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Find video protocols related to scientific articles indexed in Pubmed.
Intramolecular annulation of aromatic rings with N-sulfonyl 1,2,3-triazoles: divergent synthesis of 3-methylene-2,3-dihydrobenzofurans and 3-methylene-2,3-dihydroindoles.
Chem. Commun. (Camb.)
PUBLISHED: 11-12-2014
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The controllable synthesis of 3-methylene-2,3-dihydrobenzofurans 2 and 3-methylene-2,3-dihydroindoles 5 has been developed through Rh-catalyzed intramolecular annulation of aromatic rings with azavinyl carbenes.
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Unprecedented synthesis of aza-bridged benzodioxepine derivatives through a tandem Rh(ii)-catalyzed 1,3-rearrangement/[3+2] cycloaddition of carbonyltriazoles.
Chem. Commun. (Camb.)
PUBLISHED: 11-10-2014
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Rh(ii)-catalyzed novel tandem intramolecular cycloisomerizations of aldehydes or ketones with 1-sulfonyl 1,2,3-triazoles have been disclosed, providing a facile protocol to access a series of functionalized aza-bridged benzodioxepine heterocycles.
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Protective Effect of Intestinal Ischemic Preconditioning on Ischemia Reperfusion-Caused Lung Injury in Rats.
Inflammation
PUBLISHED: 11-01-2014
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Intestinal ischemia reperfusion (IR) causes injury of distant critical organs. Remote intestinal ischemic preconditioning (IP) may confer the cytoprotection in critical organs including lung. The authors hypothesized that intestinal IP would be a prophylactic factor in the prevention of distant lung injury induced by IR. Rats were randomly divided into IR, IP, and Sham (S) group. Compared with IR group in the serum and lung tissue, MPO, MDA, TNF-?, and IL-1 levels were significantly decreased in the IP group. Following the same pattern, NO level in the serum and lung tissue was significantly increased in the IP group. And intestinal IP markedly abolished lung injury scores in contrast to IR group. Moreover, intestinal IP significantly attenuated caspase-3 expression, leading to the low expression of Bax and the high expression of Bcl-2. The present study showed that intestinal IP ameliorates the capacity of anti-oxygen free radical, inhibits the release of pro-inflammatory cytokines and alleviates apoptosis in IR-induced lung injury in rats. Intestinal IP may provide a novel prophylactic strategy for treatment of IR-induced lung injury.
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Metal-free aminoamidiniumation employing N-iodosuccinimide: facile syntheses of bicyclic imidazolidiniums and cyclic vicinal diamines.
Chem. Commun. (Camb.)
PUBLISHED: 10-21-2014
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NIS-mediated aminoamidiniumation has been developed for the syntheses of bicyclic imidazolidinium salts, which could be readily converted into cyclic vicinal diamines.
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Pin1 is Overexpressed and Correlates with Poor Prognosis in Gastric Cancer.
Cell Biochem. Biophys.
PUBLISHED: 10-05-2014
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The prolyl isomerase Pin1, which isomerizes the p-Ser/Thr-Pro peptide bonds and effects conformational and functional changes of the bound proteins, has been identified as a regulator of phosphorylation signaling in several diseases including cancer. The aim of this study is to determine the expression status of Pin1 in gastric cancer, its relationship between clinicopathologic features and patients' outcome. The mRNA levels of Pin1 in human normal and gastric cancer tissues were analyzed using the datasets from the publicly available Oncomine database ( www.oncomine.org ). Pin1 protein levels in human gastric cancer cells and tissues were analyzed by Western blot and immunohistochemistry staining, respectively. The Pin1 protein expression levels and its clinicopathologic correlations were investigated using tumor tissue microarray including 182 cases of human gastric cancer samples with survival information. Pin1 mRNA expression was found to be overexpressed in gastric cancer by using several datasets of Oncomine database analyzing. Pin1 protein expression is higher in 10 gastric cancer cell lines than that in normal gastric epithelial cell line GES-1. Pin1 positive expression was observed in 109 of 182 (59.9 %) gastric cancer samples and in 55 of 182 (30.2 %) normal gastric tissues (P < 0.001). Correlation analysis showed that high expression of Pin1 was significantly associated with pT (P = 0.017), pN (P = 0.043), TNM staging (P = 0.027), Lauren's classification (P < 0.001), as well as shorter overall survival in gastric cancer patients (29 mos vs. 47 mos. P = 0.048). Moreover, Pin1 expression, pT, and differentiation were independent prognostic factors of gastric cancer in Cox regression analysis. Pin1 is overexpressed in gastric cancer and correlates with clinicopathologic features, which might predict poor prognosis of gastric cancer patients.
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Enhancer of zeste homolog 2 is widely expressed in T-cell neoplasms, is associated with high proliferation rate and correlates with MYC and pSTAT3 expression in a subset of cases.
Leuk. Lymphoma
PUBLISHED: 09-30-2014
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Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator and H3k27-specific histone methyltransferase, is important for transcriptional regulation. EZH2 has been found to be overexpressed in B-cell lymphomas, as well as some T-cell lymphomas. Here we investigated the expression of EZH2 by immunohistochemical staining in a wide range of T-cell neoplasms. We found that EZH2 is highly expressed in all categories of T-cell neoplasia studied, and its expression strongly correlates with a high proliferation rate. Although up-regulation of EZH2 has been reported to be modulated by the pSTAT3-MYC pathway, our data indicate that EZH2 expression is correlated with MYC and/or pSTAT3 expression in only a subset of T-cell lymphomas, and that other mechanisms may control the overexpression of EZH2 in many T-cell lymphomas. The high level of EZH2 expression in T cell lymphomas suggest that these neoplasms may benefit from targeted treatment with a small molecule inhibitor of EZH2 currently in use in clinical trials.
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Function of interleukin?17 and ?35 in the blood of patients with hepatitis B?related liver cirrhosis.
Mol Med Rep
PUBLISHED: 09-18-2014
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Intrahepatic T helper (Th)17 cytokine and serum interleukin (IL)?17 levels in patients with hepatitis B are positively correlated with the progression of liver cirrhosis (LC). IL?35 can significantly inhibit the differentiation of Th17 cells and the synthesis of IL?17. The present study aimed to investigate the function and expression of IL?17 and IL?35 in the blood of patients with hepatitis B?related LC. The levels of IL?17 and IL?35 in the peripheral blood of 30 patients with chronic hepatitis B (CHB), 79 with LC, 14 with chronic severe hepatitis B (CSHB), and 20 normal controls were detected by ELISA. Quantitative polymerase chain reaction was used to evaluate Epstein?Barr virus?induced gene 3 (EBI3), forkhead box (FOX)P3 and IL?17 mRNA expression levels in peripheral blood mononuclear cells (PBMCs). Western blotting was used to determine protein expression. The liver function of patients and normal controls was measured. EBI3, IL?17 and FOXP3 mRNA expression levels in PBMCs from patients with LC, CHB and CSHB were higher than those in cells from the controls. IL?17 mRNA levels differed significantly according to the Child?Pugh classification and exhibited an upward trend over time in contrast to a downward trend for EBI3 and FOXP3 mRNA. The changes in protein expression in the peripheral blood were consistent with the changes in mRNA expression. Serum IL?17 levels were positively correlated with total bilirubin (TBIL), alanine aminotransferase (ALT) and Child?Pugh grade, and were negatively correlated with albumin. These observed differences were significant. Serum IL?35 levels were negatively correlated with albumin, but not with Child?Pugh grade, ALT and TBIL. IL?17 and IL?35 may be critically involved in the pathogenesis of hepatitis B?related LC.
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A Phosphine-Catalyzed Novel Asymmetric [3+2] Cycloaddition of C,N-Cyclic Azomethine Imines with ?-Substituted Allenoates.
Chemistry
PUBLISHED: 09-09-2014
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Catalytic asymmetric [3+2] cycloadditions of C,N-cyclic azomethine imines with ?-substituted allenoates have been developed in the presence of (S)-Me-f-KetalPhos, affording functionalized tetrahydroquinoline frameworks in good yields with high diastereo- and good enantioselectivities under mild condition. The substrate scope has been also examined. This is the first time that ?-substituted allenoates have been applied as a ?,?-C?C bond participated C2 synthon in asymmetric synthesis.
