OAc)2 can be renewable after undergoing an oxidative reaction.
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NdhP is an exclusive subunit of large complex of NADPH dehydrogenase essential to stabilize the complex in Synechocystis sp. strain PCC 6803.
J. Biol. Chem.
PUBLISHED: 05-20-2014
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Two major complexes of NADPH dehydrogenase (NDH-1) have been identified in cyanobacteria. A large complex (NDH-1L) contains NdhD1 and NdhF1, which are absent in a medium size complex (NDH-1M). They play important roles in respiration, cyclic electron transport around photosystem I, and CO2 acquisition. Two mutants sensitive to high light for growth and impaired in NDH-1-mediated cyclic electron transfer were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in sml0013 encoding NdhP, a single transmembrane small subunit of the NDH-1 complex. During prolonged incubation of the wild type thylakoid membrane with n-dodecyl ?-d-maltoside (DM), about half of the NDH-1L was disassembled to NDH-1M and the rest decomposed completely without forming NDH-1M. In the ndhP deletion mutant (?ndhP), disassembling of NDH-1L to NDH-1M occurred even on ice, and decomposition to a small piece occurred at room temperature much faster than in the wild type. Deletion of the C-terminal tail of NdhP gave the same result. The C terminus of NdhP was tagged by YFP-His6. Blue native gel electrophoresis of the DM-treated thylakoid membrane of this strain and Western analysis using the antibody against GFP revealed that NdhP-YFP-His6 was exclusively confined to NDH-1L. During prolonged incubation of the thylakoid membrane of the tagged strain with DM at room temperature, NDH-1L was partially disassembled to NDH-1M and the 160-kDa band containing NdhP-YFP-His6 and possibly NdhD1 and NdhF1. We therefore conclude that NdhP, especially its C-terminal tail, is essential to assemble NdhD1 and NdhF1 and stabilize the NDH-1L complex.
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Atmospheric peroxy radical measurements using dual-channel chemical amplification cavity ringdown spectroscopy.
Anal. Chem.
PUBLISHED: 05-16-2014
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Peroxy (HO2 and RO2) radicals are important intermediates in tropospheric oxidation of hydrocarbons, and their accurate atmospheric measurements remain challenging. In this work, the peroxy radical chemical amplification (PERCA) method was combined with cavity ringdown spectroscopy (CRDS) to develop a dual-channel instrument for measurements of atmospheric peroxy radicals. In the amplification channel, the peroxy radicals were converted in an excess amount of NO and CO into a higher level of NO2 and measured along with the background NO2, while in the reference channel, only the background NO2 (ambient NO2 and NO2 converted from O3 reaction with NO) was monitored. The NO2 levels from both channels were measured simultaneously at a high time resolution (~1 s) using two identical CRDS systems with one 408.5-nm diode laser, and their difference gave the amplified NO2 from PERCA. The peroxy radical concentration was obtained from the amplified NO2 and the calibrated amplification factor or chain length (CL). The optimized CL was 190 ± 20 (1?) using laboratory-generated HO2 and CH3O2 radical sources. The detection sensitivity was 4 ppt/10 s (3?). Ambient measurements in Riverside, CA were carried out. This dual-channel diode-laser PERCA-CRDS instrument was compact and capable of providing real-time, in situ, and sensitive measurements of atmospheric peroxy radicals with fast time response.
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Theoretical and experimental evidence of non-symmetric doubly localized rogue waves.
Proc. Math. Phys. Eng. Sci.
PUBLISHED: 04-17-2014
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We present determinant expressions for vector rogue wave (RW) solutions of the Manakov system, a two-component coupled nonlinear Schrödinger (NLS) equation. As a special case, we generate a family of exact and non-symmetric RW solutions of the NLS equation up to third order, localized in both space and time. The derived non-symmetric doubly localized second-order solution is generated experimentally in a water wave flume for deep-water conditions. Experimental results, confirming the characteristic non-symmetric pattern of the solution, are in very good agreement with theory as well as with numerical simulations, based on the modified NLS equation, known to model accurately the dynamics of weakly nonlinear wave packets in deep water.
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Site-selective nitrogen isotopic ratio measurement of nitrous oxide using a TE-cooled CW-RT-QCL based spectrometer.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 04-17-2014
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The feasibility of laser spectroscopic isotopic composition measurements of atmospheric N2O was demonstrated, although making them useful will require further improvements. The system relies on a thermoelectrically (TE) cooled continuous-wave (CW) room temperature (RT) quantum cascade laser source emitting wavelength of around 4.6?m, where strong fundamental absorption bands occur for the considered specie and its isotopomers. The analysis technique is based on wavelength modulation spectroscopy with second-harmonic detection and the combination of long-path absorption cell. Primary laboratory tests have been performed to estimate the achievable detection limits and the signal reproducibility levels in view of possible measurements of (15)N/(14)N and (18)O/(16)O isotope ratios. The experiment results showed that the site-selective (15)N/(14)N ratio can be measured with a precision of 3‰ with 90s averaging time using natural-abundance N2O sample of 12.7ppm.
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BMP-functionalised coatings to promote osteogenesis for orthopaedic implants.
Int J Mol Sci
PUBLISHED: 04-17-2014
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The loss of bone integrity can significantly compromise the aesthetics and mobility of patients and can be treated using orthopaedic implants. Over the past decades; various orthopaedic implants; such as allografts; xenografts and synthetic materials; have been developed and widely used in clinical practice. However; most of these materials lack intrinsic osteoinductivity and thus cannot induce bone formation. Consequently; osteoinductive functionalisation of orthopaedic implants is needed to promote local osteogenesis and implant osteointegration. For this purpose; bone morphogenetic protein (BMP)-functionalised coatings have proven to be a simple and effective strategy. In this review; we summarise the current knowledge and recent advances regarding BMP-functionalised coatings for orthopaedic implants.
