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Find video protocols related to scientific articles indexed in Pubmed.
Sc(OTf)3-mediated 1,3-dipolar cycloaddition-ring cleavage-rearrangement: a highly stereoselective access to Z-?-enaminonitriles.
Org. Biomol. Chem.
PUBLISHED: 11-07-2014
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A novel and highly stereoselective synthesis of Z-?-enaminonitriles from azides and ?,?-unsaturated nitriles is reported. The reaction proceeds via a 1,3-dipolar cycloaddition-ring cleavage-rearrangement cascade mediated by a catalytic amount of Sc(OTf)3. A plausible reaction mechanism for this process is depicted.
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Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.
Sci Transl Med
PUBLISHED: 10-29-2014
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A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer.
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Associations between epidermal growth factor receptor gene mutation and serum tumor markers in advanced lung adenocarcinomas: a retrospective study.
Chin. Med. Sci. J.
PUBLISHED: 09-30-2014
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To investigate the associations between epidermal growth factor receptor (EGFR) gene mutations and serum tumor markers in advanced lung adenocarcinomas.
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[Effects of conservation tillage on soil CO2 and N2O emission during the following winter-wheat season].
Huan Jing Ke Xue
PUBLISHED: 09-24-2014
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In order to study the effect of conservation tillage on soil CO2 and N2O emissions in the following crop-growing season, field experiments were conducted in the winter wheat-growing season. Four treatments were conventional tillage (T), no-tillage with no straw cover (NT), no-tillage with straw cover (NTS), and conventional tillage with straw incorporation (TS), respectively. The CO2 and N2O fluxes were measured using a static chamber-gas chromatograph technique. The results showed that in the following winter wheat-growing season, conservation tillage did not change the seasonal pattern of CO2 and N2O emission fluxes from soil, and had no significant effect on crop biomass. Conservation tillage significantly reduced the accumulative amount of CO2 and N2O. Compared with the T treatment, the accumulative amount of CO2 under TS, NT, and NTS treatments were reduced by 5.95% (P = 0.132), 12.94% (P = 0.007), and 13.91% (P = 0.004), respectively, and the accumulative amount of N2O were significantly reduced by 31.23% (P = 0.000), 61.29% (P = 0.000), and 33.08% (P = 0.000), respectively. Our findings suggest that conservation tillage significantly reduced CO2 and N2O emission from soil in the following winter wheat-growing season.
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A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the ? opioid receptor gene OPRM1 via hnRNPH interactions.
J. Neurosci.
PUBLISHED: 08-15-2014
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Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype-based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype. In vitro studies such as electrophoretic mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the major binding partner for the G-containing SNP site. The G-to-A transition weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex with the AG genotype of this SNP when compared with the GG genotype. Interestingly, the altered splicing led to an increase in hMOR-1 protein levels despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent increase in single transmembrane domain variants that have a chaperone-like function on MOR-1 protein stability. Our studies delineate the role of this SNP as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest a functional link between an SNP-containing splicing modifier and the severity of heroin addiction.
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Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents.
Eur J Med Chem
PUBLISHED: 08-12-2014
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Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The new compounds 5a-5t showed stronger anti-proliferative activity than AA, especially compound 5b was found to be the best inhibition activity on HepG2 cell line. In addition, the mechanism of compound 5b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometric, qRT-PCR (quantitative real-time PCR) and Western blot. Compound 5b induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis showed that compound 5b mainly arrested HepG2 cells in G1 stage.
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One-pot stepwise approach to ?-enaminoketoesters through "masked" 1,3-aza-dipoles.
Org. Lett.
PUBLISHED: 07-23-2014
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t-BuOK-mediated rearrangement of 1,3-ketoesters with 2-(azidomethyl) aromatics in a two-step, one-pot telescoped sequence affords ?-enaminoketoesters in moderate to good yields. A novel pathway is proposed in which the umpolung of the azide is achieved from electrophilicity to nucleophilicity via deprotonation and undergoes nucleophilic attack onto the 1,3-ketoester.
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Enhanced Levels of Interleukin-8 Are Associated with Hepatitis B Virus Infection and Resistance to Interferon-Alpha Therapy.
Int J Mol Sci
PUBLISHED: 07-21-2014
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The objective of this study was to analyze the expression levels of IL-8 in serum and liver tissues from patients with chronic hepatitis B (CHB) infection and to investigate whether IL-8 may antagonize interferon-alpha (IFN-?) antiviral activity against HBV. IL-8 expression in serum was determined by enzyme linked immunosorbent assay (ELISA), and fluorescence-based quantitative real-time PCR (RT-qPCR) was used to measure IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) in patients with CHB. IL-8 protein expression was detected in liver biopsy tissues by immunohistochemistry. In addition, the differences in serum IL-8 and PBMCs mRNA levels were also observed in patients with different anti-viral responses to IFN-?. Compared to normal controls, serum IL-8 protein and mRNA levels were increased in CHB patients, IL-8 levels were positively correlated with the severity of liver inflammation/fibrosis. Moreover, serum IL-8 protein and mRNA levels were positively correlated with serum alanine aminotransferase (ALT) level and negatively correlated with serum prealbumin (PA) level. IL-8 expression was mainly located in portal area of liver tissues and was increased with the severity of liver inflammation and fibrosis stage. The expression serum and mRNA levels of IL-8 in the CHB patients with a complete response to IFN-? are significantly lower than that of the patients with non-response to IFN-? treatment. It is suggested that IL-8 might play important roles in the pathogenesis of CHB. Moreover, interferon resistance may be related to the up-regulation of IL-8 expression in the patients did not respond to IFN-? treatment.
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In vitro and in vivo activities of antimicrobial peptides developed using an amino acid-based activity prediction method.
Antimicrob. Agents Chemother.
PUBLISHED: 06-30-2014
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To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The in vivo antimicrobial activity of DP7 was tested in a Staphylococcus aureus infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the S. aureus outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.
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Morphology and phylogenetic analysis of two oxytrichid soil ciliates from China, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983 (Protista, Ciliophora, Hypotrichia).
