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.
Smoking adversely affects treatment response, outcome and relapse in tuberculosis.
Eur. Respir. J.
PUBLISHED: 11-01-2014
Show Abstract
Hide Abstract
The impact of smoking on tuberculosis outcome was evaluated in a territory-wide treatment programme. 16 345 consecutive patients undergoing chemotherapy for active tuberculosis in government chest clinics in Hong Kong from 2001 to 2003 were followed up prospectively for 2 years for treatment outcome and subsequently tracked through the territory-wide tuberculosis notification registry for relapse until the end of 2012. Smoking was associated with more extensive lung disease, lung cavitation and positive sputum smear and culture at the baseline. In both current smokers and ex-smokers, sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment. Both categories of smokers were significantly less likely to achieve cure or treatment completion within 2 years. Overall, 16.7% of unsuccessful treatment outcomes were attributable to smoking, with the key contributor being default in current smokers and death in ex-smokers. Among successful treatment completers, there was a clear gradient (hazard ratios of 1.00, 1.33, and 1.63) of relapse risk from never-smokers to ex-smokers and current smokers, with an overall population attributable risk of 19.4% (current smokers: 12.2%; ex-smokers: 7.2%). Smoking adversely affects baseline disease severity, bacteriological response, treatment outcome and relapse in tuberculosis. Smoking cessation likely reduces relapse and secondary transmission.
Related JoVE Video
Modified Salicylanilide and 3-Phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione Derivatives as Novel Inhibitors of Osteoclast Differentiation and Bone Resorption.
J. Med. Chem.
PUBLISHED: 09-25-2014
Show Abstract
Hide Abstract
Inhibition of osteoclast formation is a potential strategy to prevent inflammatory bone resorption and to treat bone diseases. In the present work, the purpose was to discover modified salicylanilides and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives as potential antiosteoclastogenic agents. Their inhibitory effects on RANKL-induced osteoclastogenesis from RAW264.7 cells were evaluated by TRAP stain assay. The most potent compounds, 1d and 5d, suppressed RANKL-induced osteoclast formation and TRAP activity dose-dependently. The cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds did not result from their cytotoxicity. Moreover, both compounds downregulated RANKL-induced NF-?B and NFATc1 in the nucleus, suppressed the expression of osteoclastogenesis-related marker genes during osteoclastogenesis, and prevented osteoclastic bone resorption but did not impair osteoblast differentiation in MC3T3-E1. Therefore, these modified salicylanilides and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones could be potential lead compounds for the development of a new class of antiresorptive agents.
Related JoVE Video
Effect of elevated intraocular pressure on the thickness changes of cat laminar and prelaminar tissue using optical coherence tomography.
Biomed Mater Eng
PUBLISHED: 09-18-2014
Show Abstract
Hide Abstract
The aim of this study was to examine shape the changes of the lamina cribrosa (LC) under different intraocular pressures (IOPs) with different periods. Images of the optic nerve head were obtained using enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT). After an initial scan of the IOP at native pressure, subsequent scanning was taken when the IOP values reached 40, 60, 80 and 100 mm Hg. Then scans continued with the IOP maintained at 100 mm Hg for 1 hour, 2 hours, 3 hours and 4 hours. The thicknesses of the LC and prelaminar tissue were measured and the curvature of the LC was calculated. Our study found that as IOP increased, the thicknesses of both LC and prelaminar tissue decreased and the thickness variation of the LC correlated significantly with the increases of IOP when IOP was higher than 60 mm Hg. An exponential function was proposed to express the relationship between IOP and the thickness variations of LC and prelaminar tissue. Creep curves of the LC and prelaminar tissue was also obtained using the Prony model. In conclusion, both the thickness of the prelaminar tissue and LC thinned as the IOP elevated. The thickness of the LC also decreased after 4 hours of constant 100 mm Hg pressure.
Related JoVE Video
Raman mapping investigation of chemical vapor deposition-fabricated twisted bilayer graphene with irregular grains.
Phys Chem Chem Phys
PUBLISHED: 09-08-2014
Show Abstract
Hide Abstract
Bilayer graphene as a prototype of two-dimensional stacked material has recently attracted great attention. The twist angle between graphene layers adds another dimension to control its properties. In this study, we used Raman mapping to investigate the twist angle dependence of properties of twisted bilayer graphene (TBG) with irregular grains that was fabricated by chemical vapor deposition (CVD). Different Raman parameters including intensity, width, and position of G and 2D peaks were used to distinguish TBG with different twist angles. The statistical results from Raman imaging on the distribution of twist angle are consistent with the results from selected area election diffraction (SAED). Finally, the Raman peak at approximately 1347 cm(-1) for TBG with a large twist angle was assigned to the D-like peak, although it has similar excitation energy dependence of frequency as the defect-induced D peak. Theoretical calculation further confirmed that vacancy-like defect is not favored in the formation energy for TBG with a large twist angle as compared to monolayer graphene or TBG with other twist angles. These results will help to advance the understanding of TBG properties, especially for CVD samples with irregular grains.
Related JoVE Video
Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin-induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mitochondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice daily for 4 weeks. Body weight (BW), fasting blood glucose (FBG) level, and glucose disposal (IPGTT) were measured during or after the treatment. The results showed a dose-dependent reduction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total cholesterol and triglyceride levels in the diabetic mice. In addition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol (200 mg/kg) rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) ? was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol, resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal muscle of HFD/STZ-induced diabetic mice.
Related JoVE Video
[Chemical constituents against hepatic fibrosis from Phyllodium pulchellum roots].
Zhong Yao Cai
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
To investigate the bioactive constituents against hepatic fibrosis from the roots of Phyllodium pulchellum.
Related JoVE Video
Reference interval for osteocalcin in Chinese Han ethnic males from the Fangchenggang Area Male Health and Examination Survey.
Clin. Lab.
PUBLISHED: 08-20-2014
Show Abstract
Hide Abstract
The aim of this study was to set a reference interval (RI) for osteocalcin (OC) in a healthy Han male population from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project and study the effects of age, BMI, smoking, and alcohol consumption.
Related JoVE Video
A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.
PLoS ONE
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.
Related JoVE Video
Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma.
Biomaterials
PUBLISHED: 07-22-2014
Show Abstract
Hide Abstract
Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-?, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.
Related JoVE Video
ERCC1 expression levels predict the outcome of platinum-based chemotherapies in advanced bladder cancer: a meta-analysis.
Anticancer Drugs
PUBLISHED: 07-16-2014
Show Abstract
Hide Abstract
The objective of this study was to provide a precise evaluation of whether expression levels of excision repair cross-complementation group 1 (ERCC1) are associated with objective response, overall survival (OS), and median survival in patients with advanced bladder cancer treated with platinum-based chemotherapy. Systematic computerized searches of the electronic databases PubMed, EMBASE, Ovid, ASCO, and CNKI were performed and a meta-analysis was carried out to evaluate the correlation between ERCC1 expression levels and objective response rate, OS, or progression-free survival in patients with advanced bladder cancer receiving platinum-based chemotherapy. References within the articles identified were also searched manually. STATA package version 11.0 was used for the comprehensive quantitative analyses. A total of six studies involving 356 patients, of which ERCC1 expression was high/positive in 138 (38.8%) and low/negative in 218 (61.2%), were included in the meta-analysis. The median age of the patients was 63.7 years. The objective response rate favored patients with ERCC1 low/negative expression after platinum-based chemotherapy, but showed no significant difference [odds ratio 0.86, 95% confidence interval (CI) 0.36-2.06, P=0.734]. The median OS time and the median progression-free survival time were significantly prolonged when ERCC1 low/negative expression was compared with ERCC1 high/positive expression (hazard ratio 0.69, 95% CI 0.54-0.89, P=0.004, and hazard ratio 0.76, 95% CI 0.66-0.89, P=0.000, respectively). In conclusion, low/negative expression of ERCC1 was associated with higher objective response, median progression-free survival, and median OS in patients with advanced bladder cancer treated with platinum-based chemotherapy. ERCC1 may be a suitable marker of prognosis and sensitivity to platinum-based chemotherapy in patients with advanced bladder cancer. Larger studies and further clinical trials are warranted to confirm these findings.