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An AIE active monoimidazolium skeleton: high selectivity and fluorescence turn-on for H?PO?? in acetonitrile and ClO?? in water.
Chem. Commun. (Camb.)
PUBLISHED: 04-15-2014
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We disclose herein a monoimidazolium skeleton 1 with an aggregation-induced emission (AIE) characteristic. This fluorogenic skeleton exhibited high selectivity and fluorescence turn-on for H2PO4(-) in acetonitrile and ClO4(-) in water.
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Mice deleted for GPAT3 have reduced GPAT activity in white adipose tissue and altered energy and cholesterol homeostasis in diet-induced obesity.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 04-08-2014
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Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the synthesis of glycerolipids and glycerophospholipids. Microsomal GPAT, the major GPAT activity, is encoded by at least two closely related genes, GPAT3 and GPAT4. To investigate the in vivo functions of GPAT3, we generated Gpat3-deficient (Gpat3(-/-)) mice. Total GPAT activity in white adipose tissue of Gpat3(-/-) mice was reduced by 80%, suggesting that GPAT3 is the predominant GPAT in this tissue. In liver, GPAT3 deletion had no impact on total GPAT activity but resulted in a 30% reduction in N-ethylmaleimide-sensitive GPAT activity. The Gpat3(-/-) mice were viable and fertile and exhibited no obvious metabolic abnormalities on standard laboratory chow. However, when fed a high-fat diet, female Gpat3(-/-) mice showed decreased body weight gain and adiposity and increased energy expenditure. Increased energy expenditure was also observed in male Gpat3(-/-) mice, although it was not accompanied by a significant change in body weight. GPAT3 deficiency lowered fed, but not fasted, glucose levels and tended to improve glucose tolerance in diet-induced obese male and female mice. On a high-fat diet, Gpat3(-/-) mice had enlarged livers and displayed a dysregulation in cholesterol metabolism. These data establish GPAT3 as the primary GPAT in white adipose tissue and reveal an important role of the enzyme in regulating energy, glucose, and lipid homeostasis.
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Aqueous extract of post-fermented tea reverts the hepatic steatosis of hyperlipidemia rat by regulating the lipogenic genes expression and hepatic fatty acid composition.
BMC Complement Altern Med
PUBLISHED: 03-31-2014
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Post-fermented tea has been used for the prevention of metabolic syndrome in Western China. Present study reports the biochemical mechanism of lipid-lowering effects of Jing-wei fu tea (JWFT), a variety of post-fermented tea on high-fat diet-induced hyperglycemia and obesity in rats.
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A sensitive colorimetric and fluorescent sensor based on imidazolium-functionalized squaraines for the detection of GTP and alkaline phosphatase in aqueous solution.
Chem. Commun. (Camb.)
PUBLISHED: 03-19-2014
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Imidazolium-functionalized squaraine ImSQ8 is synthesized as a sensitive colorimetric and fluorescent chemosensor for GTP in aqueous solution. The detection limit of GTP reaches 5.4 ppb. Its applications in the live-cell imaging and enzyme activity assay have also been demonstrated.
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Assessment of calcium sparks in intact skeletal muscle fibers.
J Vis Exp
PUBLISHED: 03-19-2014
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Maintaining homeostatic Ca(2+) signaling is a fundamental physiological process in living cells. Ca(2+) sparks are the elementary units of Ca(2+) signaling in the striated muscle fibers that appear as highly localized Ca(2+) release events mediated by ryanodine receptor (RyR) Ca(2+) release channels on the sarcoplasmic reticulum (SR) membrane. Proper assessment of muscle Ca(2+) sparks could provide information on the intracellular Ca(2+) handling properties of healthy and diseased striated muscles. Although Ca(2+) sparks events are commonly seen in resting cardiomyocytes, they are rarely observed in resting skeletal muscle fibers; thus there is a need for methods to generate and analyze sparks in skeletal muscle fibers. Detailed here is an experimental protocol for measuring Ca(2+) sparks in isolated flexor digitorm brevis (FDB) muscle fibers using fluorescent Ca(2+) indictors and laser scanning confocal microscopy. In this approach, isolated FDB fibers are exposed to transient hypoosmotic stress followed by a return to isotonic physiological solution. Under these conditions, a robust Ca(2+) sparks response is detected adjacent to the sarcolemmal membrane in young healthy FDB muscle fibers. Altered Ca(2+) sparks response is detected in dystrophic or aged skeletal muscle fibers. This approach has recently demonstrated that membrane-delimited signaling involving cross-talk between inositol (1,4,5)-triphosphate receptor (IP3R) and RyR contributes to Ca(2+) spark activation in skeletal muscle. In summary, our studies using osmotic stress induced Ca(2+) sparks showed that this intracellular response reflects a muscle signaling mechanism in physiology and aging/disease states, including mouse models of muscle dystrophy (mdx mice) or amyotrophic lateral sclerosis (ALS model).
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Excessive pulse pressure response to standing in community population with orthostatic systolic hypertension.