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 06-13-2014
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The morphology and infraciliature of two hypotrichous ciliates, Oxytricha paragranulifera n. sp. and Oxytricha granulifera Foissner and Adam, 1983, collected respectively from the surface of a sandy soil in the Huguang mangrove forest, Zhanjiang, China, and the surface of soil in a forest beside Ziwu Road, Xian, north-west China, were examined. O. paragranulifera n. sp. is characterized by an elongate body with slightly tapered anterior end, two macronuclear nodules and two micronuclei, paroral and endoral in Stylonychia-pattern, colourless cortical granules distributed in clusters or irregular short rows, adoral zone occupying 37?% of the body length, marginal rows almost confluent posteriorly, six dorsal kineties and three caudal cirri, caudal cirri and dorsal bristles almost indistinguishable when viewed in vivo. The well-known O. granulifera Foissner and Adam, 1983 was also redescribed and can be separated from the novel species by having cortical granules arranged along dorsal kineties and marginal rows on both sides (vs grouped in clusters as well as in short irregular rows), paroral and endoral in Oxytricha-pattern (vs in Stylonychia-pattern), macronuclear nodules obviously detached (vs adjacent) and a non-saline terrestrial habitat (vs saline terrestrial). The separation of these two taxa is also firmly supported by the molecular data, which show a significant difference between the two in their SSU rRNA gene sequences (similarity 97.1?%). Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close relationship within the Oxytrichidae assemblage between O. paragranulifera n. sp. and O. granulifera.
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High water level impedes the adaptation of Polygonum hydropiper to deep burial: responses of biomass allocation and root morphology.
Sci Rep
PUBLISHED: 05-19-2014
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Many studies have investigated the individual effects of sedimentation or inundation on the performance of wetland plants, but few have examined the combined influence of these processes. Wetland plants might show greater morphological plasticity in response to inundation than to sedimentation when these processes occur simultaneously since inundation can negate the negative effects of burial on plant growth. Here, we evaluate this hypothesis by assessing growth of the emergent macrophyte Polygonum hydropiper under flooding (0 and 40 cm) and sedimentation (0, 5, and 10 cm), separately and in combination. Deep burial and high water level each led to low oxidation-reduction potential, biomass (except for 5-cm burial), and growth of thick, short roots. These characteristics were generally more significant under high water level than under deep burial conditions. More biomass was allocated to stems in the deep burial treatments, but more to leaves in the high water level treatments. Additionally, biomass accumulation was lower and leaf mass ratio was higher in the 40-cm water level + 10-cm burial depth treatment than both separate effects. Our data indicate that inundation plays a more important role than sedimentation in determining plant morphology, suggesting hierarchical effects of environmental stressors on plant growth.
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Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.
Cancer Cell
PUBLISHED: 05-02-2014
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Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or accelerate progression in treatment of endodermally derived colon and pancreatic cancers. In bladder, another organ of endodermal origin, we find that despite its initial presence in the cancer cell of origin Sonic hedgehog (Shh) expression is invariably lost during progression to invasive urothelial carcinoma. Genetic blockade of stromal response to Shh furthermore dramatically accelerates progression and decreases survival time. This cancer-restraining effect of Hh pathway activity is associated with stromal expression of BMP signals, which stimulate urothelial differentiation. Progression is dramatically reduced by pharmacological activation of BMP pathway activity with low-dose FK506, suggesting an approach to management of human bladder cancer.
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Ce(OTf)?-catalyzed [3 + 2] cycloaddition of azides with nitroolefins: regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles.
J. Org. Chem.
PUBLISHED: 04-25-2014
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The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and subsequent elimination reaction is described. In the presence of a catalytic amount of Ce(OTf)3, both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent yields.
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Microglial NLRP3 inflammasome activation mediates IL-1?-related inflammation in prefrontal cortex of depressive rats.
Brain Behav. Immun.
PUBLISHED: 04-02-2014
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Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1 beta (IL-1?) may play a pivotal role in the central nervous system (CNS) inflammation of depression. Here, we investigated IL-1? alteration in serum, cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS)-exposed rats, a well-documented model of depression, and further explored the molecular mechanism by which CUMS procedure induced IL-1?-related CNS inflammation. We showed that 12-week CUMS procedure remarkably increased PFC IL-1? mRNA and protein levels in depressive-like behavior of rats, without significant alteration of serum and CSF IL-1? levels. We found that CUMS procedure significantly caused PFC nuclear factor kappa B (NF-?B) inflammatory pathway activation in rats. The intriguing finding in this study was the induced activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome with the increased IL-1? maturation in PFC of CUMS rats, suggesting a new grade of regulatory mechanism for IL-1?-related CNS inflammation. Moreover, microglial activation and astrocytic function impairment were observed in PFC of CUMS rats. The increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1 (Iba1) protein expression supported that microglia in glial cells was the primary contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These alterations in CUMS rats were restored by chronic treatment of the antidepressant fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1? reduction involves both transcriptional and post-transcriptional regulatory mechanisms. These findings provide in vivo evidence that microglial NLRP3 inflammasome activation is a mediator of IL-1?-related CNS inflammation during chronic stress, and suggest a new therapeutic target for the prevention and treatment of depression.
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Proteasome Inhibition-Induced Downregulation of Akt/GSK-3? Pathway Contributes to Abnormality of Tau in Hippocampal Slice.
Mol. Neurobiol.
PUBLISHED: 03-31-2014
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Proteasome inhibition can induce abnormal accumulation and phosphorylation of microtubule-associated protein tau. The major function of tau protein is to promote microtubules assembly and stabilization, and abnormal tau protein would disturb its microtubule-binding function. In this study, proteasome inhibitor MG132 was used to treat hippocampal slices to explore the role and mechanism of Akt/glycogen synthase kinase-3? (GSK-3?) in proteasome inhibition-induced tau abnormality. During the culture period, we measure the lactate dehydrogenase (LDH) content to assay the viability of hippocampal slices. Following 2.5 and 5 ?M MG132 treatment for 6 h, we detected the expression, phosphorylation modification, and microtubule-binding function of tau protein of slices. We also analyzed the changed activities of glycogen synthase kinase-3? (GSK-3?) and protein kinase B (PKB/Akt) and the level of heat shock protein 90 (Hsp90) in the process. In addition, co-immunoprecipitation was used to investigate the interaction between Akt and Hsp90, Akt and protein phosphatase-2A (PP2A) in the MG132-treated organotypic hippocampal slices. Our results indicated that proteasome inhibition led to degradation obstacles and abnormal phosphorylation of tau protein. The downregulated Akt/GSK-3? signaling pathway might be responsible for the abnormal phosphorylation of tau protein at multiple sites which further reduced the microtubule-binding function of tau protein. Furthermore, proteasome inhibition decreased the binding capacity of Akt-Hsp90 while increased the Akt-PP2A binding ability which mediated Akt inactivity. This current study establishes a hippocampal slice model targeting Akt/GSK-3? signaling pathway to explore the pivotal role of proteasome inhibition in tau pathology.
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[Effect of interleukin-1? on expressions of activin A and its related factors in cultured endometrial stromal cells from patients with endometriosis].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 03-28-2014
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To study the effect of interleukin-1? (IL-1?) on the expressions activin A, follistatin, and cripto in cultured human endometrial stromal cells (HESCs) form patients with endometriosis.
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Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene.