Related JoVE Video
Recombinant outer membrane protein A fragments protect against Escherichia coli meningitis.
J Microbiol Immunol Infect
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
Although the mortality rates have decreased over the past few decades, neonatal meningitis is still a severe disease with high morbidity. Moreover, approximately 40% of survivors exhibit neurological sequelae. Escherichia coli is the major Gram-negative bacterial pathogen in neonatal meningitis. The N-terminal ?-barrel domain of the outer membrane protein A (OmpA) of E. coli is essential for effective protein conformation and function and contains four surface-exposed hydrophilic loops. In this study, we expressed different fragments of the four ring structures of the N-terminal domain, and investigated whether these recombinant OmpA fragments can protect mice from death after E. coli infection.
Related JoVE Video
Palladium(0)-catalyzed cross-coupling of 1,1-diboronates with vinyl bromides and 1,1-dibromoalkenes.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-08-2014
Show Abstract
Hide Abstract
Palladium-catalyzed cross-coupling reactions of 1,1-diboronates with vinyl bromides and dibromoalkenes were found to afford 1,4-dienes and allenes, respectively. These reactions utilize the high reactivities of both 1,1-diboronates and allylboron intermediates generated in the initial coupling.
Related JoVE Video
Knockdown of Aurora-B inhibits osteosarcoma cell invasion and migration via modulating PI3K/Akt/NF-?B signaling pathway.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
Show Abstract
Hide Abstract
Increasing evidences reveal that Aurora-B may be involved in metastasis of malignant tumor. In this study, we investigated the inhibitory effect of Aurora-B on invasion and migration of OS cells and the activity of PI3K/Akt/NF-?B signaling pathway in vitro. The expression of Aurora-B and p-Akt (Ser473) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between Aurora-B and p-Akt was investigated. The results showed that there was a positive correlation between Aurora-B and p-Akt protein expression. Furthermore, we down-regulated the expression of Aurora-B through a recombinant lentivirus (Lv-shAURKB). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. Results showed that silencing Aurora-B inhibited cell migratory and invasive ability of OS cells in vitro. Finally, knockdown of Aurora-B suppresses the activity of PI3K/Akt/NF-?B signaling pathway in OS cells. Our results indicated that knockdown of Aurora-B suppresses OS cells migratory and invasive ability via modulating the "PI3K/Akt/NF-?B" signaling pathway in vitro. The Aurora-B blocker may be a new therapeutic strategy in OS management.
Related JoVE Video
Multiple variants in UGT1A1 gene are factors to develop indirect hyper-bilirubinemia.
Hepatobiliary Surg Nutr
PUBLISHED: 06-12-2014
Show Abstract
Hide Abstract
Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATA box upstream of UGT1A1 associated with Gilbert's syndrome. To investigate the role of UGT1A1 in the pathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirect hyper-bilirubinemia for genotypes of promoter [(TA)6TAA6, (TA)7TAA7] and coding region [nucleotide (nt)-211, nt-686, nt-1,091 and nt-1,456] of UGT1A1. Thirty-six of the patients (45.6%) were found to have Gilbert's syndrome with 7/7 genotype; among them, 14 also carried variants at nt-686. Forty-two patients (43.3%) had the 6/7 genotype; among them, 36 patients were found to have one or more variants in the coding region. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert's syndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ?2.5 mg/dL carried the Gilbert's syndrome genotype, while only 23.9% of patients with serum total bilirubin level <2.5 mg/dL carry the same genotype (P=0.0006). Forty-one of the 61 non-Gilbert's patients had one homogenous variants or two or more heterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygous variant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia.
Related JoVE Video
NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis.
Tumour Biol.
PUBLISHED: 06-04-2014
Show Abstract
Hide Abstract
A number of studies have investigated the association between the NBS1 Glu185Gln (rs1805794, 8360 G?>?C) polymorphism and risk for urinary system cancer including bladder cancer, prostate cancer, and renal cell cancer; however, the findings are conflicting. We conducted a meta-analysis focusing on eight published studies with 3,542 cases and 4,210 controls to derive a more precise evaluation of the relationship between the NBS1 Glu185Gln polymorphism and urinary system cancer susceptibility. Overall, the NBS1 Glu185Gln polymorphism was significantly related to increased risk for urinary system cancer (homozygous model: odds ratio (OR)?=?1.23, 95 % confidence interval (95 % CI)?=?1.05-1.44, p?=?0.011; heterozygous model: OR?=?1.14, 95 % CI?=?1.04-1.26, p?=?0.008; dominant model: OR?=?1.16, 95 % CI?=?1.05-1.27, p?=?0.002; and Gln vs. Glu: OR?=?1.12, 95 % CI?=?1.04-1.20, p?=?0.002) and further stratification analysis indicated an increased risk for bladder cancer (heterozygous model: OR?=?1.13, 95 % CI?=?1.02-1.26, p?=?0.022; dominant model: OR?=?1.14, 95 % CI?=?1.03-1.26, p?=?0.014; and Gln vs. Glu: OR?=?1.09, 95 % CI?=?1.01-1.18, p?=?0.023) and Caucasian populations (homozygous model: OR?=?1.33, 95 % CI?=?1.11-1.59, p?=?0.002; heterozygous model: OR?=?1.16, 95 % CI?=?1.04-1.30, p?=?0.009; dominant model: OR?=?1.19, 95 % CI?=?1.07-1.32, p?=?0.001; and Gln vs. Glu: OR?=?1.15, 95 % CI?=?1.06-1.25, p?
Related JoVE Video
Focal fibrocartilaginous dysplasia in the thoracic vertebra: A case report.
Oncol Lett
PUBLISHED: 05-29-2014
Show Abstract
Hide Abstract
Focal fibrocartilaginous dysplasia (FFCD) is a rare, paraneoplastic disease that often presents in children and teenagers. Previous studies have reported cases of lesions in the proximal tibia and distal femur, as well as lesions in the upper extremities. The present study describes a case of FFCD on the transverse process and the rib. The imaging findings were found to correspond with the typical observations of FFCD and a biopsy from the nidus revealed pathological results similar to those of previous reports. Thus, the present study demonstrated that FFCD affects tubular bones as well as flat bones. Further studies are required to investigate the underlying mechanism and treatment of FFCD.
Related JoVE Video
Phenolic constituents from the roots of Phyllodium pulchellum.
J Asian Nat Prod Res
PUBLISHED: 04-23-2014
Show Abstract
Hide Abstract
Three new phenolic constituents 1-3 were obtained from the 95% ethanol extract of the roots of Phyllodium pulchellum (Leguminosae). Their structures were elucidated on the basis of spectroscopic analyses, such as NMR, UV, IR, HR-ESI-MS, and CD. Furthermore, in an in vitro bioassay, all compounds were tested for inhibitory effects against the proliferation of acetaldehyde-stimulated HSC-T6 cells, and compound 3 exhibited potent inhibitory activity with the IC50 value of 7.6 ?M.
Related JoVE Video
[Analysis of a case with typical Hutchinson-Gilford progeria syndrome with scleroderma-like skin changes and review of literature].
Zhonghua Er Ke Za Zhi
PUBLISHED: 04-18-2014
Show Abstract
Hide Abstract
To explore clinical, radiographical and genetic characteristics of classical Hutchinson-Gilford progeria syndrome (HGPS).
Related JoVE Video
Synthesis and luminescence properties of NaSrPO4:Eu2+, Tb3+, Mn2+ for WLED.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
Show Abstract
Hide Abstract
In order to obtain a single-host-white-light phosphor used for near ultraviolet (NUV) light emitting diodes (LEDs), the NaSrPO4:Eu2+, Tb3+, Mn2+ powder samples were synthesized via a high temperature solid-state reaction. XRD investigation shows a single phase. Energy transfer processes is discussed by analyzing the photoluminescence (PL) and photoluminescence excitation (PLE) spectra. White light emitting was observed upon the excitation of a wide range of ultraviolet (UV) wavelengths. The emission spectra are made up of blue, green and red emissions from Eu2+, Tb3+ and Mn2+ ions, respectively. The color shift is insignificant when altering the excitation wavelength from 260 nm to 400 nm. This indicates that the phosphor could exhibit good color stability when used in combination with a NUV LED.
