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Find video protocols related to scientific articles indexed in Pubmed.
Energy metabolism targeted drugs synergize with photodynamic therapy to potentiate breast cancer cell death.
Photochem. Photobiol. Sci.
PUBLISHED: 11-03-2014
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Malignant cells are highly dependent on aerobic glycolysis, which differs significantly from normal cells (the Warburg effect). Interference of this metabolic process has been considered as an innovative method for developing selective cancer therapy. A recent study demonstrated that the glycolysis inhibitor 2-deoxyglucose (2-DG) can potentiate PDT efficacy, whereas the possible mechanisms have not been carefully investigated. This study firstly proved the general potentiation of PDT efficacy by 2-DG and 3-bromopyruvate (3-BP) in human breast cancer MDA-MB-231 cells, and carefully elucidated the underlying mechanism in the process. Our results showed that both 2-DG and 3-BP could significantly promote a PDT-induced cell cytotoxic effect when compared with either monotherapy. Synergistic potentiation of mitochondria- and caspase-dependent cell apoptosis was observed, including a mitochondrial membrane potential (MMP) drop, Bax translocation, and caspase-3 activation. Besides, ROS generation and the expression of oxidative stress related proteins such as P38 MAPK phosphorylation and JNK phosphorylation were notably increased after the combined treatments. Moreover, when pretreated with the ROS scavenger N-acetylcysteine (NAC), the ROS generation, the MMP drop, cell apoptosis and cytotoxicity were differently inhibited, suggesting that ROS was vertical in the pro-apoptotic process induced by 2-DG/3-BP combined with PDT treatment. These results indicate that the combination of glycolytic antagonists and PDT may be a promising therapeutic strategy to effectively kill cancer cells.
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Developmental Origin of the Posterior Pigmented Epithelium of Iris.
Cell Biochem. Biophys.
PUBLISHED: 10-27-2014
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Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.
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Antitumor effect of sinoporphyrin sodium-mediated photodynamic therapy on human esophageal cancer eca-109 cells.
Photochem. Photobiol.
PUBLISHED: 10-07-2014
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The aim of this study was to evaluate the photodynamic effect of Sinoporphyrin sodium (DVDMS). In this study, Eca-109 cells were treated with DVDMS (5 ?g mL(-1) ) and subjected to photodynamic therapy (PDT). The uptake and subcellular localization of DVDMS were monitored by flow cytometry and confocal microscopy. The phototoxicity of DVDMS was studied by MTT assay. The morphological changes were observed by scanning electron microscopy (SEM). DNA damage, reactive oxygen species (ROS) generation and mitochondria membrane potential (MMP) changes were analyzed by flow cytometry. Studies demonstrated maximal uptake of DVDMS occurred within 3 h, with a mitochondrial subcellular localization. MTT assays displayed that DVDMS could be effectively activated by light and the phototoxicity was much higher than photofrin under the same conditions. In addition, SEM observation indicated that cells were seriously damaged after PDT treatment. Furthermore, activation of DVDMS resulted in significant increases in ROS production. The generated ROS played an important role in the phototoxicity of DVDMS. DVDMS-mediated PDT (DVDMS-PDT) also induced DNA damage and MMP loss. It is demonstrated that DVDMS-mediated PDT is an effective approach on cell proliferation inhibition of Eca-109 cells.
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Iron inhibits Escherichia coli topoisomerase I activity by targeting the first two zinc-binding sites in the C-terminal domain.
Protein Sci.
PUBLISHED: 09-13-2014
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Escherichia coli DNA topoisomerase I (TopA) contains a 67 kDa N-terminal catalytic domain and a 30 kDa C-terminal zinc-binding region (ZD domain) which has three adjacent tetra-cysteine zinc-binding motifs. Previous studies have shown that E. coli TopA can bind both iron and zinc, and that iron binding in TopA results in failure to unwind the negatively supercoiled DNA. Here, we report that each E. coli TopA monomer binds one atom of iron via the first two zinc-binding motifs in ZD domain and both the first and second zinc-binding motifs are required for iron binding in TopA. The site-directed mutagenesis studies further reveal that while the mutation of the third zinc-binding motif has very little effect on TopA's activity, mutation of the first two zinc-binding motifs in TopA greatly diminishes the topoisomerase activity in vitro and in vivo, indicating that the first two zinc-binding motifs in TopA are crucial for its function. The DNA-binding activity assay and intrinsic tryptophan fluorescence measurements show that iron binding in TopA may decrease the single-stranded (ss) DNA-binding activity of ZD domain and also change the protein structure of TopA, which subsequently modulate topoisomerase activity.
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[Analyze of the residue level of acrylic acid in cosmetics by ion chromatography method].
Wei Sheng Yan Jiu
PUBLISHED: 09-10-2014
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To develop a method for acrylic acid analysis in cosmetics by ion chromatography.
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Herpes zoster in Crohn's disease during treatment with infliximab.
Eur J Gastroenterol Hepatol
PUBLISHED: 08-29-2014
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Infliximab is widely used in both inducing and maintaining remission of patients with Crohn's disease (CD). The efficacy of infliximab has been undoubtedly proven; however, various opportunistic infections have emerged. Herpes virus infections (being a type of opportunistic infection) in CD patients treated with infliximab alone with no other concomitant medications are, however, rare and have not aroused enough attention. Gastroenterologists have limited knowledge of the immunization status of patients with CD, and rarely do they take an adequate immunization history before immunosuppressive therapy. Here we report two herpes zoster (HZ) events in CD patients while using infliximab alone: in the first case, HZ occurred during the patient's 12th infusion for maintance therapy, and in the second case, HZ occurred during the patient's first course of infliximab after surgery for therapy of inducing remission. We hope to increase the gastroenterologists' awareness of this potential infection in CD patients during treatment with infliximab.
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Comparison of protoporphyrin IX produced cell proliferation inhibition between human breast cancer MCF-7 and MDA-MB-231 cells.
Pharmazie
PUBLISHED: 08-28-2014
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Protoporphyrin IX (PpIX) is an effective hematoporphyrin derivative, widely adopted in photodynamic therapy (PDT) and sonodynamic therapy (SDT). As a sensitizer, PpIX could significantly enhance laser light or ultrasound causing tumor cell damage in PDT/SDT studies. However, the biological function of PpIX itself has not been carefully defined. Recently, studies indicate that PpIX alone can inhibit Hela cell proliferation, but the potential mechanism was unclear. Therefore, in the present study it was investigated whether the proliferation inhibition effect generally occurred in human breast cancer MCF-7 and MDA-MB-231 cells. Different sensitivities and the involved mechanisms were carefully explored. Our results show that PpIX preferentially accumulated and selectively caused cell damage in human breast cancer MCF-7 and MDA-MB-231 cells compared with mouse embryonic fibroblast NIH-3T3. In vitro, PpIX induced cell viability decrease, intracellular ROS (reactive oxygen species) generation, and DNA damage in a concentration-dependent and cell-specific manner. MCF-7 was more sensitive to PpIX than MDA-MB-231 cells at the same PpIX dose. Western blots showed obvious enhancement of P53, and PUMA in a concentration dependent manner in MCF-7 cells, but not in MDA-MB-231 cells. In cell-free system, we also found that PpIX could interact with some large biological molecules, such as calf thymus DNA, and induce hyperchromic effects in spectroscopic analysis. Our findings imply that DNA might be one of the main targets of PpIX, and PpIX alone can cause significant tumor cell damage through ROS generation, while P53 status may play an important role in these processes.
