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Find video protocols related to scientific articles indexed in Pubmed.
Functional investigation on aromatase in endometrial hyperplasia in polycystic ovary syndrome cases.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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To explore the possible significance of aromatase P450 in endometrial hyperplasia with a background of polycystic ovary syndrome (PCOS).
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[Synergistic Killing Effect of Arsenic Trioxide Combined with Curcumin on KG1a Cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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This study was aimed to explore the effect of arsenic trioxide combined with curcumin on proliferation and apoptosis of KG1a cells and its potential mechanism. The cell survival rate was mesured by MTT; colony formation capacity was examined by methylcellulose colony formation test; flow cytometry was used to analyse the cell surface molecules, cell apoptosis rate and cell cycle; the cell morphology was observed with Wright-Giemsa staining and the protein expression of BCL-2, BAX, PARP was detected by Western blot. The results showed that the phenotype of KG1a cells was CD34(+)CD38(-), while the phenotype of HL-60 cell was CD34(+)CD38(+). The former possessed a stronger colony ability than the latter. Effect of curcumin and arsenic trioxide alone on cell proliferation and inhibition was in dose-dependent manner. Compared with single drug-treatment group, the cell survival rate and colony number were lower, and the apoptosis rate was higher in combined drug-treatment group. Protein expression of BCL-2 and PARP was upregulated, while the protein expression of PARP was downregulated in the combined treatment group. It is concluded that compared with HL-60 cells, KG1a cells are the earlier leukemia stem/progenitor cells. Arsenic trioxide combined with curcumin can effectively inhibit the KG1a cell proliferation and induce apoptosis, which may be associated with the downregulation of BCL-2 and PARP protein expression and the upregulation of BAX protein expression.
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Hydrophobicity of whey protein hydrolysates enhances the protective effect against oxidative damage on PC 12 cells.
J. Dairy Res.
PUBLISHED: 10-08-2014
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The relationship between hydrophobicity and the protective effect of whey protein hydrolysates (WPHs) against oxidative stress was studied. Whey protein was first hydrolysed by pepsin and trypsin to obtain WPHs. After absorbed by macroporous adsorption resin DA201-C, three fractions named as M20, M40, and M60 were eluted by various concentrations of ethanol. The hydrophobicity showed a trend of increase from M20 to M60. Antioxidant ability test in vitro indicated that all the three components of WPHs displayed reasonably good antioxidant ability. Moreover, with the increase of hydrophobicity, antioxidant ability of WPHs improved significantly. Then rat pheochromocytoma line 12 (PC12) cells oxidative model was built to evaluate the suppression of oxidative stress of three components on PC12 cells induced by H2O2. Morphological alterations, cell viability, apoptosis rate, and intracellular antioxidase system tests all indicated that WPHs exert significant protection on PC cells against H2O2-induced damage. Among them, M60 had the highest protective effect by increasing 19·3% cell survival and reducing 28·6% cell apoptosis. These results suggested hydrophobicity of WPHs was contributing to the antioxidant ability and the protective effect against oxidative damage.
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Estrogen inhibits BMP4-induced BMP4 expression in cardiomyocytes: a potential mechanism of estrogen-mediated protection against cardiac hypertrophy.
Br. J. Pharmacol.
PUBLISHED: 10-06-2014
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Estrogen inhibits cardiac hypertrophy and bone morphogenetic protein-4 (BMP4) induces cardiac hypertrophy. The present study was designed to test whether estrogen inhibited BMP4 expression in cardiomyocytes.
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P-glycoprotein-evading anti-tumor activity of a novel tubulin and HSP90 dual inhibitor in a non-small-cell lung cancer model.
J. Pharmacol. Sci.
PUBLISHED: 09-03-2014
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P-glycoprotein (P-gp)-induced drug resistance is a major road block for successful cancer chemotherapy. Through phenotypic screening, the compound 2-(2-chlorophenylimino)-5-(4-dimethylaminobenzylidene) thiazolidin-4-one (CDBT) was discovered to have potent anti-tumor activity in P-gp over-expressing drug-resistant non-small-cell lung cancer (NSCLC) H460TaxR cells. Here, we report mechanistic investigations of the P-gp-evading anti-tumor activity of CDBT. CDBT is evidently not a P-gp substrate and escapes the P-gp efflux pump. As a novel microtubule and heat shock protein 90 (HSP90) dual targeting inhibitor, CDBT causes the destabilization of microtubules and degradation of HSP90 client proteins CRAF-1 and ERBB2, resulting in cell cycle arrest at the G2/M phase and apoptosis. Furthermore, CDBT effectively inhibits tumor growth by 60.4% relative to the vehicle control after intraperitoneal administration at 30 mg/kg for 11 days and shows no toxicity in normal tissues in the NSCLC H460TaxR xenograft mouse model. Our data suggest a novel drug discovery strategy to combat P-gp over-expressing drug-resistant NSCLC cancer cells with a single therapeutic agent.
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Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China.
Environ Sci Pollut Res Int
PUBLISHED: 08-18-2014
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A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (<5 ng/L for most pharmaceuticals) were lower than previous studies in other countries. In addition, ten and six pharmaceuticals were measured in raw water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.
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Small-size circulating endothelial microparticles in coronary artery disease.
PLoS ONE
PUBLISHED: 08-12-2014
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Several recent lines of evidence indicate that endothelial microparticles are a new biomarker that can be used to monitor endothelial dysfunction in coronary artery disease (CAD). However, data concerning the detection of small microparticles (diameter <0.5 µm) are lacking. The aim of this study was to detect small-size endothelial microparticles (SEMPs) in CAD patients to monitor endothelial dysfunction.
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Association of the ENPP1 K121Q polymorphism with susceptibility to type 2 diabetes in different populations: evidence based on 40 studies.
Endocr. J.
PUBLISHED: 08-08-2014
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The K121Q gene polymorphism of ectoenzyme nucleotide pyrophosphate phosphodiesterase 1(ENPP1) has been widely investigated, however, results have been somewhat conflicting. The aim of this meta-analysis was to establish a precise estimation of the association between ENPP1 gene polymorphisms and type 2 diabetes (T2D). A literature search in PubMed, Embase, Cochrane Library and China Biology Medicine (CBM) databases was conducted on publications published prior to November 21(st), 2013. The combined odds ratio (OR) with 95% confidence intervals (95%CI) was calculated to estimate the strength of the association using a random-effects/fixed-effects model. Statistical analyses were performed using the STATA 11.0 software. For the overall population, there was a significant association between ENPP1 gene polymorphisms and T2D when comparing the Q allele versus K allele (OR=1.29, 95%CI 1.16-1.44, p=0.000). Considering diverse ethnic groups, effect sizes were consistent for patients of Caucasian and Asian descent (OR=1.20, 95%CI=1.08-1.33 and OR=1.47, 95%CI=1.15-1.89, respectively); however, effect size was not consistent for those of African descent. Under other models of inheritance, significant associations were also observed. Sensitivity analyses did not leading to differing he results. In summary, the Q allele of the ENPP1 K121Q gene may contribute to the susceptibility for T2D in Caucasians and Asians.