Related JoVE Video
Towards the next generation of dual Bcl-2/Bcl-xL inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
Structural modifications of the left-hand side of compound 1 were identified which retained or improved potent binding to Bcl-2 and Bcl-xL in in vitro biochemical assays and had strong activity in an RS4;11 apoptotic cellular assay. For example, sulfoxide diastereomer 13 maintained good binding affinity and comparable cellular potency to 1 while improving aqueous solubility. The corresponding diastereomer (14) was significantly less potent in the cell, and docking studies suggest that this is due to a stereochemical preference for the RS versus SS sulfoxide. Appending a dimethylaminoethoxy side chain (27) adjacent to the benzylic position of the biphenyl moiety of 1 improved cellular activity by approximately three-fold, and this activity was corroborated in cell lines overexpressing Bcl-2 and Bcl-xL.
Related JoVE Video
The effect of chromium picolinate supplementation on the pancreas and macroangiopathy in type II diabetes mellitus rats.
J Diabetes Res
PUBLISHED: 02-27-2014
Show Abstract
Hide Abstract
The aim was to explore the effect of the chromium picolinate (CrPic) administration on the pancreas and macroangiopathy of type II diabetes mellitus rats.
Related JoVE Video
Laboratory study of nitrification, denitrification and anammox processes in membrane bioreactors considering periodic aeration.
J. Environ. Manage.
PUBLISHED: 02-24-2014
Show Abstract
Hide Abstract
The possibility of using membrane bioreactors (MBRs) in simultaneous nitrification-anammox-denitrification (SNAD) by considering periodic aeration cycles was investigated. Two separate reactors were operated to investigate the effect of different anammox biomass in the presence of nitrifying and denitrifying biomass on the final nitrogen removal efficiency. The results illustrated that the reactor with higher anammox biomass was more robust to oxygen cycling. Around 98% Total Nitrogen (TN) and 83% Total Organic Carbon (TOC) removal efficiencies were observed by applying one hour aeration over a four-hour cycle. Decreasing the aeration time to 30, 15, and 2 min during a four-hour cycle affected the final TN removal efficiencies. However, the effect of decreasing aeration on the TN removal efficiencies in the reactor with higher anammox biomass was much lower compared to the regular reactor. The nitrous oxide (N2O) emission was a function of aeration as well, and was lower in the reactor with higher anammox biomass. The results of q-PCR analysis confirmed the simultaneous co-existence of nitrifiers, anammox, and denitrifiers in both of the reactors. To simulate the TN removal in these reactors as a function of the aeration time, a new model, based on first order reaction kinetics for both denitrification and anammox was developed and yielded a good agreement with the experimental observations.
Related JoVE Video
A unique amidoanthraquinone derivative displays antiproliferative activity against human hormone-refractory metastatic prostate cancers through activation of LKB1-AMPK-mTOR signaling pathway.
Naunyn Schmiedebergs Arch. Pharmacol.
PUBLISHED: 02-17-2014
Show Abstract
Hide Abstract
Hormone-refractory metastatic prostate cancer (HRMPC), which is metastatic and resistant to hormone therapy, is an intractable problem in clinical treatment. Anthraquinone-based natural products and synthetic compounds have shown anticancer activity. However, cardiac toxicity is a major adverse reaction in these compounds. CC-36, a unique anthraquinone derivative, displayed higher antiproliferative activity in HRMPC than that in H9c2 cardiomyoblasts and normal prostate cells with the selectivity of five and twelve times, respectively. CC-36 caused G1 arrest of the cell cycle associated with an upregulation of p21 and downregulated levels of cyclin D1 and cyclin E expressions. Immunoprecipitation assay and Western blotting analysis showed that CC-36 triggered an increase of TSC1/TSC2 association and suppressed the phosphorylation of mammalian target of rapamycin (mTOR) (Ser2448) and p70 ribosomal protein S6 kinase (p70S6K) (Thr389), indicating the inhibition of both kinases' activities. CC-36 induced liver kinase B1 (LKB1) phosphorylation at Thr189, leading to LKB1 translocation from nucleus to cytosol for AMPK? phosphorylation (Thr172) and the kinase activation. The signaling pathway was validated using small interfering RNA (siRNA) technique with LKB1 knockdown. The combination treatment of MK2206 (a specific Akt inhibitor) with CC-36 showed a synergistic apoptosis in PC-3 cells indicating a potential combination strategy for LKB1 activators. Taken together, the data suggest that CC-36 displays anti-HRMPC activity through the activation of LKB1-AMPK pathway, leading to an inhibition of mTOR signaling and the induction of G1 arrest of the cell cycle. The combination use of Akt inhibitors with agents acting through LKB1-AMPK-mTOR pathway is a potential strategy for HRMPC treatment.
Related JoVE Video
Try113His and His139Arg polymorphisms in the microsomal epoxide hydrolase gene are not associated with risk of breast cancer.
Tumour Biol.
PUBLISHED: 02-17-2014
Show Abstract
Hide Abstract
Breast cancer may be caused by several factors, including polymorphisms in the microsomal epoxide hydrolase (mEH) gene. Previous work suggested an association between mEH polymorphism and risk of breast cancer, but the results have been inconsistent. PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure database were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphisms and susceptibility to breast cancer. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess the strength of the association. Seven studies involving 6,357 cases and 8,089 controls were included in this study. The Tyr113His mEH polymorphism did not affect breast cancer risk in the allelic contrast model (OR?=?0.99, 95 % CI?=?0.94-1.04, P?=?0.58), the dominant genetic model (OR?=?1.14, 95 % CI?=?0.88-1.48, P?=?0.33), or the recessive genetic model (OR?=?1.03, 95 % CI?=?0.96-1.10, P?=?0.43). Similarly, the His139Arg mEH polymorphism was not associated with breast cancer risk in the allelic contrast model (OR?=?0.97, 95 % CI?=?0.91-1.04, P?=?0.44), the dominant genetic model (OR?=?1.01, 95 % CI?=?0.84-1.21, P?=?0.94), or the recessive genetic model (OR?=?1.04, 95 % CI?=?0.96-1.12, P?=?0.35). The mEH polymorphisms Tyr113His and His139Arg are not risk factors for breast cancer. Further, large and well-designed studies are required to confirm this conclusion.
Related JoVE Video
A sensitive quantum dots-based "OFF-ON" fluorescent sensor for ruthenium anticancer drugs and ctDNA.
Colloids Surf B Biointerfaces
PUBLISHED: 02-17-2014
Show Abstract
Hide Abstract
In this contribution, a simple and sensitive fluorescent sensor for the determination of both the three ruthenium anticancer drugs (1 to 3) and calf thymus DNA (ctDNA) was established based on the CdTe quantum dots (QDs) fluorescence "OFF-ON" mode. Under the experimental conditions, the fluorescence of CdTe QDs can be effectively quenched by ruthenium anticancer drugs because of the surface binding of these drugs on CdTe QDs and the subsequent photoinduced electron transfer (PET) process from CdTe QDs to ruthenium anticancer drugs, which render the system into fluorescence "OFF" status. The system can then be "ON" after the addition of ctDNA which brought the restoration of CdTe QDs fluorescence intensity, since ruthenium anticancer drugs broke away from the surface of CdTe QDs and inserted into double helix structure of ctDNA. The fluorescence quenching effect of the CdTe QDs-ruthenium anticancer drugs systems was mainly concentration dependent, which could be used to detect three ruthenium anticancer drugs. The limits of detection were 5.5 × 10(-8) M for ruthenium anticancer drug 1, 7.0 × 10(-8) M for ruthenium anticancer drug 2, and 7.9× 10(-8) M for ruthenium anticancer drug 3, respectively. The relative restored fluorescence intensity was directly proportional to the concentration of ctDNA in the range of 1.0 × 10(-8) M ? 3.0 × 10(-7) M, with a correlation coefficient (R) of 0.9983 and a limit of detection of 1.1 × 10(-9) M. The relative standard deviation (RSD) for 1.5 × 10(-7) M ctDNA was 1.5% (n = 5). There was almost no interference to some common chemical compounds, nucleotides, amino acids, and proteins. The proposed method was applied to the determination of ctDNA in three synthetic samples with satisfactory results. The possible reaction mechanism of CdTe QDs fluorescence "OFF-ON" was further investigated. This simple and sensitive approach possessed some potential applications in the investigation of interaction between drug molecules and DNA.