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One-pot tandem diastereoselective and enantioselective synthesis of functionalized oxindole-fused spiropyrazolidine frameworks.
Chemistry
PUBLISHED: 08-28-2014
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A highly efficient palladium(0)-catalyzed asymmetric [3+2] cycloaddition using 3-diazooxindoles serving as dipolarophiles affords functionalized pyrazolidine derivatives in an atom-economical way. In addition, by trapping the pyrazolidine derivatives with maleimides, the corresponding spiropyrazolidine oxindoles containing multiple stereogenic centers have been obtained in high yields along with moderate to good levels of diastereoselectivity and enantioselectivity under mild conditions. Thus, a novel three-component one-pot tandem reaction has been developed.
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Cinchona alkaloid squaramide/AgOAc cooperatively catalyzed diastereo- and enantioselective Mannich/cyclization cascade reaction of isocyanoacetates and cyclic trifluoromethyl ketimines.
Org. Lett.
PUBLISHED: 08-21-2014
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An efficient diastereo- and enantioselective Mannich-type/cyclization cascade reaction of ?-substituted isocyanoacetates and cyclic trifluoromethyl ketimines cooperatively catalyzed by cinchona alkaloid-derived multi-hydrogen-bonding donor squaramide and AgOAc has been investigated, affording the optically active trifluoromethyl-substituted tetrahydroimidazo[1,5-c]quinazoline derivatives in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >15:1 dr, up to 98% ee) under mild conditions.
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Phosphine-catalyzed annulations of 4,4-dicyano-2-methylenebut-3-enoates with maleimides and maleic anhydride.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-19-2014
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A novel phosphine-catalyzed [4+1] annulation of maleimides with 4,4-dicyano-2-methylenebut-3-enoates has been developed to afford spirocyclic products, and the maleimides serves as C1 ?synthons. Moreover, a phosphine-catalyzed formal [3+2] annulation between 4,4-dicyano-2-methylenebut-3-enoates and maleic anhydride has been also achieved, and maleic anhydride behaved as a C3 ?synthon in the reaction, thus efficiently affording the functionalized cyclopentenones. A stable phosphinium-containing zwitterionic compound is the key reactive intermediate in both annulations and was successfully isolated. Plausible mechanisms have been proposed on the basis of control experiments and deuterium-labeling experiments.
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Injection of MTX for the treatment of cesarean scar pregnancy: comparison between different methods.
Int J Clin Exp Med
PUBLISHED: 07-15-2014
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The aim of this study was to analyze clinical treatment and outcome of injection MTX for Cesarean scar pregnancy (CSP). We use retrospective study to compare the time in CSP of blood chorionic gonadotropin (?-HCG) and progesterone drooped to the normal, blood flow resistance and hospitalization days. 34 patients diagnosed with CSP were reviewed in our department from 2000 to 2013, including clinical characteristics, early diagnosis, treatment methods and treatment outcome. All patients were divided into B ultrasound-guided gestational MTX inject group (Group one), local intramuscular treatment group (Group two) and uterine artery perfusion MTX group (Group three). All cases had responded well to treatment. Except three cases of local intramuscular serum ?-HCG decreased slowly MTX 10 mg intramuscular again, the average serum ?-HCG decline of 65% the 4th day after treatment. In intramuscular group, the average length of stay is 19 ± 2.1 days. Serum ?-HCG, progesterone recovery time were 20 to 89 days, an average of 54.5 days. B ultrasound-guided group hospital stay were 15 ± 3.1 days, serum ?-HCG, progesterone recovery time were 18 to 71 days, an average of 44.5 days. In Uterine artery embolization group, the average length of stay is 16 ± 2.4 days, serum ?-HCG, progesterone recovery time were 20 to 70 days, an average of 45 days. Statistical data results using T-test and chi-square test analysis. Three groups of ?-HCG, progesterone decreased to normal days the difference was statistically significant (P < 0.05), but uterine artery embolization group and ultrasound-guided group B showed no significant difference (P > 0.05). B ultrasound-guided gestational injection of MTX and uterine artery embolization perfusion MTX are the better ways to treat uterine scar pregnancy.
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Phosphorescent Polymeric Nanoparticles by Coordination Cross-Linking as a Platform for Luminescence Imaging and Photodynamic Therapy.
Chemistry
PUBLISHED: 07-10-2014
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Water-soluble phosphorescent polymeric nanoparticles with an average diameter of approximately 100?nm were synthesized by a coordination cross-linking reaction. The pyridine blocks in poly(4-vinyl pyridine-b-ethylene oxide) (P4VP-b-PEO) were cross-linked by the iridium chloride-bridged dimer in DMF solution. Owing to the presence of an iridium complex with different ligands in the core of the polymeric nanoparticles, NP-1, NP-2, and NP-3 showed bright green, yellow, and red phosphorescence, respectively. PEG chains in the shell gave the polymeric nanoparticles solubility and biocompatibility, which was confirmed by an MTT assay using HeLa cells as a model cancer cell line. The flow cytometry and laser confocal fluorescence microscopy results revealed NP-2, as an example, could be effectively uptaken by HeLa cells. Therefore, these polymeric nanoparticles can be used as luminescent probes for living cells. In addition, (1) O2 could be effectively generated in the presence of NP-2 upon irradiation with visible light (?>400?nm, 300?mW?cm(-2) ), which was confirmed by a clear decrease in the fluorescence intensity of 9,10-dimethylanthracene (DMA). After incubation with NP-2 at a concentration of 200??g?mL(-1) for 6?h, approximately 90?% of HeLa cells were effectively ablated upon irradiation with visible light for only 10?min, indicating the potential for photodynamic therapy with polymeric nanoparticles.
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Phosphine-catalyzed asymmetric [4+1] annulation of activated ?,?-unsaturated ketones with Morita-Baylis-Hillman carbonates: enantioselective synthesis of spirooxindoles containing two adjacent quaternary stereocenters.
Chem. Commun. (Camb.)
PUBLISHED: 07-01-2014
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The asymmetric [4+1] annulation of activated ?,?-unsaturated ketones with MBH carbonates catalyzed by bifunctional thiourea-phosphine catalysts derived from an axially chiral binaphthyl scaffold has been developed, giving spirooxindoles with two adjacent quaternary stereocenters in good yields with high enantioselectivities and moderate diastereoselectivities under mild conditions.
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A novel KLF4/LDHA signaling pathway regulates aerobic glycolysis in and progression of pancreatic cancer.
Clin. Cancer Res.
PUBLISHED: 06-19-2014
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Krüppel-like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its effect on aerobic glycolysis in pancreatic tumors. Therefore, we investigated the clinical significance, biologic effects, and mechanisms of dysregulated KLF4 signaling in aerobic glycolysis in pancreatic cancer cells.
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The miR156-SPL9-DFR pathway coordinates the relationship between development and abiotic stress tolerance in plants.
Plant J.
PUBLISHED: 06-15-2014
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Young organisms have relatively strong resistance to diseases and adverse conditions. When confronted with adversity, the process of development is delayed in plants. This phenomenon is thought to result from the rebalancing of energy, which helps plants coordinate the relationship between development and stress tolerance. However, the molecular mechanism underlying this phenomenon remains mysterious. In this study, we found that miR156 integrates environmental signals to ensure timely flowering, thus enabling the completion of breeding. Under stress conditions, miR156 is induced to maintain the plant in the juvenile state for a relatively long period of time, while under good conditions, miR156 is suppressed to accelerate the developmental transition. Blocking the miR156 signaling pathway in Arabidopsis thaliana with 35S::MIM156 (via target mimicry) increased the plant's sensitivity to stress treatment, while overexpression of miR156 increased stress tolerance. In fact, this mechanism is also conserved in rice. We also identified downstream genes of miR156, i.e., SQUAMOSA PROMOTER BINDING PROTEIN-LIKE9 (SPL9) and DIHYDROFLAVONOL-4-REDUCTASE (DFR), which take part in this process by influencing the metabolism of anthocyanin. Our results uncover a molecular mechanism for plant adaptation to the environment through the miR156-SPLs-DFR pathway, which coordinates development and abiotic stress tolerance. This article is protected by copyright. All rights reserved.
