JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Transumbilical single-incision laparoscopic resection of focal hepatic lesions.
JSLS
PUBLISHED: 11-14-2014
Show Abstract
Hide Abstract
Transumbilical single-incision laparoscopic surgery (SILS) is gaining in popularity as a minimally invasive technique. The reduced pain and superior cosmetic appearance it affords make it attractive to many patients. For this study, we focused on SILS, analyzing the outcomes of transumbilical single-incision laparoscopic liver resection (SILLR) achieved at our institution between January 2010 and February 2013.
Related JoVE Video
Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-13-2014
Show Abstract
Hide Abstract
Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P?
Related JoVE Video
Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
Show Abstract
Hide Abstract
As an important component of the NDC80 kinetochore complex, NUF2 is essential for kinetochore-microtubule attachment and chromosome segregation. Previous studies also suggested its involvement in development of various kinds of human cancers, however, its expression and functions in human hepatocellular carcinoma (HCC) are still unclear.
Related JoVE Video
Multicolor (Vis-NIR) mesoporous silica nanospheres linked with lanthanide complexes using 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline for in vitro bioimaging.
Dalton Trans
PUBLISHED: 11-07-2014
Show Abstract
Hide Abstract
A novel mesoporous nanosphere functionalized with 3-(aminopropyl)triethoxysilane (APTES) and 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline (5-Br-Tip) was synthesized (denoted as Tip-MSS). With the coordinating function of the 5-Br-Tip to lanthanide (Ln) ions, for the first time, LnL3(5-Br-Tip) complexes were linked to the mesoporous nanospheres. The derived materials, named Ln-Tip-MSS (Ln = Eu, Tb, Sm, Nd, Yb), were characterized by Fourier-transform infrared (FT-IR) spectroscopy, TEM, XRD (wide-angle and small-angle), N2 adsorption/desorption analysis, and fluorescence spectroscopy. Upon excitation in the ligand absorption, the Ln-Tip-MSS nanomaterials show characteristic visible (Eu, Tb, Sm) and NIR (Sm, Nd, Yb) luminescence (multicolor emission covered from 450 nm to 1400 nm spectral region). Of importance is that, with low cytotoxicity and good biocompatibility given by the methyl thiazolyl tetrazolium (MTT) assay, the Eu-Tip-MSS was successfully applied to cell imaging in vitro based on the Eu(3+) luminescence (under 405 nm excitation).
Related JoVE Video
Black Tea Increased Survival of Caenorhabditis elegans under Stress.
J. Agric. Food Chem.
PUBLISHED: 11-05-2014
Show Abstract
Hide Abstract
The present study examined the effects of black tea (Camellia sinensis) extracts (BTE) in Caenorhabditis elegans under various abiotic stressors. Results showed BTE increased nematode resistance to osmosis, heat, and UV irradiation treatments. However, BTE could not increase nematodes' lifespan under normal culture conditions and MnCl2-induced toxicity at concentrations we used. Further studies showed that BTE decreased reactive oxygen species and up-regulated some antioxidant enzymes, including GSH-PX, and genes, such as gsh-px and sod-3. However, only a slight extension in mev-1 mutants mean lifespan was observed without significance. These results indicated that the antioxidant activity of BTE might be necessary but not sufficient to protect against aging to C. elegans. Moreover, BTE increased the mRNA level of stress-response genes such as sir-2.1 and sek-1. Our finding demonstrated BTE might increase heat and UV stress resistance in a sir.2.1-dependent manner. Taken together, BTE enhanced stress resistance with multiple mechanisms in C. elegans.
Related JoVE Video
Systematic review comparing the safety and efficacy of conventional and drug-eluting-bead transarterial chemoembolization for inoperable hepatocellular carcinoma.
Hepatol. Res.
PUBLISHED: 11-02-2014
Show Abstract
Hide Abstract
Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB-TACE compares with cTACE.
Related JoVE Video
One-Year Outcomes of Emergency Department Patients With Atrial Fibrillation: A Prospective, Multicenter Registry in China.
Angiology
PUBLISHED: 10-26-2014
Show Abstract
Hide Abstract
There is lack of data about patient characteristics, practice patterns, and long-term adverse outcomes in patients with atrial fibrillation (AF) attending emergency departments (EDs) in China. A total of 2016 patients from 20 representative EDs were included. During 1 year, all-cause mortality was 291 (14.6%) cases, stroke/noncentral nervous system systemic embolism rate was 159 (8.0%) cases, and major bleeding was 26 (1.3%) cases. Heart failure, the major cause of mortality, accounted for 43.0% of deaths. Of 375 (18.6%) patients who used warfarin at baseline, only 217 (57.9%) patients were still on anticoagulation therapy during 1-year follow-up. Compared with the patients who continued on warfarin, the mortality rate was higher in those who did not continue (15.9% vs 5.5%, P < .001). Patients seen in ED with AF appear to have a high incidence rate of long-term all-cause mortality and inadequate anticoagulation rate.
Related JoVE Video
Comparative analysis of the pathogenic mechanisms of street rabies virus strains with different virulence levels.
Biomed. Environ. Sci.
PUBLISHED: 10-25-2014
Show Abstract
Hide Abstract
To characterize two strains of street rabies virus (RABV) isolated from the brain tissue of cattle from Inner Mongolia. Differences in the histopathological and ultrastructural changes in the brain tissue of infected mice were determined to reveal variation in the pathogenesis of infection between street rabies virus strains.
Related JoVE Video
A distinguishable photovoltaic performance on dye-sensitized solar cells using ruthenium sensitizers with a pair of isomeric ancillary ligands.
Dalton Trans
PUBLISHED: 10-14-2014
Show Abstract
Hide Abstract
A pair of isomeric ruthenium sensitizers and , having TIP based ancillary ligands with a 9-phenylcarbazole tail at the ? or ? position of the thiophene unit, shows a distinguishable photovoltaic performance on DSCs (PCEs: 7.33% and 5.33% for and as compared with 6.07% for the standard N3-dye).
Related JoVE Video
Losartan inhibits LPS + ATP-induced IL-1beta secretion from mouse primary macrophages by suppressing NALP3 inflammasome.
Pharmazie
PUBLISHED: 10-03-2014
Show Abstract
Hide Abstract
IL-1beta is a potent proinflammatory, pro-fibrogenetic and pro-athrosclerosis cytokine which has been shown to play an important role in an expanding number of noninfectious, chronic inflammatory conditions including cardiovascular disease, renal fibrosis, rheumatoid arthritis and even type 2 diabetes. Losartan is an angiotensin II receptor antagonist widely used for the treatment of hypertension, diabetic nephropathy and congestive heart failure. In this study, we attempted to clarify whether losartan has an inhibitory effect on IL-1beta. To further elucidate the molecular mechanism underlying the anti-IL-1beta property of losartan, we studied the LPS+ATP-induced activation of NALP3 inflammasome which controls the muturation and secretion of IL-1beta.
Related JoVE Video
An Iminocoumarin Sulfonamide Based Turn-On Fluorescent Probe for the Detection of Biothiols in Aqueous Solution.
Chem Asian J
PUBLISHED: 09-09-2014
Show Abstract
Hide Abstract
A new chemodosimeter for the highly selective sensing and imaging of biothiols was designed and realized in phosphate-buffered saline solution at pH?7.4 through a fluorescence "off-on" response. A unique mechanism featuring a two-step cascade (biothiols?H2 O) sequence for this remarkable recognition is disclosed for the first time.
Related JoVE Video
AMPD1 functional variants associated with autism in Han Chinese population.