Pain
PUBLISHED: 03-27-2014
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?-Opioids remain vastly important for the treatment of pain, and would represent ideal analgesics if their analgesic effects could be separated from their many side effects. A recently synthesized compound, iodobenzoylnaltrexamide (IBNtxA), acting at 6-transmembrane (6-TM) splice variants of the ?-opioid receptor gene, was shown to have potent analgesic actions against acute, thermal pain accompanied by a vastly improved side-effect profile compared to 7-TM-acting drugs such as morphine. Whether such analgesia can be seen in longer-lasting and nonthermal algesiometric assays is not known. The current study demonstrates potent and efficacious IBNtxA inhibition of a wide variety of assays, including inflammatory and neuropathic hypersensitivity and spontaneous pain. We further demonstrate the dependence of such analgesia on 6-TM ?-opioid receptor variants using isobolographic analysis and the testing of Oprm1 (the ?-opioid receptor gene) exon 11 null mutant mice. Finally, the effect of nerve damage (spared nerve injury) and inflammatory injury (complete Freund's adjuvant) on expression of ?-opioid receptor variant genes in pain-relevant central nervous system loci was examined, revealing a downregulation of the mMOR-1D splice variant in the dorsal root ganglion after spared nerve injury. These findings are supportive of the potential value of 6-TM-acting drugs as novel analgesics.
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Molecular phylogeny and taxonomy of two novel brackish water hypotrich ciliates, with the establishment of a new genus, Antiokeronopsis gen. n. (Ciliophora, Hypotrichia).
J. Eukaryot. Microbiol.
PUBLISHED: 02-23-2014
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Two novel brackish water urostyloid ciliates, Anteholosticha paramanca sp. n. and Antiokeronopsis flava gen. n., sp. n., isolated from the Shenzhen Mangrove Nature Protection Area on the coast of the South China Sea, were investigated using live observation and protargol impregnation techniques. Anteholosticha paramanca sp. n. is characterized by its spherical yellowish cortical granules arranged in lines, shortened midventral complex and three transverse cirri. Morphogenesis is similar to that in Anteholosticha manca. The new genus Antiokeronopsis is diagnosed by having a continuous adoral zone of membranelles, frontal cirri arranged in a bicorona, midventral complex composed of midventral pairs only, one marginal cirral row on each side, the presence of frontoterminal and transverse cirri, and the lack of buccal and caudal cirri. The type species A. flava sp. n. is characterized by its elongated body shape, brown to yellowish body color and two types of cortical granules. Small subunit ribosomal RNA gene sequence data justify the classification of both species. Phylogenetic analyses indicate that A. paramanca clusters with Bakuella subtropica within a clade that includes two other Anteholosticha species, while Antiokeronopsis groups within the core urostylids and is most closely related to the well-known genera Pseudokeronopsis and Uroleptopsis.
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REST and stress resistance in ageing and Alzheimer's disease.
Nature
PUBLISHED: 02-21-2014
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Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid ?-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid ?-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
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Synthesis and antitumor activities of novel ?-aminophosphonate derivatives containing an alizarin moiety.
Eur J Med Chem
PUBLISHED: 02-19-2014
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A series of novel ?-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca(2+) and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.
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A novel methodology for synthesis of dihydropyrazole derivatives as potential anticancer agents.
Org. Biomol. Chem.
PUBLISHED: 02-12-2014
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A novel, simple, and efficient method for the synthesis of 4,5-dihydropyrazole derivatives has been developed. The reaction proceeded through the base-induced isomerization of easily accessible propargyl alcohols followed by cyclization of ?,?-unsaturated hydrazones. Furthermore, selected compounds 3ab and 3ac exhibited good activities against Bel-7404 (human hepatoma cancer), HepG2 (human liver cancer), NCI-H460 (human lung cancer) and SKOV3 (human ovarian cancer) cell lines with IC50 in the range of 22-46 ?mol L(-1).
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Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats.
J. Nutr. Biochem.
PUBLISHED: 02-05-2014
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Fructose is a nutritional composition of fruits and honey. Its excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Quercetin, a natural flavonoid, has been reported to ameliorate high fructose-induced rat insulin resistance and hyperlipidemia. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed rats. Rats were fed 10% fructose in drinking water for 10 weeks. After 4 weeks, these animals were orally treated with quercetin (50 and 100 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Quercetin effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Furthermore, quercetin was found to reduce metabolic nutrient sensors adenosine monophosphate-activated protein kinase (AMPK) activation and thioredoxin-interacting protein (TXNIP) overexpression, as well as the glutamine-glutamate cycle dysfunction in the hypothalamus of high fructose-fed rats. Subsequently, it ameliorated high fructose-caused hypothalamic inflammatory lesions in rats by suppressing the activation of hypothalamic nuclear factor ?B (NF-?B) pathway and NOD-like receptor 3 (NLRP3) inflammasome with interleukin 1? maturation. Allopurinol had similar effects. These results provide in vivo evidence that quercetin-mediated down-regulation of AMPK/TXNIP and subsequent inhibition of NF-?B pathway/NLRP3 inflammasome activation in the hypothalamus of rats may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, quercetin with the central activity may be a therapeutic for high fructose-induced insulin resistance and hyperlipidemia in humans.
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Copper-mediated cross-coupling-cyclization-oxidation: a one-pot reaction to construct polysubstituted pyrroles.
Chem. Commun. (Camb.)
PUBLISHED: 02-01-2014
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A novel and efficient procedure for the synthesis of polysubstituted pyrroles has been developed in this work. The polysubsituted pyrroles were synthesized directly from terminal alkenes, amines and ?-keto esters through cross-coupling-cyclization-oxidation in the presence of a catalytic amount of cuprous chloride. This method provides a one-pot synthesis route from terminal alkenes to polysubstituted pyrroles for the first time and opens a new area in cuprous catalysis.
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Vascular Endothelial Growth Factor expression in peripheral blood of patients with pregnancy induced hypertension syndrome and its clinical significance.
Pak J Med Sci
PUBLISHED: 01-30-2014
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This study was conducted was to detect vascular endothelial growth factor (VEGF) levels in peripheral blood of patients with pregnancy-induced hypertension (PIH) syndrome and to investigate VEGF correlation with PIH occurrence.
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Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model.
Oncol. Rep.