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[Changes of fingerprints with crude and processed cassiae semen in xuezhiling tablets].
Zhong Yao Cai
PUBLISHED: 08-07-2014
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To establish an effective and convenient method for HPLC fingerprints of Xuezhiling tablets and new Xuezhiling tablets, and to observe the changes of fingerprint with crude and processed Cassiae Semen in Xuezhiling tablets.
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[Effects of moxibustion at "Ganshu" (BL 18) on serum alpha-fatoprotein and liver livin levels in rats with precancerous lesion of primary hepatocellular carcinoma].
Zhen Ci Yan Jiu
PUBLISHED: 07-30-2014
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To observe the effect of moxibustion at "Ganshu" (BL18) on levels of Livin (a novel member of the inhibitors of apoptosis family and plays crucial roles in apoptosis, cell proliferation, and cell cycle control) in the liver tissue in rats with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore its mechanism underlying improvement of HCC.
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Effect of piglitazone and metformin on retinol-binding protein-4 and adiponcetin in patients with type 2 diabetes mellitus complicated with non-alcohol fatty acid liver diseases.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 07-07-2014
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To compare the effects of piglitazone and metformin on retinol-binding protein-4(RBP-4)and adiponcetin(APN)in patients with type 2 diabetes mellitus(T2DM)complicated with Non alcohol fatty acid liver disease(NAFLD).
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[Relation of intermediate-conductance Ca(2+)-activated K(+) channels with ability of proliferation,migration,invasion and IgE secretion of multiple myeloma cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-04-2014
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This study was aimed to investigate the effects of the intermediate-conductance Ca(2+)-activated K(+) (IKCa1) channels on the proliferation, migration, invasion ability and monoclonal immunoglobulin (IgE) secretion of multiple myeloma (MM) cells. Trypan blue exclusion was used to evaluate the impact of clotrimazole (CLO, an inhibitor of the KCa1) on the survival ability of MM cell line U266; transwell chamber and matrigel experiments were used to evaluate the impact of CLO on the ability of the migration and invasion of U266 cells; the influence of CLO on IgE secretion in U266 cells was detected by ELISA. The results showed that small dose of CLO ( ? 1.0 µmol/L) could not inhibit the viability of U266 cells. The Transwell and Matrigel invasing tests displayed that the cell number moving into lower chamber of transwell decreased after U266 cells treated with small dose of CLO ( ? 1.0 µmol/L). After treating the cells with 1.00 µmol/L CLO for 24 h and 48 h, the concentration of IgE in cell supernatant was (4.98 ± 0.39) and (4.38 ± 0.32) ng/ml, while those in control group were (15.41 ± 1.88) and (19.73 ± 2.01) ng/ml, respectively, suggesting significant difference between them(P < 0.05). It is concluded that CLO can decrease the ability of migration and monoclonal immunoglobulin secretion of multiple myeloma cells by blocking the IKCa1, thus this study provides a new think for the targeted therapy of MM.
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A novel cleaning process for industrial production of xylose in pilot scale from corncob by using screw-steam-explosive extruder.
Bioprocess Biosyst Eng
PUBLISHED: 05-11-2014
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Steam explosion is the most promising technology to replace conventional acid hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw-steam-explosive extruder was designed and explored for xylose production and lignocellulose biorefinery at the pilot scale. We investigated the effect of different chemicals on xylose yield in the screw-steam-explosive extrusion process, and the xylose production process was optimized as followings: After pre-impregnation with sulfuric acid at 80 °C for 3 h, corncob was treated at 1.55 MPa with 9 mg sulfuric acid/g dry corncob (DC) for 5.5 min, followed by countercurrent extraction (3 recycles), decoloration (activated carbon dosage 0.07 g/g sugar, 75 °C for 40 min), and ion exchange (2 batches). Using this process, 3.575 kg of crystal xylose was produced from 22 kg corncob, almost 90 % of hemicellulose was released as monomeric sugar, and only a small amount of by-products was released (formic acid, acetic acid, fural, 5-hydroxymethylfurfural, and phenolic compounds were 0.17, 1.14, 0.53, 0.19, and 1.75 g/100 g DC, respectively). All results indicated that the screw-steam-explosive extrusion provides a more effective way to convert hemicellulose into xylose and could be an alternative method to traditional sulfuric acid hydrolysis process for lignocellulose biorefinery.
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Troxerutin protects against 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD(+)-depletion.
J. Hazard. Mater.
PUBLISHED: 04-29-2014
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Emerging evidence indicates that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD(+)-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD(+)-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-?B p65 and the acetylation of NF-?B p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.
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Nuclear erythroid 2 p45-related factor-2 Nrf2 ameliorates cigarette smoking-induced mucus overproduction in airway epithelium and mouse lungs.
Microbes Infect.
PUBLISHED: 04-14-2014
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Nuclear erythroid 2 p45-related factor-2 (Nrf2) is known to play important roles in airway disorders, whereas little has been investigated about its direct role in airway mucus hypersecretion. The aim of this study is to determine whether this factor could protect pulmonary epithelium and mouse airway from cigarette-induced mucus overproduction.
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Clopidogrel improves aspirin response after off-pump coronary artery bypass surgery.
J Biomed Res
PUBLISHED: 04-01-2014
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We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass (OPCAB) surgery, and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery. Sixty patients who underwent standard OPCAB surgery were randomized into two groups. One group (30 patients) received mono-antiplatelet treatment (MAPT) with aspirin 100?mg daily and the other group received dual antiplatelet treatment (DAPT) with aspirin 100?mg daily plus clopidogrel 75?mg daily. Platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (ADP) (PLADP) were measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet agents were administered. A PLAA level above 20% was defined as aspirin resistance. Postoperative bleeding and other perioperative variables were also recorded. There were no significant differences between the two groups in baseline characteristics, average number of distal anastomosis, operation time, postoperative bleeding, ventilation time and postoperative hospital stay. However, the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given (62.1% vs. 32.1%, 34.5% vs. 10.7%, respectively, both P < 0.05). There was no significant difference in postoperative complication between the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure. Moreover, clopidogrel reduces the incidence of OPCAB-related aspirin resistance.
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Glucuronidation of aurantio-obtusin: identification of human UDP-glucuronosyltransferases and species differences.