Eur Arch Psychiatry Clin Neurosci
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
Autism is a childhood neurodevelopmental disorder with high heterogeneity. Following our genome-wide associated loci with autism, we performed sequencing analysis of the coding regions, UTR and flanking splice junctions of AMPD1 in 830 Chinese autism individuals as well as 514 unrelated normal controls. Fourteen novel variants in the coding sequence were identified, including 11 missense variants and 3 synonymous mutations. Among these missense variants, 10 variants were absent in 514 control subjects, and conservative and functional prediction was carried out. Mitochondria activity and lactate dehydrogenase assay were performed in 5 patients' lymphoblast cell lines; p.P572S and p.S626C showed decreased mitochondrial complex I activity, and p.S626C increased lactate dehydrogenase release in medium. Conclusively, our data suggested that mutational variants in AMPD1 contribute to autism risk in Han Chinese population, uncovering the contribution of mutant protein to disease development that operates via mitochondria dysfunction and cell necrosis.
Related JoVE Video
High delta-like ligand 4 (DLL4) is correlated with peritumoral brain edema and predicts poor prognosis in primary glioblastoma.
Medicine (Baltimore)
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox proportional hazard model.The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P?
Related JoVE Video
Vertically Architectured Stack of Multiple Graphene Field-Effect Transistors for Flexible Electronics.
Small
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
Vertically architectured stack of multiple graphene field-effect transistors (GFETs) on a flexible substrate show great mechanical flexibility and robustness. The four GFETs are integrated in the vertical direction, and dually gated GFETs with graphene channel, PMMA dielectrics, and graphene gate electrodes are realized.
Related JoVE Video
Dinuclear Cu(II) complexes based on two flexible Schiff-base ligands and one unusual in situ formed diphenolate 2,6-piperidin-4-one derivative.
Dalton Trans
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
A dinuclear Cu(ii) complex [Cu2(L3)2]·2H2O, having an unprecedented in situ formed diphenolate 2,6-piperidin-4-one derived ligand produced from the flexible Schiff-base ligand HL1, can be yielded as a side product in the presence of Cu(OAc)2·H2O-NH3·H2O dissolved in methanol and acetone in addition to the expected dinuclear Cu(ii) complex [Cu2(L1)4].
Related JoVE Video
Comparison of the clinical features and outcomes in two age-groups of elderly patients with atrial fibrillation.
Clin Interv Aging
PUBLISHED: 08-12-2014
Show Abstract
Hide Abstract
Atrial fibrillation (AF) disproportionately affects older adults. However, direct comparison of clinical features, medical therapy, and outcomes in AF patients aged 65-74 and ? 75 years is rare. The objective of the present study was to evaluate the differences in clinical characteristics and prognosis in these two age-groups of geriatric patients with AF.
Related JoVE Video
Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy.
Cancer Chemother. Pharmacol.
PUBLISHED: 08-09-2014
Show Abstract
Hide Abstract
Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum-paclitaxel treatment.
Related JoVE Video
Topological surface state enhanced photothermoelectric effect in Bi2Se3 nanoribbons.
Nano Lett.
PUBLISHED: 07-23-2014
Show Abstract
Hide Abstract
The photothermoelectric effect in topological insulator Bi2Se3 nanoribbons is studied. The topological surface states are excited to be spin-polarized by circularly polarized light. Because the direction of the electron spin is locked to its momentum for the spin-helical surface states, the photothermoelectric effect is significantly enhanced as the oriented motions of the polarized spins are accelerated by the temperature gradient. The results are explained based on the microscopic mechanisms of a photon induced spin transition from the surface Dirac cone to the bulk conduction band. The as-reported enhanced photothermoelectric effect is expected to have potential applications in a spin-polarized power source.
Related JoVE Video
Advantage of the N-Alkylation Strategy for Retaining the Molecular Planarity for Oligothiophene/Imidazole/1,10-Phenanthroline-Based Heterocyclic Semiconducting and Fluorescent Compounds.
Chem Asian J
PUBLISHED: 07-19-2014
Show Abstract
Hide Abstract
A family of planar oligothiophene/imidazole/1,10-phenanthroline (OTIP)-based heterocyclic, aromatic, semiconducting, and fluorescent compounds with N-substituted alkyl chains (allyl, n-butyl, n-octyl, n-dodecyl, and n-cetyl) have been designed and synthesized. They all have specific N-coordination sites, various donor-acceptor spacers, good molecular planarity, suitable solubility, and high thermal stability. In comparison with conventional double ?-alkylation of the thiophene ring, our results reveal that the single imidazole N-alkylation strategy for OTIPs has the advantage of maintaining the planarity of the whole molecule, in addition to improving the solubility, which can be clearly verified by the small dihedral angles between adjacent thiophene/imidazole/1,10-phenanthroline (TIP) rings in eight X-ray single-crystal structures. In particular, n-dodecyl- and n-cetyl-substituted OTIPs (7 and 8) with the same molecular length of 2.37?nm (MW =939 and 1052), show good molecular planarity with the aforementioned dihedral angles of 8.9(5) and 10.4(5)°. Furthermore, special attention has been paid to the physicochemical properties of seven symmetrical OTIPs (6-8, 13-15, and 19), including two to six thiophene rings in the middle of their molecular structures. To the best of our knowledge, this is the first synthetic, structural, and spectral investigation into the N-alkylation of OTIP-based compounds.
Related JoVE Video
The Roles of Neurotensin and its Analogues in Pain.
Curr. Pharm. Des.
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role of NT is thought to be mediated by both neurotensin receptor subtype 1 (NTS1) and neurotensin receptor subtype 2 (NTS2). NT and its receptors are widely distributed in the pain circuits in central nervous system. Thus NT might modulate pain in many structures of pain pathway, such as spinal cord, rostroventral medulla (RVM) and periaqueductal gray (PAG). Actually either intrathecal application of NT or direct injection of NT into RVM or PAG or intracerebroventricular injection of NT showed analgesic effects. NT exerted its antinociceptive effects in both acute pain and chronic pain models. The analgesic effects of NT were originally found in acute pain experiments. In the case of pathological pain, for example, formalin injection induced inflammatory pain and sciatic nerve constriction induced neuropathic pain, NT also shows antinociceptive effects. The effects exist in somatic pain as well as visceral pain induced by noxious colorectal distension (CRD) or writhing test. It should be noted that NT plays an important role in stress-induced antinociception (SIAN), especially in higher intensity stress experiments. However as a neuropeptide, NT is susceptible to degradation by peptidases and cannot cross the blood-brain barrier (BBB). Great efforts have been made to find NT analogues that are more biologically stable and could inhibit pain by systematic administration. The present review focuses on the analgesic role and the underlying mechanisms of NT and its analogues in pain, especially in chronic pain models.
Related JoVE Video
Magnetic moments in graphene with vacancies.
Nanoscale
PUBLISHED: 06-24-2014
Show Abstract
Hide Abstract
Vacancies can induce local magnetic moments in graphene, paving the way to make magnetic functional graphene. Due to the interaction between magnetic moments and conduction carriers, the magnetotransport properties of graphene can be modulated. Here, the effects of vacancy induced magnetic moments on the electrical properties of graphene are studied via magnetotransport measurements and spin-polarized density functional theory calculations. We show by quantum Hall measurements that a sharp resonant V? state is introduced in the midgap region of graphene with vacancies, resulting in the local magnetic moment. The coupling between the localized V? state and the itinerant carrier is tuned by varying the carrier concentration, temperature, magnetic field, and vacancy density, which results in a transition between hopping transport and the Kondo effect and a transition between giant negative magnetoresistance (MR) and positive MR. This modulated magnetotransport is valuable for graphene based spintronic devices.
Related JoVE Video
Attenuation of early liver fibrosis by herbal compound "Diwu Yanggan" through modulating the balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition.
BMC Complement Altern Med
PUBLISHED: 06-20-2014
Show Abstract
Hide Abstract
Diwu Yanggan (DWYG) is a Chinese compound herbal preparation which consists of five Chinese herbs. This study investigates the preventative effects of DWYG on liver fibrosis induced by carbon tetrachloride (CCl4) and explores its possible mechanisms of action.