Related JoVE Video
Interaction effect of work excitement and work frustration on the professional commitment of nurses in Taiwan.
J Nurs Res
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
The current shortage of professional nurses in Taiwan both undermines hospital quality of care and raises hospitals' human resource management costs. Few studies have concurrently investigated the interaction effect between professional commitment and, respectively, the positive and negative work attitudes of nurses. Results of this investigation may help improve strategies designed to raise nurse retention rates.
Related JoVE Video
Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance.
Mol Oncol
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
The mitotic kinesin KIF11 (also called Eg5) plays critical roles in spindle functions. Although a number of small-molecule inhibitors of KIF11 are currently in clinical development, drug-resistance could be developed through compensation by another kinesin called KIF15. Using a newly developed infrared-based cell system, we discovered that the effectiveness of one of the latest generations of KIF11 inhibitor (SB743921) could be enhanced with several inhibitors of Aurora A kinase. Evidence including live-cell imaging and isobologram analysis indicated that targeting KIF11 and Aurora A together promoted monoastral spindle formation and mitotic catastrophe synergistically, supporting a model of parallel pathways of centrosome regulation by Aurora A and KIF11. We also developed a KIF15-dependent SB743921-resistance cell model. Significantly, the drug-resistance could also be overcome with Aurora A inhibitors. These results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance.
Related JoVE Video
Ring fusion strategy for the synthesis of anthra[2,3-d]oxazole-2-thione-5,10-dione homologues as DNA topoisomerase inhibitors and as antitumor agents.
Eur J Med Chem
PUBLISHED: 02-07-2014
Show Abstract
Hide Abstract
The efficient synthesis of mono-substituted anthraquinones and ring fusion into anthra[2,3-d]oxazole-2-thione-5,10-dione derivatives were developed, and all the compounds were tested for their cytotoxicity against PC-3 cancer cell lines. Compounds 8, 14, 17 and 23 were selected by the NCI and 12, 17 and 19 were evaluated for topoisomerase I-mediated DNA relaxation. Among them, 17 appeared to be the most active compound of this series and not only showed higher inhibition when indicated from the low IC50 values against PC-3 cancer cell line but also attenuated the in vitro topoisomerase I-mediated DNA relaxation at low micromolar concentrations. All test compounds exhibited different cytostatic and cytotoxic activities for further developing potential anticancer drugs.
Related JoVE Video
Effects of storage time on Cytomegalovirus DNA stability in plasma determined by quantitative real-time PCR.
J. Virol. Methods
PUBLISHED: 02-01-2014
Show Abstract
Hide Abstract
Quantitative real-time PCR (QRT-PCR) assays are faster, more precise, and more sensitive quantitative laboratory methods for monitoring serial CMV DNA viral load in patients undergoing organ or hematopoietic stem cell transplantation. Clinical laboratories often face practical concerns about the storage of specimens from these patients to ensure the accuracy and reproducibility of CMV viral load test results. Different studies that have assessed CMV DNA stability have shown mixed results. Therefore, we analyzed CMV DNA stability of 30 EDTA plasma samples in samples containing between 300 and 100,000copies/ml over a 21 day period. The concentration of CMV DNA in all samples stored at 4°C for 21 days did not differ significantly from the baseline viral load (t=0.242, p=0.810), and no trend was evident to indicate continued degradation over a 2 week period.
Related JoVE Video
Valproate pretreatment protects pancreatic ?-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3?.
J. Biomed. Sci.
PUBLISHED: 02-01-2014
Show Abstract
Hide Abstract
Reduction of pancreatic ?-cells mass, major secondary to increased ?-cells apoptosis, is increasingly recognized as one of the main contributing factors to the pathogenesis of type 2 diabetes (T2D), and saturated free fatty acid palmitate has been shown to induce endoplasmic reticulum (ER) stress that may contribute to promoting ?-cells apoptosis. Recent literature suggests that valproate, a diffusely prescribed drug in the treatment of epilepsy and bipolar disorder, can inhibit glycogen synthase kinase-3? (GSK-3?) activity and has cytoprotective effects in neuronal cells and HepG2 cells. Thus, we hypothesized that valproate may protect INS-1 ?-cells from palmitate-induced apoptosis via inhibiting GSK-3?.
Related JoVE Video
RNA interference-mediated knockdown of Aurora-B alters the metastatic behavior of A549 cells via modulation of the phosphoinositide 3-kinase/Akt signaling pathway.
Oncol Lett
PUBLISHED: 01-29-2014
Show Abstract
Hide Abstract
Accumulating evidence has revealed that an elevated expression level of Aurora-B is associated with metastasis in various types of malignant tumor. However, it is currently unclear whether this molecule is involved in non-small lung cancer (NSCLC) metastasis, and the molecular mechanisms associated with Aurora-B and metastasis remain unknown. In the present study, in order to investigate whether Aurora-B is involved in the development and metastasis of NSCLC, the Aurora-B protein expression in NSCLC tissues was detected by immunohistochemistry and its association with metastasis was analyzed. The results revealed that the expression levels of the Aurora-B protein in tissues obtained from NSCLC patients with lymph node metastasis were significantly higher than those without metastatic disease. Furthermore, the effect of Aurora-B inhibition on A549 cell migration and invasion, as well as the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was evaluated. Aurora-B was inhibited in the A549 cells using short hairpin RNA, and the cell migration and invasion rates were investigated using wound healing and Transwell invasion assays. In addition, the expression of the main proteins in the PI3K/Akt/nuclear factor-?B (NF-?B) signaling pathway, and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot analysis. The results demonstrated that cell migration and invasion were decreased as a result of silencing Aurora-B. Furthermore, the activity of the PI3K/Akt/NF-?B signaling pathway and the expression of MMP-2 and -9 protein were suppressed by silencing Aurora-B. The results of the present study indicate that the knockdown of Aurora-B suppresses A549 cell invasion and migration via the inhibition of the PI3K/Akt signaling pathway in vitro and thus, targeting Aurora-B may present a potential treatment strategy for NSCLC.
Related JoVE Video
Comparative in vitro activity of sitafloxacin against bacteremic isolates of carbapenem resistant Acinetobacter baumannii complex.
J Microbiol Immunol Infect
PUBLISHED: 01-23-2014
Show Abstract
Hide Abstract
The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) complex has posed a great challenge to clinicians worldwide. Sitafloxacin has been shown to have in vitro activity against pathogens resistant to other fluoroquinolones. However, data comparing the anti-CRAB activity of sitafloxacin with that of other antimicrobial agents are limited.
Related JoVE Video
A salicylate-based small molecule HS-Cm exhibits immunomodulatory effects and inhibits dipeptidyl peptidase-IV activity in human T cells.
Eur. J. Pharmacol.