J Am Soc Hypertens
PUBLISHED: 03-18-2014
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The postural change of pulse pressure (PP) in the persons with orthostatic hypertension (OHT) is unclear. This study included 2849 (65.0 ± 9.3 years) community participants. Blood pressures (BPs) in supine and standing positions were measured. The differences between upright and supine BP and PP were recorded as ?BP and ?PP. The criteria for OHT was ?BP ?10 mm Hg, for orthostatic hypotension (OH) was ?-10 mm Hg and for orthostatic normotension (ONT) was -9 to 9 mm Hg. Fasting blood lipids and glucose were measured. The supine SBP of the sOHT group were similar to that of sONT group (140.9 ± 20.2 mm Hg vs 138.2 ± 19.7 mm Hg), but significantly lower than that of sOH group (151.9 ± 19.2 mm Hg; P < .05). Their PPs were 65.3 ± 15.9, 62.8 ± 14.7, and 71.1 ± 15.1 mm Hg, respectively, and with the similar group difference like SBP. When the position changed from supine to standing, the sOHT group showed PP rise, while sOH and sONT groups showed PP reduction (3.8 ± 7.1 mm Hg vs -17.0 ± 8.5 mm Hg and -5.8 ± 6.6 mm Hg; both P < .05). Thus, the standing PP in the sOHT group was significantly higher than in the sONT (69.1 ± 18.0 mm Hg vs 57.0 ± 15.8 mm Hg; P < .05) and in the sOH (54.2 ± 15.2 mm Hg; P < .05) groups. The postural PP profile varies with the postural responses of SBP. The sOHT group has obviously increased PP and significantly higher standing PP compared with the sONT group.
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Decreased risk of secondary brain herniation with intracranial pressure monitoring in patients with haemorrhagic stroke.
BMC Anesthesiol
PUBLISHED: 03-14-2014
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Intracranial-pressure (ICP) monitoring is considered standard care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in patients with hemorrhagic stroke has not been rigorously assessed. In this study, we investigated the clinical value of ICP monitoring in patients with hemorrhagic stroke.
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Dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells upon drug-induced DNA damage under hypoxia.
Mol. Pharmacol.
PUBLISHED: 03-13-2014
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Intratumoral hypoxia has been proposed to create a "mutator" phenotype through downregulation of DNA repair, leading to increased genomic instability and drug resistance. Such downregulation of DNA repair has been proposed to sensitize hypoxic cancer cells to DNA-damaging agents and inhibitors of DNA repair. Here, we showed that prostate cancer cells with mutant p53 were resistant to the poly(ADP-ribose) polymerase inhibitor, veliparib (2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, dihydrochloride; Abbott Laboratories, Abbott Park, IL), and the DNA-damaging topoisomerase I inhibitor camptothecin-11 (CPT-11) or SN38 (7-ethyl-10-hydroxycamptothecin) under hypoxia. Upregulation of Rad51 by E2F1 upon DNA damage under hypoxia contributed to such resistance, which was reversed by either inhibiting RAD51 transcription with small interfering RNA or by expressing wild-type p53 in the p53 null prostate cancer line. Accumulation of endogenous p53 but not E2F1 and suppressed RAD51 transcription was observed in prostate cancer line with wild-type p53 after DNA damage under hypoxia. Combining veliparib with CPT-11 significantly enhanced DNA damage and apoptosis under both hypoxic and normoxic culture conditions. Such enhanced DNA damage and antitumor activities were seen in the presence of Rad51 upregulation and confirmed in vivo with PC3 mouse xenografts. These data illustrate a dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells' response to hypoxia and DNA damage. The veliparib and CPT-11 combination can be further explored as a treatment of metastatic castration-resistant prostate cancers that have frequent p53 mutations and enriched genomic instability.
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The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo.
Int. J. Oncol.
PUBLISHED: 03-05-2014
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Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in many types of cancer cells by inhibiting Cdk7 and Cdk9, which control transcription. SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7 and Cdk9 and has emerged in clinical trials. Here, we examined the viability of MCF-7 and MDA-MB-435 breast cancer cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 had a direct apoptosis-inducing effect through both the extrinsic and intrinsic apoptotic pathways in breast cancer cells as shown by a dose-dependent increase in Annexin V-positive cells and terminal deoxynucleotidyl transferase-mediated dUTP nick?end labeling (TUNEL)-positive cells, as well as activation of caspase-8, -9 and poly(ADP-ribose) polymerase (PARP). At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and blocked RNA synthesis. Consistent with the inherently rapid turnover rates of their transcripts and proteins, the anti-apoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) were rapidly reduced on exposure to SNS-032. Our results also indicated that SNS-032 suppressed the growth of breast cancer xenografts in mice. These data demonstrate that the use of SNS-032 may be a rational and novel therapeutic strategy for human breast cancer and warrants further clinical investigation.
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Nickel-catalyzed chelation-assisted direct arylation of unactivated C(sp3)-H bonds with aryl halides.
Chem. Commun. (Camb.)
PUBLISHED: 03-05-2014
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In this work, we have disclosed the nickel-catalyzed unactivated ?-C(sp(3))-H bond arylation of aliphatic acid derivatives with aryl iodides/bromides via bidentate chelation-assistance of an 8-aminoquinoline moiety. These preliminary results indicate the intrinsic catalytic potential of nickel metal for unactivated C(sp(3))-H bond arylation.
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Synthesis of unsymmetrical imidazolium salts by direct quaternization of N-substituted imidazoles using arylboronic acids.
Chem. Commun. (Camb.)
PUBLISHED: 03-05-2014
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Imidazolium salts were conveniently prepared by direct aryl quaternization using arylboronic acids. This process features the tolerance of a broad range of functional groups and excellent chemoselectivity, and is especially effective for the synthesis of unsymmetrical imidazolium salts.
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Poly (ADP-ribose) polymerase inhibitor: an evolving paradigm in the treatment of prostate cancer.
Asian J. Androl.