Xenobiotica
PUBLISHED: 03-11-2014
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1. The aurantio-obtusin's glucuronide was detected when aurantio-obtusin was incubated with human liver microsomes (HLMs). Recombinant UGT isoforms screening experiment showed that UGT1A8 was the major isoform contributed to the glucuronidation. 2. The metabolic profiles for aurantio-obtusin in liver microsomes from different species were similar, however, the intrinsic clearance values (Vmax/Km) among the species were: Monkey?>?Human?>?Rat?>?Rabbit?>?Dog?>?Pig?>?Mouse?>?Guinea pig.
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Polymorphisms of vascular endothelial growth factor on prognosis in osteosarcoma patients.
Pak J Med Sci
PUBLISHED: 02-28-2014
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We conducted a cohort study to investigate the association of three common SNPs of vascular endothelial growth factors (VEGF) gene (+1612G/A, -634C/G and +936G/C) with clinical outcome of osteosarcoma in a Chinese population.
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Effects of voltage-gated K+ channel on cell proliferation in multiple myeloma.
ScientificWorldJournal
PUBLISHED: 02-26-2014
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To study the effects and underlying mechanisms of voltage-gated K(+) channels on the proliferation of multiple myeloma cells.
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Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-17-2014
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A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 ?M and 1.06 to 12.89 ?M, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.
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Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats.
Brain Res. Bull.
PUBLISHED: 02-13-2014
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The emotional components of pain are far less studied than the sensory components. Previous studies have indicated that the rostral anterior cingulate cortex (rACC) is implicated in the affective response to noxious stimuli. Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been documented to play an important role in diverse kinds of pathological pain states. We used formalin-induced conditioned place aversion (F-CPA) in rats, an animal model believed to reflect the emotional response to pain, to investigate the involvement of p38 MAPK in the rACC after the induction of affective pain. Intraplantar formalin injection produced a significant activation of p38 MAPK, as well as mitogen-activated kinase kinase (MKK) 3 and MKK6, its upstream activators, in the bilateral rACC. p38 MAPK was elevated in both NeuN-positive neurons and Iba1-positive microglia in the rACC, but not GFAP-positive cells. Blocking p38 MAPK activation in the bilateral rACC using its specific inhibitor SB203580 or SB239063 dose-dependently suppressed the formation of F-CPA. Inhibiting p38 MAPK activation did not affect formalin-induced two-phase spontaneous nociceptive response and low intensity electric foot-shock induced CPA. The present study demonstrated that p38 MAPK signaling pathway in the rACC contributes to pain-related negative emotion. Thus, a new pharmacological strategy targeted at the p38 MAPK cascade may be useful in treating pain-related emotional disorders.
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Synthesis, in vitro antimicrobial and cytotoxic activities of novel pyrimidine-benzimidazol combinations.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-12-2014
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A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.
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Simultaneous determination and pharmacokinetic comparisons of multi-ingredients after oral administration of radix salviae miltiorrhizae extract, hawthorn extract, and a combination of both extracts to rats.
J Anal Methods Chem
PUBLISHED: 02-10-2014
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A simple and sensitive HPLC method was developed for simultaneous determination of danshensu (DSS), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid B (SAB), and hyperoside (HP) in rat plasma. This method validated was successfully applied to the pharmacokinetic study of the main active ingredients after oral administration of Radix Salviae Miltiorrhizae extract (SME), hawthorn extract (HTE), and a combination of both extracts (2.5?:?1) to rats. The results indicated that there have been great differences in pharmacokinetics between a single extract and a combination of both extracts. A combination of both extracts can enhance their bioavailabilities and delay the elimination of SAB and DSS in rats.
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Synthesis and antimicrobial activities of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-23-2014
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A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.
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X-ray crystallographic studies of family 11 xylanase Michaelis and product complexes: implications for the catalytic mechanism.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 01-15-2014
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Xylanases catalyze the hydrolysis of plant hemicellulose xylan into oligosaccharides by cleaving the main-chain glycosidic linkages connecting xylose subunits. To study ligand binding and to understand how the pH constrains the activity of the enzyme, variants of the Trichoderma reesei xylanase were designed to either abolish its activity (E177Q) or to change its pH optimum (N44H). An E177Q-xylohexaose complex structure was obtained at 1.15?Å resolution which represents a pseudo-Michaelis complex and confirmed the conformational movement of the thumb region owing to ligand binding. Co-crystallization of N44H with xylohexaose resulted in a hydrolyzed xylotriose bound in the active site. Co-crystallization of the wild-type enzyme with xylopentaose trapped an aglycone xylotriose and a transglycosylated glycone product. Replacing amino acids near Glu177 decreased the xylanase activity but increased the relative activity at alkaline pH. The substrate distortion in the E177Q-xylohexaose structure expands the possible conformational itinerary of this xylose ring during the enzyme-catalyzed xylan-hydrolysis reaction.
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SIP30 is required for neuropathic pain-evoked aversion in rats.
J. Neurosci.
PUBLISHED: 01-10-2014
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SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. We put rats in a chamber with one half painted white (light area) and the other half painted black (dark area), and measured neuropathic pain-evoked place escape/avoidance paradigm (PEAP) to quantify the level of negative emotion evoked by painful stimuli using a Von Frey hair. Inhibition of CCI-mediated induction of SIP30 by intra-rACC injection of shRNA targeting the rat sip30 gene reduced PEAP. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain such as heat hyperalgesia and mechanical allodynia. Neither did it affect general learning and memory. CCI-induced upregulation of SIP30 was correlated with activation of ERK, PKA, and CREB in the rACC. Intra-rACC administration of PKA or ERK inhibitors suppressed CCI-induced SIP30 upregulation and blocked the induction of PEAP. Additionally, knockdown of SIP30 suppressed the frequency of mEPSCs and increased paired-pulse ratios in rACC slices and decreased extracellular glutamate concentrations. Together, our results highlight SIP30 as a target of PKA and ERK in the rACC to mediate neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission.
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Synthesis and anticancer activities of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives.
Eur J Med Chem
PUBLISHED: 01-08-2014
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Trying to develop potent and selective anticancer agents, two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were designed and synthesized. Their antitumor activities were evaluated by MTT method against four selected human cancer cell lines (MGC-803, EC-9706, HeLa and MCF-7). Our results showed that compound 11h exhibited good anticancer activities compared to 5-fluorouracil against the four tested cell lines, with IC50 values ranging from 2.0 to 4.5 ?M. Flow cytometry analysis indicated that compound 11h induced the cellular early apoptosis and cell cycle arrest at G2/M phase in EC-9706.
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Immunomodulation of nanoparticles in nanomedicine applications.
Biomed Res Int
PUBLISHED: 01-07-2014
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Nanoparticles (NPs) have promising applications in medicine. Immune system is an important protective system to defend organisms from non-self matters. NPs interact with the immune system and modulate its function, leading to immunosuppression or immunostimulation. These modulating effects may bring benefits or danger. Compositions, sizes, and surface chemistry, and so forth, affect these immunomodulations. Here we give an overview of the relationship between the physicochemical properties of NPs, which are candidates to be applied in medicine, and their immunomodulation properties.