Related JoVE Video
Traditional Chinese medicine treatment for ruptured lumbar disc herniation: clinical observations in 102 cases.
Orthop Surg
PUBLISHED: 06-03-2014
Show Abstract
Hide Abstract
To explore the therapeutic effects of a traditional Chinese medicine (TCM) regimen on patients with ruptured lumbar disc herniation, including assessing its effects on prognosis and protrusion size.
Related JoVE Video
SLC39A5 mutations interfering with the BMP/TGF-? pathway in non-syndromic high myopia.
J. Med. Genet.
PUBLISHED: 06-02-2014
Show Abstract
Hide Abstract
High myopia, with the characteristic feature of refractive error, is one of the leading causes of blindness worldwide. It has a high heritability, but only a few causative genes have been identified and the pathogenesis is still unclear.
Related JoVE Video
Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
Chin J Nat Med
PUBLISHED: 05-28-2014
Show Abstract
Hide Abstract
To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.
Related JoVE Video
[Community structure characteristics of phytoplankton and related affecting factors in Hengshan Reservoir, Zhejiang, China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 05-17-2014
Show Abstract
Hide Abstract
In order to reveal the community structure characteristics of phytoplankton and the relationships with environmental factors in Hengshan Reservoir, the phytoplankton species composition, abundance, biomass and 12 environmental factors at 4 sampling sites were analyzed from March 2011 to February 2012. A total of 246 phytoplankton species were identified, which belong to 78 genera and 7 phyla. The dominant species were Melosira varians, M. granulate, Cyclotella meneghiniana, Asterianella formosa, Synedra acus, Achnanthes exigua, Ankistrodesmus falcatus, Oscillatoria lacustris, Cryptomonas erosa, Chroomonas acuta, Phormidium tenue and Microcystis aeruginosa, etc. Seasonal variations of species were obvious. The annual abundance and biomass of the phytoplankton were 0.51 x 10(5)-14.22 x 10(5) ind x L(-1) and 0.07-1.27 mg x L(-1), respectively. The values of the Margelef index, Pielou index and Shannon index of the phytoplankton community were 1.10-3.33, 0.26-0.81 and 0.51-2.38, respectively. The phytoplankton community structure was of Bacillariophyta-Cryptophyta type in spring and winter, of Chlorophyta-Cyanophyta type in summer, and of Bacillariophyta type in autumn. Canonical correlation analysis (CCA) showed that temperature, transparency, chemical oxygen demand and pH had the closest relationships with the phytoplankton community structure in the reservoir. Water quality evaluation showed that Hengshan Reservoir was in a secondary pollution with a meso-trophic level.
Related JoVE Video
Fabrication and electrical properties of stacked graphene monolayers.
Sci Rep
PUBLISHED: 04-07-2014
Show Abstract
Hide Abstract
We develop a simple method to fabricate the two-stacked graphene monolayers and investigate the electronic transport in such a system. The independence of the two graphene monolayers gives rise to the asymmetric resistance-gate voltage curves and an eight-fold degeneracy of Landau level. The position of the maximum resistance of the transfer curves shifts towards higher gate voltage with increasing magnetic field, which is attributed to the magnetic field induced interlayer decoupling of the stacked graphene monolayers.
Related JoVE Video
An N-rich metal-organic framework with an rht topology: high CO2 and C2 hydrocarbons uptake and selective capture from CH4.
Chem. Commun. (Camb.)
PUBLISHED: 04-07-2014
Show Abstract
Hide Abstract
We report the storage capacities and separation selectivity of an rht-type s-heptazine-based metal organic framework (MOF), [Cu3(TDPAH)(H2O)3]·13H2O·8DMA, 1, (where TDPAH is 2,5,8-tris(3,5-dicarboxylphenylamino)-s-heptazine and DMA is N,N-dimethylacetamide) for C2 hydrocarbons and CO2 over CH4. MOF 1 displays the highest C2H2/CH4 selectivity of 80.9 as well as record high C2H4 and C2H6 adsorption enthalpies. Theoretical calculations reveal that s-heptazine and NH groups within the framework have synergistic effects on CO2 binding.
Related JoVE Video
APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.
World J. Gastroenterol.
PUBLISHED: 03-27-2014
Show Abstract
Hide Abstract
To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.
Related JoVE Video
Uncertain data clustering-based distance estimation in Wireless Sensor Networks.
Sensors (Basel)
PUBLISHED: 03-24-2014
Show Abstract
Hide Abstract
For communication distance estimations in Wireless Sensor Networks (WSNs), the RSSI (Received Signal Strength Indicator) value is usually assumed to have a linear relationship with the logarithm of the communication distance. However, this is not always true in reality because there are always uncertainties in RSSI readings due to obstacles, wireless interferences, etc. In this paper, we specifically propose a novel RSSI-based communication distance estimation method based on the idea of interval data clustering. We first use interval data, combined with statistical information of RSSI values, to interpret the distribution characteristics of RSSI. We then use interval data hard clustering and soft clustering to overcome different levels of RSSI uncertainties, respectively. We have used real RSSI measurements to evaluate our communication distance estimation method in three representative wireless environments. Extensive experimental results show that our communication distance estimation method can effectively achieve promising estimation accuracy with high efficiency when compared to other state-of-art approaches.
Related JoVE Video
Facile fabrication of redox-responsive thiol-containing drug delivery system via RAFT polymerization.
Biomacromolecules
PUBLISHED: 03-17-2014
Show Abstract
Hide Abstract
A novel kind of redox-responsive polymeric drug delivery system has been designed and prepared successfully through the coupling of the multithiol branched polymers and thiol-containing drugs. The branched poly((S-(4-vinyl) benzyl S'-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate)) (poly(VBPT-co-PEGMA)) was synthesized by one-pot reaction via reversible addition-fragmentation chain transfer (RAFT) copolymerization. Subsequently, the hydrophobic thiol-containing anticancer drug 6-mercaptopurine (MP) was conjugated to poly(VBPT-co-PEGMA) by thiol-disulfide exchange reaction, resulting in the formation of poly(VBPT-co-PEGMA)-S-S-MP conjugate. Due to its amphiphilicity, poly(VBPT-co-PEGMA)-S-S-MP conjugate self-assembled into amphiphilic micelles in aqueous solution. Under a reductive environment, the disassembly of polymeric micelles resulted in the MP release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that the poly(VBPT-co-PEGMA)-S-S-MP micelles could be taken up by Raji cells (a Burkitt lymphoma cell line). The viability of the Raji cells incubated with the glutathione (GSH) mediated poly(VBPT-co-PEGMA)-S-S-MP micelles was investigated by Cell Counting Kit-8 (CCK-8) assay. The experimental results showed that the viability of the glutathione monoester (GSH-OEt) pretreated cells was lower than that without pretreatment, while the viability of the buthionine sulfoximine (BSO) pretreated cells was higher than that without pretreatment. The poly(VBPT-co-PEGMA)-S-S-MP micelles could induce the apoptosis of Raji cells, and the apoptosis behavior was dose-dependent. This redox-responsive polymer-drug conjugate provides a promising platform for the delivery of thiol-containing biological molecules.
Related JoVE Video
Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients.
Int. J. Cancer
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p?=?0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p?=?0.003; HR 1.691, p?=?0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p?
Related JoVE Video
Single nucleotide polymorphisms of DNA base-excision repair genes (APE1, OGG1 and XRCC1) associated with breast cancer risk in a Chinese population.
Asian Pac. J. Cancer Prev.
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (? 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ? 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.
Related JoVE Video
A vessel active contour model for vascular segmentation.