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
Activated T cells are key players in chronic inflammatory diseases, including atherosclerosis. Salicylates, like aspirin, display not only anti-inflammatory, anti-thrombotic, anti-atherosclerotic activities, but also immunomodulatory effects in T cells at high dosages. Here, we aimed to identify potent immunomodulators for T cells through cell-based screening from a mini-library of 300 salicylate-based small molecules, and elucidate the mechanisms. Human peripheral blood T cells were isolated from buffy coat. Phorbol 12-myristate 13-acetate plus ionomycin (P/I) was used to stimulate T cells. Cytokine production was measured by enzyme-linked immunosorbent assays. T cell activation markers were determined by flow cytometry. The activation of transcription factors and kinases was analyzed by western blotting, electrophoretic mobility shift assay, or kinase assay. Through library screening, we identified a small molecule named HS-Cm [C13H9ClFNO2; N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide] that exhibited potent immunomodulatory effects on T cells with low cytotoxicity. In P/I-stimulated T cells, HS-Cm inhibited the production of interleukin-2, tumor necrosis factor-alpha, and interferon-gamma and suppressed the expression of surface activation markers CD25, CD69, and CD71, but not CD45RO. HS-Cm down-regulated DNA-binding activities of activator protein-1 and nuclear factor-kappa B, but not nuclear factor of activated T-cells, through inhibiting c-Jun N-terminal kinase/p38 and inhibitor of kappaB alpha (I?B?) kinase (IKK)/I?B? pathways, respectively. On the basis of structure-activity relationship, HS-Cm exerted considerable inhibition of dipeptidyl-peptidase IV/CD26 activity in T cells. Our results suggested that the small molecule HS-Cm exhibiting immunomodulatory effects on T cells may be useful for therapeutics in chronic inflammatory diseases, like atherosclerosis, diabetes and autoimmune arthritis.
Related JoVE Video
Presence of cytomegalovirus DNA in leucocytes is associated with increased oxidative stress and subclinical atherosclerosis in healthy adults.
Biomarkers
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
Investigate the latent cytomegalovirus (CMV) infection as a biomarker of oxidative stress and atherosclerosis.
Related JoVE Video
NSC746364, a G-quadruplex-stabilizing agent, suppresses cell growth of A549 human lung cancer cells through activation of the ATR/Chk1-dependent pathway.
J. Pharmacol. Sci.
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
The telomere is considered to be a potential target for cancer therapy. NSC746364, a novel G-quadruplex-stabilizing agent, has been found to have cytotoxic effects on various cancer cells. To date, its pharmacological mechanisms are still unknown. The goal of this study was to investigate the molecular mechanisms of NSC746364 on the A549 human lung adenocarcinoma cell line. For this, we used a wide variety of in vitro assays. The intracellular signaling pathways including DNA damage sensing and response proteins, cell cycle regulatory proteins, and some key executors involved in apoptosis were evaluated in this study. Our study suggested that NSC746364 induced cell cycle arrest at the G2/M phase and triggers programming cell death on A549 human lung cancer cells, whose effects are modulated through the activation of the ATR/Chk1 pathway, the downregulation of cyclin B1 expression, and the activation of caspase-3. Consequently, our results indicated that NSC746364 may have therapeutic potential as a chemotherapy for non-small-cell lung cancers.
Related JoVE Video
Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
To investigate the effects of diallyl trisulfide (DATS), a garlic-derived organosulfur compound, in pancreatic cancer cells.
Related JoVE Video
Inhibition of Aurora-B suppresses osteosarcoma cell migration and invasion.
Exp Ther Med
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
Previous studies have suggested that Aurora-B may be involved in cancer metastasis. However, its role has been poorly evaluated in osteosarcoma (OS). The aim of this study was to investigate the correlation between Aurora-B expression and metastasis in human OS. The human OS cell line, U2-OS, and OS biopsy specimens were used in the study. The expression of Aurora-B protein was examined using immunohistochemistry and western blotting in OS tissues and U2-OS cells, respectively. AZD1152-hydroxyquinazoline-pyrazol-anilide, an inhibitor of Aurora-B, was used to inhibit Aurora-B expression in U2-OS cells. The effect of Aurora-B inhibition on U2-OS cell proliferation, invasion and migration was assessed using MTT, colony formation, wound healing and Transwell assays. The results showed that positive expression of the Aurora-B protein was observed in the nucleus, and that Aurora-B expression levels in the cases with pulmonary metastases were significantly higher than in those without metastasis. In vitro, the proliferation, invasion and migration of U2-OS cells were suppressed by the inhibition of Aurora-B. These results suggest that Aurora-B may be involved in OS metastasis, and may be a promising target in the treatment of OS metastasis.
Related JoVE Video
Let-7g reverses malignant phenotype of osteosarcoma cells by targeting Aurora-B.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Accumulating studies revealed that the expression levels of several miRNAs are up or down-regulated in osteosarcoma (OS). The aim of this study was to investigate the functional significance and molecular of the let-7g in OS cells. The expression levels of let-7g was significantly down-regulated in OS cell lines U2-OS and HOS cell compared to osteoblast cell lines HOB cell. Moreover, bioinformatic prediction suggested that Aurora-B, which is overexpressed and functions as an oncogene in OS cells, is a putative target gene of let-7g. Using mRNA and protein expression analysis and luciferase assays, we further identified let-7g directly regulated Aurora-B expression in OS cells. Functional investigation revealed both restoration of let-7g and silencing Aurora-B induce cell apoptosis and suppressed cell viability, migratory and invasive ability in OS cells. Finally, we found that silencing Aurora-B in OS cells could partly dampen anti-let-7g mediated tumor promotion. Thus, our findings suggested that let-7g inhibits OS cell malignant phenotype at least partly through targeting Aurora-B. Targeting of let-7g and Aurora-B may be a novel therapeutic strategy for treating OS.
Related JoVE Video
Serum iron concentration, but not hemoglobin, correlates with TIMI risk score and 6-month left ventricular performance after primary angioplasty for acute myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Anemia is associated with high mortality and poor prognosis after acute coronary syndrome (ACS). Increased red cell distribution width (RDW) is a strong independent predictor for adverse outcomes in ACS. The common underlying mechanism for anemia and increased RDW value is iron deficiency. It is not clear whether serum iron deficiency without anemia affects left ventricular (LV) performance after primary angioplasty for acute myocardial infarction (AMI). We investigated the prognostic value of serum iron concentration on LV ejection fraction (EF) at 6 months and its relationship to thrombolysis in myocardial infarction (TIMI) risk score in post MI patients.
Related JoVE Video
Over-expressed Testis-specific Protein Y-encoded 1 as a novel biomarker for male hepatocellular carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Hepatocellular carcinoma (HCC) is a male-predominant cancer. Previous studies have focused on the sex-related disparity in HCC, but the underlying mechanism remains unclear. Here, we aimed to discover characteristic biomarkers for male HCC. Clinical samples were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. Seventy-three differential proteins containing 16 up-regulated and 57 down-regulated proteins were screened out in the male HCC group compared to that in female HCC group. Testis-specific Protein Y-encoded 1(TSPY1) is characteristically present in male HCC and was chosen for further investigation. The data from the functional effects of TSPY1 indicated that over-expression of TSPY1 could potentiate HCC cell proliferation, increase soft agar colonization, induce higher cell invasive ability and correlate with the metastatic potential of the HCC cell lines. In addition, TSPY1 and androgen receptor (AR) were co-expressed simultaneously in HCC cell lines as well as in HCC tissue. TSPY1 up- or down-regulation could lead to a high or low level expression of AR. These results implied that TSPY1 may be included in the regulation of AR expression involved in male HCC and it may act as a novel biomarker for male HCC.
Related JoVE Video
[Comprehensive analysis of genomic detection for a patient with myelodysplastic syndrome].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
Show Abstract
Hide Abstract
This study was purposed to investigate the significance of genomic comprehensine analysis information in diagnosis, therapy and prognosis of MDS through comprehensive analysis of a patient with MDS. The bone marrow specimen from a patient with MDS was comprehensively analyzed by a combination of genomic approaches, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), genome scanning using Affymetrix high density SNP microarray platform, and next-generation sequencing (NGS) analysis using IonTorrent Cancer Gene Panel. The results showed that an abnormal clone was identified by standard G-banding karyotyping and confirmed by FISH, which contains interstitial deletions on the long arms of chromosome 5 and 11 respectively. SNP-array analysis defined the two genomic deletions to be an 81 Mb interstitial deletion on the long are of chromosome 5 and a 24 Mb interstitial deletion on the long are of chromosome 11. Meanwhile, SNP-array detected two genomic regions with acquired loss of heterozygosity (LOH), a 58 Mb region on the short arm of chromosome 1 and a 39 Mb region on the distal end of the long arm of chromosome 14. In addition, SNP-array identified multiple genomic regions with long stretch of absence of heterozygosity, representing about 5.3% of autosomal genome, indication a certain level of consanguinity between the parents. No clinically significant gene mutation was identified using IonTorrent 50 Cancer Gene Panel while 6 polymorphisms within 6 genes were observed including APC, FGFR3, KDR, KIT, PDGFRA, and RET. It is concluded that the combined genomic techniques are necessary to provide a full picture of the patients genomic alterations. Some of the acquired genomic findings are important for the diagnosis and therapy selection. Germline genomic alterations warrant genetic counseling and are useful for further studies to explore the mechanisms leading to tumorigenesis of MDS patient.