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Targeted discovery and validation of plasma biomarkers of Parkinson's disease.
J. Proteome Res.
PUBLISHED: 06-11-2014
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Despite extensive research, an unmet need remains for protein biomarkers of Parkinson's disease (PD) in peripheral body fluids, especially blood, which is easily accessible clinically. The discovery of such biomarkers is challenging, however, due to the enormous complexity and huge dynamic range of human blood proteins, which are derived from nearly all organ systems, with those originating specifically from the central nervous system (CNS) being exceptionally low in abundance. In this investigation of a relatively large cohort (?300 subjects), selected reaction monitoring (SRM) assays (a targeted approach) were used to probe plasma peptides derived from glycoproteins previously found to be altered in the CNS based on PD diagnosis or severity. Next, the detected peptides were interrogated for their diagnostic sensitivity and specificity as well as the correlation with PD severity, as determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The results revealed that 12 of the 50 candidate glycopeptides were reliably and consistently identified in plasma samples, with three of them displaying significant differences among diagnostic groups. A combination of four peptides (derived from PRNP, HSPG2, MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753 (sensitivity: 90.4%; specificity: 50.0%). Additionally, combining two peptides (derived from MEGF8 and ICAM1) yielded significant correlation with PD severity, that is, UPDRS (r = 0.293, p = 0.004). The significance of these results is at least two-fold: (1) it is possible to use a targeted approach to identify otherwise very difficult to detect CNS related biomarkers in peripheral blood and (2) the novel biomarkers, if validated in independent cohorts, can be employed to assist with clinical diagnosis of PD as well as monitoring disease progression.
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Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin?induced Src activation in gastric cancer cells.
Mol Med Rep
PUBLISHED: 05-29-2014
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Oxaliplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat, are potent antitumor agents. The aim of this study was to investigate the effect of SAHA on the antitumor efficacy of oxaliplatin in gastric cancer and the interaction between oxaliplatin and SAHA. Cell growth inhibition was evaluated using Cell Counting Kit?8 and colony formation assays. Xenografts established in nude mice were used to assess tumor growth in vivo. Western blot analysis was used to detect the expression of acetyl?histone H3, phosphorylated histone H2AX (?H2AX), B?cell lymphoma 2 (Bcl?2), cleaved caspase?3, cleaved poly (ADP?ribose) polymerase (PARP), phosphorylated- (p-)Src, Src, Akt and p?Akt in gastric cancer cells. The in vitro growth of SGC?7901, Hs746T and MKN28 gastric cancer cells was found to be dose?dependently inhibited by oxaliplatin and SAHA. Furthermore, combined treatment was observed to be more effective in inhibiting cancer cell growth and colony formation than monotherapy. Similar effects were found in the xenografts. A positive interaction was identified between oxaliplatin and SAHA (between?subject effects of oxaliplatin and SAHA, P<0.001). In addition, combined exposure to oxaliplatin and SAHA increased ?H2AX expression and decreased Bcl?2 expression. The expression of cleaved caspase?3 and PARP was also increased with combination treatment. Oxaliplatin?induced Src phosphorylation was detected in gastric cancer cells, as we have previously reported. However, this effect was inhibited by SAHA. The oxaliplatin?induced Src phosphorylation was not impaired with Akt inhibition. In conclusion, oxaliplatin and SAHA exhibited a positive interaction when used in combination and were found to suppress gastric cancer cell survival and growth. The reversal of oxaliplatin?induced Src activation may be responsible for this positive interaction.
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Chronic intermittent hypobaric hypoxia ameliorates ischemia/reperfusion-induced calcium overload in heart via Na/Ca2+ exchanger in developing rats.
Cell. Physiol. Biochem.
PUBLISHED: 05-16-2014
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Chronic intermittent hypobaric hypoxia (CIHH) protects the heart against ischemia/reperfusion (I/R) injury. This study investigated the calcium homeostasis mechanism and the role of Na(+)/Ca(2+) exchanger (NCX) in the cardiac protective effect of CIHH in developing rats.
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Plasma exosomal ?-synuclein is likely CNS-derived and increased in Parkinson's disease.
Acta Neuropathol.
PUBLISHED: 05-13-2014
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Extracellular ?-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum ?-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived ?-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled ?-synuclein into mouse brain, that CSF ?-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of ?-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF ?-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal ?-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF ?-synuclein, a significant correlation between plasma exosomal ?-synuclein and disease severity (r = 0.176, p = 0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal ?-synuclein were comparable to those determined by CSF ?-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS ?-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.
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Catalyst-dependent divergent synthesis of pyrroles from 3-alkynyl imine derivatives: a noncarbonylative and carbonylative approach.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-13-2014
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A novel Ru(0)- and Rh(I)-catalyzed noncarbonylative and carbonylative cycloisomerization of readily available 3-alkynyl imine derivatives has been developed to provide 3,4-fused or nonfused pyrrole derivatives efficiently in moderate to excellent yields. The key steps involve the formation of a ruthenium carbenoid intermediate or a rhodacycle intermediate, respectively. In these reactions, CO can serve as a ligand or a reagent.
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Disentangling pooled triad genotypes for association studies.
Ann. Hum. Genet.
PUBLISHED: 05-05-2014
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Association studies that genotype affected offspring and their parents (triads) offer robustness to genetic population structure while enabling assessments of maternal effects, parent-of-origin effects, and gene-by-environment interaction. We propose case-parents designs that use pooled DNA specimens to make economical use of limited available specimens. One can markedly reduce the number of genotyping assays required by randomly partitioning the case-parent triads into pooling sets of h triads each and creating three pools from every pooling set, one pool each for mothers, fathers, and offspring. Maximum-likelihood estimation of relative risk parameters proceeds via log-linear modeling using the expectation-maximization algorithm. The approach can assess offspring and maternal genetic effects and accommodate genotyping errors and missing genotypes. We compare the power of our proposed analysis for testing offspring and maternal genetic effects to that based on a difference approach and that of the gold standard based on individual genotypes, under a range of allele frequencies, missing parent proportions, and genotyping error rates. Power calculations show that the pooling strategies cause only modest reductions in power if genotyping errors are low, while reducing genotyping costs and conserving limited specimens.
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Clinical efficacy and safety of traditional Chinese medicine combined with Western Medicine in patients with diabetic acute ischemic stroke.
J Tradit Chin Med
PUBLISHED: 05-03-2014
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To observe the clinical efficacy and safety of Traditional Chinese Medicine (TCM) combined with Western Medicine (WM) in patients with diabetic acute ischemic stroke.
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Thoracoscopic resection of a vagal schwannoma in the superior mediastinum: A case report.
Oncol Lett
PUBLISHED: 04-16-2014
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Neurogenic tumors are the most common type of mediastinal tumor and constitute the majority of neoplasms of the posterior mediastinum. Schwannomas originating from the intrathoracic vagus nerve are extremely rare. The present study describes the case of a 58-year-old man with a large vagal schwannoma in the left superior mediastinum. A large tumor with a round shape was identified in the left superior mediastinum. The tumor originated from and encased the vagus nerve. Using video-assisted thoracoscopic surgery, the tumor was completely excised with amputation of the vagus nerve encased within in the tumor. One year post-surgery, the patient was free of recurrence with no symptoms other than hoarseness.
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Asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)-piperidine-2 carboxylates.
Org. Biomol. Chem.
PUBLISHED: 04-14-2014
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We developed an asymmetric organocatalytic synthesis of 4,6-bis(1H-indole-3-yl)-piperidine-2-carboxylates using 10 mol% of a chiral phosphoric acid. The products, which are novel bisindole-piperidine-amino acid hybrids, can be obtained in one step from 3-vinyl indoles with imino esters in dichloromethane at room temperature after 1 h of reaction time. A variety of these compounds could be synthesized in up to 70% yield and 99% ee, and they were experimentally and computationally analyzed regarding their relative and absolute stereochemistry.