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Macrophage inhibitory cytokine 1 (MIC-1/GDF15) as a novel diagnostic serum biomarker in pancreatic ductal adenocarcinoma.
BMC Cancer
PUBLISHED: 08-08-2014
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Macrophage inhibitory cytokine 1 (MIC-1/GDF15) has been identified as a potential novel biomarker for detection of pancreatic cancer (PCa). However, the diagnostic value of serum MIC-1 for pancreatic ductal adenocarcinoma (PDAC), particularly for those at the early stage, and the value for treatment response monitoring have not yet been investigated.
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Coagulation state in patients with Crohn's disease: the effect of infliximab therapy.
Eur J Gastroenterol Hepatol
PUBLISHED: 07-30-2014
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Growing evidence has shown that coagulation processes play an important role in disease pathogenesis and/or disease progression in patients with inflammatory bowel disease. However, no study has ever focused on the possible influence of infliximab (IFX) therapy on the coagulation status in patients with Crohn's disease (CD).
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A new acorane sesquiterpene from the aerial parts of Psychotria yunnanensis.
Nat. Prod. Res.
PUBLISHED: 07-10-2014
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Psycacoraone A (1), a new acorane-type sesquiterpene possessing rare spirobicyclic carbon skeleton, was isolated from the aerial parts of Psychotria yunnanensis. Its structure was elucidated on the basis of spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. The absolute configuration of 1 was determined by calculation of electronic circular dichroism using density functional theory.
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New cassane-type diterpenoids from Caesalpinia bonduc.
Chem. Pharm. Bull.
PUBLISHED: 07-04-2014
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Six new cassane diterpenoids, named caesalls H-M (1-6), were isolated from the seed kernels of Caesalpinia bonduc. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. The absolute configurations of compounds 1 and 3 were determined by a single-crystal X-ray study using a mirror CuK? radiation and circular dichroism (CD) spectra, respectively. None of the compounds were cytotoxic against HepG-2, MCF-7 and MG-63 cells.
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Direct CO oxidation by lattice oxygen on the SnO2(110) surface: a DFT study.
Phys Chem Chem Phys
PUBLISHED: 05-17-2014
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As a noble-metal-free catalyst for CO oxidation, SnO2 has sparked worldwide interest owing to its highly reactive lattice oxygen atoms and low cost. The current density functional theory (DFT) results demonstrate the process of CO oxidation by lattice oxygen on the SnO2(110) surface and the recovery of the reduced surface by O2. It is found that CO can be easily oxidized on the SnO2(110) surface following the Mars-van Krevelen mechanism. The adsorbed oxygen turns into various oxygen species by transferring electron(s) to the chemisorbed oxygen, which is only found on the partially reduced SnO2-x surface, but not on the perfect SnO2(110) surface: O2(gas) ? O2(ad) ? O2(-)(ad) ? O2(2-)(ad) ? O(2-)(lattice) + O(-)(ad). The calculated stretching frequencies would help to distinguish the various adsorbed species observed in experiment and of course help in the assignment of vibrational modes in the experimental spectra.
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A new method to fabricate an electrochemical aptasensor to assay adenosine deaminase concentration using an assistance DNA.
J Immunoassay Immunochem
PUBLISHED: 03-15-2014
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A novel strategy for the fabrication of electrochemical aptasensor is proposed in this work. This strategy has been employed to develop an aptasensor for the detection of adenosine deaminase concentration. A probe which contains adenosine aptamer and modified with ferrocene is adopted in our strategy as the core element. Moreover, an assistance DNA which can hybridize with the probe was also been employed in our strategy. The enzymatic reaction of adenosine catalyzed by adenosine deaminase plays a key role as well in the regulation of the hybridized complex. The formation of these regions of rigid, duplex DNA prevents the ferrocene tag from approaching the electrode surface, suppressing amperometric currents. The electroactive probe is to reflect the concentration of the enzyme indirectly but accurately. The detection limit is 1 U L(-1), which can be acceptable for clinical applications.
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Sinoporphyrin sodium: a novel sensitizer in sonodynamic therapy.
Anticancer Drugs
PUBLISHED: 03-13-2014
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The aim of this paper was to investigate whether sinoporphyrin sodium (DVDMS) could be a novel sonosensitizer in sonodynamic therapy. We used two kinds of leukemia cells (K562, U937) as main tumor cell models and cells (peripheral blood mononuclear cells, spleen lymphocytes) separated from healthy ICR mice as normal cell models. The multivolume spectrophotometer system and fluorescence spectrophotometer were used to determine the spectral characteristics of DVDMS. The uptake of DVDMS by tumor cells and normal cells was measured by flow cytometry. The MTT assay was used to examine the cytotoxicity and sonotoxicity of DVDMS. The absorption spectra showed that DVDMS had five distinct peaks at 359, 514, 548, 580, and 631 nm, respectively, and the maximum peak was at ?359 nm. The fluorescence emission spectra showed that DVDMS fluorescence emission was at 642 nm. DVDMS showed an advantage of quick cellular uptake and selectively accumulated in tumor cells compared with normal healthy cells. The cytotoxicity of DVDMS by the MTT method was dose dependent, and DVDMS had little cytotoxicity to normal cells. The sonotoxicity of DVDMS showed that in the presence of DVDMS, under appropriate conditions, the cell-damaging effect of ultrasound was significantly enhanced. The present study showed that the newly synthesized sensitizer, DVDMS, under appropriate experiment conditions, can act as a potential sonosensitizer for tumors in sonodynamic therapy.
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Cytotoxic effect of protoporphyrin IX to human Leukemia U937 cells under ultrasonic irradiation.
Cell. Physiol. Biochem.
PUBLISHED: 03-11-2014
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Sonodynamic therapy (SDT) is an alternative strategy that manages malignancies via the generation of cytotoxic factors during ultrasound-activated sono-sensitive agents. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on U937 cells.
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Structural elucidation of new urinary tamoxifen metabolites by liquid chromatography quadrupole time-of-flight mass spectrometry.
J Mass Spectrom
PUBLISHED: 03-06-2014
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In this study, tamoxifen metabolic profiles were investigated carefully. Tamoxifen was administered to two healthy male volunteers and one female patient suffering from breast cancer. Urinary extracts were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry using full scan and targeted MS/MS techniques with accurate mass measurement. Chromatographic peaks for potential metabolites were selected by using the theoretical [M?+?H](+) as precursor ion in full-scan experiment and m/z 72, 58 or 44 as characteristic product ions for N,N-dimethyl, N-desmethyl and N,N-didesmethyl metabolites in targeted MS/MS experiment, respectively. Tamoxifen and 37 metabolites were detected in extraction study samples. Chemical structures of seven unreported metabolites were elucidated particularly on the basis of fragmentation patterns observed for these metabolites. Several metabolic pathways containing mono- and di-hydroxylation, methoxylation, N-desmethylation, N,N-didesmethylation, oxidation and combinations were suggested. All the metabolites were detected in the urine samples up to 1?week.
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Primary malignant cardiac tumors.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-27-2014
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The literature on primary malignant cardiac tumors is relatively limited because of their rare incidence. This study aimed to provide a proposed treatment strategy for primary malignant cardiac tumors.