PUBLISHED: 03-05-2014
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Recent phase I studies have reported single-agent activities of poly (ADP-ribose) polymerase (PARP) inhibitor in sporadic and in BRCA-mutant prostate cancers. Two of the most common genetic alterations in prostate cancer, ETS gene rearrangement and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in preclinical models. Emerging evidence also suggests that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor (AR) and ETS gene rearrangement. In this article, the preclinical work and early-phase clinical trials in developing PARP inhibitor-based therapy as a new treatment paradigm for metastatic prostate cancer are reviewed.
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Monoacylglycerol acyltransferase-2 is a tetrameric enzyme that selectively heterodimerizes with diacylglycerol acyltransferase-1.
J. Biol. Chem.
PUBLISHED: 02-25-2014
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Acyl-CoA:monoacylglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze the two consecutive steps in the synthesis of triacylglycerol, a key process required for dietary fat absorption into the enterocytes of the small intestine. In this report, we investigated the tendency of MGAT2 to form an enzyme complex with DGAT1 and DGAT2 in intact cells. We demonstrated that in addition to the 38-kDa monomer of the MGAT2 enzyme predicted by its peptide sequence, a 76-kDa moiety was detected in SDS-PAGE without reducing agent and heat inactivation. The 76-kDa MGAT2 moiety was greatly enhanced by treatment with a cross-linking reagent in intact cells. Additionally, the cross-linking reagent dose-dependently yielded a band corresponding to the tetramer (152 kDa) in SDS-PAGE, suggesting that the MGAT2 enzyme primarily functions as a homotetrameric protein and as a tetrameric protein. Likewise, DGAT1 also forms a homodimer under nondenaturing conditions. When co-expressed in COS-7 cells, MGAT2 heterodimerized with DGAT1 without treatment with a cross-linking reagent. MGAT2 also co-eluted with DGAT1 on a gel filtration column, suggesting that the two enzymes form a complex in intact cells. In contrast, MGAT2 did not heterodimerize with DGAT2 when co-expressed in COS-7 cells, despite high sequence homology between the two enzymes. Furthermore, systematic deletion analysis demonstrates that N-terminal amino acids 35-80 of DGAT1, but not a signal peptide at the N terminus of MGAT2, is required for the heterodimerization. Finally, co-expression of MGAT2 with DGAT1 significantly increased lipogenesis in COS-7 cells, indicating the functional importance of the dimerization.
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Gold-catalyzed C(sp3)-H/C(sp)H coupling/cyclization/oxidative alkynylation sequence: a powerful strategy for the synthesis of 3-alkynyl polysubstituted furans.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-15-2014
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In sharp contrast to the gold-catalyzed reactions of alkynes/allenes with nucleophiles, gold-catalyzed oxidative cross-couplings and especially C-H/C-H cross-coupling have been under represented. By taking advantage of the unique redox property and carbophilic ??acidity of gold, this work realizes the first gold-catalyzed direct C(sp(3))-H alkynylation of 1,3-dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region-defined approach to 3-alkynyl polysubstituted furans.
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Transition-metal-catalyzed C-H bond functionalizations: feasible access to a diversity-oriented ?-carboline library.
Chemistry
PUBLISHED: 02-12-2014
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Diversification of the ?-carboline skeleton has been demonstrated to assemble a ?-carboline library starting from the tetrahydro-?-carboline framework. This strategy affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkynyl-substituted ?-carbolines at the C1, C3, or C8 position through three categorically different types of transition-metal-catalyzed C?C bond-forming reactions, in the presence of multiple potentially reactive positions. These site-selective functionalizations include; 1) the Cu-catalyzed C1/C3-selective decarboxylative C?sp?3?C?sp?2 and C?sp?3?Csp coupling of hexahydro-?-carboline-3-carboxylic acid with a C?H bond of a heteroarene or terminal alkyne; 2) the chelation-assisted Pd-catalyzed C1/C8-selective C?H arylation of hexahydro-?-carboline with aryl boron reagents; and 3) the chelation-assisted Pd-catalyzed C1/C3-selective oxidative C?H/C?H cross-coupling of ?-carboline-N-oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro-?-carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and perlolyrine. We believe that these strategies could provide inspiration for late-stage diversifications of bioactive core scaffolds.
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Structure-guided optimization of small molecule c-Abl activators.
J. Comput. Aided Mol. Des.
PUBLISHED: 02-11-2014
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c-Abl kinase is maintained in its normal inactive state in the cell through an assembled, compact conformation. We describe two chemical series that bind to the myristoyl site of the c-Abl kinase domain and stimulate c-Abl activation. We hypothesize that these molecules activate c-Abl either by blocking the C-terminal helix from adopting a bent conformation that is critical for the formation of the autoinhibited conformation or by simply providing no stabilizing interactions to the bent conformation of this helix. Structure-based molecular modeling guided the optimization of binding and activation of c-Abl of these two chemical series and led to the discovery of c-Abl activators with nanomolar potency. The small molecule c-Abl activators reported herein could be used as molecular tools to investigate the biological functions of c-Abl and therapeutic implications of its activation.
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Silver-catalyzed one-pot cyclization/fluorination of 2-alkynylanilines: highly efficient synthesis of structurally diverse fluorinated indole derivatives.
Chem. Commun. (Camb.)
PUBLISHED: 02-07-2014
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Highly efficient approaches to obtain structurally diverse fluorinated indole derivatives have been realized through the Ag-catalyzed one-pot cyclization/fluorination of 2-alkynylanilines in the presence of NFSI or Selectfluor.
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Unexpected regioselective carbon-hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles.
Nat Commun
PUBLISHED: 01-29-2014
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Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4+2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.