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(DHQ)2AQN-catalyzed asymmetric substitution of isatin-derived hydrazones with O-Boc-protected Morita-Baylis-Hillman adducts: A strategy for synthesizing enantioenriched azo compounds incorporating an oxindole scaffold.
J. Org. Chem.
PUBLISHED: 04-02-2014
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The first example for the preparation of enantioenriched azo compounds from hydrazones and Morita-Baylis-Hillman adducts has been developed, affording azo compounds incorporating an oxindole scaffold in up to 91% yield along with a 93% ee value under the catalysis of (DHQ)2AQN.
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Proteomic analysis of saliva from patients with oral chronic graft-versus-host disease.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-26-2014
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Chronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa, including the salivary glands, is affected in the majority of patients with cGVHD; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from patients with and without oral cGVHD-cGVHD(+) and cGVHD(-), respectively-using isobaric tags for relative and absolute quantification labeling, followed by tandem mass spectrometry. Among 249 salivary proteins identified by tandem mass spectrometry, 82 exhibited altered expression in the oral cGVHD(+) group compared with the cGVHD(-) group. Many of the identified proteins function in innate or acquired immunity, or are associated with tissue maintenance functions, such as proteolysis or the cytoskeleton. Using ELISA immunoassays, we further confirmed that 2 of these proteins, IL-1 receptor antagonist and cystatin B, showed decreased expression in patients with active oral cGVHD (P < .003). Receiver operating curve characteristic analysis revealed that these 2 markers were able to distinguish oral cGVHD with a sensitivity of 85% and specificity of 60%, and showed slightly better discrimination in newly diagnosed patients evaluated within 12 months of allo-HSCT (sensitivity, 92%; specificity 73%). In addition to identifying novel potential salivary cGVHD biomarkers, our study demonstrates that there is coordinated regulation of protein families involved in inflammation, antimicrobial defense, and tissue protection in oral cGVHD that also may reflect changes in salivary gland function and damage to the oral mucosa.
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Effects of methyl jasmonate and salicylic acid on tanshinone production and biosynthetic gene expression in transgenic Salvia miltiorrhiza hairy roots.
Biotechnol. Appl. Biochem.
PUBLISHED: 03-25-2014
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Tanshinone is a group of active diterpenes, which are widely used in the treatment of cardiovascular disease. In this study, methyl jasmonate (MJ) and salicylic acid (SA) were used to investigate their effects on tanshinone accumulation and biosynthetic gene expression in the hairy roots of geranylgeranyl diphosphate synthase (SmGGPPS) overexpression line (G50) in Salvia miltiorrhiza. High-performance liquid chromatography analysis showed that total tanshinone content in G50 was obviously increased by 3.10-fold (11.33 mg/g) with MJ at 36 H and 1.63 times (5.95 mg/g) after SA treatment for 36 H in comparison with their mimic treatment control. Furthermore, quantitative reverse-transcription PCR analysis showed that the expression of isopentenyl-diphosphate delta-isomerase (SmIPPI), SmGGPPS, copalyl diphosphate synthase (SmCPS), and kaurene synthase-like (SmKSL) increased significantly with MJ treatment. However, the expression of SmIPPI reached the highest level at 144 H, whereas those of SmGGPPS, SmCPS, and SmKSL only increased slightly with SA treatment. The two elicitor treatments suggested that tanshinone accumulation positively correlated to the expression of key genes such as SmGGPPS, SmCPS, and SmKSL. Meanwhile, the study also indicated that it was a feasible strategy to combine elicitor treatment with transgenic technology for the enhancement of tanshinone, which paved the way for further metabolic engineering of tanshinone biosynthesis.
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Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on colon cancer.
Cancer Lett.
PUBLISHED: 03-22-2014
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Inhibitory effects and potential mechanisms of capecitabine metronomic chemotherapy on colon cancer were investigated in this study. Metronomic chemotherapy with fluorouracil or capecitabine inhibited proliferation of colon cancer cells both in vitro and in vivo. Capecitabine metronomic chemotherapy demonstrated equal effects as CTX metronomic chemotherapy. Metronomic capecitabine or CTX chemotherapy decreased vascular endothelial growth factor (VEGF) but elevated thrombospondin-1 (TSP-1) expression, reduced CEP levels and decreased microvessel density (MVD). These results indicated anti-angiogenesis may be correlated with the antitumor effects of metronomic capecitabine in colon cancer.
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Highly Efficient and Stereoselective Construction of Bispirooxindole Derivatives via a Three-Component 1,3-Dipolar Cycloaddition Reaction.
ChemistryOpen
PUBLISHED: 03-13-2014
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A highly regio- and stereoselective synthesis of bispirooxindoles by 1,3-dipolar cycloaddition of in situ generated azomethine ylides from isatin and proline to different electron-deficient alkenes has been developed. The synthesis affords the desired bispiro scaffold compounds in excellent yields with high regioselectivity under mild conditions. The stereochemistry was determined by single-crystal X-ray analysis.
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Increased accumulation of the cardio-cerebrovascular disease treatment drug tanshinone in Salvia miltiorrhiza hairy roots by the enzymes 3-hydroxy-3-methylglutaryl CoA reductase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
Funct. Integr. Genomics
PUBLISHED: 03-12-2014
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Tanshinone is widely used for treatment of cardio-cerebrovascular diseases with increasing demand. Herein, key enzyme genes SmHMGR (3-hydroxy-3-methylglutaryl CoA reductase) and SmDXR (1-deoxy-D-xylulose 5-phosphate reductoisomerase) involved in the tanshinone biosynthetic pathway were introduced into Salvia miltiorrhiza (Sm) hairy roots to enhance tanshinone production. Over-expression of SmHMGR or SmDXR in hairy root lines can significantly enhance the yield of tanshinone. Transgenic hairy root lines co-expressing HMGR and DXR (HD lines) produced evidently higher levels of total tanshinone (TT) compared with the control and single gene transformed lines. The highest tanshinone production was observed in HD42 with the concentration of 3.25 mg g(-1) DW. Furthermore, the transgenic hairy roots showed higher antioxidant activity than control. In addition, transgenic hairy root harboring HMGR and DXR (HD42) exhibited higher tanshinone content after elicitation by yeast extract and/or Ag(+) than before. Tanshinone can be significantly enhanced to 5.858, 6.716, and 4.426 mg g(-1) DW by YE, Ag(+), and YE-Ag(+) treatment compared with non-induced HD42, respectively. The content of cryptotanshinone and dihydrotanshinone was effectively elevated upon elicitor treatments, whereas there was no obvious promotion effect for the other two compounds tanshinone I and tanshinone IIA. Our results provide a useful strategy to improve tanshinone content as well as other natural active products by combination of genetic engineering with elicitors.
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Rhodium(II)-catalyzed intramolecular cycloisomerizations of methylenecyclopropanes with N-sulfonyl 1,2,3-triazoles.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-25-2014
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A novel rhodium(II)-catalyzed tandem cycloisomerization of methylenecyclopropanes (MCPs) with N-sulfonyl 1,2,3-triazoles is disclosed. The reaction produces a series of highly functionalized polycyclic N?heterocycles via a rhodium imino carbene intermediate. A distinct feature of this divergent synthesis is that different types of substrates control the reaction pathways. Moreover, several interesting transformations of these products to construct diazabicyclo[3.2.1]octane derivatives are also reported.
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Applications of chiral phosphine-based organocatalysts in catalytic asymmetric reactions.
Chem Asian J
PUBLISHED: 02-24-2014
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Chiral phosphines are versatile Lewis basic catalysts that are capable of promoting a wide range of asymmetric reactions. In particular, recently designed chiral phosphines based on the concept of bi-/multifunctionality have been demonstrated to be effective catalysts for many types of asymmetric reactions, such as (aza)-MBH reactions, cycloaddition reactions, and nucleophilic addition reactions. This short overview summarizes the recent advances in this field and highlights the most-significant achievements.