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Quantitative analysis of glycerol levels in human urine by liquid chromatography-tandem mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 02-12-2014
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Glycerol has the latent capacity to act as a plasma volume expander and disguise blood doping practices. Therefore, it has been prohibited in sports as a masking agent by the World Anti-Doping Agency (WADA) since January 2010 and a urinary threshold (1mg/mL) was recommended recently [1]. The purpose of this study was to establish and validate a novel quantitative method for the determination of urinary glycerol concentrations using a liquid chromatography-tandem mass spectrometry approach. This simple yet highly specific method made use of the derivatization of glycerol by benzoyl chloride in aqueous solution at 40°C followed by analysis via LC-ESI-MS/MS without sample pre-concentration or cleanup. The assay was linear over the concentration range of 1.0-1000?g/mL for glycerol in human urine. The lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were 0.3?g/mL and 1.0?g/mL, respectively. The intra- and inter-day precision of the method at three concentration levels (3, 500 and 900?g/mL) was less than 12.2%. The method also afforded satisfactory results in terms of accuracy, derivatization yield, extraction recovery, matrix effect and specificity. The method has been successfully applied to the detection of glycerol in "Quality Assurance Program" samples provided by the World Association of Anti-Doping Scientists (WAADS) and routine doping-control samples in our laboratory.
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Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease.
J. Clin. Microbiol.
PUBLISHED: 01-31-2014
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Dysbiosis in the intestinal microbiota of persons with inflammatory bowel disease (IBD) has been described, but there are still varied reports on changes in the abundance of Bifidobacterium and Lactobacillus organisms in patients with IBD. The aim of this investigation was to compare the compositions of mucosa-associated and fecal bacteria in patients with IBD and in healthy controls (HCs). Fecal and biopsy samples from 21 HCs, 21 and 15 Crohn's disease (CD) patients, and 34 and 29 ulcerative colitis (UC) patients, respectively, were analyzed by quantitative real-time PCR targeting the 16S rRNA gene. The bacterial numbers were transformed into relative percentages for statistical analysis. The proportions of bacteria were uniformly distributed along the colon regardless of the disease state. Bifidobacterium was significantly increased in the biopsy specimens of active UC patients compared to those in the HCs (4.6% versus 2.1%, P = 0.001), and the proportion of Bifidobacterium was significantly higher in the biopsy specimens than in the fecal samples in active CD patients (2.7% versus 2.0%, P = 0.012). The Lactobacillus group was significantly increased in the biopsy specimens of active CD patients compared to those in the HCs (3.4% versus 2.3%, P = 0.036). Compared to the HCs, Faecalibacterium prausnitzii was sharply decreased in both the fecal and biopsy specimens of the active CD patients (0.3% versus 14.0%, P < 0.0001 for fecal samples; 0.8% versus 11.4%, P < 0.0001 for biopsy specimens) and the active UC patients (4.3% versus 14.0%, P = 0.001 for fecal samples; 2.8% versus 11.4%, P < 0.0001 for biopsy specimens). In conclusion, Bifidobacterium and the Lactobacillus group were increased in active IBD patients and should be used more cautiously as probiotics during the active phase of IBD. Butyrate-producing bacteria might be important to gut homeostasis.
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Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells.
Ultrasound Med Biol
PUBLISHED: 01-22-2014
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It is well accepted that sonodynamic therapy (SDT) exerts cytotoxicity and anti-tumor activity in many human tumors through the induction of cell apoptosis. The aim of the work described here was to study the effect of chlorin e6 (Ce6)-mediated SDT on human chronic myelogenous leukemia K562 cells. Our results indicate that Ce6-mediated SDT can suppress the viability of K562 cells. SDT caused apoptosis as analyzed by annexin V-phycoerythrin/7-amino-actinomycin D staining as well as cleavage of caspase 3 and the polypeptide poly(ADP-ribose) polymerase. After SDT exposure, loss of mitochondrial membrane potential, translocation of Bax from cytoplasm to mitochondria and activation of caspase 9 indicated that the mitochondrial-related apoptotic pathway might be activated. This process was accompanied by rapid generation of reactive oxygen species (ROS). Scavenging of ROS significantly blocked caspase-3 expression and the killing effect of SDT on K562 cells. Stress-activated protein kinases c-jun NH2-terminal kinase (JNK) and the p38 mitogen-activated protein kinase were activated after SDT treatment. Together, these findings indicate that Ce6-mediated SDT triggers mitochondria- and caspase-dependent apoptosis; oxidative injury may play a vital role in apoptotic signaling cascades.
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Activation of microbubbles by low-level therapeutic ultrasound enhances the antitumor effects of doxorubicin.
Eur Radiol
PUBLISHED: 01-20-2014
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To prove that DNA damage, intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP) are contributing factors for the inhibition of cell proliferation induced by doxorubicin (DOX) administration combined with microbubble-assisted low-level therapeutic ultrasound (US) in K562 cells.
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ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells.
Gen. Physiol. Biophys.
PUBLISHED: 01-13-2014
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This study was to investigate the cell killing effect of chlorin-e6 (Ce6) mediated sonodynamic therapy (SDT) on human leukemia U937 cells and explore the role of ERK signal pathway in the process. The ultrastructure changes of U937 cells induced by ultrasonic irradiation were evaluated by scanning electron microscope (SEM) and transmission electron microscope (TEM). The viability of cells was evaluated by viacount assay. Apoptosis was analyzed using ?ow cytometer as well as ?uorescence microscopy with 4'-6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to analyze the expression of mitogen-activated protein kinase (MAPK). Intracellular reactive oxygen species (ROS) and mitochondria membrane potential (MMP) levels were also analyzed by ?ow cytometer after exposure. Our experiments showed that several distinct sonochemical effects were found after Ce6-mediated SDT treatment. Western blotting analysis indicated that the MAPK were activated. Especially, pre-treatment with ERK inhibitor U0126 could additionally enhance SDT-induced cell viability loss, early- and late-apoptotic rate, chromatin condensation, DNA fragmentation and caspase-3 activation. Besides, a mass of ROS accumulation and a conspicuous loss of mitochondrial membrane potential were detected in U937 cells. These ?ndings suggested ERK signal pathway may deliver a survival signal which counteracts SDT-induced cell death, while combination with U0126 could significantly potentiate the SDT-induced cytotoxic effect in U937 cells.
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Control efficacy of an endophytic Bacillus amyloliquefaciens strain BZ6-1 against peanut bacterial Wilt, Ralstonia solanacearum.
Biomed Res Int
PUBLISHED: 01-12-2014
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We aimed to isolate and identify endophytic bacteria that might have efficacy against peanut bacterial wilt (BW) caused by Ralstonia solanacearum. Thirty-seven endophytic strains were isolated from healthy peanut plants in R. solanacearum-infested fields and eight showed antagonistic effects against R. solanacearum. Strain BZ6-1 with the highest antimicrobial activity was identified as Bacillus amyloliquefaciens based on morphology, biochemistry, and 16S rRNA analysis. Culture conditions of BZ6-1 were optimized using orthogonal test method and inhibitory zone diameter in dual culture plate assay reached 34.2 mm. Furthermore, main antimicrobial substances of surfactin and fengycin A homologues produced by BZ6-1 were analyzed by high performance liquid chromatography electrospray ionization tandem mass spectrometry. Finally, pot experiments were adopted to test the control efficiency of BZ6-1 against peanut BW. Disease incidence decreased significantly from 84.5% in the control to 12.1% with addition of 15 mL (10(8) cfu mL(-1)) culture broth for each seedling, suggesting the feasibility of strain BZ6-1 in the biological control of peanut plants BW.