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Loss of caveolin-1 and adiponectin induces severe inflammatory lung injury following LPS challenge through excessive oxidative/nitrative stress.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 01-17-2014
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Excessive reactive oxygen/nitrogen species have been associated with the onset, progression, and outcome of sepsis, both in preclinical and clinical studies. However, the signaling pathways regulating oxidative/nitrative stress in the pathogenesis of sepsis-induced acute lung injury and acute respiratory distress syndrome are not fully understood. Employing the novel mouse model with genetic deletions of both caveolin-1 (Cav1) and adiponectin (ADPN) [double knockout (DKO) mice], we have demonstrated the critical role of Cav1 and ADPN signaling cross talk in regulating oxidative/nitrative stress and resulting inflammatory lung injury following LPS challenge. In contrast to the inhibited inflammatory lung injury in Cav1(-/-) mice, we observed severe lung inflammation and markedly increased lung vascular permeability in DKO mice in response to LPS challenge. Accordingly, the DKO mice exhibited an 80% mortality rate following a sublethal dose of LPS challenge. At basal state, loss of Cav1 and ADPN resulted in a drastic increase of oxidative stress and resultant nitrative stress in DKO lungs. Scavenging of superoxide by pretreating the DKO mice with MnTMPYP (a superoxide dismutase mimetic) restored the inflammatory responses to LPS challenge including reduced lung myeloperoxidase activity and vascular permeability. Thus oxidative/nitrative stress collectively modulated by Cav1 and ADPN signalings is a critical determinant of inflammatory lung injury in response to LPS challenge.
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The incidence of acute myocardial infarction in relation to overweight and obesity: a meta-analysis.
Arch Med Sci
PUBLISHED: 01-05-2014
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Epidemiological evidence suggests that overweight and obesity have been associated with acute myocardial infarction (AMI). However, data on this issue are controversial. This study aims to use meta-analysis to determine whether overweight and obesity are related to AMI.
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Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction.
Nat. Chem. Biol.
PUBLISHED: 01-05-2014
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Although therapeutic interventions of signal-transduction cascades with targeted kinase inhibitors are a well-established strategy, drug-discovery efforts to identify targeted phosphatase inhibitors have proven challenging. Herein we report a series of allosteric, small-molecule inhibitors of wild-type p53-induced phosphatase (Wip1), an oncogenic phosphatase common to multiple cancers. Compound binding to Wip1 is dependent on a 'flap' subdomain located near the Wip1 catalytic site that renders Wip1 structurally divergent from other members of the protein phosphatase 2C (PP2C) family and that thereby confers selectivity for Wip1 over other phosphatases. Treatment of tumor cells with the inhibitor GSK2830371 increases phosphorylation of Wip1 substrates and causes growth inhibition in both hematopoietic tumor cell lines and Wip1-amplified breast tumor cells harboring wild-type TP53. Oral administration of Wip1 inhibitors in mice results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth. To our knowledge, GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase.
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The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro.
Biomed Rep
PUBLISHED: 01-02-2014
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The purpose of this study was to determine the effect of aspirin plus cisplatin (CDDP) in the chemotherapy of gastric cancer. We cultured SGC7901/CDDP cells by long-term exposure of SGC7901 cells to small doses of CDDP in vitro. The cells were treated with aspirin, CDDP or aspirin plus CDDP for 24 h and cell growth was assessed by the MTT assay, the apoptotic rate by flow cytometry, the survivin mRNA expression by RT-PCR and the survivin protein expression by western blotting. The results revealed that the cell growth in the aspirin plus CDDP group was significantly inhibited. The apoptotic rate in the aspirin plus CDDP was significantly higher compared to that in the other groups. The survivin mRNA and protein expression were also significantly reduced in the aspirin plus CDDP group. Our data suggest that the combination of aspirin and CDDP exhibited a higher degree of toxicity against SGC7901/CDDP cells compared to that of aspirin or CDDP alone. Thus, the combination of aspirin plus CDDP may reduce the expression of survivin and induce the apoptosis of SGC7901/CDDP cells.
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Expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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SIRT6, a member of the class III histone deacetylase, has been shown to inhibit glycolysis and promote DNA double strand break repairs. Despite of its proposed tumor suppressor role, no significant differences in SIRT6 mRNA levels among normal bladder urothelium, non-muscle invasive, and muscle invasive urothelial carcinoma were noted in the two largest bladder cancer gene expression datasets available in Oncomine(TM). We therefore studied the expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder. Immunohistochemistry studies of SIRT6 on radical cystectomy samples showed a dramatic decline of SIRT6 expression when bladder cancer progressed from T2 to T4. Functional study with bladder cancer cell lines confirmed its role in inhibiting glycolysis and cell proliferation. Reducing SIRT6 with siRNA, however, did not sensitize bladder cancer cells to drug induced DNA damage. The differential expression patterns of SIRT6 amongst different T stages of muscle invasive bladder cancers indicate less reliance on glycolysis when urothelial carcinoma invades deeper through the bladder and into the adjacent tissues.
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The choice of regimens based on bortezomib for patients with newly diagnosed multiple myeloma.
PLoS ONE
PUBLISHED: 01-01-2014
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Bortezomib has significantly improved multiple myeloma (MM) response rates, but strategies for choosing bortezomib-based regimens for initial MM therapy are not standardized. Here, we describe four bortezomib-based therapies in Chinese MM patients to determine the optimal chemotherapeutic approach.
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Palladium-catalyzed tandem N-H/C-H arylation: regioselective synthesis of N-heterocycle-fused phenanthridines as versatile blue-emitting luminophores.
Org. Biomol. Chem.