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Relationship of serum levels of VEGF and TGF-?1 with radiosensitivity of elderly patients with unresectable non-small cell lung cancer.
Tumour Biol.
PUBLISHED: 01-06-2014
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This study aimed to evaluate the relationship of serum levels of vascular endothelial growth factor (VEGF) and transforming growth factor-?1 (TGF-?1) with radiosensitivity of elderly patients with unresectable non-small cell lung cancer (NSCLC) receiving three-dimensional conformal radiation therapy (3D-CRT). Fifty-eight elderly patients with unresectable NSCLC and 40 healthy controls were enrolled in this study. Serum levels of VEGF and TGF-?1 were detected by the enzyme-linked immunosorbent assay (ELISA) method before and after 3D-CRT. Clinical performances of serum VEGF and TGF-?1 levels in predicting radiosensitivity of NSCLC patients with 3D-CRT were evaluated. Serum VEGF and TGF-?1 levels of NSCLC patients were higher than those of health controls (all p??0.05). Serum levels of VEGF and TGF-?1 after 3D-CRT in the effective group were lower compared with the levels before 3D-CRT treatment (p?
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Characterization of surface layer proteins and its role in probiotic properties of three Lactobacillus strains.
Int. J. Biol. Macromol.
PUBLISHED: 01-06-2014
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The objective of this study was the characterization of the surface layer proteins (SLPs) and their functional role in the probiotic activity of Lactobacillus helveticus fb213, L. acidophilus fb116 and L. acidophilus fb214. SLPs were extracted and identified by SDS-PAGE, circular dichroism spectra and LC-MS analysis. The results revealed that the molecular masses of the three proteins were 49.7 kDa, 46.0 kDa and 44.6 kDa, respectively. The secondary structures and amino acid compositions of the three proteins were found to be similar. After removing SLPs, the survival of the three lactobacilli in simulated gastric and intestinal juices was reduced by 2-3log as compared with survival of the intact cells. And the adhesion ability of the three strains to HT-29 cells decreased by 61%, 65% and 92%, respectively. SLPs also inhibited the adhesion and invasion of Escherichia coli ATCC 43893 to HT-29 cells. These results suggest that SLPs are advantageous barriers for lactobacilli in the gastrointestinal tract, and these proteins help make it possible for lactobacilli to serve their probiotic functions.
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Circulating CD62P small microparticles levels are increased in hypertension.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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The study aims to find a new biomarker in hypertension. Our study is the first time to demonstrate that the CD62P small microparticle (diameter is <0.5 um) was a new microparticle population and a new biomarker in hypertension.
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Blocking TRAIL-DR5 signaling with soluble DR5 alleviates acute kidney injury in a severely burned mouse model.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Acute kidney injury (AKI) predicts high mortality in severely burned patients. Apoptosis plays a significant role during AKI; however, the apoptotic mechanisms underlying AKI induced by burn injury are not clear. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-Death receptor 5 (DR5) signaling in the pathogenesis of AKI. C57BL/6 male mice were subjected to full thickness scald burn. Apoptosis was significantly up-regulated in mouse kidney 24 h after the burn. Meanwhile, the TRAIL and DR5 expression levels were significantly increased in the kidney 24 h after the burn. Soluble DR5 treatment reduced apoptotic cell death and alleviated kidney injury induced by the burn through blocking the interaction of endogenous TRAIL with DR5. These results demonstrated that TRAIL plays a deleterious role in AKI pathogenesis induced by scald burns. Inhibition of TRAIL function in the kidney may represent a novel protective strategy to treat AKI in patients with burns.
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Interaction of obesity and central obesity on elevated urinary albumin-to-creatinine ratio.
PLoS ONE
PUBLISHED: 01-01-2014
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Microalbuminuria was much more common among obese individuals indicating a probable association with obesity. However, association of microalbuminuria with interaction between obesity and central obesity has not yet been studied.
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Ovariectomy results in variable changes in nociception, mood and depression in adult female rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.
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Peripheral TGF-?1 Signaling Is a Critical Event in Bone Cancer-Induced Hyperalgesia in Rodents.
J. Neurosci.
PUBLISHED: 12-06-2013
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Pain is the most common symptom of bone cancer. TGF-?, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-?1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-?1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGF?RI and TGF?RII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-? receptors by the TGF?RI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection of TGF-?1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not in Trpv1(-/-) mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application of TGF-?1 significantly potentiated TRPV1 currents and increased [Ca(2+)]i in DRG neurons. Pharmacological studies revealed that the TGF-?1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-?R-mediated Smad-independent PKC? and TGF-? activating kinase 1-p38 pathways. These findings suggest that TGF-?1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting of TGF-?1 may ameliorate the bone cancer pain in advanced cancer.
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Involvement of spinal microglia and interleukin-18 in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.
Neurosci. Lett.
PUBLISHED: 11-23-2013
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Dexmedetomidine, a selective alpha 2-adrenoceptor (?2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the ?2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.
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Comparative pharmacokinetics of baicalin, wogonoside, baicalein and wogonin in plasma after oral administration of pure baicalin, radix scutellariae and scutellariae-paeoniae couple extracts in normal and ulcerative colitis rats.
Iran J Pharm Res
PUBLISHED: 11-20-2013
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The aim of this study was to investigate the pharmacokinetic profiles of baicalin, wogonoside, baicalein and wogonin after oral administration of pure baicalin, Radix scutellariae and Scutellariae-Paeoniae couple extracts were administered and the pharmacokinetics profiles were compared between normal and ulcerative colitis rats. The plasma concentrations of the four flavonoids were determined by using a simple and rapid high-performance liquid chromatography method. All the rats were divided randomly into two groups (ulcerative colitis and normal groups). Each group contained three subgroups: pure baicalin, Radix scutellariae and Scutellariae-Paeoniae couple extracts subgroup. Each group received oral administration of pure baicalin, Radix Scutellariae and Scutellariae-Paeoniae couple extracts at the same dose of 200 mg/kg baicalin. The results showed that wogonoside, possibily as a methylated product of baicalin, was found in plasma after oral administration of pure baicalin or formulas to rats. Baicalin and wogonoside demonstrated bimodal phenomenon. Baicalin and wogonoside in Scutellariae-Paeoniae couple extract had shown better absorption than which in pure baicalin and Radix Scutellariae extract. Whether oral administration of pure baicalin, Radix Scutellariae or Scutellariae-Paeoniae couple extracts, ulcerative colitis rats showed better absorption than normal rats. For example AUC (0-t) of baicalin were: (41.46 ± 0.62), (59.12 ± 6.42) and (104.87 ± 0.86) (?g/mL)·h in UC groups vs (17.77 ± 0.66), (28.04 ± 4.06) and (49.01 ± 4.61) (?g/mL)·h in normal groups, respectively. The pharmacokinetics properties of the four flavonoids differed between ulcerative colitis and normal rats, including AUC ( 0-t ) and Cmax (p < 0.05).