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Cassane-type diterpenoids from the seed kernels of Caesalpinia bonduc.
Fitoterapia
PUBLISHED: 01-03-2014
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Seven new cassane diterpenoids (1-7), along with three known compounds (8-10), were isolated from the seed kernels of Caesalpinia bonduc. The structures were elucidated by extensive 1D and 2D NMR (HSQC, HMBC and ROESY) and mass (HRESIMS) spectroscopic data analyses. The structure and absolute configuration of compound 1 were confirmed by a single-crystal X-ray diffraction experiment. All isolates were tested for their cytotoxicity against HepG-2, MCF-7 and MG-63 cells, and 8-10 showed weak inhibitory activities.
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Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Sonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line.
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Investigating migration inhibition and apoptotic effects of Fomitopsis pinicola chloroform extract on human colorectal cancer SW-480 cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Fomitopsis pinicola (Sw. Ex Fr.m) Karst (FPK) which belongs to the Basidiomycota fungal class is one of the most popular medical fungi in China. It has been used for many diseases: cancer, heart diseases, diabetes and so on. However, little study on the pro-apoptotic effect and migration inhibition of FPK chloroform extract (FPKc) has been reported and the possible involved mechanism has not been illuminated.
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Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study.
PLoS ONE
PUBLISHED: 01-01-2014
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Genetic variants make some contributions to inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More than 100 susceptibility loci were identified in Western IBD studies, but susceptibility gene has not been found in Chinese IBD patients till now. Sequencing of individuals with an IBD family history is a powerful approach toward our understanding of the genetics and pathogenesis of IBD. The aim of this study, which focuses on a Han Chinese CD family, is to identify high-risk variants and potentially novel loci using whole exome sequencing technique.
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CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced colitis in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis.
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Anti-cancer effect and the underlying mechanisms of gypenosides on human colorectal cancer SW-480 cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Gypenosides (Gyp), the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480.
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PpIX induces mitochondria-related apoptosis in murine leukemia L1210 cells.
Drug Chem Toxicol
PUBLISHED: 12-16-2013
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Abstract Context: Protoporphyrin IX (PpIX), a well-known sensitizer that can enhance laser light or ultrasound induced cytotoxicity in photodynamic and sonodynamic therapy. However, PpIX alone could effectively cause anti-tumor effect and the underlying mechanisms are rarely been reported. Therefore, this study was to investigate the possible mechanism by which PpIX revealed anti-proliferative effect on murine leukemia L1210 cells. Materials and methods: The accumulation of PpIX in L1210 cells and normal peripheral blood mononuclear cells (PBMCs) was evaluated with flow cytometry. The subcellular localization of PpIX and apoptosis-inducing factor (AIF) translocation were determined by confocal microscope. The cell viability was examined by MTT assay. Annexin V-PE/7-AAD and DAPI staining were used to detect apoptotic cells. The mitochondrial membrane potential (MMP) changes were tested by rhodamine123 staining. DNA damage was measured by comet assay. Results: PpIX preferentially accumulated in L1210 cells compared to PBMCs and PpIX mainly located in the mitochondria of L1210 cells. PpIX at a concentration of 1?µg/ml or above exerted significant anti-tumor effect and the cell viability loss presented PpIX dose-dependent manner. Typical apoptotic features such as chromatin condensation were observed by DAPI staining. Annexin V-PE/7-AAD analysis showed 5?µg/ml PpIX could induce about 24% cell apoptosis, which was inhibited by cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore. In addition, the PpIX caused MMP loss, AIF translocation to nucleus and serious DNA damage were also suppressed by CsA. Conclusion: The results indicate mitochondria-dependent apoptosis were involved in PpIX caused cell damage on L1210 cells.
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Efficacy of Chlorin e6-Mediated Sono-Photodynamic Therapy on 4T1 Cells.
Cancer Biother. Radiopharm.
PUBLISHED: 11-09-2013
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Abstract Purpose: The present study aims to investigate the antitumor effect and possible mechanisms of chlorin e6 (Ce6)-mediated sono-photodynamic therapy (Ce6-SPDT) on murine 4T1 mammary cancer cells in vitro. Materials: Cellular uptake and intracellular distribution of Ce6 in 4T1 cells were detected by flow cytometry and confocal microscope. Cells after loading with 1??g/mL Ce6 were exposed to ultrasound at 1.0?MHz for up to 1 minute with an intensity of 0.36?W/cm(2) and laser light with total radiation dose of 1.2?J/cm(2). Cell viability and clonogenicity were determined by MTT assay and colony formation assay. Apoptosis was analyzed by DAPI staining, Western blots were used to detect the activity of Caspase-3. DNA damage, mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS) of 4T1 cells were also evaluated by flow cytometry. FD500 was employed to detect changes of membrane permeability after ultrasound. Results: Ce6 rapidly entered 4T1 cells within 4 hours after it has been added and displayed a mitochondria-localization pattern. Compared with sonodynamic therapy (SDT) and photodynamic therapy (PDT) alone, the combined SPDT treatment further enhanced cell viability loss, DNA damage, and clonogenicity inhibition. DAPI staining and western blots analysis reflected that cells with apoptotic morphological characteristics and the activity of Caspase-3 were apparently increased in the combined group. Besides, SPDT caused obvious MMP loss and intracellular ROS generation at early 1 hour post treatment. Interestingly, the SPDT induced cell viability loss and cell apoptosis was greatly inhibited by pre-treatment with ROS scavenger N-acetylcysteine and Caspase inhibitor z-VAD-fmk. FD500 detection showed that ultrasound enhanced cell membrane permeability, implying much higher uptake of Ce6 might be involved in PDT therapy by pre-ultrasound treatment. Conclusions: The findings demonstrated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, a Caspase-dependent apoptosis and loss of MMP, generation of ROS may be involved.
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Tumor Necrosis Factor-Related Apoptosis Inducing Ligand Gene Polymorphisms are Correlated with Gastric Cancer in Central China.
Pharm. Res.
PUBLISHED: 09-20-2013
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To investigate the association of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) gene polymorphisms with gastric cancer in Chinese Han population in central China.
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An Improved Liquid Chromatography-Tandem Mass Spectrometric Method to Quantify Formoterol in Human Urine.
J Chromatogr Sci
PUBLISHED: 09-12-2013
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Formoterol is a new threshold substance in the prohibited list 2012 according to World Anti-Doping Agency. Extracted by ethyl acetate using formoterol-D6 as internal standard, formoterol underwent a constant flow rate gradient elution separation in reversed-phase liquid chromatography. Subsequently, mass spectrometry analysis was conducted by tandem mass spectrometry in the multiple reaction monitoring mode. According to the proposed method, a calibration curve was constructed in the range of 0.2-500 ng/mL (r(2) = 1) with a limit of quantification 0.2 ng/mL. The mean extracted recovery assessed at three different concentrations (1, 30 and 100 ng/mL) was more than 80%. The method was validated by the analysis of three quality control samples from World Association of Anti-Doping Scientists. In conclusion, the developed and validated method was sensitive, accurate and precise for the quanti?cation of formoterol in human urine for doping control purposes.