Biomed Res Int
PUBLISHED: 03-04-2014
Show Abstract
Hide Abstract
This paper proposes a vessel active contour model based on local intensity weighting and a vessel vector field. Firstly, the energy function we define is evaluated along the evolving curve instead of all image points, and the function value at each point on the curve is based on the interior and exterior weighted means in a local neighborhood of the point, which is good for dealing with the intensity inhomogeneity. Secondly, a vascular vector field derived from a vesselness measure is employed to guide the contour to evolve along the vessel central skeleton into thin and weak vessels. Thirdly, an automatic initialization method that makes the model converge rapidly is developed, and it avoids repeated trails in conventional local region active contour models. Finally, a speed-up strategy is implemented by labeling the steadily evolved points, and it avoids the repeated computation of these points in the subsequent iterations. Experiments using synthetic and real vessel images validate the proposed model. Comparisons with the localized active contour model, local binary fitting model, and vascular active contour model show that the proposed model is more accurate, efficient, and suitable for extraction of the vessel tree from different medical images.
Related JoVE Video
The ABI4-induced Arabidopsis ANAC060 transcription factor attenuates ABA signaling and renders seedlings sugar insensitive when present in the nucleus.
PLoS Genet.
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
Seedling establishment is inhibited on media containing high levels (? 6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a quantitative trait locus (QTL) analysis was performed for seedling sensitivity to high sugar in a Col/C24 F2 population of Arabidopsis thaliana. A glucose and fructose-sensing QTL, GSQ11, was mapped through selective genotyping and confirmed in near-isogenic lines in both Col and C24 backgrounds. Allelism tests and transgenic complementation showed that GSQ11 lies within the ANAC060 gene. The Col ANAC060 allele confers sugar insensitivity and was dominant over the sugar-sensitive C24 allele. Genomic and mRNA analyses showed that a single-nucleotide polymorphism (SNP) in Col ANAC060 affects the splicing patterns of ANAC060 such that 20 additional nucleotides are present in the mRNA. The insertion created a stop codon, resulting in a truncated ANAC60 protein lacking the transmembrane domain (TMD) that is present in the C24 ANAC060 protein. The absence of the TMD results in the nuclear localization of ANAC060. The short version of the ANAC060 protein is found in ? 12% of natural Arabidopsis accessions. Glucose induces GSQ11/ANAC060 expression in a process that requires abscisic acid (ABA) signaling. Chromatin immunoprecipitation-qPCR and transient expression analysis showed that ABI4 directly binds to the GSQ11/ANAC060 promoter to activate transcription. Interestingly, Col ANAC060 reduced ABA sensitivity and Glc-induced ABA accumulation, and ABI4 expression was also reduced in Col ANAC060 lines. Thus, the sugar-ABA signaling cascade induces ANAC060 expression, but the truncated Col ANAC060 protein attenuates ABA induction and ABA signaling. This negative feedback from nuclear ANAC060 on ABA signaling results in sugar insensitivity.
Related JoVE Video
Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers.
World J. Gastroenterol.
PUBLISHED: 02-26-2014
Show Abstract
Hide Abstract
To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.
Related JoVE Video
STAT3 Tyr705 phosphorylation affects clinical outcome in patients with newly diagnosed supratentorial glioblastoma.
Med. Oncol.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
STAT3 tyrosine705 phosphorylation (p-STAT3, Tyr705), a molecular hub for several signal transduction pathways of glioma, plays a central role in glioblastoma (GBM) carcinogenesis and progression. However, it is still controversial whether p-STAT3 expression is associated with the clinical outcome of patients with glioblastoma. Such evidence would contribute to further illustrate whether STAT3 inhibition is suitable for clinical treatment. Here, we examined the expression of p-STAT3 in the tumor tissues from 90 patients with newly diagnosed supratentorial GBM via immunohistochemical technique and evaluated the influences of its expression on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Immunohistochemical assay indicated increased expression of p-STAT3 in GBM tissue compared to adjacent normal brain tissue without p-STAT3 expression. There were no observed associations between p-STAT3 expression and patients' gender (P = 0.660), age (P = 0.867) or preoperative Karnofsky Performance Status (KPS) (P = 0.121). Univariate survival analysis revealed significant correlations of high p-STAT3 expression with shorter PFS (P = 0.012) and OS (P = 0.009). Multivariate survival analysis confirmed high p-STAT3 expression as a significant prognostic indicator for shorter PFS (HR 2.158, P = 0.019) and OS (HR 2.120, P = 0.031), independent of age, KPS and chemoradiotherapy. In summary, the high percentage of p-STAT3 positive tumor cells is a significant independent prognostic indicator for poor clinical outcome in patients with GBM, in addition to advanced age, poor performance status and nonstandard chemoradiotherapy, suggesting that STAT3 might be as a promising therapeutic target in GBM.
Related JoVE Video
Fluorofenidone attenuates inflammation by inhibiting the NF-?B pathway.
Am. J. Med. Sci.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
Accumulated evidence indicates that inflammation plays a critical role in the progression of many renal diseases. Fluorofenidone (AKF-PD) has been shown to attenuate renal fibrosis in a number of experimental renal fibrosis models. The aim of this study was to assess the anti-inflammatory effect of AKF-PD.
Related JoVE Video
Risk factors and incidence of stroke and MACE in Chinese atrial fibrillation patients presenting to emergency departments: a national wide database analysis.
Int. J. Cardiol.
PUBLISHED: 02-15-2014
Show Abstract
Hide Abstract
Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism in patients with atrial fibrillation (AF) are largely derived from western cohorts. The purpose of the present study is to assess the potential risk factors for stroke and major adverse cardiac events (MACE) in a large population of Chinese AF patients presenting to emergency department.
Related JoVE Video
Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
Mol. Biol. Rep.
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were "Probably Damaging". The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case-control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95% CI 2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population.
Related JoVE Video
Regulation of Differentiation and Function of Helper T Cells by Lymphocyte-Derived Catecholamines via ?1- and ?2-Adrenoceptors.
Neuroimmunomodulation
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
Objective: Recently, we have reported that lymphocyte-derived endogenous catecholamines (CAs) facilitate a shift in the T helper (Th)1/Th2 balance towards Th2. The purpose of this study was to explore the involvement of adrenoreceptors (ARs) in Th differentiation and function modulation by lymphocyte-derived CAs. Methods: Lymphocytes were separated from the mesenteric lymph nodes of mice, stimulated with concanavalin A (Con A) and treated with pargyline, an inhibitor of CA degradation. Results: Pargyline downregulated the expression of Th1-relative factors, T-bet, interferon (IFN)-? and interleukin (IL)-2, but upregulated the expression of Th2-relative factors, GATA-3, IL-4 and IL-10. Pargyline reduced the percentage of IFN-?-producing CD4+ cells and the CD4+IFN-?+/CD4+IL-4+ cell ratio, although it did not alter the proportion of IL-4-producing CD4+ cells. In addition, the percentage of CD4+CD26+ T cells and the CD4+CD26+/CD4+CD30+ cell ratio were also reduced in the pargyline-treated group. Furthermore, Con A-activated T cells treated with pargyline produced a lower level of IFN-? and a higher level of IL-4 than the control group. All these effects were blocked by the ?1-AR antagonist corynanthine or the ?2-AR antagonist ICI 118551, but not by the ?2-AR antagonist yohimbine or ?1-AR antagonist atenolol. Conclusions: These results imply that lymphocyte-derived CAs promote polarization of differentiation and function towards Th2 cells and that this effect is mediated by ?1-AR and ?2-AR. © 2014 S. Karger AG, Basel.
Related JoVE Video
Modulation of immune function by glutamatergic neurons in the cerebellar interposed nucleus via hypothalamic and sympathetic pathways.
Brain Behav. Immun.