PUBLISHED: 10-22-2013
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A general and highly regioselective synthetic protocol for structurally diverse N-heteroaryl-fused phenanthridines has been developed. Varieties of fluorescence molecules comprising imidazole-fused, benzoimidazole-fused, indole-fused and pyrrole-fused phenanthridines were obtained by this modular approach, some of which exhibit excellent blue-emitting performance, high quantum yields, long fluorescence lifetimes, interesting electrochemical properties, and thermal stabilities.
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Inhibition of p38 MAPK Phosphorylation Is Critical for Bestatin to Enhance ATRA-Induced Cell Differentiation in Acute Promyelocytic Leukemia NB4 Cells.
Am J Ther
PUBLISHED: 10-22-2013
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Bestatin has been known as an immunomodulating agent in anti-leukemia treatment. The mechanism by which Bestatin enhances all-trans retinoic acid (ATRA)-induced cell differentiation of acute promyelocytic leukemia (APL) cells is generally attributed to inhibition of cell surface CD13/aminopeptidase N activity. Bestatin also exerts its biological activities besides its ability to inhibit aminopeptidase N enzymatic activity. This article provides data to support an alternative mechanism regarding an important role of inhibition of p38 mitogen-activated protein kinase (MAPK) signal pathway in Bestatins anti-leukemia effect. Bestatin enhanced ATRA-induced differentiation and inhibited ATRA-driven phosphorylation of p38 MAPK in ATRA-sensitive APL NB4 cells. In contrast, Bestatin could not reverse the differentiation block in ATRA-resistant APL MR2 cells, in which ATRA was unable to induce phosphorylation of p38 MAPK. Moreover, CD13 ligation with anti-CD13 antibody WM-15 resulted in phosphorylation of p38 MAPK, reduced the inhibition of Bestatin on the phosphorylation of p38 MAPK, and completely abolished the enhancement of Bestatin on ATRA-inducing differentiation in NB4 cells. This study shows that inhibition of p38 MAPK phosphorylation is critical for Bestatin to enhance ATRA-induced cell differentiation in ATRA-sensitive APL NB4 cells. Results suggested that pharmacological inhibition of the p38 MAPK pathway might enhance ATRA-dependent differentiation.
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Highly selective fluorescent recognition of sulfate in water by two rigid tetrakisimidazolium macrocycles with peripheral chains.
J. Am. Chem. Soc.
PUBLISHED: 09-27-2013
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The reinforced molecular recognition of two rigid tetrakisimidazolium macrocycles resulted in highly selective fluorescent recognition of sulfate dianion in water with an unprecedentedly high association constant of 8.6 × 10(9) M(-2). Besides the electrostatic interaction, the single crystal X-ray analysis revealed that sulfate was encapsulated in a pseudohexahedral cavity of a sandwich structure by two orthogonally packed macrocycles via eight hydrogen bonds between the C2 hydrogen atoms of the imidazolium units and the oxygen atoms of sulfate. This sandwich structure was reinforced by the ?-? stacking between the phenyl and the triazinonide rings and multiple charge-assisted hydrogen bonds between the peripheral chains and the rigid backbones. Notably, these peripheral-backbone hydrogen bonds rendered the flexible peripheral chains to coil around the sandwich structure to shield sulfate inaccessible to water. This binding process was visible by fluorescence enhancement, which was attributed to a restrained rotation and better conjugation of the macrocycle backbone upon binding to sulfate.
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Identification and characterization of the related immune-enhancing proteins in crab Scylla paramamosain stimulated with rhubarb polysaccharides.
Mol. Immunol.
PUBLISHED: 08-29-2013
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Recently, considerable interest has been focused on immunostimulants to reduce diseases in crab aquaculture. However, information regarding to the related immune-enhancing proteins in crabs is not available yet. In this study, rhubarb polysaccharides were tested for enhancement of the immune activity in crab Scylla paramamosain. Compared with those in the control group, values of, phenoloxidase (PO), alkaline phosphatase (AKP) and alkaline phosphatasein (ACP) activity in the, experimental group were improved significantly 4 d after the treatment. Furthermore, 15 and 17 altered proteins from haemocytes and hepatopancreas, respectively, were found in rhubarb polysaccharide-treated crabs using 2-DE approach. Of these, hemocyanin, chymotrypsin, cryptocyanin, C-type lectin receptor, and ferritin protein were identified by mass spectrometry. In addition, RT-PCR, analysis showed that the mRNA levels of hemocyanin and chymotrypsin increased about 2.4- and 1.4-fold in the experiment group. Moreover, the hemocyanin gene in S. paramamosain (SpHMC) was, cloned and characterized. SpHMC contains one open reading frame of 2022 bp and encodes a polypeptide of 673 amino acids. It is clustered into one branch along with crab hemocyanin in a phylogenetic tree. The mRNA transcripts of SpHMC were detected mainly in the tissues of, hepatopancreas, hemocyte and intestines, and its levels were up-regulated significantly in hemocytes, of S. paramamosain treated with Vibrio parahemolyticus, Beta streptococcus or poly I:C for 6-48h. Taken together, these studies found 5 related immune-enhancing proteins and a novel heomcyanin homologue with potential pathogen-resistant activities in crab.
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Aerobic Ru-catalyzed direct C2-olefination of N-heteroarenes with alkenes directed by a removable N-dimethylcarbamoyl group.
Chem. Commun. (Camb.)
PUBLISHED: 08-21-2013
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A highly efficient and selective Ru-catalyzed direct C2-olefination of indoles, pyrroles, and carbazoles assisted by a removable N-dimethylcarbamoyl group has been developed by using O2 as the terminal oxidant. Both electron-deficient and unactivated alkenes are applicable to the protocol.
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Ultraviolet Photodissociation Dynamics of the o-Pyridyl Radical.