Related JoVE Video
Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors.
J. Med. Chem.
PUBLISHED: 12-20-2013
Show Abstract
Hide Abstract
Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.
Related JoVE Video
Formal Carbon Insertion of N-Tosylhydrazone into B-B and B-Si Bonds: gem-Diborylation and gem-Silylborylation of sp(3) Carbon.
Org. Lett.
PUBLISHED: 12-18-2013
Show Abstract
Hide Abstract
A convenient method is developed to synthesize 1,1-diboronates from the corresponding N-tosylhydrazones. This method is also applicable to synthesize 1-silyl-1-boron compounds. Meanwhile, derivatization and consecutive Pd-catalyzed cross-coupling reactions with 1,1-boronates were explored, demonstrating the synthetic potential of 1,1-diboronates.
Related JoVE Video
Cyclophilin-A: a novel biomarker for untreated male essential hypertension.
Biomarkers
PUBLISHED: 10-28-2013
Show Abstract
Hide Abstract
Abstract Vascular cytokines, total nitrite, and cyclophilin-A (CyP-A) may be related to the pathogenesis of untreated hypertension. Forty males with normotensive and untreated essential hypertension were recruited in this cytokines survey. Body mass index (BMI), hyperlipidemia, and plasma CyP-A were increased in the hypertensive group (p?
Related JoVE Video
Inhibiting valosin-containing protein suppresses osteosarcoma cell metastasis via AKT/nuclear factor of kappa B signaling pathway in vitro.
Indian J Pathol Microbiol
PUBLISHED: 10-25-2013
Show Abstract
Hide Abstract
The strategies of targeting valosin-containing protein (VCP) may have therapeutic potential for treating cancer metastasis. In this study, we aim to investigate the correlation of VCP protein expression in osteosarcoma (OS) tissues with pulmonary metastasis and its possible molecular mechanism.
Related JoVE Video
Synthesis, characterization, and anticancer activity of a series of ketone-N(4)-substituted thiosemicarbazones and their ruthenium(II) arene complexes.
Inorg Chem
PUBLISHED: 10-21-2013
Show Abstract
Hide Abstract
A series of ketone-N(4)-substituted thiosemicarbazone (TSC) compounds (L1-L9) and their corresponding [(?(6)-p-cymene)Ru(II)(TSC)Cl](+/0) complexes (1-9) were synthesized and characterized by NMR, IR, elemental analysis, and HR-ESI-mass spectrometry. The molecular structures of L4, L9, 1-6, and 9 were determined by single-crystal X-ray diffraction analysis. The compounds were further evaluated for their in vitro antiproliferative activities against the SGC-7901 human gastric cancer, BEL-7404 human liver cancer, and HEK-293T noncancerous cell lines. Furthermore, the interactions of the compounds with DNA were followed by electrophoretic mobility spectrometry studies.
Related JoVE Video
Habituation of steady-state visual evoked potentials in response to high-frequency polychromatic foveal visual stimulation.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
Show Abstract
Hide Abstract
In an attempt to develop safe and robust methods for monitoring migraineurs brain states, we explores the feasibility of using white, red, green and blue LED lights flickering around their critical flicker fusion (CFF) frequencies as foveal visual stimuli for inducing steady-state visual evoked potentials (SSVEP) and causing discernible habituation trends. After comparing the habituation indices, the multi-scale entropies and the time dependent intrinsic correlations of their SSVEP signals, we reached a tentative conclusion that sharp red and white light pulses flickering barely above their CFF frequencies can replace commonly used 13Hz stimuli to effectively cause SSVEP habituation among normal subjects. Empirical results showed that consecutive short bursts of light can produce more consistent responses than a single prolonged stimulation. Since these high frequency stimuli do not run the risk of triggering migraine or seizure attacks, further tests of these stimuli on migraine patients are warranted in order to verify their effectiveness.
Related JoVE Video
Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA topoisomerase I inhibitory properties.
Bioorg. Med. Chem.
PUBLISHED: 08-09-2013
Show Abstract
Hide Abstract
A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50=1.66 ?M) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs.
Related JoVE Video
Phylogenetically related and ecologically similar carnivores harbour similar parasite assemblages.
J Anim Ecol
PUBLISHED: 07-30-2013
Show Abstract
Hide Abstract
Most parasites infect multiple hosts, but what factors determine the range of hosts a given parasite can infect? Understanding the broad scale determinants of parasite distributions across host lineages is important for predicting pathogen emergence in new hosts and for estimating pathogen diversity in understudied host species. In this study, we used a new data set on 793 parasite species reported from free-ranging populations of 64 carnivore species to examine the factors that influence parasite sharing between host species. Our results showed that parasites are more commonly shared between phylogenetically related host species pairs. Additionally, host species with higher similarity in biological traits and greater geographic range overlap were also more likely to share parasite species. Of three measures of phylogenetic relatedness considered here, the number divergence events that separated host species pairs most strongly influenced the likelihood of parasite sharing. We also showed that viruses and helminths tend to infect carnivore hosts within more restricted phylogenetic ranges than expected by chance. Overall, our results underscore the importance of host evolutionary history in determining parasite host range, even when simultaneously considering other factors such as host ecology and geographic distribution.
Related JoVE Video
Reference values of serum rheumatoid factor in coastal residents.
Clin. Lab.
PUBLISHED: 07-20-2013
Show Abstract
Hide Abstract
This study aims to investigate the reference values of serum rheumatoid factor (RF) in coastal residents.
Related JoVE Video
Biochemical characteristics of a fibrinolytic enzyme purified from a marine bacterium, Bacillus subtilis HQS-3.
Int. J. Biol. Macromol.
PUBLISHED: 07-01-2013
Show Abstract
Hide Abstract
A fibrinolytic enzyme isolated from marine Bacillus subtilis HQS-3 was purified to electrophoretic homogeneity using ammonium sulphate precipitation, alkaline solution treatment, membrane concentration, dialysis, ion exchange, and gel filtration chromatography. SDS-PAGE and gel filtration chromatography showed that it was a monomeric protein with an apparent molecular weight of 26kDa. The purified enzyme was active at pH 6.0-10.0 with an optimum pH of 8.0. It was stable at temperatures ranging from 25 to 37°C, exhibiting maximum activity between 45°C and 50°C. The isoelectric point of the enzyme was 9.0-9.2, which was higher than those of other known fibrinolytic enzymes from Bacillus species. PMSF, EDTA, Cu(2+), Zn(2+), and Co(2+) inhibited the enzyme activity significantly. This enzyme did not cause hemolysis in vitro and preferred direct degradation of fibrin in the following order: ?, ?, and ?-? chains. Thus, these results suggest that the marine-derived enzyme is a plasmin-like serine metalloprotease, which is distinct from other fibrinolytic enzymes from genus Bacillus.