PUBLISHED: 02-08-2014
Show Abstract
Hide Abstract
Our recent work has shown that the cerebellar interposed nucleus (IN) contains glutamatergic neurons that send axons directly to the hypothalamus. In the present study, we aimed to demonstrate modulation of cellular and humoral immunity by glutamatergic neurons in the cerebellar IN by means of gene interventions of glutaminase (GLS), an enzyme for glutamate synthesis, and to reveal pathways transmitting the immunomodulation. Injection of GLS-shRNA lentiviral vector into bilateral cerebellar IN downregulated GLS expression in the IN. The silencing of GLS gene in the cerebellar IN decreased interleukin (IL)-2 and interferon (IFN)-? production, B-cell number, and IgM antibody level in response to antigen bovine serum albumin (BSA). On the contrary, injection of GLS lentiviral vector into bilateral cerebellar IN upregulated GLS expression in the IN. The GLS gene overexpression in the IN caused opposite immune effects to the GLS gene knockdown. Simultaneously, the GLS gene silencing in the cerebellar IN reduced and the GLS overexpression elevated glutamate content in the hypothalamus, but they both did not affect glycine and GABA contents in the hypothalamus. In addition, the immune changes caused by the GLS gene interventions in the IN were accompanied by alteration in norepinephrine content in the spleen and mesenteric lymph nodes but not by changes in adrenocortical and thyroid hormone levels in serum. These findings indicate that glutamatergic neurons in the cerebellar IN regulate cellular and humoral immune responses and suggest that such immunoregulation may be conveyed by cerebellar IN-hypothalamic glutamatergic projections and sympathetic nerves that innervate lymphoid tissues.
Related JoVE Video
Penostatin derivatives, a novel kind of protein phosphatase 1b inhibitors isolated from solid cultures of the entomogenous fungus Isaria tenuipes.
Molecules
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes diseases. In a continuing search for new protein phosphatase inhibitors from fungi, we have isolated a new compound, named penostatin J (1), together with three known ones, penostatin C (2), penostatin A (3), and penostatin B (4), from cultures of the entomogenous fungus Isaria tenuipes. The structure of penostatin J (1) was elucidated by extensive spectroscopic analysis. We also demonstrate for the first time that penostatin derivatives exhibit the best PTP1B inhibitory action. These findings suggest that penostatin derivatives are a potential novel kind of PTP1B inhibitors.
Related JoVE Video
High-mobility Bi2Se3 nanoplates manifesting quantum oscillations of surface states in the sidewalls.
Sci Rep
PUBLISHED: 01-03-2014
Show Abstract
Hide Abstract
Magnetotransport measurements of topological insulators are very important to reveal the exotic topological surface states for spintronic applications. However, the novel properties related to the surface Dirac fermions are usually accompanied by a large linear magnetoresistance under perpendicular magnetic field, which makes the identification of the surface states obscure. Here, we report prominent Shubnikov-de Haas (SdH) oscillations under an in-plane magnetic field, which are identified to originate from the surface states in the sidewalls of topological insulator Bi2Se3 nanoplates. Importantly, the SdH oscillations appear with a dramatically weakened magnetoresistance background, offering an easy path to probe the surface states directly when the coexistence of surface states and bulk conduction is inevitable. Moreover, under a perpendicular magnetic field, the oscillations in Hall conductivity have peak-to-valley amplitudes of 2?e(2)/h, giving confidence to achieve a quantum Hall effect in this system. A cross-section view of the nanoplate shows that the sidewall is (015) facet dominant and therefore forms a 58° angle with regard to the top/bottom surface instead of being perpendicular; this gives credit to the surface states' behavior as two-dimensional transport.
Related JoVE Video
Two species of Naididae (Annelida, Clitellata) from southern Tibet, China.
Zookeys
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
One new species of Naidinae (Oligochaeta, Naididae), Naisbadia sp. n. and one new record species from China, Tubifexmontanus Kowalewski, 1919 (Tubificinae) are found in southern Tibet. The new species is distinguished from congeners by its large area of reddish brown pigment in the anterior segments I-VIII, serrate hairs, pectinate needles with 1-2 intermediate teeth, ventral chaetae partly with 1-2 fine intermediate teeth and wave-like movements. The new material of the species Tubifexmontanus differs slightly from the previous descriptions by its vas deferens entering atrium subapically, wide ental end of penial sheath and smooth hair chaetae.
Related JoVE Video
Fluorofenidone Offers Improved Renoprotection at Early Interventions during the Course of Diabetic Nephropathy in db/db Mice via Multiple Pathways.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease (ESRD), a situation that is in part attributable to the lack of effective treatments. Fluorofenidone is a newly developed reagent with anti-fibrotic activity. While fluorofenidone was previously demonstrated to possess renoprotection from DN pathogenesis in db/db mice, the protective process and its underlying mechanisms have not been well studied. To characterize fluorofenidone-derived renoprotection, we treated 5, 8, or 12-week old db/db mice with daily doses of placebo, fluorofenidone, or losartan until 24 weeks of age; the time at which diabetes and DN were fully developed in placebo-treated animals. In comparison to db/db mice receiving fluorofenidone at 12-weeks old, those treated at 5-weeks had less glomerular expansion and better preservation of renal functions, judged by serum creatinine levels, albumin to creatinine ratio, and urinary albumin excretion (mg/24 hours). These benefits of early treatment were associated with significant reductions of multiple DN-promoting events, such as decreased expression of TGF-?1 and the p22phox subunit of NADPH oxidase as well as downregulated activation of protein kinase C-zeta (?), ERK and AKT. This improvement in renoprotection following early interventions is not a unique property of DN pathogenesis, as losartan does not apparently offer the same benefits and is not more renoprotective than fluorofenidone. Additionally, the enhanced renoprotection provided by fluorofenidone did not affect the diabetic process, as it did not alter serum levels of glycated serum proteins, glucose, triglyceride or cholesterol. Collectively, we provide evidence that fluorofenidone offers improved renoprotection at early stages of DN pathogenesis.
Related JoVE Video
Morphological evidence for a neurotensinergic periaqueductal gray-rostral ventromedial medulla-spinal dorsal horn descending pathway in rat.
Front Neuroanat
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Neurotensin (NT) is an endogenous neuropeptide that exerts potent opioid-independent analgesic effects, most likely via the type 2 NT receptor (NTR2). Previous morphological and electrophysiological studies suggested that the NT-NTR2 system is primarily localized in structures that constitute the descending pain control pathway, such as the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal dorsal horn (SDH). However, relevant morphological evidence for this neurotensinergic (NTergic) circuit is lacking. Thus, the aim of the present study was to morphologically elucidate the potential sites and connections in the NT-NTR2 system that are involved in the descending pain control pathway. Based on light and electron microscopy combined with anterograde and retrograde tracing, we found evidence that NTR2-immunoreactive (IR) neurons in the RVM receive NT-IR projections originating from the PAG; express NT, serotonin (5-HT), or both; and send projections that terminate in laminae I and II of the SDH. These results suggest that NTR2 may contribute to pain control by binding to NT in the PAG-RVM-SDH pathway. In conclusion, our data provide morphological evidence for an NTergic PAG-RVM-SDH pathway, implicating novel mechanisms of NT-induced analgesia.
Related JoVE Video
Association of pSTAT3-VEGF signaling pathway with peritumoral edema in newly diagnosed glioblastoma: an immunohistochemical study.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
It is well recognized that peritumoral edema is vasogenic cerebral edema in malignant glioma, and vascular endothelial growth factor (VEGF) induced by phosphorylated signal transducer and activator of transcription factor 3 (pSTAT3) strongly contributes to tumor angiogenesis in glioblastoma. However, there is no study with regard to the correlation between pSTAT3 or VEGF and peritumoral edema. Such evidence may contribute to providing new targets for the management of peritumoral cerebral. In this study, newly diagnosed glioblastoma tissues from 84 patients were collected to investigate pSTAT3 and VEGF expression by immunohistochemistry, and peritumoral edema was detected by preoperative magnetic resonance imaging. We found that a significantly positive correlation emerged between VEGF and pSTAT3 expression (P = 0.000) in glioblastoma tissues, but they were not related to patient gender and age (P > 0.05); the expression of pSTAT3 and VEGF were associated with peritumoral edema extent (P = 0.005), but not with edema shape (P > 0.05). Therefore, the pSTAT3-VEGF signaling pathway, which is correlated with peritumoral edema extent, might be a regulatory mechanism in the course of peritumoral edema formation during glioblastoma tumorigenesis and progression, thereby suggesting that STAT3 inhibition might be helpful for alleviation of peritumoral cerebral edema.