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A novel PI3K inhibitor displays potent preclinical activity against an androgen-independent and PTEN-deficient prostate cancer model established from the cell line PC3.
Toxicol. Lett.
PUBLISHED: 02-15-2014
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Recent studies demonstrated that targeting the phosphatidylinositide 3-kinase (PI3K)/AKT signaling pathway is a major strategy for the treatment of androgen-independent prostate cancer. In the present study, we developed an analog BENC-511 from a recently reported PI3K inhibitor S14161 by structural optimization. Using PC3 and DU145 as the model cell lines, we found PTEN-deficient PC3 cells were more sensitive than PTEN-expressing DU145 ones in terms of cell proliferation, apoptosis, and caspase-3 activation. These findings were consistent with the inhibition on PI3K/AKT signals. BENC-511 preferably suppressed AKT activation in PC3 over DU145 cells. Notably, PTEN restoration attenuated BENC-511 induced apoptosis. Moreover, BENC-511 displayed great therapeutic efficacy in a PC3-derived prostate cancer model in nude mice. With an oral dosage of 50mg/kg, BENC-511 decreased tumor growth more than 50% in 27 days, which was accompanied with PARP cleavage, but did not show overt toxicity. This study lays a solid rationale for the development of BENC-511 as a drug for the treatment of PTEN-deficient and androgen-independent prostate cancers.
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Signal amplification in capillary electrophoresis based chemiluminescent immunoassays by using an antibody-gold nanoparticle-DNAzyme assembly.
Talanta
PUBLISHED: 02-09-2014
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A signal amplification strategy based on antibody-gold nanoparticle-DNAzyme assembly in capillary electrophoresis based chemiluminescent immunoassays (CE-CLIA) was developed. In this CE-CLIA, antibody-AuNP-G-quadruplex/hemin was incubated with limited amount of antigen, and the formed immunocomplex and unreacted antibody-AuNP-G-quadruplex/hemin were then separated by CE and detected by CL. Due to the strong CL catalytic ability of G-quadruplex/hemin DNAzyme and a high loading ratio of DNAzyme on each AuNP, the assay was very sensitive. By taking carbohydrate antigen 19-9 (CA19-9), one of the most important carbohydrate tumor marker as the model analyte, the proposed CE-CLIA method for CA19-9 detection showed a linear range from 0.025 to 1.00 U/mL with a detection limit of 0.016 U/mL (signal/noise=3), which was more sensitive than the methods previously reported for CA19-9 quantification. The method was applied to quantify CA19-9 in human serum samples, and analytical results were in a good agreement with those obtained by using an established ELISA method.
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Capecitabine plus irinotecan versus 5-FU/leucovorin plus irinotecan in the treatment of colorectal cancer: a meta-analysis.
Clin Colorectal Cancer
PUBLISHED: 01-28-2014
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The XELIRI regimen and FOLFIRI regimen are used as the first-line treatment of metastatic colorectal cancer. A comparison of findings from different studies that examined the efficacy and safety of these 2 regimens often show conflicting results. This metaanalysis compared the XELIRI and FOLFIRI regimens in the treatment of mCRC.
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Rhodium(II)-catalyzed intramolecular annulation of 1-sulfonyl-1,2,3-triazoles with pyrrole and indole rings: facile synthesis of N-bridgehead azepine skeletons.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-27-2014
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A convenient and efficient synthetic method has been developed to construct highly functionalized N-bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular C-H functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.
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A novel in situ gel formulation of ranitidine for oral sustained delivery.
Biomol Ther (Seoul)
PUBLISHED: 01-26-2014
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The main purpose of this study was to develop a novel, in situ gel system for sustained delivery of ranitidine hydrochloride. Ranitidine in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of preparation, viscosity and in vitro release. The viscosity of the gellan gum formulations in solution increased with increasing concentrations of gellan gum. In vitro study showed that the release of ranitidine from these gels was characterized by an initial phase of high release (burst effect) and translated to the second phase of moderate release. Single photon emission computing tomography technique was used to evaluate the stomach residence time of gel containing (99m)Tc tracer. The animal experiment suggested in situ gel had feasibility of forming gels in stomach and sustained the ranitidine release from the gels over the period of at least 8 h. In conclusion, the in situ gel system is a promising approach for the oral delivery of ranitidine for the therapeutic effects improvement.
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Thyroid lymphoma on a background of Hashimoto's thyroiditis: PET/CT appearances.
Clin Imaging
PUBLISHED: 01-21-2014
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Primary thyroid lymphoma is a rare thyroid tumor accounting for only 5% of all thyroid malignancies. It is more common in patients with a background history of chronic thyroiditis. PET/CT is helpful in the initial staging and for follow up to assess treatment response.
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Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma.
Oncol. Rep.
PUBLISHED: 01-09-2014
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer worldwide. In the present study, we investigated the diagnostic and biological significance of microRNA-194 (miR-194) in PDAC. miRNA expression profiling of human PDACs and adjacent normal pancreatic tissues identified a total of 16 genes including miR-194 with >1.15-fold expression changes (8 overexpressed and 8 underexpressed). Quantitative real-time polymerase chain reaction (PCR) revealed elevation of serum miR-194 levels were significantly greater in PDAC patients than in duodenal adenocarcinoma patients and healthy controls. Receiver operating characteristic analysis demonstrated that serum miR-194 had a sensitivity of 54.3% and a specificity of 57.5% for discriminating PDAC patients from healthy controls. Combined analysis of the 3 groups yielded a sensitivity of 84.0 and a specificity of 75.0% for the combined detection of miR-192 and miR-194 in the diagnosis of PDAC. Ectopic expression of miR-194 in PANC-1 pancreatic cancer cells enhanced cell proliferation, migration and colony formation, which was coupled with decreased expression of the tumor suppressor DACH1. miR-194 overexpression increased tumor growth and local invasion and suppressed the expression of DACH1 in an orthotopic pancreatic cancer mouse model. In conclusion, upregulation of miR-194 contributes to tumor growth and progression in PDAC, possibly through suppression of DACH1. However, serum miR-194 has a low capacity for detection of PDAC. Combined detection of serum miR-192 and miR-194 levels may serve as a sensitive diagnostic biomarker for PDAC.
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Molecular Identification of Two Prophenoloxidase-Activating Proteases From the Hemocytes of Plutella xylostella (Lepidoptera: Plutellidae) and Their Transcript Abundance Changes in Response to Microbial Challenges.
J. Insect Sci.
PUBLISHED: 01-01-2014
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The phenoloxidase (PO) activation system plays an important role in insect innate immunity, particularly in wound healing and pathogen defense. A key member of this system is prophenoloxidase-activating protease (PAP), which is the direct activator of prophenoloxidase (proPO). Despite their importance in the insect PO activation system, content of studies is limited. In this article, we identify two complementary DNAs (cDNAs), PxPAPa and PxPAPb, encoding possible PAPs, from immunized larval hemocytes of the diamondback moth, Plutella xylostella (L.), by RACE method. PxPAPa is 1,149-bp long and encodes a 382-residue open reading frame (ORF) with a predicted 17-residue signal peptide, a clip domain, and a Tryp_Spc domain. PxPAPb is 1,650-bp long and encodes a 440-residue ORF with a predicted 20-residue signal peptide, two clip domains, and a Tryp_Spc domain. PxPAPa and PxPAPb have a high sequence similarity to Manduca sexta (L.) PAP1 and PAP3, respectively. We also examined the transcript patterns of PxPAPa, PxPAPb, and pxPAP3, another clip-domain serine protease gene, response to different microbial challenges by using real-time quantitative polymerase chain reaction. The results show that the transcript abundance of PxPAPa is significantly increased by Micrococcus luteus and Escherichia coli but not Candida albicans. PxPAPb is induced only by Mi. luteus, whereas pxPAP3 could be induced by all the microbes in the test, but the transcript patterns of Mi. luteus, E. coli, and C. albicans are completely different. This study provides new insights into the molecular events that occur during the immune response, particularly melanization cascade that is involved in encapsulation and nodulation of pathogen or parasite invaders via hemocytes in host insects.