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[Involvement of peripheral NF?B in tetanic sciatic stimulation-induced neuropathic pain].
Sheng Li Xue Bao
PUBLISHED: 10-17-2013
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Tetanic stimulation of the sciatic nerve (TSS) induces long-term potentiation (LTP) of both C- and A-fiber-evoked field potentials in the spinal dorsal horn and long-lasting mechanical allodynia in rats. Though central mechanisms underlying those phenomena have been well studied, peripheral mechanisms still remain poorly known. Nuclear factor kappa B (NF?B) is an important transcription factor. In the spinal cord, NF?B plays a key role in regulating the expression of numerous pro-inflammation factors and contributes to glial activation in central nervous system, suggesting the involvement of spinal NF?B in central sensitization. To address whether NF?B in the dorsal root ganglion (DRG) participates in peripheral sensitization, we examined NF?B expression in the DRG and the effect of inhibiting NF?B activation on neuropathic pain using behavior test, Western blot analysis and immunohistochemical approaches. The results showed that TSS induced long-lasting mechanical allodynia in bilateral hind paws and increased phospho-NF?B expression in the bilateral DRG. The activated NF?B mainly expressed in nuclei not only of neurons, but also of Schwann cells and satellite glial cells. Moreover, NF?B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly alleviated TSS-induced allodynia. Our results suggest that peripheral NF?B may be involved in TSS-induced neuropathic pain, and provide new evidence for the peripheral mechanism of mirror pain.
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Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.
Brain Behav. Immun.
PUBLISHED: 09-27-2013
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Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. Inhibition of IL-23 signaling attenuated TSS-induced allodynia and decreased the induction of glial fibrillary acidic protein (GFAP, an astrocytic marker). Conversely, intrathecally delivered IL-23 induced a persistent allodynia. Similar to IL-23 signaling, an increase in IL-18 and its receptor, IL-18R, as well as CX3CL1 and its receptor, CX3CR1, was simultaneously observed in the spinal dorsal horn after TSS. Interestingly, IL-18 and CX3CR1 were exclusively expressed in microglia, while IL-18R was mainly localized in astrocytes. In contrast, CX3CL1 was predominately expressed in neurons and secondarily in astrocytes. The functional inhibition of CX3CL1 and IL-18 signaling attenuated TSS-induced allodynia and suppressed IL-23 and IL-23R upregulation. Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.
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[Effect of different forms of inorganic nitrogen on the photodegradation of antipyrine in water].
Huan Jing Ke Xue
PUBLISHED: 09-14-2013
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The photodegradation performance and mechanisms of antipyrine (ANT, a member of anti-inflammatory analgesics) under simulated irradiation using a 300 W Xenon lamp were explored in this study. And the variation of the photodegradation of ANT in the presence of different forms of nitrogen and different pE values in the aqueous environment were also investigated. The results demonstrated that ANT photodegradation proceeds via pseudo first-order kinetics in all cases. Photodegradation of ANT in water occurs through direct photodegradation and self-sensitization via reactions with hydroxyl radical (*OH) and singlet oxygen (1O2). Presence of different forms of inorganic nitrogen (NH4+, NO2- and NO3-) showed rather different effects. At low pE value (< 5), NH4+ was the main form of inorganic nitrogen, and little effect was observed on ANT photodegradation. With the increase of pE value from 4.82 to 6.85, nitrogen form changed from NH4+ to NO2- accordingly, and the inhibiting effect increased gradually due to their competitive absorption for the irradiation and NO2- acting as a scavenger of *OH. At pE 6.85, NO2- was the main form of inorganic nitrogen, which showed a maximum inhibiting rate of 35.31%. When the pE value continued to increase from 6.85 to 8.15, the nitrogen form changed from NO2- to NO3-, and the suppression effect on ANT photodegradation decreased.
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Super-resolution scanning laser microscopy through virtually structured detection.
Biomed Opt Express
PUBLISHED: 09-01-2013
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High resolution microscopy is essential for advanced study of biological structures and accurate diagnosis of medical diseases. The spatial resolution of conventional microscopes is light diffraction limited. Structured illumination has been extensively explored to break the diffraction limit in wide field light microscopy. However, deployable application of the structured illumination in scanning laser microscopy is challenging due to the complexity of the illumination system and possible phase errors in sequential illumination patterns required for super-resolution reconstruction. We report here a super-resolution scanning laser imaging system which employs virtually structured detection (VSD) to break the diffraction limit. Without the complexity of structured illumination, VSD provides an easy, low-cost and phase-artifact free strategy to achieve super-resolution in scanning laser microscopy.
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Coherent neutron scattering and collective dynamics in the protein, GFP.
Biophys. J.
PUBLISHED: 08-09-2013
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Collective dynamics are considered to be one of the major properties of soft materials, including biological macromolecules. We present coherent neutron scattering studies of the low-frequency vibrations, the so-called boson peak, in fully deuterated green fluorescent protein (GFP). Our analysis revealed unexpectedly low coherence of the atomic motions in GFP. This result implies a low amount of in-phase collective motion of the secondary structural units contributing to the boson peak vibrations and fast conformational fluctuations on the picosecond timescale. These observations are in contrast to earlier studies of polymers and glass-forming systems, and suggest that random or out-of-phase motions of the ?-strands contribute greater than two-thirds of the intensity to the low-frequency vibrational spectra of GFP.
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[Effect of dynamic high-pressure micro-fluidization on the structure of maize amylose].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-03-2013
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The effect of dynamic high-pressure micro-fluidization (DHPM) at 80, 120, 160, and 200 MPa on the structure of maize amylose was investigated using scanning electron microscopy (SEM), atomic force microscope (AFM), Xray diffraction, and FT-IR spectroscopy. SEM analysis showed that the surface appearances of maize amylose were altered and the starch granules were partially congregated together after DHPM treatment. AFM images showed that the treated starch molecules are cross-linked to each other and arranged in a close mesh structure. Xray diffraction spectra and IR spectra indicated that relative crystallinity declined gradually with the pressure increasing. The results provide a theoretical basis for starch modification of DHPM.
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Antitumor activity of (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one, a novel microtubule-depolymerizing agent, in U87MG human glioblastoma cells and corresponding mouse xenograft model.