PUBLISHED: 01-27-2014
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Radiation therapy is a conventional strategy for treating advanced lung cancer yet is accompanied by serious side-effects. Its combination with other strategies, such as antiangiogenesis and gene therapy, has shown excellent prospects. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in the antiangiogenic gene therapy of tumors. In the present study, LL/2 cells were infected with a recombinant adenovirus encoding endostatin (Ad-endostatin) to express endostatin. The results showed that LL/2 cells infected with the Ad-endostatin efficiently and longlastingly expressed endostatin. In order to further explore the role of Ad-endostatin combined with irradiation in the treatment of cancer, a murine lung cancer model was established and treated with Ad-endostatin combined with low-dose irradiation. The results showed that the combination treatment markedly inhibited tumor growth and metastasis, and prolonged the survival time of the tumor-bearing mice. Furthermore, this significant antitumor activity was associated with lower levels of microvessel density and anoxia factors in the Ad-Endo combined with irradiation group, and with an increased apoptotic index of tumor cells. In addition, no serious side-effects were noted in the combination group. Based on our findings, Ad-endostatin combined with low-dose irradiation may be a rational alternative treatment for lung cancer and other solid tumors.
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RASAL1 influences the proliferation and invasion of gastric cancer cells by regulating the RAS/ERK signaling pathway.
Hum. Cell
PUBLISHED: 01-21-2014
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The aim of this study was to investigate the biological characteristics of the RASAL1 gene in a well-differentiated gastric cancer cell line MKN-28 and a poorly differentiated gastric cancer cell line BGC-823 cells, using RNA interference and gene transfection technology, respectively. MKN-28 cells were transfected with the shRNA of RASAL1 and BGC-823 cells were transfected with the pcDNA 3.1 plasmid vector containing RASAL1. RT-PCR and western blotting were then used to detect the expression of RASAL1 mRNA and protein. The activities of RAS and extracellular signal-regulated kinase 1/2 were analyzed by the pull-down method and western blotting. The proliferate capacity, apoptosis rate, invasive and migratory potentials of MKN-28 or BGC-823 cells were also measured by Cell Counting Kit-8 cell proliferation assay, propidium iodide/Annexin V staining coupled with flow cytometry, and transwell chamber assays, respectively. Measurement of RASAL1 mRNA and protein expression in two cells revealed successful transfection of the shRNA of RASAL1 and RASAL1-pcDNA3.1 plasmid into these two cells. Moreover, decreased expression of RASAL1 in MKN-28 cells resulted in increased expression of RAS-GTP and p-ERK1/2. Interestingly, decreased expression of RASAL1 inhibited apoptosis and facilitated cell proliferation, invasion and migration. The increased expression of RASAL1 in BGC-823 cells caused declined expression of RAS-GTP and p-ERK1/2, as well as promoted apoptosis and restrained cell proliferation, invasion and migration. The down-regulation of RASAL1 promoted the proliferation, invasion and migration of gastric cancer MKN-28 cells, and up-regulation of RASAL1 inhibited the proliferation, invasion and migration of BGC-823 gastric cancer cells by regulating the RAS/ERK signaling pathway. Thus, our results suggest that RASAL1 may play an important role as a tumor suppressor gene in gastric cancer.
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Synthesis and antitumor activities of novel dipeptide derivatives derived from dehydroabietic acid.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-20-2014
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A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway.
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Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2.
Mol. Cancer
PUBLISHED: 01-16-2014
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A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2.
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Differential Expressions of the Alternatively Spliced Variant mRNAs of the µ Opioid Receptor Gene, OPRM1, in Brain Regions of Four Inbred Mouse Strains.
PLoS ONE
PUBLISHED: 01-01-2014
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The µ opioid receptor gene, OPRM1, undergoes extensive alternative pre-mRNA splicing in rodents and humans, with dozens of alternatively spliced variants of the OPRM1 gene. The present studies establish a SYBR green quantitative PCR (qPCR) assay to more accurately quantify mouse OPRM1 splice variant mRNAs. Using these qPCR assays, we examined the expression of OPRM1 splice variant mRNAs in selected brain regions of four inbred mouse strains displaying differences in µ opioid-induced tolerance and physical dependence: C56BL/6J, 129P3/J, SJL/J and SWR/J. The complete mRNA expression profiles of the OPRM1 splice variants reveal marked differences of the variant mRNA expression among the brain regions in each mouse strain, suggesting region-specific alternative splicing of the OPRM1 gene. The expression of many variants was also strain-specific, implying a genetic influence on OPRM1 alternative splicing. The expression levels of a number of the variant mRNAs in certain brain regions appear to correlate with strain sensitivities to morphine analgesia, tolerance and physical dependence in four mouse strains.
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Morphology and phylogenetic position of the oxytrichid ciliates, Urosoma salmastra (Dragesco and Dragesco-Kernéis, 1986) Berger, 1999 and U. karinae sinense nov. sspec. (Ciliophora, Hypotrichia).
Eur. J. Protistol.
PUBLISHED: 01-01-2014
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The morphology and infraciliature of two hypotrichous ciliates, Urosoma salmastra and U. karinae sinense nov. sspec., were investigated for populations collected from the surface of intertidal gravel in the Huguang Mangrove Forest, Zhanjiang, China and the upper 10cm layer of soil in the Sangke Grass Land in the southern part of Gansu Province, China, respectively. Urosoma salmastra is characterized by its elongate-elliptical body with no tail-like structure; two macronuclear nodules; cortical granules colourless, less than 1?m across, and arranged in short rows; adoral zone occupying 25% of body length in vivo; paroral conspicuously short and located in front of endoral. Urosoma karinae sinense nov. sspec. is characterized by its elongate-elliptical body with no tail; 2-4 macronuclear nodules; cortical granules colourless, less than 1?m across, and arranged in short rows; adoral zone occupying 30% of body length in vivo; paroral shorter than, and located ahead of endoral. Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close relationship between U. salmastra, U. karinae sinense nov. sspec. and Oxytricha granulifera within the Oxytrichinae assemblage.
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Optimizing the synthesis of CdS/ZnS core/shell semiconductor nanocrystals for bioimaging applications.
Beilstein J Nanotechnol
PUBLISHED: 01-01-2014
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In this study, we report on CdS/ZnS nanocrystals as a luminescence probe for bioimaging applications. CdS nanocrystals capped with a ZnS shell had enhanced luminescence intensity, stronger stability and exhibited a longer lifetime compared to uncapped CdS. The CdS/ZnS nanocrystals were stabilized in Pluronic F127 block copolymer micelles, offering an optically and colloidally stable contrast agents for in vitro and in vivo imaging. Photostability test exhibited that the ZnS protective shell not only enhances the brightness of the QDs but also improves their stability in a biological environment. An in-vivo imaging study showed that F127-CdS/ZnS micelles had strong luminescence. These results suggest that these nanoparticles have significant advantages for bioimaging applications and may offer a new direction for the early detection of cancer in humans.