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DNA damage and cell cycle arrest induced by protoporphyrin IX in sarcoma 180 cells.
Cell. Physiol. Biochem.
PUBLISHED: 08-26-2013
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Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX), a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180) cells.
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Efficacy of combined therapy with paclitaxel and low-level ultrasound in human chronic myelogenous leukemia cell line K562.
J Drug Target
PUBLISHED: 08-19-2013
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Sonochemotherapy, which applies ultrasound in cancer chemotherapy, has been proven to be a promising therapeutic modality by some previous researches.
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High intestinal and systemic levels of interleukin-23/t-helper 17 pathway in chinese patients with inflammatory bowel disease.
Mediators Inflamm.
PUBLISHED: 07-14-2013
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Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohns disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population.
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Protoporphyrin IX-mediated sonodynamic action induces apoptosis of K562 cells.
Ultrasonics
PUBLISHED: 07-14-2013
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The present study aims to investigate apoptosis of human leukemia K562 cells induced by protoporphyrin IX (PpIX)-mediated sonodynamic therapy (PpIX-SDT).
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Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy.
Int. J. Radiat. Biol.
PUBLISHED: 07-08-2013
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To elucidate the underlying events in Chlorin e6 (Ce6)-mediated sonodynamic therapy (SDT) (Ce6-SDT)-induced apoptosis of human leukemia cell line U937.
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Enantioseparation of racemic trans-?-viniferin using high speed counter-current chromatography based on induced circular dichroism technology.
J Chromatogr A
PUBLISHED: 07-01-2013
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A preparative chiral high speed counter-current chromatography (HSCCC) method based on induced circular dichroism (ICD) spectrum was developed to separate trans-?-viniferin (TVN) enantiomers successfully. The important parameters for the chiral HSCCC separation process, including the type of chiral selector (CS), the concentration of chiral selector and the equilibrium temperature, were optimized using induced circular dichroism spectrum. The final separation procedure was established with a biphasic solvent system composed of n-hexane-ethyl acetate-25mmolL(-1) hydroxypropyl-?-cyclodextrin aqueous solution (5:5:10, v/v/v) in the head-to-tail elution mode at 5°C. Under optimum chiral HSCCC separation conditions, 8.2mg of (7S, 8S)-TVN (1) and 9.4mg of (7R, 8R)-TVN (2) were successfully separated from 20mg TVN enantiomers with the purity of 99.51% and 99.36%, respectively.
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The effects of Ce6-mediated sono-photodynamic therapy on cell migration, apoptosis and autophagy in mouse mammary 4T1 cell line.
Ultrasonics
PUBLISHED: 06-30-2013
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Sono-Photodynamic therapy (SPDT) is an alternative therapy which claims to enhance the anti-cancer effects by combining sonodynamic therapy (SDT) with photodynamic therapy (PDT). In the present study, we investigated the effects of chlorin e6 (Ce6) mediated SPDT on migration, apoptosis and autophagy in mouse mammary 4T1 cancer cells, and its underlying mechanisms.
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RRBS-analyser: a comprehensive web server for reduced representation bisulfite sequencing data analysis.
Hum. Mutat.
PUBLISHED: 06-28-2013
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In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested with the restriction enzyme and then subjected to next-generation sequencing, which enables detection and quantification of DNA methylation at whole-genome scale with low cost. However, the data processing, interpretation, and analysis of the huge amounts of data generated pose a bioinformatics challenge. We developed RRBS-Analyser, a comprehensive genome-scale DNA methylation analysis server based on RRBS data. RRBS-Analyser can assess sequencing quality, generate detailed statistical information, align the bisulfite-treated short reads to reference genome, identify and annotate the methylcytosines (5mCs) and associate them with different genomic features in CG, CHG, and CHH content. RRBS-Analyser supports detection, annotation, and visualization of differentially methylated regions (DMRs) for multiple samples from nine reference organisms. Moreover, RRBS-Analyser provides researchers with detailed annotation of DMR-containing genes, which will greatly aid subsequent studies. The input of RRBS-Analyser can be raw FASTQ reads, generic SAM format, or self-defined format containing individual 5mC sites. RRBS-Analyser can be widely used by researchers wanting to unravel the complexities of DNA methylome in the epigenetic community. RRBS-Analyser is freely available at http://122.228.158.106/RRBSAnalyser/.
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Comparison between sonodynamic and photodynamic effect on MDA-MB-231 cells.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 05-17-2013
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Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are therapeutic modalities for tumors. In this study we investigated the combined cytotoxic effect of 0.36W/cm(2) and 0.72W/cm(2) ultrasound with various Ce6 concentrations (1, 2, 5, 10?g/ml), and that of 1?g/ml Ce6 with different laser light dose (650nm; 10.4mW/cm(2); 0.3, 0.6, 1.2 and 2.5J/cm(2)) on MDA-MB-231 cells. Both high reactive oxygen species (ROS) production and a decline in mitochondrial membrane potential (MMP) were detected with high Ce6 concentrations (5 and 10?g/ml) combined with 0.72W/cm(2) ultrasound and 1.2, 2.5J/cm(2) laser light with 1?g/ml Ce6. In addition, cell membrane integrity was evaluated by using propidium iodide (PI), revealing membrane damage was aggravated with the increasing ultrasound intensity, but no significant difference on cell membrane integrity could be observed after PDT treatment. These results suggest ROS may play an important role both in SDT and PDT. Besides, mitochondria may be an initial target in PDT while SDT can cause multi-site damages in MDA-MB-231 cells.
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The ethyl acetate fraction of Polytrichum commune L.ex Hedw induced cell apoptosis via reactive oxygen species in L1210 cells.
J Ethnopharmacol
PUBLISHED: 05-16-2013
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Polytrichum commune L.ex Hedw is a traditional Chinese herb for treatment of fever, hemostatic, uterine prolapse and especially for leukemia. Previous studies indicated its anti-leukemia effect but the potential mechanisms have not been fully explained.
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Elevated risk of opportunistic viral infection in patients with Crohns disease during biological therapies: a meta analysis of randomized controlled trials.
Eur. J. Clin. Pharmacol.
PUBLISHED: 03-20-2013
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Biological agents have been widely used in the treatment of Crohns disease (CD). These drugs carry the risk of excessive immunosuppression, indicating possible opportunistic infections including opportunistic viral infections, but no meta analysis has ever focused on this issue.
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Apoptosis of U937 cells induced by hematoporphyrin monomethyl ether-mediated sonodynamic action.
Cancer Biother. Radiopharm.
PUBLISHED: 03-18-2013
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The present study aims to investigate apoptosis of U937 cells induced by hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT).
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Ultrasound enhances the efficacy of chlorin E6-mediated photodynamic therapy in MDA-MB-231 cells.