Related JoVE Video
Out of the tropics, but how? Fossils, bridge species, and thermal ranges in the dynamics of the marine latitudinal diversity gradient.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-12-2013
Show Abstract
Hide Abstract
Latitudinal diversity gradients are underlain by complex combinations of origination, extinction, and shifts in geographic distribution and therefore are best analyzed by integrating paleontological and neontological data. The fossil record of marine bivalves shows, in three successive late Cenozoic time slices, that most clades (operationally here, genera) tend to originate in the tropics and then expand out of the tropics (OTT) to higher latitudes while retaining their tropical presence. This OTT pattern is robust both to assumptions on the preservation potential of taxa and to taxonomic revisions of extant and fossil species. Range expansion of clades may occur via "bridge species," which violate climate-niche conservatism to bridge the tropical-temperate boundary in most OTT genera. Substantial time lags (?5 Myr) between the origins of tropical clades and their entry into the temperate zone suggest that OTT events are rare on a per-clade basis. Clades with higher diversification rates within the tropics are the most likely to expand OTT and the most likely to produce multiple bridge species, suggesting that high speciation rates promote the OTT dynamic. Although expansion of thermal tolerances is key to the OTT dynamic, most latitudinally widespread species instead achieve their broad ranges by tracking widespread, spatially-uniform temperatures within the tropics (yielding, via the nonlinear relation between temperature and latitude, a pattern opposite to Rapoports rule). This decoupling of range size and temperature tolerance may also explain the differing roles of species and clade ranges in buffering species from background and mass extinctions.
Related JoVE Video
[Discectomy and discectomy plus Coflex fixation for lumbar disc herniation, a clinical comparison study].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
To compare clinical efficacy between discectomy and discectomy plus Coflex fixation for lumbar disc herniation.
Related JoVE Video
Efficacy of copper-silver ionization for controlling fungal colonization in water distribution systems.
J Water Health
PUBLISHED: 05-28-2013
Show Abstract
Hide Abstract
The purpose of this study was to identify the prevalence of fungal colonization in water systems and to evaluate the effect of decreasing fungal colonization by a copper-silver ionization system. Environmental samples were collected for fungal culture prospectively during a 1-year period (2011-2012) at the study hospital. A total of 392 water samples were examined from five buildings on March 1, 2011 and February 29, 2012. Fungi were isolated in 13 (3.4%) of 392 water samples from five buildings. The prevalence of fungal colonization in buildings was decreased from 4.76% (9/189) to 1.97% (4/203), a reduction of more than 40%, in pre-ionization and post-ionization treatment (p < 0.001). Thirteen (3.4%) of 392 water samples yielded fungi including Fusarium species (n = 7), Penicillium species (n = 2), Scedosporium species (n = 2), Aspergillus species (n = 1), and one unidentifiable mold. The number of isolated Fusarium species in ionized water samples (0.5% (1/203)) was statistically lower than those in nonionized (3.2% (6/189)) (p = 0.003). Our finding may determine if this ionization method can be applied for control of waterborne fungi colonization in hospital water systems.
Related JoVE Video
Effect of N-ethylmaleimide, chymotrypsin, and H2 O2 on the viscoelasticity of human erythrocytes: Experimental measurement and theoretical analysis.
J Biophotonics
PUBLISHED: 05-22-2013
Show Abstract
Hide Abstract
The physiological functions of erythrocytes depend critically on their morphology, deformability, and aggregation capability in response to external physical and chemical stimuli. The dynamic deformability can be described in terms of their viscoelasticity. We applied jumping optical tweezers to trap and stretch individual red blood cells (RBCs) to characterize its viscoelasticity in terms of the Youngs modulus and viscosity by analyzing the experimental data of dynamic deformation using a 2-parameter Kelvin solid model. The effects of three chemical agents (N -ethylmaleimide, Chymotrypsin, and Hydrogen peroxide) on RBCs mechanical properties were studied by comparing the Youngs modulus and viscosity of RBCs with and without these chemical treatments. Although the effects of each of these chemicals on the molecular structures of RBC may not be exclusive, based on the dominant effect of each chemical, we attempted to dissect the main contributions of different constituents of the RBC membrane to its viscosity and elasticity. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
Related JoVE Video
Triptolide alters barrier function in renal proximal tubular cells in rats.
Toxicol. Lett.
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
Alteration of the tight junction complex in renal epithelial cells can affect renal barrier function and perturb normal kidney homeostasis. The objective of the present study was to determine whether triptolide could affect tight junctions in the proximal tubule epithelial cells both in vivo and in vitro. Wistar rats were gavaged with triptolide at 0, 100, 200 or 400 ?g/kg/day for 28 days. Pathologic examination of the kidney showed that triptolide primarily affected the proximal tubules. The nephrotoxicity of triptolide is morphologically characterized by the detachment of the proximal tubular epithelial cells from each other. Immunohistochemical analysis showed that there was marked alteration in the localization of Zonula Occludens 1 protein (ZO-1) in the proximal tubule epithelium. Additionally, the uptake of FITC-dextran, a marker of fluid phase endocytosis in the proximal tubule, was considerably lower in triptolide-treated animals than in normal rats. Supported by these results, we detected significant increases in blood urea nitrogen (BUN) but not of creatinine (Cr) in rats treated with triptolide, indicating damage to the proximal tubules. Furthermore, triptolide treatment caused an alteration of the tight junction complex, resulting in changes in paracellular permeability in NRK-52E cells in vitro. Taken together, these results suggest that triptolide induced renal toxicity in rats and that the mechanism of toxicity was related to the disruption of cell-cell junctions and alterations of the paracellular permeability in the proximal tubule.
Related JoVE Video
Enhancing the selectivity of enzyme detection by using tailor-made nanoparticles.
Anal. Chem.
PUBLISHED: 05-10-2013
Show Abstract
Hide Abstract
Development of effective ways to specifically and reversibly block the activity of an enzyme is highly desirable for enhancing the selectivity of enzyme assays. Here we demonstrate a novel approach for selective detection of enzyme activities in complex biological samples by using tailor-made nanoparticles. Employing deoxyribonuclease I (DNase I) as a model enzyme template, we prepared surface imprinted polymers over magnetic nanoparticles with monomers screened out of commonly used functional monomers. The resultant Fe3O4@MIP nanoparticles can not only block the activity of the target enzyme via selective adsorption but also quantitatively release the bound enzyme under mild conditions with the assistance of metal ion cofactors, which offers a very useful tool for enhancing the selectivity in enzyme detection. The approach enables sequential detection of the activities of 3-5 exonuclease and DNase I in cell lysates. The strategy may be further extended to the detection of other enzyme proteins.
Related JoVE Video
Poly (AT) deletion/insertion polymorphism of the XPC gene contributes to urinary system cancer susceptibility: a meta-analysis.
Gene
PUBLISHED: 05-03-2013
Show Abstract
Hide Abstract
Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT -/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT -/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs.
Related JoVE Video
Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.
Eur J Med Chem
PUBLISHED: 04-07-2013
Show Abstract
Hide Abstract
By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI??, TGI and LC??, respectively. Among them, all were moderate selectivity toward leukemia cancer except for 4 exhibited distinctive selectivity of CNS and renal cancer with 7.403 and 6.475. The overall of test compounds exhibited different cytostatic and cytotoxic activities for further developing potential application as anticancer drugs.
Related JoVE Video
mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.
Neuron
PUBLISHED: 02-27-2013
Show Abstract
Hide Abstract
Abnormalities during brain development are thought to cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restricted brain regions of adults, and disruptions of these processes could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that Disc1 knockdown specifically in adult-born dentate gyrus (DG) neurons results in increased mTOR signaling, hyperexcitability, and neuronal structure deficits. Disc1 knockdown also resulted in pronounced cognitive and affective deficits, which could be reversed when the affected DG neurons were inactivated. Importantly, reversing increases in mTOR signaling with an FDA-approved inhibitor both prevented and treated these behavioral deficits, even when associated structural deficits were not reversed. Our findings suggest that a component of the affective and cognitive phenotypes in neurodevelopmental disorders may be caused by disruptions in adult-born neurons. Consequently, treatments directed at this cell population may have a significant impact on these phenotypes.
Related JoVE Video
Cerebral white matter hyperintensity in Parkinsons disease: a major risk factor for mild cognitive impairment.
Parkinsonism Relat. Disord.
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
Mild cognitive impairment (MCI) and dementia contribute to a poor quality of life among patients with PD. The influence of cerebral ischemia as a risk factor for MCI in PD has not been adequately investigated. To address this issue, we examined the influence of the volume and distribution of white matter hyperintensity (WMH) as a risk factor for MCI in early PD.
Related JoVE Video
A comparison study of the blood component quality of whole blood held overnight at 4°c or room temperature.