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Dendritic cells decreased the concomitant expanded Tregs and Tregs related IL-35 in cytokine-induced killer cells and increased their cytotoxicity against leukemia cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Regulatory T cells (Tregs) are potent immunosuppressive cells and essential for inducing immune tolerance. Recent studies have reported that Tregs and Tregs related cytokines can inhibit the antitumor activity of cytokine-induced killer (CIK) cells, but dendritic cells co-cultured CIK (DC-CIK) cells can be used for induction of a specific immune response by blocking of Tregs and TGF-?, IL-10. As a novel identified cytokine, IL-35 is specially produced by Tregs and plays an essential role in immune regulation. However, it remains unknown whether IL-35 roles in tumor immunotherapy mediated by CIK and DC-CIK cells. In this study, we cultured CIK and DC-CIK cells from the same healthy adult samples, and investigated their phenotype, proliferation, cytotoxic activity against leukemia cell lines K562 and NB4 by FCM and CCK-8, measured IL-35, TGF-? and IL-10 protein by ELISA, detected Foxp3, IL-35 and IL-35 receptor mRNA by Real-time PCR, respectively. We found Tregs and IL-35 concomitantly expanded by a time-dependent way during the generation of CIK cells, but DC significantly down-regulated the expression of them and simultaneously up-regulated the proliferation ability as well as cytotoxic activity of CIK cells against leukemia cell lines. Therefore, our data suggested that DC decreased concomitant expanded Tregs and Tregs related IL-35 in CIK cells and might contribute to improve their cytotoxicity against leukemia cells in vitro.
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Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern china.
PLoS ONE
PUBLISHED: 01-01-2014
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The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.
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[Effect of Interfering the ?-catenin by Lentiviral Vector-mediated RNAi on the Biological Behavior of Mouse Bone Marrow Mesenchymal Stem Cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
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This study was aimed to investigate the effect of Wnt/?-catenin signaling pathway on the biologic behavior of mouse bone marrow mesenchymal stem cells(mBM-MSC) by constructing a RNAi lentiviral vector specific to ?-catenin. Three pairs of shRNA coding sequences directed against different sites of ?-catenin mRNA were designed and were linked into lentiviral vector plasmid PLB for constructing the PLB-?-catenin/shRNA1, PLB-?-catenin/shRNA2 and PLB-?-catenin/ shRNA3. Those plasimds and lentiviral packaging plasimds were co-transfected into the packaging cells 293FT, then the virus particles were collected and the viral titer was assayed after concentration, and these viral particles were infected to MSC. The flow cytometry was used to sort GFP (+)cells, Western blot and RT-PCR were used to verify the inhibitory effect of those cells on expression of ?-catenin gene in cells, CCK-8 method was used to detect the cell proliferation level, Annexin-V/7-AAD was used to determine the cell apoptosis after interference, the cell scratch and transwell tests were used to detect the migration capalbility of MSC. The results showed that the efficient inhibition of ?-catenin mRNA and protein expression, and the suppression of MSC proliferation were observed in group of PLB-?-catenin/shRNA2(inteference group), while there was no significant changes of MSC proliferation between negative group(PLB group) and the normal group (control group). The flow cytometric detection indicated that after induced by serum starvation for 72 h, the apoptosis of MSC increased in inteference group, but there was no difference between PLB and control groups(P > 0.05). The cell scratch and transwell tests demonstrated that the migration capability of MSC in inteference group dicreased significantly, while the migration capability of MSC in control group was not changed obvi-ously. It is concluded that the constructed specific RNAi lentivirus can effectively inhibit the expression of ?-catenin gene, decrease expression level of ?-catenin mRNA and protein. The Wnt/?-catenin signaling pathway plays an important role in biological behavior of BM-MSC.
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[Distribution and activation of dendritic cells in immune thrombocytopenia patients].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
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Defective dendritic cell (DC) functions have been implicated in ITP. The purpose of this study was to investigate the distribution and activation of dendritic cells in immune thrombocytopenia (ITP) patients. ITP patients were divided into 3 groups:the newly diagnosed, refractory and effective treatment group. The distributions of plasmacytoid dendritic cells(pDC) and myeloid dendritic cells(mDC) in peripheral blood, bone marrow and spleen were detected with flow cytometry. The expression level of CD80 and CD86 on surface of pDC and mDC was also detected with flow cytometry. The results indicated that the percentage of mDC was higher than that of pDC in all sites of all groups. The percentage of mDC and pDC in all site of refractory group was higher than that in newly diagnosed and effective groups, but the percentage of mDC in spleen of refractory group was obviously higher than that in other sites. The percentage of pDC was no significant different in all groups. The expression level of CD86 in all groups was higher than that of CD80, the expression level of CD80 was lower in mDC and pDC of all groups, but there was no obvious difference in all sites. The CD86 expression in all site of refractory group was higher than that in newly diagnosed and effective treatment groups, while the CD86 expression of mDC in spleen of newly diagnosed group obviouly higher than that in other sites. It is concluded that the distribntion abnormality of mDC and pDC exists in ITP patients, the mDC are more accumulated in spleen, and differentiation of mDC to maturity is more obvious in spleen, spleen-derived mDC significantly express CD86, spleen-derived mDC may play an important role in the pathogenesis of ITP.
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[Effects of endoplasmic reticulum stress related proteins and their mediated apoptosis in the formation of deep tissue injury of pressure ulcer in rats].
Zhonghua Shao Shang Za Zhi
PUBLISHED: 12-24-2013
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To explore the effects of endoplasmic reticulum stress (ERS) related proteins and their mediated apoptosis in the formation of deep tissue injury of pressure ulcer in rats.
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Samarium(III)-Catalyzed C(sp(3))-H Bond Activation: Synthesis of Indolizines via C-C and C-N Coupling between 2-Alkylazaarenes and Propargylic Alcohols.
Org. Lett.
PUBLISHED: 12-20-2013
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A new rare earth metal and samarium-catalyzed C(sp(3))-H bond activation is reported in which 2-alkylazaarenes and propargylic alcohols were converted to indolizines. This process operates under mild conditions and solvent-free conditions. A broad scope of coupling partners has been established, and a likely mechanism has also been suggested.
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Betaine Reduces Serum Uric Acid Levels and Improves Kidney Function in Hyperuricemic Mice.
Planta Med.
PUBLISHED: 12-11-2013
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Betaine as a dietary alkaloid has attracted the attention of patients with kidney diseases. This study aimed to investigate the effects of betaine on serum uric acid levels and kidney function, and explore their underlying mechanisms in potassium oxonate-induced hyperuricemic mice. Betaine at 5, 10, 20, and 40?mg/kg was orally administered to hyperuricemic mice for 7 days and found to significantly reduce serum uric acid levels and increase fractional excretion of uric acid in hyperuricemic mice in a dose-dependent manner. It effectively restored renal protein level alterations of urate transport-related molecular proteins urate transporter 1, glucose transporter 9, organic anion transporter 1, and ATP-binding cassette subfamily G member 2 in this model, possibly resulting in the enhancement of kidney urate excretion. Moreover, betaine reduced serum creatinine and blood urea nitrogen levels and affected urinary levels of beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase as well as upregulated renal protein levels of organic cation/carnitine transporters OCT1, OCTN1, and OCTN2, resulting in kidney function improvement in hyperuricemic mice. The findings from this study provide evidence that betaine has anti-hyperuricemic and nephroprotective actions by regulating protein levels of these renal organic ion transporters in hyperuricemic mice.