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KRAS and DAXX/ATRX gene mutations are correlated with the clinicopathological features, advanced diseases, and poor prognosis in chinese patients with pancreatic neuroendocrine tumors.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Pancreatic neuroendocrine tumor (pNET) is a clinically rare and heterogeneous group of tumors; its pharmacogenetic characteristics are not fully understood. This study was designed to examine the relationship between key gene variations and disease development and prognosis among Chinese patients with pNET.
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Clinical observation of laparoscopic radical hysterectomy for cervical cancer.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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To evaluate safety, feasibility and the improvement of surgical method of laparoscopic extensive hysterectomy and pelvic lymph node dissection in patients with early-stage cervical cancer. Clinical data were prospectively collected from patients with IA2-IIA cervical cancer who underwent laparoscopic extensive hysterectomy (n1=22) and laparotomy (n2=23) in Department of Obstetrics and Gynecology in the Subei People's Hospital from June 2010 to August 2013. The successful rates in two groups of operation were 100%. Blood loss, postoperative hospital stay, complication rate, postoperative recovery of gastrointestinal tract and bladder function of the laparoscopy group of the laparoscopic group were all better than those of the laparotomy group, and there were significant differences (all P < 0.05). But in the laparoscopy group, the operative time was longer than the laparotomy group with statistical significance (P < 0.05). There was no statistically significant difference in the number of excised lymph nodes and the duration time of postoperative urinary catheterization between the two groups (P > 0.05). Laparoscopic extensive hysterectomy and pelvic lymph node dissection can fully meet the requirement of laparotomy. It has the properties of minor trauma and rapid recovery. The clinical efficacy is superior to laparotomy surgery. The results indicated laparoscopic is an ideal method for the treatment of early cervical cancer.
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Acute and subacute toxicity of the extract of Aristolochiae Fructus and honey-fried Aristolochiae Fructus in rodents.
Biol. Pharm. Bull.
PUBLISHED: 12-26-2013
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Aristolochiae Fructus (AF) and honey-fried Aristolochiae Fructus (HAF) have been used in China for thousands of years as an anti-tussive and expectorant drug. Few clinical cases were reported associated with the toxicity of AF and HAF, although relatively high contents of aristolochic acids (AAs) were found in them. This work was designed to compare the acute and subacute toxicity of AF and HAF in order to provide references for safe clinical use and to evaluate the possibility of reducing toxicity of AF by honey-processing. The extracts of the herb were fed to mice or rats via gastric tube. Various toxic signs and symptoms, body weights, serum biochemical assay, organ weights and histopathology were used to evaluate the toxic effects. The median lethal dose (LD50) of AF and HAF are 34.1 ± 7.2 g/kg/d and 62.6 ± 8.0 g/kg/d with a 95% average trustable probability (P = 0.95), respectively. The subacute results showed a dose-dependant relationship of the toxicity of AF and HAF. Even in the high dose groups, only moderate toxicity was observed. Honey-frying and decoction with water can decrease the contents of AAs, and attenuate the toxic effects of AF. But sufficient attention should be still paid to the safety of AF and HAF due to the existence of AAs.
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Blockage of STAT3 Signaling Pathway with a Decoy Oligodeoxynucleotide Inhibits Growth of Human Ovarian Cancer Cells.
Cancer Invest.
PUBLISHED: 12-14-2013
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Transcription factor decoy oligodeoxynucleotides (ODN) represent a novel tool for targeted inhibition of the STAT3 signaling pathway. To investigate its therapeutic potential in ovarian cancer, a double-stranded decoy ODN mimicking STAT3-specific cis-elements was transfected into two ovarian cancer cell lines OVCAR3 and SKOV3. The STAT3 decoy ODN treatment specifically blocked STAT3 signaling, and inhibited cell proliferation by inducing apoptosis and cell cycle arrest. These results suggest that targeted blockade of the STAT3 signaling pathway with a decoy ODN may represent a potential therapeutic approach in the treatment of ovarian cancer.
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Regulation of photosynthetic performance and antioxidant capacity by (60)Co ?-irradiation in Zizania latifolia plants.
J Environ Radioact
PUBLISHED: 11-10-2013
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The aim of the present work was to investigate the photosynthetic performance and antioxidant enzyme activities in response to ?-irradiation of an aquatic plant Zizania latifolia. The Z. latifolia seedlings at 6-leaf stage were exposed to 25, 50 and 100 Gy of ? rays from a (60)Co source. The growth parameters, chlorophyll contents, photosynthetic gas exchange, chlorophyll fluorescence, malondialdehyde (MDA) content, antioxidant enzyme activities and antioxidant contents were examined at 1-5 weeks post-irradiation (WPI). The results showed that plant height, leaf number and tiller (branch close to ground) number were significantly suppressed by 50 and 100 Gy irradiation at 5, 3-5 and 4-5 WPI, respectively, but they were not significantly different from control by 25 Gy irradiation. Chlorophyll a, chlorophyll b, and total chlorophyll contents were also found to be significantly decreased by irradiation. The net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci) and transpiration rate (Tr) generally declined in a dose-dependent manner. As for the chlorophyll fluorescence parameters, maximum quantum efficiency of PSII photochemistry (Fv/Fm), actual photochemical efficiency of PSII (?PSII) and photochemical quenching (qP) were observed to be significantly decreased compared to the control at 3 WPI, while non-photochemical quenching (NPQ) significantly increased by 100 Gy. ?-irradiation induced substantial increase in MDA content, ascorbate peroxidase (APX) activity, reduced ascorbate (AsA) content and reduced glutathione (GSH) content, suggesting a protective mechanism of Z. latifolia plant against oxidative stress when exposed to ?-irradiation.
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Gold-Catalyzed Tandem Reactions of Methylenecyclopropanes and Vinylidenecyclopropanes.
Acc. Chem. Res.
PUBLISHED: 10-30-2013
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Gold catalysis is often the key step in the synthesis of natural products, and is a powerful tool for tandem or domino reaction processes. Both gold salts and complexes are among the most powerful soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds toward a variety of nucleophiles. The core of these reactions relies on the interaction between gold catalysts and ?-bonds of alkenes, alkynes, and allenes. Activation of functional groups by gold complexes provides a useful and important method for facilitating many different organic transformations with high atom efficiency. Although they are highly strained, methylenecyclopropanes (MCPs) and vinylidenecyclopropanes (VDCPs) are readily accessible molecules that have served as useful building blocks in organic synthesis. Because of their unique structural and electronic properties, significant developments have been made in the presence of transition metal catalysts such as nickel, rhodium, palladium, and ruthenium during the past decades. However, less attention has been paid to the gold-catalyzed chemistry of MCPs and VDCPs. In this Account, we describe gold-catalyzed chemical transformations of MCPs and VDCPs developed both in our laboratory and by other researchers. Chemists have demonstrated that MCPs and VDCPs have amphiphilic properties. When MCPs or VDCPs are activated by a gold catalyst, subsequent nucleophilic attack by other reagents or ring-opening (ring-expansion) of the cyclopropane moiety will occur. However, the C-C double bonds of MCPs and VDCPs can also serve as nucleophilic reagents while more electrophilic reagents are present and activated by gold catalyst, and then further cascade reactions take place as triggered by the release of ring strain of cyclopropane. Based on this strategy, both our group and others have found some interesting gold-catalyzed transformations in recent years. These transformations of MCPs and VDCPs can produce a variety of polycyclic and heterocyclic structures, containing different sized skeletons. Moreover, we have carried out some isotopic labeling experiments and computational studies for mechanistic investigation. These reactions always give the desired products with high level control of chemo-, regio-, and diastereoselectivities, making them highly valuable for the synthesis of natural products and to the pharmaceutical industry and medicine in general.
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Reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles for doxorubicin delivery.