J Blood Transfus
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Background. The use of plasma frozen within 24?hrs is likely to increase. Whole blood (WB) and buffy coats (BCs) can be held for a few hrs or overnight before processing. Methods. Twenty-four bags of WB for plasma and 12 bags for platelet (PLT) concentrates were collected. The fresh frozen plasma (FFP) was prepared within 6?hrs. I-FP24 and II-FP24 samples were prepared either from leukodepleted WB that was held overnight or from WB that was held overnight before leukodepletion. The PLT concentrates (PCs) were prepared from BCs within 6?hrs (PC1) and within 18 to 24?hrs (PC2). The typical coagulation factors and some biochemical parameters were determined. Results. Compared to the FFP samples, the levels of FVII and FVIII in the I-FP24 and II-FP24 samples decreased significantly. The pH, Na(+), LDH, and FHb levels differed significantly between II-FP24 and FFP. Compared to PC1, PC2 exhibited lower pH, pO2, and Na(+) levels, a higher PLT count, and increased pCO2, K(+), Lac, and CD62P expression levels. Conclusion. FP24 is best prepared from WB that was stored overnight at 4°C and then leukodepleted and separated within 24?hrs. PCs are best produced from BCs derived from WB that was held overnight at room temperature.
Related JoVE Video
NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway.
Int. J. Biochem. Cell Biol.
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
NANOG is a major transcription factor essential to the stem cell self-renewal and is associated with tumor malignancy, but the NANOG signaling in cancer metastasis is still elusive. In this study, we determined the expression of NANOG in hepatocellular carcinoma (HCC) and investigated its underlying mechanism in the metastasis of HCC. The expression levels of NANOG were examined in tumor tissues by immunohistochemistry. Functional effect of NANOG was investigated both in vivo and in vitro. Our data shows that high level of NANOG expression correlates with metastasis and low survival rate in HCC. HCC cells overexpressing NANOG are characterized by active epithelial-mesenchymal transition (EMT), and exhibit increased ability of invasion, soft agar colonization, sphere formation and drug resistance, whereas SB-431542, an antagonist of activin receptor-like kinase (ALK) receptors, attenuates EMT and invasion of HCC cells. NANOG activates NODAL and CRIPTO-1 to promote SMAD3 phosphorylation and SNAIL expression. The transcriptional activity of NODAL gene is dependent on two NANOG binding motifs in its promoter region. This study shows a significant correlation between the NANOG expression and the expression of NODAL, P-SMAD3 or SNAIL, and the combination of NANOG and P-SMAD3 is a potential predictor of poor prognosis of HCC. Additionally, cells in the tumor edge area displays higher NANOG expression than cells in the tumor center. These results present novel mechanistic insight into an important role of NANOG in HCC metastasis, and suggest a potential application of NANOG in HCC prognosis and treatment.
Related JoVE Video
Effects of tolerogenic dendritic cells generated by siRNA-mediated RelB silencing on immune defense and surveillance functions of T cells.
Cell. Immunol.
PUBLISHED: 02-05-2013
Show Abstract
Hide Abstract
Dendritic cells (DCs) can initiate immune responses or induce immune tolerance, according to their level of maturation. In this study, we inhibited RelB expression in immature (im)DCs using small interfering RNA (siRNA) to maintain their immature status. RelB-silenced DCs induced donor-specific hyporesponsiveness in T cells. In contrast, T cells primed by RelB-silenced DCs maintained normal proliferation and cytokine secretion when stimulated by influenza virus antigen. Proliferation was similar between T cells stimulated with syngeneic tumor antigen or donor-specific antigen stimulation, but was significantly lower compared with T cells stimulated with influenza virus antigen. Moreover, an altered pattern of micro181a and micro155 transcriptional levels in T cells was involved in the differential regulation. This study demonstrates that RelB-silenced DCs could induce donor-specific hyporesponsiveness and slightly impair immune surveillance of T cells, while retaining their immune defense functions.
Related JoVE Video
Tumor suppressive microRNA-424 inhibits osteosarcoma cell migration and invasion via targeting fatty acid synthase.
Exp Ther Med
PUBLISHED: 02-01-2013
Show Abstract
Hide Abstract
Numerous studies have recently suggested that miRNAs contribute to the development of various types of human cancer as well as to their invasive and metastatic capacities. The aim of this study was to investigate the functional significance of miR-424 and to identify its possible target genes in osteosarcoma (OS) cells. Previously, inhibition of fatty acid synthase (FASN) has been shown to suppress OS cell proliferation, invasion and migration. The prediction was made using the microRNA.org and TargetScan.human6.0.database. The results showed that FASN is a promising target gene of miR-424. FASN may be a direct target of miR-424 as shown by the luciferase reporter assays. Furthermore, miR-424 expression was increased in osteosarcoma cells by transfection with has-miR-424. FASN mRNA and protein expression levels were measured by RT-PCR and western blot analysis. Cell migration and invasion was measured using Transwell migration and Transwell invasion assays. Expression levels of FASN mRNA and protein were greatly decreased in U2OS cells transfected with has-miR-424. The migration and invasion of cells was significantly decreased by the upregulation of miR-424. These findings suggested that miR-424 plays a key role in inhibiting OS cell migration and invasion through targeting FASN.
Related JoVE Video
A simple QD-FRET bioprobe for sensitive and specific detection of hepatitis B virus DNA.
J Fluoresc
PUBLISHED: 01-23-2013
Show Abstract
Hide Abstract
We report here a simple quantum dot-FRET (QD-FRET) bioprobe based on fluorescence resonance energy transfer (FRET) for the sensitive and specific detection of hepatitis B virus DNA (HBV DNA). The proposed one-pot HBV DNA detection method is very simple, rapid and convenient due to the elimination of the washing and separation steps. In this study, the water-soluble CdSe/ZnS QDs were prepared by replacing the trioctylphosphine oxide on the surface of QDs with mercaptoacetic acid (MAA). Subsequently, DNA was attached to QDs surface to form the functional QD-DNA bioconjugates by simple surface ligand exchange. After adding 6-carboxy-X-rhodamine (ROX)-modified HBV DNA (ROX-DNA) into the QD-DNA bioconjugates solution, DNA hybridization between QD-DNA bioconjugates and ROX-DNA was formed. The resulting hybridization brought the ROX fluorophore, the acceptor, and the QDs, the donor, into proximity, leading to energy transfer from QDs to ROX. When ROX-DNA was displaced by the unlabeled HBV DNA, the efficiency of FRET was dramatically decreased. Based on the changes of both fluorescence intensities of QDs and ROX, HBV DNA could be detected with high sensitivity and specificity. Under the optimized conditions, the linear range of HBV DNA determination was 2.5 - 30 nmol L(-1), with a correlation coefficient (R) of 0.9929 and a limit of detection (3? black) of 1.5 nmol L(-1). The relative standard deviation (R.S.D.) for 12 nmol L(-1) HBV DNA was 0.9% (n = 5). There was no interference to non-complementary DNA. Time-resolved fluorescence spectra and fluorescence images were performed to verify the validity of this method and the results were satisfying.
Related JoVE Video
The glutathione S-transferase P1 341C>T polymorphism and cancer risk: a meta-analysis of 28 case-control studies.
PLoS ONE
PUBLISHED: 01-14-2013
Show Abstract
Hide Abstract
GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.
Related JoVE Video
Brand name or generic? What are the health professionals prescribed for treating diabetes? A longitudinal analysis of the National Health Insurance reimbursement database.
Pharmacoepidemiol Drug Saf
PUBLISHED: 01-13-2013
Show Abstract
Hide Abstract
This study aimed to explore whether physicians prescribe more brand-name oral hypoglycemic agents (OHA) for diabetic patients with medical training background (MP) than for general patients (GP).
Related JoVE Video
New approaches of PARP-1 inhibitors in human lung cancer cells and cancer stem-like cells by some selected anthraquinone-derived small molecules.
PLoS ONE
PUBLISHED: 01-12-2013
Show Abstract
Hide Abstract
Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCIs 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.
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.