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Morphine Regulates Expression of MOR-1A, an Intron-retention Carboxyl Terminal Splice Variant of the ? Opioid Receptor (OPRM1) Gene Via miR-103/miR-107.
Mol. Pharmacol.
PUBLISHED: 12-03-2013
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The ? opioid receptor (MOR-1) gene, OPRM1, undergoes extensive alternative splicing, generating an array of splice variants. Of these variants, MOR-1A, an intron-retention carboxyl terminal splice variant identical to MOR-1 except for the terminal intracellular tail encoded by exon 3b, is quite abundant and conserved from rodent to humans. Increasing evidence indicates that miroRNAs (miRNAs) regulate MOR-1 expression and ? agonists such as morphine modulate miRNA expression. However, little is known about miRNA regulation of the OPRM1 splice variants. Using 3 rapid amplification cDNA end (RACE) and Northern blot analyses, the present study identified the complete 3 untranslated region (3-UTR) for both mouse and human MOR-1A and their conserved polyadenylation site, and defined the role the 3-UTR in mRNA stability using a luciferase reporter assay. Computer models predicted a conserved miR 103/107 targeting site in the 3-UTR of both mouse and human MOR-1A. The functional relevance of miR-103/107 in regulating expression of MOR-1A protein through the consensus miR-103/107 binding sites in the 3- UTR was established by using mutagenesis and a miR-107 inhibitor in transfected HEK293 cells and Be(2)C cells that endogenously express human MOR-1A. Chronic morphine treatment significantly upregulated miR-103 and miR-107 levels, leading to downregulation of polyribosome-associated MOR-1A in both Be(2)C cells and the striatum of a morphine tolerant mouse, providing a new perspective on understanding the roles of miRNAs and OPRM1 splice variants in modulating the complex actions of morphine in animals and humans.
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Rheumatoid arthritis.
Aust Fam Physician
PUBLISHED: 11-13-2013
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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. RA is considered an autoimmune disease. A study in the UK found the population minimum prevalence of RA is 1.16% in women and 0.44% in men. In Australia, the estimated prevalence is 0.6%. Using BEACH data from April 2011 to March 2013, we examined the rate of RA and its management in Australian general practice.
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UCH-L1 Inhibition Involved in CREB Dephosphorylation in Hippocampal Slices.
J. Mol. Neurosci.
PUBLISHED: 11-12-2013
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Ubiquitin C-terminal hydrolase L1 (UCH-L1) is abundantly expressed in the brain and is critical for the normal function of synapses. cAMP response element binding protein (CREB) is a transcription factor which initiates the expression of proteins that related to the regulation of synaptic plasticity and memory function. Studies have shown that UCH-L1 can influence the expression and activity of CREB, but the underlying mechanisms remain unclear. In this study, we used UCH-L1 inhibitor LDN to treat mice hippocampal slices and found that UCH-L1 inhibition caused the dephosphorylation of CREB at Ser133 site. Meanwhile, hyperphosphorylation of microtubule-associated protein tau; increased expression of synaptic protein components of PSD-95 and synapsin-1, and decreased activity of tyrosine kinase Fyn were observed after UCH-L1 inhibition. Moreover, all these alternations have an influence on the normal function of N-methyl-D-aspartate (NMDA) receptor NR2B subunit which is likely to result in the dephosphorylation of CREB. We also found that LDN treatment mediated protein kinase A (PKA) deactivation was involved in the dephosphorylation of CREB. Thus, our study introduces a novel possible mechanism for elaborating the effects of UCH-L1 inhibition on the CREB activity and the implicated signaling pathways.
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[Prediction of methane emission of paddy field based on the support vector regression model].
Huan Jing Ke Xue
PUBLISHED: 11-07-2013
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The methane emission data of paddy fields was obtained by using the static chamber and gas chromatography, and six parameters including atmospheric temperature, soil temperature at 5 cm depth, pH of soil, Eh of soil, soil moisture and ground biomass were selected as the primary influencing factors of methane emission. The support vector regression (epsilon-SVR) model was built on the optimization of structural risk minimization, and the parameters of the epsilon-SVR model were optimized using Leave-one-out Cross Validation (LOOCV). The prediction accuracy of model was evaluated by k-fold cross validation with the mean relative error (MRE) and the root mean square error (RMSE). In addition, the accuracy of the epsilon-SVR model was analyzed by comparison with the Back Propagation-Artificial Neural Network (BP-ANN) model. The results indicated that the predicted value of the epsilon-SVR model with the parameters C and epsilon optimized by LOOCV was in good agreement with the measured value, and the average MRE of test samples was 44% and the average RMSE was 16.21 mg x (m2 x h)(-1) in the process of 11-fold cross validation. Compared with the BP-ANN model, the correlation coefficient was 0.863, and all the indicators were better. It demonstrated that the 8-SVR model could be applied to the prediction of methane emission of paddy fields.
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IL-15 improves the cytotoxicity of cytokine-induced killer cells against leukemia cells by upregulating CD3+CD56+ cells and downregulating regulatory T cells as well as IL-35.
J. Immunother.
PUBLISHED: 10-23-2013
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Cytokine-induced killer (CIK) cells are usually generated from peripheral blood mononuclear cells with the stimulation of IL-2 in vitro. Unlike the conventional IL-2-stimulated CIK cells (IL-2-CIK cells), we investigated the characteristics and potential mechanism of IL-15-stimulated CIK cells (IL-15-CIK cells) in this study. Compared with IL-2-CIK cells, the percentage of CD3CD56 cells was significantly increased in IL-15-CIK cells, but the expression of regulatory T (Treg) cells and IL-35 was significantly decreased in IL-15-CIK cells. Meanwhile, the in vitro cytotoxicity against human myeloid leukemia cells K562 of IL-15-CIK cells was significantly augmented compared with IL-2-CIK cells. These data suggest that IL-15 may improve the cytotoxicity of CIK cells against leukemia cells by upregulating CD3CD56 cells and downregulating Treg cells and IL-35.
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Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice.
Neurosciences (Riyadh)
PUBLISHED: 10-22-2013
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To investigate whether lithium modifies open-field and elevated plus maze behavior, and brain phospho-glycogen synthase kinase 3 (P-GSK3beta) expression in Fmr1 knockout mice.