J Phys Chem A
PUBLISHED: 08-19-2013
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Ultraviolet (UV) photodissociation dynamics of jet-cooled o-pyridyl radical (o-C5H4N) was studied in the photolysis region 224-246 nm using the high-n Rydberg atom time-of-flight (HRTOF) technique. The o-pyridyl radicals were produced from 193 nm photolysis of 2-chloropyridine and 2-bromopyridine precursors. The H-atom photofragment yield (PFY) spectrum contains a broad peak in this wavelength region and reveals the UV absorption feature of o-pyridyl for the first time. The translational energy distributions of the H-atom loss product channel, P(ET)s, peak at ?7 kcal/mol, and the fraction of average translational energy in the total excess energy, ?fT?, is nearly constant at ?0.18 in the region 224-242 nm. The P(ET) distribution indicates the production of the lowest energy dissociation products, H + cyanovinylacetylene. The H-atom product angular distribution is isotropic. The dissociation mechanism is consistent with unimolecular dissociation of the hot o-pyridyl radical to H + cyanovinylacetylene after internal conversion from the electronically excited state.
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N-Oxide as a Traceless Oxidizing Directing Group: Mild Rhodium(III)-Catalyzed C?H Olefination for the Synthesis of ortho-Alkenylated Tertiary Anilines.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-15-2013
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Double role: A traceless directing group also acts as an internal oxidant in a novel Rh(III) -catalyzed protocol developed for the synthesis of ortho-alkenylated tertiary anilines. A five-membered cyclometalated Rh(III) complex is proposed as a plausible intermediate and confirmed by X-ray crystallographic analysis.
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Decreased risk of acute kidney injury with intracranial pressure monitoring in patients with moderate or severe brain injury.
J. Neurosurg.
PUBLISHED: 08-02-2013
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The authors undertook this study to evaluate the effects of continuous intracranial pressure (ICP) monitoring-directed mannitol treatment on kidney function in patients with moderate or severe traumatic brain injury (TBI).
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Iron-Catalyzed Oxidative C?H/C?H Cross-Coupling: An Efficient Route to ?-Quaternary ?-Amino Acid Derivatives.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-16-2013
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Fully loaded: A coordinating activation strategy has been developed to furnish ?-quaternary ?-amino acids through the iron(III)-catalyzed oxidative functionalization of ?-C(sp(3) )?H bonds of ?-tertiary ?-amino acid esters. The reaction exhibits a broad substrate scope for both ?-amino acids and nucleophiles (Nu) as well as good functional-group tolerance (see scheme, DTBP=di-tert-butyl peroxide, DCE=1,2-dichloroethane).
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[Diffusion tensor imaging map of anterior cruciate ligament contrasted with MRI in healthy adults].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 07-06-2013
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To measure anterior cruciate ligament (ACL) by diffusion tensor imaging (DTI), combined with ACL half quantitative measurement magnetic resonance imaging (MRI) method as the contrast, and to preliminarily investigate the feasibility of DTI for ACL.
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Sequencing systemic therapies in metastatic castration-resistant prostate cancer.
Cancer Control
PUBLISHED: 07-02-2013
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Men with prostate cancer will not die of the disease until it progresses to the metastatic castration resistant stage. At that stage, the median survival is 9 to 30 months.
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Isolation, purification, and immunological activities of a low-molecular-weight polysaccharide from the Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes).
Int J Med Mushrooms
PUBLISHED: 06-26-2013
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To obtain a low-molecular-weight polysaccharide with immuno-enhancing activity, hot water extract of Ganoderma lucidum fruit bodies was separated by membrane ultrafiltration, anion exchange, and gel filtration chromatography, and the immunological activities of fractions were assessed on the basis of nitric oxide production by RAW 264.7 macrophages. A novel polysaccharide (TB3-2-2) was successfully isolated and purified. TB3-2-2 is a homogeneous polysaccharide, with a relative molecular weight of 5.11 × 103 Da, identified by high-performance liquid chromatography and was composed of galactose and glucose in a molar ratio of 2:3 determined by high-performance anion exchange chromatography. TB3-2-2 had a carbohydrate content of 99%, as measured using the phenol-sulfuric acid method. Proliferation of mouse spleen lymphocytes and the expression level of interleukin-6 was significantly increased by TB3-2-2. Results indicate that the low-molecular-weight polysaccharide with immunological activity in G. lucidum is worthy of further research and development.
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Altered Ca2+ concentration, permeability and buffering in the myofibre Ca2+ store of a mouse model of malignant hyperthermia.
J. Physiol. (Lond.)
PUBLISHED: 06-24-2013
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? Malignant hyperthermia (MH) is linked to mutations in the type 1 ryanodine receptor, RyR1, the Ca2+ channel of the sarcoplasmic reticulum (SR) of skeletal muscle. The Y522S MH mutation was studied for its complex presentation, which includes structurally and functionally altered cell cores. Imaging cytosolic and intra-SR [Ca2+] in muscle cells of heterozygous YS mice we determined Ca2+ release flux activated by clamp depolarization, permeability (P) of the SR membrane (ratio of flux and [Ca2+] gradient) and SR Ca2+ buffering power (B). In YS cells resting [Ca2+]SR was 45% of the value in normal littermates (WT). P was more than doubled, so that initial flux was normal. Measuring [Ca2+]SR(t) revealed dynamic changes in B(t). The alterations were similar to those caused by cytosolic BAPTA, which promotes release by hampering Ca2+-dependent inactivation (CDI). The [Ca2+] transients showed abnormal breaks, decaying phases after an initial rise, traced to a collapse in flux and P. Similar breaks occurred in WT myofibres with calsequestrin reduced by siRNA; calsequestrin content, however, was normal in YS muscle. Thus, the Y522S mutation causes greater openness of the RyR1, lowers resting [Ca2+]SR and alters SR Ca2+ buffering in a way that copies the functional instability observed upon reduction of calsequestrin content. The similarities with the effects of BAPTA suggest that the mutation, occurring near the cytosolic vestibule of the channel, reduces CDI as one of its primary effects. The unstable SR buffering, mimicked by silencing of calsequestrin, may help precipitate the loss of Ca2+ control that defines a fulminant MH event.