Ultrasound Med Biol
PUBLISHED: 03-12-2013
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Sono-photodynamic therapy (SPDT) is a new modality for cancer treatment. Some studies have reported enhanced tumor cytotoxicity when sonodynamic therapy (SDT) is combined with photodynamic therapy (PDT). In this study, we investigated the cytotoxic effect of SPDT-activated chlorin e6 (Ce6) on MDA-MB-231 cells. Ce6 was found to localize mainly in mitochondria, with maximal uptake within 4 h. Cell survival was estimated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide tetrazolium) assay 24 h after irradiation; the combined therapy enhanced cytotoxicity to a greater extent. Apoptosis was analyzed using annexin V-PE/7-ADD (7-aminoactinomycin D) staining as well as DAPI (4, 6-diamidino-2-phenylindole) staining, and the results indicated that the cells with apoptotic characteristics were significantly increased in groups given combined therapy. Rhodamine-123 staining and cytochrome c release revealed more serious damage of mitochondria after combined treatment. The generation of reactive oxygen species detected by flow cytometry was greatly increased in cells treated with the combination therapy, and the loss in cell viability could be effectively rescued with the reactive oxygen species inhibitor N-acetylcysteine. Moreover, enhancement of cell membrane permeability after ultrasound treatment was evaluated using FD-500, and it was found that the much higher uptake of Ce6 might be involved in PDT therapy with pre-treatment ultrasound. These results suggest that ultrasound enhances the cytotoxicity of Ce6-mediated PDT, possibly because of the increased intracellular Ce6 level and ROS formation by ultrasound pre-treatment.
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Increasing age associated with elevated cardio-ankle vascular index scores in patients with type 2 diabetes mellitus.
J. Int. Med. Res.
PUBLISHED: 03-07-2013
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The study investigated the relationship between arterial stiffness calculated using the cardio-ankle vascular index (CAVI), diagnosis of type 2 diabetes mellitus and type 2 diabetes-related cardiovascular complications, in patients with type 2 diabetes mellitus (type 2 diabetes) and nondiabetic patients.
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Novel electrochemical biosensor based on functional composite nanofibers for sensitive detection of p53 tumor suppressor gene.
Anal. Chim. Acta
PUBLISHED: 02-16-2013
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A novel electrochemical biosensor based on functional composite nanofibers for sensitive hybridization detection of p53 tumor suppressor using methylene blue (MB) as an electrochemical indicator is developed. The carboxylated multi-walled carbon nanotubes (MWNTs) doped nylon 6 (PA6) composite nanofibers (MWNTs-PA6) was prepared using electrospinning, which served as the nanosized backbone for pyrrole (Py) electropolymerization. The functional composite nanofibers (MWNTs-PA6-PPy) used as supporting scaffolds for ssDNA immobilization can dramatically increase the amount of DNA attachment and the hybridization sensitivity. The biosensor displayed good sensitivity and specificity. The target wild type p53 sequence (wtp53) can be detected as low as 50 fM and the discrimination is up to 57.5% between the wtp53 and the mutant type p53 sequence (mtp53). It holds promise for the early diagnosis of cancer development and monitoring of patient therapy.
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Cardiac capillary hemangioma: A case report and brief review of the literature.
J Clin Ultrasound
PUBLISHED: 01-17-2013
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Among primary cardiac tumors, hemangiomas are relatively rare, with a reported incidence of 2.8%. To date, less than 100 cases have been reported in literature. We report the case of a 61-year-old woman who complained from chest discomfort since 3 years and in whom transthoracic echocardiography revealed a pedunculated tumor in the left ventricle. The tumor was successfully resected and its histopathological examination revealed a capillary hemangioma. The patient had an uneventful recovery without any complication. © 2013 Wiley Periodicals, Inc.
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A solid-state electrochemiluminescence sensing platform for detection of catechol based on novel luminescent composite nanofibers.
Talanta
PUBLISHED: 01-06-2013
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A solid-state electrochemiluminescence (ECL) sensing platform based on the novel luminescent composite nanofibers for detection of catechol has been developed. The carboxylated multi-walled carbon nanotubes (MWNTs) and ruthenium(II) tris-(bipyridine) (Ru(bpy)3(2+)) doped nylon 6 (PA6) luminescent composite nanofibers (Ru-MWNTs-PA6) were successfully fabricated by a one-step electrospinning technique. The Ru-MWNTs-PA6 nanofibers, with unique 3D nanostructure, large specific surface area and a larger amount of immobilized-Ru(bpy)3(2+), maintained the photoelectric properties of the Ru(bpy)3(2+) ions and exhibited excellent ECL behaviors on glassy carbon (GC) electrode. As a solid-state ECL sensing platform, the Ru-MWNTs-PA6 nanofibers can sensitively detect low concentration catechol by monitoring the phenol-dependent ECL intensity change. The detection limit for catechol is 1.0 nM, which is comparable or better than that in the reported assays. The solid-state ECL sensor displayed wide linear range, high sensitivity and good stability. It holds promise for the electrospun nanofibers-based ECL sensors have a great potential for routine analyses.
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High anemia prevalence in western China.
Southeast Asian J. Trop. Med. Public Health
PUBLISHED: 10-17-2011
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We assessed the prevalence of anemia among schoolchildren in western China as determined by seven cross-sectional surveys involving 12,768 children aged 8-12 years. Subjects were selected randomly from 283 primary schools in 41 economically disadvantaged counties of Ningxia, Qinghai, Shaanxi and Sichuan Provinces. Data were collected through questionnaires and hemoglobin levels were measured. The anemia prevalence was 34% using the WHO hemoglobin cutoff of < 120 g/l. Boarding students and girls were more likely to be anemic. The prevalence of anemia in schoolchildren was high. Iron deficiency is a significant nutrition issue in China.
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Preoperative assessment of mitral valve prolapse and chordae rupture using real time three-dimensional transesophageal echocardiography.
Echocardiography
PUBLISHED: 08-19-2011
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Mitral valve (MV) repair provides a better outcome in patients with significant mitral regurgitation than MV replacement. Valve repair requires a thorough understanding of MV morphology. Recently developed real time three-dimensional transesophageal echocardiography (RT3D TEE) can provide online acquisition and accurate information of cardiac structures. The study aim was to evaluate the feasibility and accuracy of using RT3D TEE to assess mitral valve prolapse (MVP) and chordae rupture for surgical planning purposes.
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Apoptosis induced by sonodynamic treatment by protoporphyrin IX on MDA-MB-231 cells.
Ultrasonics
PUBLISHED: 08-09-2011
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Sonodynamic therapy (SDT) is a promising modality for cancer treatment, involving the synergistic interaction of ultrasound and some chemical compounds termed as sono-sensitizers. It has been found that SDT can lead to apoptotic cell death because of the induction of direct sonochemical and subsequent redox reactions. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on MDA-MB-231 cells. The fluorescence microscope was used to detect the sub-cellular localization of PpIX. Several distinct sonochemical effects were found after SDT treatment, including the decrease of cell viability, generation of intracellular ROS, the loss of mitochondrial membrane potential. The activation of some special apoptosis-associated proteins [Caspase-9, Caspase-3 and polypeptide poly (ADP-robose) polymerase] was evaluated by western blotting. The results show that PpIX mediated SDT (PpIX-SDT) treatment could obviously inhibit the proliferation of MDA-MB-231 cells, and which was significantly reduced by the pan-Caspase inhibitor z-VAD-fmk and the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC). Further, SDT induced a conspicuous loss of mitochondrial membrane potential (MMP) and a mass of ROS accumulation in MDA-MB-231 cells at 1h post-treatment and the SDT-treated cells showed obvious Caspase-3 and Caspase-9 activation, and PARP cleavage at 6h after treatment. And, the general apoptosis marker-Caspase-3 activation-was also greatly relieved by NAC. These findings primarily indicate a Caspase-depended apoptosis could be induced by PpIX-SDT in MDA-MB-231 cells, and the intracellular ROS was involved during the apoptotic process.