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[Effects of immature dendritic cells to express CCR7 on graft-versus-host disease in allogeneic bone marrow transplant mouse model].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 10-10-2013
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To investigate the effects of immature dendritic cells(imDC)expressing chemokine receptor-7(CCR7) on acute graft-versus-host disease(aGVHD) in allogeneic bone marrow transped (allo-BMT) mouse model.
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Synthesis and antitumor activities of novel rhein ?-aminophosphonates conjugates.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-29-2013
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Several rhein ?-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32?M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA.
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[Study on all-time multi-wavelength fusion fingerprint of Qizhiweitong granules and multi-component quantitative analysis].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-17-2013
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To control the quality of Qizhiweitong granules with the all-time multi-wavelength fusion fingerprint quantification as the major technique.
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Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-25-2013
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Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1?M). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest.
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[The effect of Bcl-2 gene silencing on the sensitivity of cell line A549 to chemotherapeutic drugs].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 07-17-2013
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To investigate the effects of miRNA-mediated down-regulation of the Bcl-2 gene on the chemotherapeutic sensitivities and mRNA transcriptions of sensitivity associated genes in human lung adenocarcinoma cell line A549 cells, and therefore to provide experimental data for improving the chemotherapeutic effects on non-small cell lung cancer (NSCLC).
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Robust joint analysis with data fusion in two-stage quantitative trait genome-wide association studies.
Comput Math Methods Med
PUBLISHED: 07-06-2013
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Genome-wide association studies (GWASs) in identifying the disease-associated genetic variants have been proved to be a great pioneering work. Two-stage design and analysis are often adopted in GWASs. Considering the genetic model uncertainty, many robust procedures have been proposed and applied in GWASs. However, the existing approaches mostly focused on binary traits, and few work has been done on continuous (quantitative) traits, since the statistical significance of these robust tests is difficult to calculate. In this paper, we develop a powerful F-statistic-based robust joint analysis method for quantitative traits using the combined raw data from both stages in the framework of two-staged GWASs. Explicit expressions are obtained to calculate the statistical significance and power. We show using simulations that the proposed method is substantially more robust than the F-test based on the additive model when the underlying genetic model is unknown. An example for rheumatic arthritis (RA) is used for illustration.
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[Effect of different therapeutic regimens on regulatory T cells in patients of primary immune thrombocytopenia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 07-06-2013
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To investigate the change of CD4?CD25(high)CD127(low) regulatory T cells (Tregs) percentage in patients with primary immune thrombocytopenia (ITP) treated by different methods.
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[Construction of shRNA expression vector targeting AATF and establishment of stably transfected U937 cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-03-2013
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This study was aimed to construct the targeting AATF shRNA eukaryotic expression vector and establish the stably transfected U937 cell lines. The sequence of AATF mRNA was obtained from GenBank. After excluding homeology, three plasmid expression vectors coding shRNA targeting 228 ? 249, 303 ? 324 and 443 ? 464 of AATF gene sequence were synthesized. Two terminals of shRNA carried BamHI and HindIII restriction sites. The selected nucleotides were cloned into the plasmid pSilencer 3.1-H1 neo respectively, and the resultant recombinant plasmids were named as pSA-1, pSA-2, pSA-3. The sequences of the recombinant plasmids were identified by DNA sequencing. The recombinant plasmids were transfected into the cell line U937 by electroporation with Neon(TM) Transfection System. The transfected cells were persistently screened under G418 (500 mg/L), and isolated with a limited dilution for 8 weeks. The inhibition of AATF mRNA and protein expression was respectively detected by RT-PCR and Western blot. The results indicated that RNAi eukaryotic expression vectors targeting AATF had correct reading frame and nucleotide sequence. Real-time PCR revealed that AATF shRNA effectively silenced mRNA expression of AATF. Western blot analysis found that AATF shRNA obviously suppressed protein expression of AATF (P < 0.05). It is concluded that the shRNA eukaryotic expression vector has been successfully constucted which can inhibit the expression of AATF, and the establishment of stably transfected U937 cell lines provide a original route for exploring the mechanism of AATF in human Leukemia further.
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Stabilization of the ?-opioid receptor by truncated single transmembrane splice variants through a chaperone-like action.
J. Biol. Chem.
PUBLISHED: 06-11-2013
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The ?-opioid receptor gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, as illustrated by the identification of an array of splice variants generated by both 5 and 3 alternative splicing. The current study reports the identification of another set of splice variants conserved across species that are generated through exon skipping or insertion that encodes proteins containing only a single transmembrane (TM) domain. Using a Tet-Off system, we demonstrated that the truncated single TM variants can dimerize with the full-length 7-TM ?-opioid receptor (MOR-1) in the endoplasmic reticulum, leading to increased expression of MOR-1 at the protein level by a chaperone-like function that minimizes endoplasmic reticulum-associated degradation. In vivo antisense studies suggested that the single TM variants play an important role in morphine analgesia, presumably through modulation of receptor expression levels. Our studies suggest the functional roles of truncated receptors in other G protein-coupled receptor families.
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Impacts of dung combustion on the carbon cycle of alpine grassland of the north Tibetan plateau.
Environ Manage
PUBLISHED: 06-07-2013
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Alpine grassland of Tibet is a frangible ecosystem in terms of carbon (C) emission. Yak dung is an important resident energy with about 80 % of yak dung combusted for energy in the north Tibetan plateau. This paper investigated the impact of dung combustion on the C cycle of the alpine grassland ecosystem in north Tibet, China. During the growing season of 2011, from a field survey and household questionnaires, the main impacts of dung collection for fuel on the C cycle of the ecosystem were identified. (1) The C sequestration and storage capacity, including the dung-derived C stored in soil and C captured by vegetation, decreased. The net primary production decreased remarkably because of the reduction of dung returned to soil. (2) In a given period, more C was emitted to the atmosphere in the dung combustion situation than that in the dung returned to soil situation. (3) The energy grazing alpine meadow ecosystem changed into a net C source, and the net biome production of the ecosystem dropped to -15.18 g C/m2 year in the dung combustion situation, 42.95 g C/m2 year less than that in the dung returned situation. To reduce the CO2 emission derived from dung use, the proportion of dung combustion should be reduced and alternative renewable energy such as solar, wind, or hydro energy should be advocated, which is suitable for, and accessible to, the north Tibetan plateau.
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Wuling san ameliorates urate under-excretion and renal dysfunction in hyperuricemic mice.
Chin J Nat Med
PUBLISHED: 06-04-2013
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The present study was undertaken to characterize the effects of Wuling San on urate excretion and renal function, and explore its possible mechanisms of action in hyperuricemic mice.
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[Efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-22-2013
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To compare the efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia (ITP).
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Myeloid-derived suppressor cells as a Trojan horse: A cellular vehicle for the delivery of oncolytic viruses.