J. Pharmacol. Sci.
PUBLISHED: 07-24-2013
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Glioblastoma is the most lethal brain cancer. In spite of intensive therapy, the prognosis of patients with glioblastoma is very poor. To discover novel therapeutic agents, we screened a combinatorial compound library containing 372 thiazolidinone compounds using U87MG human glioblastoma cells. (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one (HBPT) was identified as the most potent anti-glioblastoma compound. HBPT inhibits U87MG human glioblastoma cell proliferation with an IC50 of 20 ?M, which is almost 5-fold more potent than temozolomide (a widely used drug for treating malignant glioma in the clinic). Mechanistic investigation demonstrated that HBPT is a novel microtubule-depolymerizing agent, which arrests cancer cells at the G2/M phase of the cell cycle and induces cell apoptosis. In the mouse U87MG xenograft model, HBPT elicits a robust tumor inhibitory effect. More importantly, no obvious toxicity was observed for HBPT therapy in animal experiments. These findings indicate that HBPT has the potential to be developed as a novel agent for the treatment of glioblastoma. [Supplementary Tables: available only at http://dx.doi.org/10.1254/jphs.13064FP].
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Isolation and identification of antioxidant peptides derived from whey protein enzymatic hydrolysate by consecutive chromatography and Q-TOF MS.
J. Dairy Res.
PUBLISHED: 07-24-2013
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To isolate and identify antioxidant peptides from enzymatically hydrolysed whey protein, whey protein isolate was hydrolysed by different protease (trypsin, pepsin, alcalase 2·4L, promatex, flavourzyme, protease N). The hydrolysate generated by alcalase 2·4L had the highest antioxidant activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, superoxide radicals and in a linoleic acid peroxidation system induced by Fe2+. The IC50 values of DPPH and superoxide radical scavenging activities of the hydrolysate decreased significantly (6·89 and 38·88%, respectively) after treatment with macroporous adsorption resin. Seven different peptides showing strong antioxidant activities were isolated from the hydrolysate using consecutive chromatographic methods including gel filtration chromatography and high-performance liquid chromatography. The molecular mass and amino acids sequences of the purified peptides were determined using a Quadrupole time-of-flight mass spectrometer (Q-TOF MS). One of the antioxidative peptides, Trp-Tyr-Ser-Leu, displayed the highest DPPH radical scavenging activity (IC50=273·63 ?m) and superoxide radical scavenging activity (IC50=558·42 ?m). These results suggest that hydrolysates from whey proteins are good potential source of natural antioxidants.
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[Glycosylated hemoglobin A1c for the diagnosis of diabetes mellitus: a meta-analysis].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 05-29-2013
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To assess the diagnostic value of glycosylated hemoglobin A1c (HbA1c) ? 6.5% for diabetes in Chinese adults with oral glucose tolerance test (OGTT) as the reference standard.
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[Initial experience of percutaneous coronary intervention guided by computed tomography coronary angiography derived roadmap and magnetic navigation system].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 05-29-2013
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To evaluate the feasibility, efficacy and safety of the percutaneous coronary intervention (PCI)guided by computed tomography (CT) coronary angiography derived roadmap and magnetic navigation system (MNS).
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[Correlation between schistosomiasis endemic situation and Oncomelania snail status in Yizheng City, Jiangsu province from 2002 to 2011].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 05-22-2013
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To understand the correlation between schistosomiasis endemic situation and Oncomelania snail status, and discuss the control strategy and measures.
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In vivo optical coherence tomography of light-driven melanosome translocation in retinal pigment epithelium.
Sci Rep
PUBLISHED: 05-13-2013
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Optical coherence tomography (OCT) may revolutionize fundamental investigation and clinical management of age-related macular degeneration and other eye diseases. However, quantitative OCT interpretation is hampered due to uncertain sub-cellular correlates of reflectivity in the retinal pigment epithelium (RPE) and photoreceptor. The purpose of this study was twofold: 1) to test OCT correlates in the RPE, and 2) to demonstrate the feasibility of longitudinal OCT monitoring of sub-cellular RPE dynamics. A high resolution OCT was constructed to achieve dynamic imaging of frog eyes, in which light-driven translocation of RPE melanosomes occurred within the RPE cell body and apical processes. Comparative histological examination of dark- and light-adapted eyes indicated that the RPE melanin granule, i.e., melanosome, was a primary OCT correlate. In vivo OCT imaging of RPE melanosomes opens the opportunity for quantitative assessment of RPE abnormalities associated with disease, and enables longitudinal investigation of RPE kinetics correlated with visual function.
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Anatomical study of endoscope-assisted far lateral keyhole approach to the ventral craniocervical region with neuronavigational guidance.
Chin. Med. J.
PUBLISHED: 05-09-2013
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Image-guided neurosurgery, endoscopic-assisted neurosurgery and the keyhole approach are three important parts of minimally invasive neurosurgery and have played a significant role in treating skull base lesions. This study aimed to investigate the potential usefulness of coupling of the endoscope with the far lateral keyhole approach and image guidance at the ventral craniocervical junction in a cadaver model.
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Extracellular signal-regulated protein kinase activation in spinal cord contributes to pain hypersensitivity in a mouse model of type 2 diabetes.
Neurosci Bull
PUBLISHED: 05-03-2013
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Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that (1) db/db mice (with a leptin receptor-null mutation and characterized by obesity and hyperglycemia) showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; (2) phosphorylated extracellular signalregulated kinase (pERK), but not total ERK in the spinal cord and dorsal root ganglia in db/db mice signifi cantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAPexpressing astrocytes, but not in Iba-1-expressing microglia; (3) both single and consecutive (for 5 days) intrathecal injections of U0126 (2 nmol per day), a selective MEK (an ERK kinase) inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreaves test; and (4) db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.
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Use of immuno-dominant epitope derived from genotype 4 as a diagnostic reagent for detecting the antibodies against Hepatitis E Virus.
Virol. J.
PUBLISHED: 04-18-2013
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Despite the genotype 4 has become the dominant cause of hepatitis E disease in China, none antigen derived from genotype 4 of hepatitis E virus (HEV) was used in current commercial anti-HEV immunoassay, and the serological reactivity of antigen derive from genotype 4 is not well-charactered.
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Anti-tumor selectivity of a novel tubulin and HSP90 dual-targeting inhibitor in non-small cell lung cancer models.
Biochem. Pharmacol.