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Autophagic and apoptotic response to sonodynamic therapy induced cell damage in leukemia l1210 cells in vitro.
Cancer Biother. Radiopharm.
PUBLISHED: 05-05-2011
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The present study was initiated to study the autophagic and apoptotic response to sonodynamic therapy (SDT) in murine leukemia L1210 cells in vitro.
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Pharmacokinetic study of a novel sonosensitizer chlorin-e6 and its sonodynamic anti-cancer activity in hepatoma-22 tumor-bearing mice.
Biopharm Drug Dispos
PUBLISHED: 03-12-2011
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The sonodynamically induced anti-tumor effect of chlorin-e6 (Ce6) was studied in mice bearing hepatoma-22 solid tumors.
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Discrete Ag6L6 coordination nanotubular structures based on a T-shaped pyridyl diphosphine.
Chem. Commun. (Camb.)
PUBLISHED: 02-14-2011
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Ag(6)L(6)-type coordination nanotubular structures have been assembled from 6 Ag(I) ions and 6 T-shaped ligands, 4-(3,5-bis(diphenylphosphino)phenyl)pyridine; the nanotubes represent a discrete molecular architecture of a number of polymeric structures assembled from dimeric building blocks.
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Rapid discovery of death ligands with one-bead-two-compound combinatorial library methods.
ACS Comb Sci
PUBLISHED: 02-08-2011
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The one-bead-one-compound (OBOC) technology enables one to generate thousands to millions of chemical molecules on resin beads (90 ?m diameter) such that each bead displays 10(13) copies of the same chemical entity. Whole-cell binding assays have been developed to screen OBOC combinatorial libraries for ligands that bind to specific cell surface receptors. While very powerful, this screening method does not address the downstream cell signaling properties of the binding ligand. We have modified the OBOC technology by introducing a fixed known cell adhesion ligand to the outer layer of each bead. This one-bead-two-compound (OB2C) library configuration allows the bound cells to interact with the random immobilized chemical molecules on each bead. The bound cells can then be probed for specific cellular responses such as apoptosis and activation or inhibition of a specific cell signaling pathway. To validate this concept, an OB2C combinatorial library was created such that a random hexapeptide plus a high affinity lymphoma targeting ligand LLP2A were displayed on each bead. This LLP2A-X(6) OB2C library was then screened with human T-cell leukemia cells (Molt-4) for cell death responses. After 5 days of incubation, propidium iodide was added to the bead library to stain dead cells. Beads coated by red fluorescent cells were isolated for sequence analysis. Two ligands identified by this method, when added to the lymphoid cancer cells, were able to induce cell death.
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Mass spectrometric characterization of toremifene metabolites in human urine by liquid chromatography-tandem mass spectrometry with different scan modes.
Analyst
PUBLISHED: 11-29-2010
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The metabolism and excretion of toremifene were investigated in one healthy male volunteer after a single oral administration of 120 mg toremifene citrate. Different liquid chromatographic/tandem mass spectrometric (LC/MS/MS) scanning techniques were carried out for the characterization of the metabolites in human urine for doping control purposes. The potential characteristic fragmentation pathways of toremifene and its major metabolites were presented. An approach for the metabolism study of toremifene and its analogs by liquid chromatography-tandem mass spectrometry was established. Five different LC/MS/MS scanning methods based on precursor ion scan (precursor ion scan of m/z 72.2, 58.2, 44.2, 45.2, 88.2 relative to five metabolic pathways) in positive ion mode were assessed to recognize the metabolites. Based on product ion scan and precursor ion scan techniques, the metabolites were proposed to be identified as 4-hydroxy-toremifene (m/z 422.4), 4-hydroxy-toremifene (m/z 422.4), ?-hydroxy-toremifene (m/z 422.4), 3,4-dihydroxy-toremifene (m/z 404.2), toremifene acid (m/z 402.2), 3-hydroxy-4-methoxy-toremifene (m/z 456.2), dihydroxy-dehydro-toremifene (m/z 440.2), 3,4-dihydroxy-toremifene (m/z 438.2), N-demethyl-4-hydroxy-toremifene (m/z 408.3), N-demethyl-3-hydroxy-4-methoxy-toremifene (m/z 438.3). In addition, a new metabolite with a protonated molecule at m/z 390.3 was detected in all urine samples. The compound was identified by LC/MS/MS as N-demethyl-4,4-dihydroxy-tamoxifene. The results indicated that 3,4-dihydroxy-toremifene (m/z 404.2), toremifene acid (m/z 402.2) and N-demethyl-4,4-dihydroxy-tamoxifene (m/z 390.3) were major metabolites in human urine.
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Sonodynamically induced anti-tumor effect with protoporphyrin IX on hepatoma-22 solid tumor.
Ultrasonics
PUBLISHED: 10-12-2010
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The purpose of this study was to evaluate sonodynamically induced anti-tumor effect of protoporphyrin IX (PPIX) in mice bearing hepatoma-22 (H-22) solid tumors, and the possible in vivo cell damage mechanism was also investigated.
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Comparison of accumulation, subcellular location, and sonodynamic cytotoxicity between hematoporphyrin and protoporphyrin IX in L1210 cells.
Chemotherapy
PUBLISHED: 05-30-2010
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Sonodynamic therapy (SDT) is a promising modality for cancer treatment which requires the synergistic effect of ultrasound and tumor-localized sonosensitizers. Sonodynamic efficacy can be improved through a better understanding of the accumulation and subcellular location of sonosensitizers. Here, a comparison of the accumulation, sublocation, and sonodynamic effect of hematoporphyrin (Hp) and protoporphyrin IX (PpIX) was studied in L1210 cells.
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Identification of a bladder cancer-specific ligand using a combinatorial chemistry approach.
Urol. Oncol.
PUBLISHED: 04-15-2010
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To develop bladder cancer-specific ligands using a combinatorial chemistry approach.
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Comparison of pharmacokinetics, intracellular localizations and sonodynamic efficacy of endogenous and exogenous protoporphyrin IX in sarcoma 180 cells.
Ultrasonics
PUBLISHED: 04-10-2010
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The aim of the present study was to investigate the differences in pharmacokinetics, sub-cellular localizations and sonodynamic efficacy between endogenous and exogenous protoporphyrin IX (endo-PpIX and exo-PpIX) in sarcoma 180 (S180) cells.
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Cytotoxic tirucallane C26 triterpenoids from the stem barks of Aphanamixis grandifolia.
Phytochemistry
PUBLISHED: 03-26-2010
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Five tirucallane type C(26) triterpenoids, accompanied by two known compounds, 3?-hydroxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone and 3-oxo-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, were isolated from the stem barks of Aphanamixis grandifolia. Their structures were established mainly by means of a combination of 1D and 2D NMR spectroscopic and mass spectrometry techniques as 3?-hydroxyl-21?-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3?-hydroxy-21?-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3-oxo-21?-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, 3-oxo-21?-methoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone, and 3-oxo-21?-ethoxy-24,25,26,27-tetranortirucall-7-ene-23(21)-lactone. All isolates were in vitro evaluated for their cytotoxic activities against five tumor cell lines (MCF-7, HeLa, HepG2, SGC-7901 and BGC-823).