Related JoVE Video
Co-expression and co-purification of archaeal and eukaryal box C/D RNPs.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Box C/D ribonucleoprotein particles (RNPs) are 2'-O-methylation enzymes required for maturation of ribosomal and small nuclear RNA. Previous biochemical and structural studies of the box C/D RNPs were limited by the unavailability of purified intact RNPs. We developed a bacterial co-expression strategy based on the combined use of a multi-gene expression system and a tRNA-scaffold construct that allowed the expression and purification of homogeneous archaeal and human box C/D RNPs. While the co-expressed and co-purified archaeal box C/D RNP was found to be fully active in a 2'-O-methylation assay, the intact human U14 box C/D RNP showed no detectable catalytic activity, consistent with the earlier findings that assembly of eukaryotic box C/D RNPs is nonspontaneous and requires additional protein factors. Our systems provide a means for further biochemical and structural characterization of box C/D RNPs and their assembly factors.
Related JoVE Video
STAT3 serine 727 phosphorylation influences clinical outcome in glioblastoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Besides STAT3 tyrosine 705 phosphorylation (pTyr705-STAT3), phosphorylation of STAT3 at serine 727 (pSer727-STAT3) is shown to contribute to tumorigenesis and be closely related with resistance to radiotherapy and chemotherapy in glioma, but there is currently no study regarding its relevance to prognosis in glioblastoma (GBM). Here, the expression of phosphorylated STAT3 was detected in tumor specimens from 88 patients with newly diagnosed GBM by immunohistochemistry, the Kaplan-Meier survival curve and COX proportional hazards regression model were applied to estimate its influences on progression-free survival (PFS) and overall survival (OS). Immunohistochemical assay showed elevated expression of pSer727-STAT3 in GBM compared with normal brain tissue. Univariate analysis indicated significant correlations of high percentage of pSer727-STAT3 positive tumor cells with shorter PFS (P = 0.006) and OS (P = 0.002). In multivariate analysis, high pSer727-STAT3 expression was demonstrated as an independent unfavorable prognostic indicator for PFS (HR 1.830, P = 0.022) and OS (HR 1.797, P = 0.040). And patients with high expression of both pTyr705-STAT3 and pSer727-STAT3 had a poorer prognosis compared with the remainder (P < 0.005). In conclusion, the high proportion of pSer727-STAT3 positive neoplastic cells in GBM is an independent unfavorable prognostic factor, and increased expression of both pTyr705-STAT3 and pSer727-STAT3 is predictive of poorer clinical outcome, thereby adding to the growing evidence that STAT3 inhibition may be a potential therapeutic strategy in glioblastoma.
Related JoVE Video
Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 12-12-2013
Show Abstract
Hide Abstract
Background and aims: Fluorofenidone (AKF-PD) is a novel pyridone agent. The purpose of this study is to investigate the inhibitory effects of AKF-PD on liver fibrosis in rats and the involved molecular mechanism related to hepatic stellate cells (HSCs). Methods: Rats treated with dimethylnitrosamine (DMN) or CCl4 were randomly divided into normal, model, AKF-PD treatment, and pirfenidone (PFD) treatment groups. The isolated primary rat HSCs were treated with AKF-PD and PFD respectively. Cell proliferation and cell cycle distribution were analyzed by bromodeoxyuridine (BrdU) and flow cytometry, respectively. The expression of collagen I and ?-SMA were determined by western blot, immunohistochemical staining and real-time RT-PCR. The expression of cyclin D1, cyclin E, p27(kip1), phosphorylation of MEK, ERK, Akt and 70-kDa ribosomal S6 kinase (p70S6K) were detected by western blot. Results: AKF-PD significantly inhibited PDGF-BB induced HSCs proliferation and activation by attenuating the expression of collagen I and ?-SMA, causing G0/G1 phase cell cycle arrest, reducing expression of cyclin D1, cyclin E and promoting expression of p27(kip1). AKF-PD also down-regulated PDGF-BB induced MEK, ERK, Akt and p70S6K phosphorylation in HSCs. In rat liver fibrosis, AKF-PD alleviated hepatic fibrosis by decreasing necro-inflammatory score, semiquantitative score, and reducing expression of collagen I, ?-SMA. Conclusions: AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via the ERK/MAPK and PI3K/Akt signaling pathways. AKF-PD may be used as a potential novel therapeutic agent against liver fibrosis.
Related JoVE Video
Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-02-2013
Show Abstract
Hide Abstract
Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles.
Related JoVE Video
Ni-catalyzed reductive homocoupling of unactivated alkyl bromides at room temperature and its synthetic application.
J. Org. Chem.
PUBLISHED: 10-14-2013
Show Abstract
Hide Abstract
A room-temperature Ni-catalyzed reductive approach to homocoupling of unactivated primary, secondary, and tertiary alkyl bromides is described. The catalytic system can be easily generated from air-stable and cheap materials and demonstrates broad functional group tolerance, thus allowing facile access to useful dimeric triterpene and lignan-like molecules. Moreover, the dimerization of tertiary bromide 6 efficiently establishes sterically hindered vicinal quaternary carbons (C3a and C3a), which is a key linkage of intriguing bispyrrolo[2,3-b]indoline alkaloids, thereby enabling us to complete the total syntheses of racemic chimonanthine (9) and folicanthine (10). In addition, this dimerization method can be expanded to the highly stereoselective synthesis of bisperhydrofuro[2,3-b]furan (5a) and the dimeric spiroketal 5b, signifying the involvement of possible radical species.
Related JoVE Video
Collective synthesis of several 2,7-cyclolignans and their correlation by chemical transformations.
Org. Biomol. Chem.
PUBLISHED: 10-08-2013
Show Abstract
Hide Abstract
Collective synthesis of anti-malarial 2,7-cyclolignans has been stereoselectively achieved employing (±)-cyclogalgravin (2) as a linchpin through a series of functional group conversions, including redox reactions. Interestingly, 2 can be correlated with the neolignan (±)-kadangustin J (1) isolated from a different plant source, through a highly efficient dehydrative cyclization reaction with excellent diastereotopic differentiation of the veratryl group and concomitant construction of the C1–C7 bond. It is noteworthy that the first total synthesis of stereodivergent (±)-8,8-epi-aristoligone (5), (±)-8-epi-aristoligone (7), (±)-8-epi-8-OH-aristoligone (8) and (±)-8-epi-aristoligol (9) was demonstrated.
Related JoVE Video
Off-on-off fluorescent chemosensor for pH measurement with a terbium(iii) complex based on a tripodal salicylic-acid derivative.
Org. Biomol. Chem.
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
New Tb(iii) and Eu(iii) complexes have been synthesized as potential pH probes using a tripodal substituted-salicylic ligand (H3). Among them, this carboxylate ligand is found to be a good sensitizer for Tb(iii) emission owing to the superior match of the triplet energy level of the ligand with the (5)D4 emitting level of Tb(iii). The resulting · complex exhibited high sensitivity in the physiological pH range with significant "off-on-off" fluorescence changes in aqueous solution. Furthermore, this unique rare-earth complex has been successfully used to monitor pH variations within HeLa cells and with filter papers.
Related JoVE Video
Dipyrido[3,2-a:2,3-c]phenazine-Based Donor-Acceptor Aromatic Heterocyclic Compounds with Thienyl and Triphenylamino Chromophores at the 2,7- and/or 10,13-Positions.