PUBLISHED: 04-14-2013
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Dose-limiting toxicity is a main road blocker for successful cancer chemotherapy. By phenotype screening, a novel chemical agent 2-(2-Chlorophenylimino)-5-(4-dimethylamino-benzylidene) thiazolidin-4-one (CDBT) was found to strongly inhibit the proliferation of non-small cell lung cancer (NSCLC) cells H460 and H322 while displaying no obvious toxicity to normal fast-dividing fibroblast cells NHFB and WI-38 at a concentration 100-fold higher than its EC50 to NSCLC cells. CDBT targets microtubule and heat shock protein 90 (HSP90) simultaneously with moderate affinities compared to microtubule targeting Colchicine and HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygaldanamcyin (17-DMAG). CDBT blocks microtubule formation, decreases cancer-essential proteins CRAF-1, ERBB2 and phosphorylated AKT, and causes G2/M arrest and apoptosis. The moderate inhibitory effects of CDBT on targets require a higher cellular concentration of targets, a situation only exist in cancer cells. This accounts for its good cancer selectivity. Furthermore, CDBT effectively inhibits tumor growth by 62.4% relative to the vehicle control after i.p. administration at 30 mg/kg for 11 days while showing no toxicity to normal tissues in NSCLC H460 xenograft mouse model.
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Magnetic navigation system and CT roadmap-assisted percutaneous coronary intervention: a comparison to the conventional approach.
J Invasive Cardiol
PUBLISHED: 04-04-2013
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Computed tomography coronary angiography (CTCA) has been successfully integrated with the magnetic navigation system (MNS) to facilitate a roadmap-assisted percutaneous coronary intervention (PCI). The aim of this study was to compare this new approach of PCI versus conventional PCI regarding the difference of contrast usage, x-ray exposure, procedure success, and in-hospital expenses.
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Palmitate induces apoptosis in mouse aortic endothelial cells and endothelial dysfunction in mice fed high-calorie and high-cholesterol diets.
Life Sci.
PUBLISHED: 03-30-2013
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Obesity is associated with hypertriglyceridemia and elevated circulating free fatty acids (FFA), resulting in endothelial dysfunction. Endoplasmic reticulum (ER) stress has been implicated in many of these processes. To determine if ER stress participates in palmitate-induced apoptosis, we investigated the effects of diet-induced obesity and palmitate on mouse aortic endothelial cells (MAEC) in vivo and in vitro.
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Ursolic acid improves domoic acid-induced cognitive deficits in mice.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-05-2013
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Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders.
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Effects of nanotoxicity on female reproductivity and fetal development in animal models.
Int J Mol Sci
PUBLISHED: 02-28-2013
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The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.
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Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris.
BMC Med Genomics
PUBLISHED: 02-23-2013
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In order to identify miRNAs expression profiling from genome-wide screen for diagnosis of acute myocardial infarction (AMI) and angina pectoris (AP), we investigated the altered profile of serum microRNAs in AMI and AP patients at a relative early stage.
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Reaction kinetics and transformation of antipyrine chlorination with free chlorine.
Water Res.
PUBLISHED: 02-16-2013
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Chlorine has been documented that it can effectively remove some pharmaceuticals. Recently, new active oxidants chlorine monoxide and molecular chlorine, which exist as free active chlorine in solution, were reported during pharmaceuticals chlorination. In this study, reaction kinetics, active oxidants, and transformation products during antipyrine chlorination were investigated with batch experiments. The reaction orders in [chlorine] were determined at various pH (6.53-7.62) and ranged from 1.13 ± 0.15 to 1.59 ± 0.08, which indicated that antipyrine chlorination is the concurrent existence of reactions appearing first-order and second-order in [chlorine]. The results by varying solution conditions (solution pH, chloride, ionic strength, and buffer concentration) show that chlorine monoxide and molecular chlorine play significant roles during the process of antipyrine chlorination. With kinetics modeling, the second-order rate constants for hypochlorous acid, chlorine monoxide, and molecular chlorine were obtained at 25 ± 2 °C (units: M(-1) s(-1)): kHOCl = 3.23 × 10(3), kCL2 = 2.86 × 10(7), kCL2O= 8.38 × 10(9) (R(2) = 0.9801). At pH 7, hypochlorous acid and chlorine monoxide are the main contributors to the degradation of antipyrine, about 80% and 20%, respectively (calculated by kHOCl, kCL2 and kCL2O. By applying these rate constants to predict the antipyrine elimination in real water matrixes (surface water, ground water), a good agreement was obtained, particularly in ground water. Moreover, liquid chromatography-tandems mass spectrometry (LC-MS/MS) and gas chromatograph-mass spectrometry (GC-MS) were used for products identification. Two main intermediate products and three stable products were observed during the process of antipyrine chlorination. The possible routes for antipyrine chlorination were proposed, which mainly consisted of halogenations, dealkylations and hydroxylations.
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Combating P-glycoprotein-mediated multidrug resistance using therapeutic nanoparticles.
Curr. Pharm. Des.
PUBLISHED: 01-31-2013
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The development of multidrug resistance (MDR) to chemotherapy is a major obstacle for the successful treatment of cancer. A number of mechanisms have been postulated to account for MDR in cancer. The most common and best-studied mechanism of resistance is mediated through the drug efflux protein P-glycoprotein (P-gp), which is overexpressed in drug-resistant cancer cells and is responsible for the removal of many chemotherapeutic agents. Therapeutic nanoparticles (NPs) have emerged as an innovative and promising option to combat P-gp-mediated MDR and have shown enhanced therapeutic efficacy and reduced toxicity compared to their small molecule counterparts. This review focuses on recent studies using therapeutic NPs to circumvent P-gp-mediated MDR in cancer therapy. The advantages and strategies by which therapeutic NPs were used to overcome P-gp-mediated MDR in cancer are discussed.
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Toward a better understanding of pharmacokinetics of nanomaterials.
Curr. Pharm. Des.
PUBLISHED: 01-31-2013
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Nanotechnology has promising applications in biomedicine, such as in drug delivery, diagnosis, and tissue engineering. The pharmacokinetics of nanomaterials significantly affects their biological behavior in vivo, affecting their biomedical applications and potential nanotoxicity. In this review, we highlight some recent advances in the pharmacokinetic studies of representative nanomaterials. We focus on the relationships between the physicochemical properties of nanomaterials and physiological consequences.
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Heterologous expression, purification, crystallization and preliminary X-ray analysis of Trichoderma reesei xylanase II and four variants.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.
PUBLISHED: 01-11-2013
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Xylanase II from Trichoderma reesei catalyzes the hydrolysis of glycosidic bonds in xylan. Crystallographic studies of this commercially important enzyme have been initiated to investigate its reaction mechanism, substrate binding and dependence on basic pH conditions. The wild-type protein was heterologously expressed in an Escherichia coli host using the defined medium and four active-site amino acids were replaced to abolish its activity (E177Q and E86Q) or to change its pH optimum (N44D and N44H). Cation-exchange and size-exclusion chromatography were used to obtain >90% protein purity. The ligand-free proteins and variant complexes containing substrate (xylohexaose) or product (xylotriose) were crystallized in several different space groups and diffracted to high resolutions (from 1.07 to 1.55?Å).
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Elastic and conformational softness of a globular protein.
Phys. Rev. Lett.