Biomaterials
PUBLISHED: 09-27-2013
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We report a reducible copolymer self-assembled with superparamagnetic iron oxide nanoparticles (SPIONs) to deliver doxorubicin (DOX) for cancer therapy. The copolymer of reducible polyamidoamine (rPAA) with poly(ethylene glycol)(PEG)/dodecyl amine graft was synthesized by Michael addition. rPAA@SPIONs were formed by the alkyl grafts of reducible copolymers intercalated with the oleic acid layer capped on the surface of magnetite nanocrystals. The intercalating area formed a reservoir for hydrophobic anti-cancer drug (DOX), whilst the PEG moiety in the copolymers helped the nanoparticle well-dispersible in aqueous solution. We employed two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman (CARS) to investigate drug delivery in intra-cellular structures of live cells, and used Vivaview(®) technique to show real-time inhibition efficacy of nanoparticles in live cells. rPAA@SPIONs present efficiently drug loading with reducible responsibility in vitro tests. Finally, rPAA@SPIONs were tested in mice with xenograft MDA-MB-231 breast tumor though i.v. injection and inhibited tumor growth efficiently. MRI was used to monitor nanoparticles aggregation in tumor site. Histology and Prussian blue on kidney, liver, and heart in mice indicated that DOX/rPAA@SPIONs showed no significant toxicity for mice organs after 24 days treatment.
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[Clinicopathologic characteristics of fibrous mass-forming chronic pancreatitis].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 09-25-2013
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To investigate clinicopathological features of fibrous mass-forming chronic pancreatitis (FMCP), to compare clinicopathological and immunohistochemical characteristics between autoimmune pancreatitis (AIP) and fibrous mass-forming non-autoimmune pancreatitis (nAIP) and to provide evidence for pathological diagnosis, differential diagnosis and clinical treatment strategy.
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The complete mitochondrial genome of Neopanorpa pulchra (Mecoptera: Panorpidae).
Mitochondrial DNA
PUBLISHED: 09-20-2013
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Abstract We describe the complete mitochondrial genome sequence of Neopanorpa pulchra (Mecoptera: Panorpidae). The sequence has a length of 16,314?bp (GenBank accession number JX569848) and the A?+?T content is as high as 77.46%. The genome contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and an A?+?T-rich region. The gene arrangement is conserved. All protein-coding genes start with ATN start codon. Seven protein-coding genes use TAA as stop codon while others use incomplete stop codons "T" or "TA". The A?+?T-region is located between rrnS and trnI with a length of 1531?bp.
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The mitochondrial genome of Diadromus collaris (Hymenoptera: Ichneumonidae).
Mitochondrial DNA
PUBLISHED: 09-20-2013
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Abstract We sequenced the nearly complete mitochondrial genome of the parasitic wasps Diadromus collaris, the fourth sequenced mitogenome in the family Ichneumonidae (Insecta: Hymenoptera). The sequenced segment is 14,621?bp, including 13 protein-coding genes, 19 transfer RNA genes and 2 ribosomal RNA genes. Four tRNAs are rearranged comparing to the ancestral insect mitochondrial gene arrangements, which coincides with the fact that the most rearranged genes are tRNA genes in the Ichneumonidae, and trnI-trnQ-trnM is a hot-spot of gene rearrangement. The lrRNA secondary structure was predicted, containing six domains (I-VI) and 49 helics.
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Copper-catalyzed trifluoromethylation and cyclization of aromatic-sulfonyl-group-tethered alkenes for the construction of 1,2-benzothiazinane dioxide type compounds.
Chemistry
PUBLISHED: 09-13-2013
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A multi-talented system: An efficient copper-catalyzed tandem trifluoromethylation/annulation of an electron-deficient aromatic ring has been developed. This method provides a powerful and straightforward way to synthesize trifluoromethylated 1,2-benzothiazinane dioxides under mild conditions. The mechanism was investigated by a series of kinetic experiments and isotopic labeling studies.
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Ruthenium-catalyzed olefin metathesis accelerated by the steric effect of the backbone substituent in cyclic (alkyl)(amino) carbenes.
Chem. Commun. (Camb.)
PUBLISHED: 09-10-2013
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Three ruthenium complexes bearing backbone-monosubstituted CAACs were prepared and displayed dramatic improvement in catalytic efficiency not only in RCM reaction but also in the ethenolysis of methyl oleate, compared to those bearing backbone-disubstituted CAACs.
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Cinchona alkaloid squaramide catalyzed enantioselective hydrazination/cyclization cascade reaction of ?-isocyanoacetates and azodicarboxylates: synthesis of optically active 1,2,4-triazolines.
J. Org. Chem.
PUBLISHED: 08-28-2013
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An efficient enantioselective hydrazination/cyclization cascade reaction of ?-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazolines in excellent yields (up to 99%) and good to excellent enantioselectivities (up to 97% ee) under mild conditions.
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Synthesis of iridium and rhodium complexes with new chiral phosphine-NHC ligands based on 1,1-binaphthyl framework and their application in asymmetric hydrogenation.
Dalton Trans
PUBLISHED: 07-30-2013
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The first series of chiral phosphine-imidazole carbene ligands based on a 1,1-binaphthyl framework were synthesized from (R)-2-amine-2-(diphenylphosphino)-1,1-binaphthyl (1) in a four-step pathway. After deprotonation of these phosphine-imidazolium salts with LiO(t)Bu, and subsequent complexation with [Ir(COD)Cl]2 and anion exchange with NaBArF, phosphine-carbene chelated iridium complexes (R)-6a and (R)-6b were obtained. Their structures have been characterized by NMR and X-ray diffraction analysis. The NHC-phosphine rhodium complex (R)-6c has been also obtained by a similar synthetic method. These iridium complexes have been applied to catalyze the asymmetric hydrogenation of alkenes to give the corresponding products in moderate to excellent conversion (up to 99%) and moderate enantioselectivities under mild conditions (up to 61% ee).
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Overexpression of cyclooxygenase-1 correlates with poor prognosis in renal cell carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-27-2013
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The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative real- time polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients.
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Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study.
BMC Med. Genet.
PUBLISHED: 07-18-2013
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Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.
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Complete mitochondrial genome of Neochauliodes bowringi (MacLachlan) (Megaloptera: Corydalidae).
Mitochondrial DNA
PUBLISHED: 07-18-2013
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Abstract We describe and analyze the complete mitochondrial genome of Neochauliodes bowringi (MacLachlan) (Megaloptera: Corydalidae). The length of the genome is 16,064?bp (GenBank accession No. JQ351950), the longest mitochondrial genome in the order Megaloptera already got, which includes 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNAs and an A?+?T-rich region. The gene arrangement is similar to that of Drosophila yakuba, the presumed ancestral insect mitochondrial gene arrangement. All protein-coding genes start with ATN start codon except for the gene ND4, which uses GTG as start codon. Eight protein-coding genes use TAA as stop codon and others use incomplete stop codons "T" or "TA". The A?+?T-rich region is located between rrnS and trnI with a length of 1328?bp.
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Signaling of miRNAs-FOXM1 in cancer and potential targeted therapy.
Curr Drug Targets
PUBLISHED: 06-28-2013
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The transcription factor Forkhead box protein M1 (FOXM1) is overexpressed in the majority of cancer patients. This overexpression is implicated to play a role in the pathogenesis, progression, and metastasis of cancer. This important role of FOXM1 demonstrates its significance to cancer therapy. MicroRNAs (miRNAs) are small noncoding, endogenous, single-stranded RNAs that are pivotal posttranscriptional gene expression regulators. MiRNAs aberrantly expressed in cancer cells have important roles in tumorigenesis and progression. Currently, miRNAs are being studied as diagnostic and prognostic biomarkers and therapeutic tools for cancer. The rapid discovery of many target miRNAs and their relevant pathways has contributed to the development of miRNA-based therapeutics for cancer. In this review, we summarize the latest and most significant findings on FOXM1 and miRNA involvement in cancer development and describe the role/roles of miRNA/FOXM1 signaling pathways in cancer initiation and progression. Targeting FOXM1 via regulation of miRNA expression may have a role in cancer treatment, although the miRNA delivery method remains the key challenge to the establishment of this novel therapy.