Chem Asian J
PUBLISHED: 09-21-2013
Show Abstract
Hide Abstract
A series of T- and H-shaped donor-acceptor (D-A) types of dipyrido[3,2-a:2,3-c]phenazine (DPPZ)-based molecules, extended by thienyl and triphenylamino chromophores at the 2,7-(bottom) and/or 10,13-positions (top), have been designed and prepared successfully. Synthetic, structural, thermal, spectral, and computational comparisons have been carried out for related compounds because of their adjustable intramolecular charge-transfer properties. It is noted that a pair of structural isomers (5 and 6) has been obtained, respectively, where distinguishable UV/Vis and fluorescence spectra, electrochemical activity, thermal stability, and bandgaps are observed. Furthermore, compounds 6, 8, 10, 11, 13, and 15 exhibit excellent thermal stability, and the Td10 values for them are found to range from 524 to 646?°C, which can be regarded as one of the best groups of thermally stable compounds among organic small molecules. In addition, theoretical calculations were performed, and the structure-property relationships were examined to reveal the effects of the position and number of donor arms on the DPPZ acceptor core.
Related JoVE Video
Asymmetrical/symmetrical D-?-A/D-?-D thiazole-containing aromatic heterocyclic fluorescent compounds having the same triphenylamino chromophores.
J. Org. Chem.
PUBLISHED: 08-28-2013
Show Abstract
Hide Abstract
A family of linear asymmetrical D-?-A and symmetrical D-?-D types of thiazole-based aromatic heterocyclic fluorescent compounds bearing various electron-donating and electron-withdrawing tails (bromo, triphenylamino, pyridyl, thienyl and benzoic acid) have been designed and prepared successfully. Synthetic, structural, thermal, spectral and computational comparisons have been carried out for related compounds because of their adjustable electronic properties. It is interesting to mention that compound 2 can be prepared from 5-bromothiazole by one-pot Suzuki-Miyaura coupling and subsequent C-H activation reactions via a 5-TPA-substituted thiazole intermediate 1. X-ray single-crystal structures of six compounds indicate that they all crystallize in the triclinic P1 space group and the thiazole core exhibits different dihedral angles with its adjacent benzene ring of the triphenylamino group (3.6(3)-40.8(3)°). The photophysical and electrochemical results demonstrate that compound 7 exhibits high electrochemical activity with a green fluorescence emission. Meanwhile, compounds 1, 2, and 6 show high luminescence quantum yields, and compound 8 exhibits excellent thermal stability (T(d(10)) = 503 °C).
Related JoVE Video
Synthesis, structures, and magnetic properties of a family of 3d-4f [Na2Fe6Ln2] complexes (Ln = Y, Gd and Dy): effect of ligands on the connection of inorganic subunits.
Dalton Trans
PUBLISHED: 08-24-2013
Show Abstract
Hide Abstract
A family of 3d-4f heterometallic compounds [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(HL)(4)(CH(3)O)(4)(PhCO(2))(6)] (1, H(4)L = 2-{[(2-hydroxy-3-methoxyphenyl)methylene]amino}-2-(hydroxymethyl)-1,3-propanediol), [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(L)(4)(CH(3)O)(4)(PhCO(2))(6)(H(2)O)] (2, H(3)L = (E)-2-ethyl-2-(2-hydroxy-3-methoxybenzylideneamino)propane-1,3-diol), [Na(2)Fe(III)(6)Dy(III)(2)(N(3))(4)(L)(4)(CH(3)O)(4)(Bu(t)CO(2))(6)] (3) [Na(2)Fe(III)(6)Y(III)(2)(N(3))(4)(L)(4)(CH(3)O)(4)(PhCO(2))(6)(H(2)O)] (4), and [Na(2)Fe(III)(6)Gd(III)(2)(N(3))(4)(L)(4)(CH(3)O)(4)(PhCO(2))(6)(CH(3)OH)(2)] (5) have been prepared using Schiff-base ligands, trinuclear iron precursor complexes, azides and lanthanide nitrates as reactants. In compounds 1 and 2, the structure of the [Na(2)Fe(III)(6)Dy(III)(2)] cluster forms a couple of cis,trans-isomers with substitution of methyl for a free hydroxyl group which belongs to the Schiff-base ligand. When the pivalates are employed instead of bulkier benzoates, the trans-[Na(2)Fe(III)(6)Dy(III)(2)] clusters act as network nodes in the formation of rhombic grid-like layered structures in compound 2. Compounds 2, 4 and 5 have similar metallic cores, only with different crystal solvent molecules. The magnetic measurements on all the compounds indicate dominant antiferromagnetic interactions between the metal centers.
Related JoVE Video
[Changes in expression of tyrosine hydroxylase by CD4+ T lymphocytes in lymphoid tissues of DBA/1 mice with collagen-induced arthritis].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 08-15-2013
Show Abstract
Hide Abstract
To show the involvement of lymphocyte-derived catecholamines in the pathogenesis of rheumatoid arthritis (RA), we investigated the change in expression of tyrosine hydroxylase (TH), a rate-limiting enzyme of catecholamine synthesis, by CD4+ T lymphocytes in lymphoid tissues of DBA/1 mice with collagen-induced arthritis (CIA).
Related JoVE Video
Vertical graphene spin valve with Ohmic contacts.
Nanoscale
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
Evident spin valve signals are observed in Co/graphene/Co sandwich structures with both monolayer and two-layer graphene stacks at temperatures from 1.5 K to 300 K. All the devices demonstrate linear current-voltage curves, indicating that an Ohmic property is dominating rather than a tunneling effect. The vertical graphene spin valves have potential applications in high-density non-volatile memories.
Related JoVE Video
Reversible insulator-metal transition of LaAlO?/SrTiO? interface for nonvolatile memory.
Sci Rep
PUBLISHED: 07-29-2013
Show Abstract
Hide Abstract
We report a new type of memory device based on insulating LaAlO?/SrTiO? (LAO/STO) hetero-interface. The microstructures of the LAO/STO interface are characterized by Cs-corrected scanning transmission electron microscopy, which reveals the element intermixing at the interface. The inhomogeneous element distribution may result in carrier localization, which is responsible for the insulating state. The insulating state of such interface can be converted to metallic state by light illumination and the metallic state maintains after light off due to giant persistent photoconductivity (PPC) effect. The on/off ratio between the PPC and the initial dark conductance is as large as 10?. The metallic state also can be converted back to insulating state by applying gate voltage. Reversible and reproducible resistive switching makes LAO/STO interface promising as a nonvolatile memory. Our results deepen the understanding of PPC phenomenon in LAO/STO, and pave the way for the development of all-oxide electronics integrating information storage devices.
Related JoVE Video
Solution structure and backbone dynamics of human Raf-1 kinase inhibitor protein.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-10-2013
Show Abstract
Hide Abstract
Human Raf-1 kinase inhibitor protein (hRKIP) is a small multi-functional protein of 187 residues. It contains a conserved pocket, which binds a wide range of ligands from various small molecules to distinct proteins. To provide a structural basis for the ligand diversity of RKIP, we herein determined the solution structure of hRKIP, and analyzed its structural dynamics. In solution, hRKIP mainly comprises two antiparallel ? sheets, two ? helices and two 3?? helices. NMR dynamic analysis reveals that the overall structure of hRKIP is rigid, but its C-terminal helix which is close to the ligand-binding site is mobile. In addition, residues around the ligand-binding pocket exhibit significant conformational exchange on the ?s-ms timescale. Conformational flexibility may allow the ligand-binding pocket and the C-terminal helix to adopt various conformations to interact with different substrates. This work may shed light on the underlying molecular mechanisms of how hRKIP recognizes and binds diverse substrate ligands.
Related JoVE Video
IDBA-tran: a more robust de novo de Bruijn graph assembler for transcriptomes with uneven expression levels.