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Role of autophagy in sonodynamic therapy-induced cytotoxicity in S180 cells.
Ultrasound Med Biol
PUBLISHED: 03-10-2010
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Few reports have been published on the potential role of autophagy in the efficacy of sonodynamic therapy (SDT). This study was to determine whether autophagy occurred after SDT and to investigate its relationship with apoptosis by performing inhibitor studies. In vitro murine sarcoma 180 (S180) cells were examined at different time points following SDT. Transmission electron microscopy (TEM) was used to identify the formation of autophagosomes. Western blots were used to assess the processing of LC3-I to LC3-II. Confocal microscopy was performed to reveal co-localization between mitochondria and autophagic vacuoles and re-distribution of apoptosis related proteins after sono-damage. Inhibitors of apoptosis and autophagy were used to determine the contributions of the two cellular responses to SDT efficacy. Autophagy was indentified by TEM observation of the presence of double-membrane delineated autophagic vesicles and by immunoblot observation of the increased LC3-II levels. The autophagy inhibitors, both 3-methyladenine (3-MA) and Bafilomycin A1 (Ba A1), were found to significantly enhance SDT-induced cell death. Blocking autophagy also led to increased dissipation of mitochondria potential, caspase-3 activity and the ultimate cell apoptosis. Whereas the pan-caspase inhibitor, z-VAD-fmk partially prevented SDT-induced cytotoxicity but did not obviously improve the autophagic vacuolization and mitochondria depolarization. This study suggests for the first time that autophagy participate in SDT-induced cell death and combination of SDT with autophagy inhibitors, especially preventing autophagy at the early stage by 3-MA, can significantly enhance the anti-tumor effect of SDT through induction of apoptosis and necrosis.
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Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope.
J Biomed Opt
PUBLISHED: 03-10-2010
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We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm x 4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is capable of measuring kinetics as well as endpoints of protein-ligand reactions simultaneously. We present the experimental results on solution-phase protein reactions with small-molecule compound microarrays synthesized from one-bead, one-compound combinatorial chemistry and immobilized on a streptavidin-functionalized glass slide.
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Comparision between sonodynamic effects with protoporphyrin IX and hematoporphyrin on the cytoskeleton of Ehrlich ascites carcinoma cells.
Cancer Biother. Radiopharm.
PUBLISHED: 03-02-2010
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Our previous work demonstrated that the enhancement of cytotoxicity by protoporphyrin IX (Pp) was significantly higher than hematoporphyrin (Hp), when they were compared at the same ultrasound-exposure conditions, since the cytoskeleton plays a crucial role in numerous cell functions and the effect of sonodynamic therapy (SDT) on cytoskeleton has not been reported yet. So, it is very important to investigate whether SDT has some influence on the cytoskeleton, and it would also be interesting to compare Pp-/ and Hp-mediated SDT on the cytoskeleton.
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(+/-)-Praeruptorin A enantiomers exert distinct relaxant effects on isolated rat aorta rings dependent on endothelium and nitric oxide synthesis.
Chem. Biol. Interact.
PUBLISHED: 02-06-2010
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Praeruptorin A is a coumarin compound naturally occurring in the roots of Peucedanum praeruptorum Dunn., a commonly used traditional Chinese medicine for the treatment of certain respiratory diseases and hypertension. Although previous studies indicated the relaxant effects of (+/-)-praeruptorin A on tracheal and arterial preparations, little is known about the functional characteristics of the enantiomers. In the present study, the two enantiomers were successfully isolated and identified by using a preparative Daicel Chiralpak AD-H column, and their relaxant effects on aorta rings were observed and compared. (+)-Praeruptorin A showed more potent relaxation than (-)-praeruptorin A against KCl- and phenylephrine-induced contraction of rat isolated aortic rings with intact endothelium. Removal of the endothelium remarkably reduced the relaxant effect of (+)-praeruptorin A but not that of (-)-praeruptorin A. Pretreatment of aortic rings with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) or methylene blue (MB, a soluble guanylyl cyclase inhibitor) resulted in similar changes of the relaxant effects of the two enantiomers to endothelium removal. Molecular docking studies also demonstrated that (+)-praeruptorin A was in more agreement to nitric oxide synthase pharmacophores than (-)-praeruptorin A. On the other hand, the two enantiomers of praeruptorin A could slightly attenuate the contraction of rat aortic rings induced by internal Ca(2+) release from sarcoplasmic reticulum (SR). These findings indicated that (+)-praeruptorin A and (-)-praeruptorin A exerted distinct relaxant effects on isolated rat aorta rings, which might be mainly attributed to nitric oxide synthesis catalyzed by endothelial nitric oxide synthase.
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Sonodynamic effects of protoporphyrin IX disodium salt on Ehrlich ascetic tumor cells.
Ultrasonics
PUBLISHED: 02-01-2010
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The cytotoxic effect of protoporphyrin IX disodium salt (PPIX) on isolated Ehrlich ascetic tumor (EAT) cells induced by ultrasound exposure was investigated. Tumor cells suspended in air-saturated phosphate buffer solution (PBS, pH 7.2) were exposed to ultrasound at 2.2MHz for up to 60 s in the presence and absence of PPIX. The viability of cells was determined by a trypan blue exclusion test. The morphological changes of cells in SDT were observed by scanning electron microscope (SEM). And the sub-cellular localization of PPIX in EAT cells was detected by confocal laser scanning microscopy (CLSM). The ultrasonically-induced cell damage increased as PPIX concentration increased, while no cell damage was observed with PPIX alone. CLSM observation revealed that the fluorescence of PPIX and rhodamine 123 (mitochondrial probe) overlapped very well in the cytoplasm. The results indicate that PPIX could enhance the ultrasonically-induced cell damage and mitochondria may play an important role during sonodynamically induced cytotoxicity.
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[The effect of focused ultrasound on the physicochemical properties of Sarcoma 180 cell membrane].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 12-02-2009
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This study was amied to detect the changes in the cell membrane of Sarcoma 180 (S180) cells induced by focused ultrasound and to probe the underlying mechanism. The viability of tumor cells was examined at various intensities and different treatment times by ultrasound at the frequency of 2.2MHz. Flow cytometry and fluorescence microscopy were used to detect the loading of fluorescein isothiocyanate dextran (FD500) which signifies the change of membrane permeability. The results showed that after the cells were treated by ultrasound, especially when irradiated for 60s, the number of fluorescent cell, which represented the transient change of membrane permeabilization with cell survival, increased significantly. Then the damage of cell membrane was evaluated by the measurement of lactate dehydrogenase (LDH) release which became more severe as the radiation time was increasing. The generation of lipid peroxidation was estimated using the Thibabituric Acid (TBA) method after irradiation. The results reveal that the instant cell damage effects induced by ultrasound may be related to the improved membrane lipid peroxidation levels post-treatment. The physicochemical properties of S180 cell membrane were changed by focused ultrasound. The findings also imply an exposure time-dependent pattern and suggest that the lipid peroxidation produced by acoustic cavitation may play important roles in these actions.
Related JoVE Video

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.