PUBLISHED: 01-10-2013
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Flexibility, or softness, is crucial for protein function and consists of a conformational component, involving jumps between potential wells, and an elastic component, involving fluctuations within the wells. Combining molecular dynamics simulation with incoherent neutron scattering and light scattering measurements on green fluorescent protein, we reveal a relationship between the intrawell fluctuations and elastic moduli of the protein. This finding leads to a simple means of experimentally separating the conformational from the elastic atomic displacements.
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Evaluation of glutathione S-transferase genetic variants affecting type 2 diabetes susceptibility: a meta-analysis.
Gene
PUBLISHED: 01-02-2013
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Genetic polymorphisms of glutathione S-transferases (GSTs) and type 2 diabetes mellitus (T2DM) risk have been widely studied, however, the results were somewhat conflicting. To evaluate the association of GSTs (GSTM1, GSTT1 and GSTP1) gene polymorphisms with T2DM, a meta-analysis was performed before October, 2012. ORs were pooled according to random-effects model. There were a total of 1354/1666 (n=9) cases/controls (studies) for GSTM1, 1271/1470 (n=8) for GSTT1, and 1205/1250 (n=7) for GSTM1. There were significant associations between GSTM1 polymorphism, GSTT1 polymorphism and T2DM in the contrast of present genotype vs. null genotype, with pooled OR=1.99 (95%CI=1.46-2.71) and OR=1.61 (95%CI=1.19-2.17), respectively. Yet no significant association of GSTP1 polymorphism and T2DM was showed. When stratified by ethnicity, the significant associations were also existed in Asians for GSTM1 and GSTT1, but not GSTP1. No publication bias but some extent of heterogeneity was observed. Finally, the accumulated evidence proved the obvious associations of GSTM1 and GSTT1 polymorphisms with an increased risk of T2DM.
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Identification of a serine proteinase homolog (Sp-SPH) involved in immune defense in the mud crab Scylla paramamosain.
PLoS ONE
PUBLISHED: 01-01-2013
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Clip domain serine proteinase homologs are involved in many biological processes including immune response. To identify the immune function of a serine proteinase homolog (Sp-SPH), originally isolated from hemocytes of the mud crab, Scylla paramamosain, the Sp-SPH was expressed recombinantly and purified for further studies. It was found that the Sp-SPH protein could bind to a number of bacteria (including Aeromonas hydrophila, Escherichia coli, Staphylococcus aureus, Vibrio fluvialis, Vibrio harveyi and Vibrio parahemolyticus), bacterial cell wall components such as lipopolysaccharide or peptidoglycan (PGN), and ?-1, 3-glucan of fungus. But no direct antibacterial activity of Sp-SPH protein was shown by using minimum inhibitory concentration or minimum bactericidal concentration assays. Nevertheless, the Sp-SPH protein was found to significantly enhance the crab hemocyte adhesion activity (paired t-test, P<0.05), and increase phenoloxidase activity if triggered by PGN in vitro (paired t-test, P<0.05). Importantly, the Sp-SPH protein was demonstrated to promote the survival rate of the animals after challenge with A. hydrophila or V. parahemolyticus which were both recognized by Sp-SPH protein, if pre-incubated with Sp-SPH protein, respectively. Whereas, the crabs died much faster when challenged with Vibrio alginolyiicus, a pathogenic bacterium not recognized by Sp-SPH protein, compared to those of crabs challenged with A. hydrophila or V. parahemolyticus when pre-coated with Sp-SPH protein. Taken together, these data suggested that Sp-SPH molecule might play an important role in immune defense against bacterial infection in the mud crab S. paramamosain.
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Association between vitamin D insufficiency and elevated serum uric acid among middle-aged and elderly Chinese Han women.
PLoS ONE
PUBLISHED: 01-01-2013
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Association between vitamin D insufficiency and hyperuricemia has not been reported so far. We aimed to study the association of vitamin D insufficiency with elevated serum uric acid among middle-aged and elderly Chinese Han women.
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In vivo confocal imaging of fast intrinsic optical signals correlated with frog retinal activation.
Opt Lett
PUBLISHED: 12-06-2011
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Using freshly isolated animal retinas, we have conducted a series of experiments to test fast intrinsic optical signals (IOSs) that have time courses comparable to electrophysiological kinetics. In this Letter, we demonstrate the feasibility of in vivo imaging of fast IOSs in intact frogs. A rapid line-scan confocal ophthalmoscope was constructed to achieve high-speed IOS recording. By rejecting out-of-focus background light, the line-scan confocal imager provided the resolution to differentiate individual photoreceptors in vivo. Rapid confocal imaging disclosed robust IOSs with time courses comparable to retinal electroretinogram kinetics. High-resolution IOS images revealed both positive (increasing) and negative (decreasing) light responses, with subcellular complexity.
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[Study on schistosomiasis control measures in mobile boat fishermen. III. Construction and application of regional joint mechanism for schistosomiasis examination and treatment in boatmen].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 11-30-2011
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To construct the regional joint mechanism for schistosomiasis examination and treatment and the examination protocol among mobile boatmen, so as to provide effective measures for control of mobile infectious sources of schistosomiasis in the Yangtze River basin.
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[Effects of different irrigation modes on winter wheat grain yield and water- and nitrogen use efficiency].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 11-30-2011
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Taking the widely planted winter wheat cultivar Tainong 18 as test material, a field experiment was conducted to study the effects of different irrigation modes on the winter wheat grain yield and water- and nitrogen use efficiency in drier year (2009-2010) in Tai an City of Shandong Province, China. Five treatments were installed, i. e., irrigation before sowing (CK), irrigation before sowing and at jointing stage (W1), irrigation before sowing and at jointing stages and at over-wintering stage with alternative irrigation at milking stage (W2), irrigation before sowing and at jointing and flowering stages (optimized traditional irrigation mode, W3), and irrigation before sowing and at over-wintering, jointing, and milking stages (traditional irrigation mode, W4). The irrigation amount was 600 m3 hm(-2) one time. Under the condition of 119.7 mm precipitation in the winter wheat growth season, no significant difference was observed in the grain yield between treatments W2 and W4, but the water use efficiency was significantly higher in W2 than in W4. Comparing with treatment W3, treatments W2 and W4 had obviously higher grain yield, but the water use efficiency had no significant difference. The partial factor productivity from N fertilization was the highest in W2 and W4, and the NO3(-)-N accumulation amount in 0-100 cm soil layer at harvest was significantly higher in W2 than in W3 and W4, suggesting that W2 could reduce NO3(-)-N leaching loss. Under the conditions of our experiment, irrigation before sowing and jointing stages and at over-wintering stage with alternative irrigation at milking stage was the optimal irrigation mode in considering both the grain yield and the water- and nitrogen use efficiency.
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What is Visualize?

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

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

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.