Bioinformatics
PUBLISHED: 07-02-2013
Show Abstract
Hide Abstract
RNA sequencing based on next-generation sequencing technology is effective for analyzing transcriptomes. Like de novo genome assembly, de novo transcriptome assembly does not rely on any reference genome or additional annotation information, but is more difficult. In particular, isoforms can have very uneven expression levels (e.g. 1:100), which make it very difficult to identify low-expressed isoforms. One challenge is to remove erroneous vertices/edges with high multiplicity (produced by high-expressed isoforms) in the de Bruijn graph without removing correct ones with not-so-high multiplicity from low-expressed isoforms. Failing to do so will result in the loss of low-expressed isoforms or having complicated subgraphs with transcripts of different genes mixed together due to erroneous vertices/edges. Contributions: Unlike existing tools, which remove erroneous vertices/edges with multiplicities lower than a global threshold, we use a probabilistic progressive approach to iteratively remove them with local thresholds. This enables us to decompose the graph into disconnected components, each containing a few genes, if not a single gene, while retaining many correct vertices/edges of low-expressed isoforms. Combined with existing techniques, IDBA-Tran is able to assemble both high-expressed and low-expressed transcripts and outperform existing assemblers in terms of sensitivity and specificity for both simulated and real data.
Related JoVE Video
Interleukin-6 prevents NMDA-induced neuronal Ca2+ overload via suppression of IP3 receptors.
Brain Inj
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
The mechanism underlying interleukin-6 (IL-6) prevention of N-methyl-D-aspartate (NMDA)-induced neuronal Ca(2+) overload was explored at the profile of Ca(2+) channel receptors, including NMDA, inositol 1,4,5-trisphosphate and ryanodine receptors (NMDAR, IP3R and RyR, respectively).
Related JoVE Video
Graphene plasmon enhanced photoluminescence in ZnO microwires.
Nanoscale
PUBLISHED: 05-23-2013
Show Abstract
Hide Abstract
We report the temperature dependent photoluminescence (PL) properties of monolayer graphene-Au-nanoparticle-ZnO (GAZ) microwire hybrid structures. By comparing with the bare ZnO wire without coverage of graphene, a three times enhancement of PL was found in the GAZ hybrid structures. The enhancement is attributed to the coupling between the PL photons from ZnO and the graphene surface plasmons with ~1-2 nm Au as a corrugated surface. Our results may be valuable for designing graphene-ZnO hybrid based optical and photoelectrical devices.
Related JoVE Video
Tyrosine hydroxylase expression in CD4(+) T cells is associated with joint inflammatory alleviation in collagen type II-induced arthritis.
Rheumatol. Int.
PUBLISHED: 05-21-2013
Show Abstract
Hide Abstract
We have recently reported that CD4(+) T cells synthesize and secrete catecholamines that facilitate a shift of T helper 1 (Th1)/Th2 balance toward Th2 polarization. In this study, we used an animal model of human rheumatoid arthritis, collagen type II-induced arthritis (CIA), to explore relationship between catecholamine production in CD4(+) T cells and Th1-/Th2-mediated joint inflammation. Histopathological observation of ankle joints of CIA mice displayed an evident inflammatory change on day 35 and a major damage to bones on day 55 post-immunization. Expression of Th1-specific transcription factor, T-bet, and cytokines, IL-2 and IFN-?, and Th2-specific transcription factor, GATA-3, and cytokines, IL-4 and IL-10, was all upregulated on days 35 and 55 post-immunization, but the elevated Th1 response tended to decrease and the enhanced Th2 response tended to increase with the CIA progression. Expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of catecholamines, dramatically increased in ankle joints of CIA mice, although this increase was reduced on day 55 relative to that on day 35 post-immunization. In synovial tissue of CIA ankle joints but not normal joints, CD4-, T-bet-, GATA-3-, and TH-immunoreactive cells were found. Importantly, co-expressed cells with CD4 and TH, T-bet and TH, and GATA-3 and TH were observed in synovial tissue of CIA ankle joints. These results suggest that an increase in catecholamine production occurs in inflamed joints of CIA. The catecholamines are, at least in part, from Th1 and Th2 cells, and they may be related to joint inflammatory alleviation in CIA progression.
Related JoVE Video
Mitoxantrone targets human ubiquitin-specific peptidase 11 (USP11) and is a potent inhibitor of pancreatic cancer cell survival.
Mol. Cancer Res.
PUBLISHED: 05-21-2013
Show Abstract
Hide Abstract
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, with a 95% five-year mortality rate. For over a decade, gemcitabine (GEM) has been the established first-line treatment for this disease despite suboptimal response rates. The development of PARP inhibitors that target the DNA damage repair (DDR) system in PDA cells has generated encouraging results. Ubiquitin-specific peptidase 11 (USP11), an enzyme that interacts with the DDR protein BRCA2, was recently discovered to play a key role in DNA double-strand break repair and may be a novel therapeutic target. A systematic high-throughput approach was used to biochemically screen 2,000 U.S. Food and Drug Administration (FDA)-approved compounds for inhibition of USP11 enzymatic activity. Six pharmacologically active small molecules that inhibit USP11 enzymatic activity were identified. An in vitro drug sensitivity assay demonstrated that one of these USP11 inhibitors, mitoxantrone, impacted PDA cell survival with an IC50 of less than 10 nM. Importantly, across six different PDA cell lines, two with defects in the Fanconi anemia/BRCA2 pathway (Hs766T and Capan-1), mitoxantrone is 40- to 20,000-fold more potent than GEM, with increased endogenous USP11 mRNA levels associated with increased sensitivity to mitoxantrone. Interestingly, USP11 silencing in PDA cells also enhanced sensitivity to GEM. These findings establish a preclinical model for the rapid discovery of FDA-approved compounds and identify USP11 as a target of mitoxantrone in PDA. Implications: This high-throughput approach provides a strong rationale to study mitoxantrone in an early-phase clinical setting for the treatment of PDA.
Related JoVE Video
Development of a high-throughput screening-compatible assay for the discovery of inhibitors of the AF4-AF9 interaction using AlphaScreen technology.
Assay Drug Dev Technol
PUBLISHED: 05-18-2013
Show Abstract
Hide Abstract
Rearrangements of the mixed-lineage leukemia (MLL) gene occur predominately in pediatric leukemia cases and are generally predictors of a poor prognosis. These chromosomal rearrangements result in fusion of the protein MLL to one of more than 60 protein partners. MLL fusions are potent inducers of leukemia through activation of oncogene expression; therefore, targeting this transcriptional activation function may arrest MLL-rearranged (MLL-R) leukemia. Leukemic cell lines harboring the most common fusion protein, MLL-AF4, require the direct interaction of AF4 with the transcription factor AF9 to survive and self-renew; disrupting this interaction with a cell-penetrating AF4-derived peptide results in cell death, suggesting that the AF4-AF9 interaction could be a viable target for a novel MLL-R leukemia therapy. Here we describe the use of AlphaScreen technology to develop a high-throughput screening (HTS) assay to detect nonpeptidic inhibitors of AF4-AF9 binding. The assay is economical, requiring only low nanomolar concentrations of biotinylated AF4-derived peptide and FLAG-tagged AF9 in low-volume 384-well plates. A Z-factor of 0.71 and a signal-to-background ratio of 21.3 showed the assay to be robust, and sensitivity to inhibition was demonstrated with competing AF4-derived peptides. Two pilot screens comprising 5,680 compounds served as validation for HTS at Nemours and the Broad Institute. Assay artifacts were excluded using a counterscreen comprising a biotinylated FLAG peptide. This is the first reported HTS-compatible assay to identify compounds that inhibit a key binding interaction of an MLL fusion partner, and the results presented here demonstrate suitability for screening large chemical libraries in high-density, low-volume plate formats.
Related JoVE Video
High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study.
Radiat Oncol
PUBLISHED: 05-05-2013
Show Abstract
Hide Abstract
Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC.
Related JoVE Video
simple hit counter

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.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.