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Rhodium(I)-catalyzed cycloisomerization of nitrogen-tethered indoles and alkylidenecyclopropanes: convenient access to polycyclic indole derivatives.
Chemistry
PUBLISHED: 06-19-2013
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At the end of its tether: A new synthetic protocol for the preparation of polycyclic indole derivatives has been developed from a rhodium(I)-catalyzed cycloisomerization of a nitrogen-tethered indole and alkylidenecyclopropane, affording the corresponding tetrahydro-?-carboline derivatives in moderate to good yields. Further transformations give a direct and rapid route to tetracyclic compounds through transition-metal catalysis.
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Grignard Reagent/CuI/LiCl-Mediated Stereoselective Cascade Addition/Cyclization of Diynes; A Novel Pathway for the Construction of 1-Methyleneindene Derivatives.
Chemistry
PUBLISHED: 06-08-2013
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Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments.
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Regulation of Id1 expression by epigallocatechin?3?gallate and its effect on the proliferation and apoptosis of poorly differentiated AGS gastric cancer cells.
Int. J. Oncol.
PUBLISHED: 06-07-2013
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We investigated the inhibition of apoptosis and proliferation of poorly differentiated AGS gastric cancer cells by epigallocatechin-3-gallate (EGCG), to establish target genes for regulation by EGCG. The proliferation and apoptosis of AGS gastric cancer cells treated with EGCG were observed by cell counting kit (CCK)-8 and flow cytometry. Differential gene expression in AGS cells treated with EGCG was screened by gene expression microarrays. Id1 gene and protein expression were determined by quantitative PCR and western blot analysis. The effect of Id1 on EGCG-induced apoptosis and cell cycle arrest of AGS cells was verified with RNAi. The proliferation and apoptosis of AGS cells treated with siRNA?Id1 was observed by CCK-8 and flow cytometry. EGCG significantly promoted apoptosis and inhibited the proliferation of AGS cells. The Id1 gene was differentially expressed in AGS cells treated with EGCG, and Id1 mRNA and protein were downregulated in AGS cells treated with EGCG, confirmed by quantitative PCR and western blot analysis. Id1 mRNA and protein were also downregulated in AGS cells treated with siRNA-Id1. The apoptosis and proliferation of AGS cells treated with siRNA-Id1 were similar to those in cells treated with EGCG. EGCG induces apoptosis and inhibits proliferation of poorly differentiated AGS gastric cancer cells, and Id1 may be one of the target genes regulated by EGCG in cancer inhibition.
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Identification and characterization of defensin genes from the endoparasitoid wasp Cotesia vestalis (Hymenoptera: Braconidae).
J. Insect Physiol.
PUBLISHED: 06-04-2013
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Defensins are members of a large and diverse family of antimicrobial peptides (AMPs) containing three or four intramolecular disulfide bonds. They are widely distributed from vertebrates to invertebrates, and serve as critical defense molecules protecting the host from the invasion of pathogens or protozoan parasites. Cotesia vestalis is a small endoparasitoid wasp that lays eggs in larvae of Plutella xylostella, a cosmopolitan pest of cruciferous crops. We identified and characterized three full-length cDNAs encoding putative defensin-like peptides from C. vestalis, named CvDef1, CvDef2 and CvDef3. Phylogenetic analyses of these sequences showed that they are present in two clades, CITDs and PITDs, indicating a diversity of defensins in C. vestalis. We analyzed their expression patterns in larvae, pupae and adults by semi-quantitative RT-PCR. The results showed that CvDef1 mRNA was expressed from the end stage of the second instar larva, CvDef3 mRNA from the early stage of the second instar larva, and CvDef2 mRNA was expressed in all developmental stages of C. vestalis. Furthermore, CvDef1 showed antimicrobial activity against gram-positive and gram-negative bacteria. Growth kinetics of Staphylococcus aureus indicated that CvDef1 had much better antimicrobial ability than ampicillin, making it a potential candidate for practical use. Transmission electron microscopic (TEM) examination of CvDef1-treated S. aureus cells showed extensive damage to the cell membranes. Our results revealed the basic properties of three defensins in C. vestalis for the first time, which may pave the way for further study of the functions of defensins in parasitism and innate immunity of C. vestalis.
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Regulation of EMT by KLF4 in Gastrointestinal Cancer.
Curr Cancer Drug Targets
PUBLISHED: 05-30-2013
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Gastrointestinal (GI) cancer is characterized by its aggressiveness, but the underlying mechanism is not fully understood. Studies reveal that epithelial to mesenchymal transition (EMT), which is regulated by a series of transcription factors and signaling pathways, is strongly associated with GI cancer cell proliferation, invasion and metastasis. Importantly, EMT is a product of crosstalk between signaling pathways. Krüppel-like factor 4 (KLF4), a zinc finger-type transcription factor, is decreased or lost in most GI cancers. By transcriptionally regulating its downstream target genes, KLF4 plays important roles of GI cancer tumorigenesis, proliferation and differentiation. In this review, we focus on the mechanism of KLF4 in GI cancer EMT, and demonstrate that through crosstalk with TGF-?, Notch, and Wnt signaling pathways, KLF4 negatively regulates EMT of GI cancers. Finally, we indicate the challenging new frontiers for KLF4 which contributes to better understanding of the mechanism of GI cancer aggressiveness.
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MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.
Mol. Cancer
PUBLISHED: 05-15-2013
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MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined.
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The involvement of NLRX1 and NLRP3 in the development of nonalcoholic steatohepatitis in mice.
J Chin Med Assoc
PUBLISHED: 05-03-2013
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Increasing evidence suggests that innate immunity is involved in the development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The aim of this article is to explore the correlation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic steatohepatitis (NASH) in mice.
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Cheek cell-derived ?-synuclein and DJ-1 do not differentiate Parkinsons disease from control.
Neurobiol. Aging
PUBLISHED: 05-01-2013
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Recently, ?-synuclein (?-syn) and DJ-1, 2 proteins critically involved in Parkinsons disease (PD), have been shown to be present in saliva, suggesting their potential utility as biomarkers of PD. However, the origin and influence of demographic characteristics (e.g., age or sex) on these proteins are unknown. We identified cheek epithelium, which forms the majority of the cellular component of saliva and is readily accessible clinically, as 1 of several potential sources of salivary ?-syn and DJ-1. However, no PD-related trend in the cellular component was present. In the supernatant collected from 198 healthy subjects, no correlation was seen between salivary DJ-1 or ?-syn with age. When male and female subjects were analyzed separately, a weak age-dependent increase in DJ-1 level was present in male subjects, along with slightly increased ?-syn in female subjects. These results, albeit largely negative, provide critical information for understanding the salivary gland pathology and saliva as a PD biomarker source, and must be considered in future investigations of salivary changes in PD.
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Efficacy and safety of docetaxel plus oxaliplatin and capecitabine in the first line treatment of advanced gastric adenocarcinoma.
Biomed Res Int
PUBLISHED: 04-29-2013
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To evaluate the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the first line treatment of advanced gastric adenocarcinoma.
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Gold-catalyzed cyclization of 1-(indol-3-yl)-3-alkyn-1-ols: facile synthesis of diversified carbazoles.
Chemistry
PUBLISHED: 03-29-2013
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Efficient cyclization of 1-(indol-3-yl)-3-alkyn-1-ols in the presence of a cationic gold(I) complex, leading to annulated or specific substituted carbazoles, was observed. Depending on the reaction conditions and substitution pattern, divergent reaction pathways were discovered, furnishing diversified carbazole structures. Cycloalkyl-annulated [b]carbazoles are obtained through 1,2-alkyl migration of the metal-carbene intermediates; cycloalkyl-annulated [a]carbazoles are formed through a Wagner-Meerwein-type 1,2-alkyl shift; carbazole ethers are constructed through ring-opening of the cyclopropyl group by nucleophilic attack of water or an alcohol.
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What is Visualize?

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

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

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