Oncoimmunology
PUBLISHED: 05-15-2013
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We have recently demonstrated that oncolytic vesicular stomatitis viruses can be efficiently and selectively delivered to neoplastic lesions by myeloid-derived suppressor cells (MDSCs). Importantly, the loading of viruses onto MDSCs inhibited their immunosuppressive properties and endowed them with immunostimulatory and tumoricidal functions. Our study demonstrates the potential use of MDSCs as a Trojan horse for the tumor-targeted delivery of various anticancer therapeutics.
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Synthesis and antitumor activities of novel ?-aminophosphonates dehydroabietic acid derivatives.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-07-2013
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A series of novel ?-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage.
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Synthesis and antitumor activities of novel thiourea ?-aminophosphonates from dehydroabietic acid.
Eur J Med Chem
PUBLISHED: 05-03-2013
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A series of novel thiourea ?-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.
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The first palladium-catalyzed 1,4-addition of terminal alkenes to acrylate esters.
Chem. Commun. (Camb.)
PUBLISHED: 05-02-2013
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A novel and efficient procedure for the synthesis of ?,?-alkenyl esters with complete E-stereochemistry by the 1,4-addition of alkenes to acrylate esters in the presence of a catalytic amount of palladium chloride has been developed. This method provides a rapid and efficient access to substituted ?,?-alkenyl esters.
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HOXA9 Gene Expression in Acute Myeloid Leukemia.
Cell Biochem. Biophys.
PUBLISHED: 04-12-2013
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Homeobox genes encode the class of transcription factors in vertebrates and are found in clusters called A, B, C, and D on four separate chromosomes. HOXA9 gene is part of the cluster A on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The objective of this study was to determine the HOXA9 gene expression in acute myeloid leukemia (AML). For this purpose, semi-quantitative reverse transcriptase-polymerase chain reaction was used to measure HOXA9 gene expression in human erythroleukemia (HEL) cell line and bone marrow mononuclear cells from 54 AML patients and 20 healthy individuals. The data show that HOXA9 mRNA expression was negative in 20 healthy individuals but was positive in HEL cells and in 22 out of 54 (40.74 %) AML patients. The complete remission rate (45.45 %) of the patients who expressed the gene was significantly lower than that (71.86 %) in patients who did not express the gene after chemotherapy. Therefore, it was concluded that HOXA9 gene might be involved in the pathogenesis of AML and played as a worse prognostic factor in AML.
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Hypermethylation and Clinicopathological Significance of RASAL1 Gene in Gastric Cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-09-2013
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Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer.
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[Practice and experience in early clinical education of dental students in preventive dentistry].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 04-05-2013
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To help dental students acquaint the medical environment, doctor-patient communication and relationship, early clinic education was arranged in our college of stomatology. The interesting topics were chosen to enhance the learning enthusiasm of the students in the teaching practice of preventive dentistry. Students were encouraged to practice the skill of doctor-patient communication. To obtain the satisfactory teaching effect and aim, it was important to pay attention to the aspects in the groups and clinical practice. Early clinic education in preventive dentistry help the students understand the specialty of preventive dentistry.
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Work related encounters in general practice.
Aust Fam Physician
PUBLISHED: 04-04-2013
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General practitioner participants in the BEACH (Bettering the Evaluation and Care of Health) program were asked to indicate which problems managed at the encounter were considered to be work related. From April 2007 to March 2012, at least one work related problem was managed at 2.7% of all encounters (11 429 encounters). A total of 16 045 problems were managed at these encounters, of which 11 911 (74.2%) were work related. Three-quarters (75.7%) of recorded work related encounters were claimable through workers compensation.
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Association between CYP1A1 polymorphisms and esophageal cancer: a meta-analysis.
Mol. Biol. Rep.
PUBLISHED: 03-12-2013
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Cytochrome P4501A1 (CYP1A1) enzyme is a member of the CYP superfamily of enzymes. CYP1A1 A2455G and T3801C are two most commonly studied polymorphisms loci. Previous studies have reported that CYP1A1 polymorphisms increase esophageal cancer (EC) risk. However, the results remain controversial and ambiguous. To further investigate the association between CYP1A1 polymorphisms (A2455G and T3801C) and EC risk. A meta-analysis was performed to investigate the association between CYP1A1 polymorphisms and EC risk. A total of 13 articles (A2455G and T3801C: 2 papers, A2455G: 8 papers, T3801C: 3 papers) from the PubMed containing information on the CYP1A1 polymorphisms and EC were included in this meta-analysis, with summational sample size of 1,881 EC cases and 3,786 controls. Stratified analysis was performed to evaluate the ethnicity (Caucasians and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) effect. No obvious publication bias in the two polymorphisms was observed. Our meta-analysis revealed a significant association between the A2455G polymorphism and EC (OR = 1.55 per A allele, 95 % CI 1.29-1.85, P < 0.001). Stratification analysis by ethnicity and histopathology type showed significant association in the population of Asian origin (OR = 1.55, 95 % CI 1.28-1.89, P < 0.001) and in histopathology type of ESCC (OR = 1.40, 95 % CI 1.19-1.65, P < 0.001). We didnt observe the significant association between CYP1A1 T3801C polymorphism and EC. We observed a difference of allele frequencies between Caucasian and Asian population in the meta-analysis. The allele frequencies in our meta-analysis were consistent with the allele frequencies in 1000 Genome Project. Our meta-analysis demonstrated distinct evidence that CYP1A1 A2455G polymorphism was associated with the risk of EC.
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Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats.
Br. J. Pharmacol.
PUBLISHED: 02-21-2013
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Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes. In this study we investigated whether TXNIP is involved in type 1 diabetes-associated NAFLD and whether antioxidants, quercetin and allopurinol, alleviate NAFLD by targeting TXNIP.
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Interobserver agreement of confocal laser endomicroscopy for bladder cancer.
J. Endourol.
PUBLISHED: 02-14-2013
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Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer.
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Atom-economical chemoselective synthesis of 1,4-enynes from terminal alkenes and propargylic alcohols catalyzed by Cu(OTf)2.
J. Org. Chem.
PUBLISHED: 02-13-2013
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A novel and efficient Cu(OTf)2-catalyzed sp(3)-sp(2) C-C bond formation reaction through the direct coupling of propargylic alcohols with terminal alkenes has been realized under mild conditions. The reaction is tolerant to air and is atom-economical, in accordance with the concept of modern green chemistry. The present protocol provides an attractive approach to a diverse range of 1,4-enynes in high to excellent yields.
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Synthesis, cytotoxicity, DNA binding and apoptosis of rhein-phosphonate derivatives as antitumor agents.
Int J Mol Sci
PUBLISHED: 01-31-2013
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Several rhein-phosphonate derivatives (5a-c) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 µM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA.
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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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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.