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Physicochemical characterization of a high molecular weight bioactive ?-d-glucan from the fruiting bodies of Ganoderma lucidum.
Carbohydr Polym
PUBLISHED: 06-22-2013
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A purified polysaccharide coded as GLP20 was obtained by precipitating a hot-water extract from Ganoderma lucidum fruiting bodies with 20% (V/V) ethanol. Its total carbohydrate content was 95.9%. Structural analysis showed that GLP20 was a ?-(1?3)-linked d-glucan with a (1?6)-?-d-glucopyranosyl side-branching unit on every third residue. Cell culture study revealed that GLP20 can significantly increase NO production of RAW264.7 macrophages. The analysis of light scattering and high performance size exclusion chromatography (HPSEC) showed that the molecular weight and polydispersity of GLP20 was 3.75×10(6)Da and 1.36, respectively. GLP20 had a rigid chain conformation in aqueous solution. A conformation transition occurred in the alkaline solution with NaOH concentration larger than 0.15M. The transition from ordered structure to single chain happened when GLP20 was heated above 135°C in water solution and was irreversible as demonstrated by differential scanning calorimetry (DSC). GLP20 existed as random coils in DMSO.
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Non-volatile taste components of several cultivated mushrooms.
Food Chem
PUBLISHED: 06-19-2013
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Five species of dried mushrooms are commercially available in China, namely Agrocybe cylindracea, Pleurotus cystidiosus, Agaricus blazei, Pleurotus eryngii, and Coprinus comatus, and their nonvolatile taste components were studied. Trehalose (12.23-301.63mg/g) and mannitol (12.37-152.11mg/g) were considered as the major mushroom sugar/polyol in the five test species. The total free amino acid levels ranged from 4.09 to 22.73mg/g. MSG-like components contents ranged from 0.97 to 4.99mg/g. 5-Nucleotide levels ranged from 1.68mg/g in P. eryngii to 3.79mg/g in C. comatus. Fumaric acid (96.11mg/g) in P. cystidiosus were significantly higher compared with the other mushrooms, and citric acid (113.13mg/g), as the highest of any organic acid among the five mushrooms, were found in A. blazei. Equivalent umami concentrations values in these five test mushrooms ranged from 11.19 to 88.37g/100g dry weight. A. blazei, C.comatus and A. cylindracea possessed highly strong umami taste.
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Combination of low-dose mycophenolate mofetil with cyclosporine and methotrexate as GVHD prophylaxis in unrelated donor allogeneic stem cell transplantation.
Leuk. Res.
PUBLISHED: 06-11-2013
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We report the results of HLA-matched unrelated donor allogeneic stem cell transplantation with new GVHD prophylaxis regimen consisted of cyclosporine, methotrexate and low-dose mycophenolate mofetil in 139 patients with hematologic malignancies. The incidence of grades II-IV and III-IV acute GVHD were 43.0% and 17.3%, respectively. The incidence of chronic GVHD was 42.1%, with 16.5% extensive grade. The cumulative incidence of transplant-related mortality at 100 days and 3 years were 7.9% and 29.7%, respectively. Three-year overall survival, disease-free survival and relapse incidence were 58.7%, 55.3% and 19.6%, respectively. These results suggest the new regime may be effective for the prophylaxis of acute and chronic GVHD in unrelated donor transplantation.
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2-Pyridylmethyl ether: a readily removable and efficient directing group for amino acid ligand accelerated ortho-C-H olefination of phenols.
Chem. Commun. (Camb.)
PUBLISHED: 06-08-2013
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2-Pyridylmethyl ether-directed ortho-C-H olefination of phenols via a seven-membered cyclopalladated intermediate has been disclosed to construct a variety of ortho-alkenyl phenols and ortho-alkyl phenols.
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Regiospecific N-heteroarylation of amidines for full-color-tunable boron difluoride dyes with mechanochromic luminescence.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 06-05-2013
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Colors to dye for: Palladium-catalyzed regiospecific N-heteroarylations of amidines with 2-halo-N-heteroarenes leads to a structurally diverse library of BF2 /amidine-based complexes. These dyes not only present full-visible-color solid-state emissions with large Stokes shifts and high fluorescence quantum yields, but also exhibit a full-color-tunable mechanofluorochromic nature.
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One-step synthesis of imidazoline-containing macrocycles and their complexation with fullerenes C60 and C70.
Chem. Commun. (Camb.)
PUBLISHED: 05-30-2013
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A new family of imidazoline-arylene macrocycles have been constructed through the simultaneous formation of four imidazoline rings in one step. These macrocycles can efficiently complex with fullerenes C60 and C70 through the formation of ground-state complexes.
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Copper-catalyzed direct aryl quaternization of N-substituted imidazoles to form imidazolium salts.
J. Org. Chem.
PUBLISHED: 05-10-2013
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Diaryliodonium salts are employed to directly quaternize N-substituted imidazoles by using a copper catalyst to construct aryl imidazolium salts in moderate to excellent yields. This transformation is tolerant to a broad range of functional groups and provides a straightforward, efficient, and versatile route to synthesize aryl imidazolium as well as triazolium salts, especially the unsymmetric version.
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