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Find video protocols related to scientific articles indexed in Pubmed.
Large-scale gene-centric analysis identifies polymorphisms for resistant hypertension.
J Am Heart Assoc
PUBLISHED: 11-12-2014
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Resistant hypertension (RHTN), defined by lack of blood pressure (BP) control despite treatment with at least 3 antihypertensive drugs, increases cardiovascular risk compared with controlled hypertension. Yet, there are few data on genetic variants associated with RHTN.
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On the origin of near-infrared extragalactic background light anisotropy.
Science
PUBLISHED: 11-08-2014
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Extragalactic background light (EBL) anisotropy traces variations in the total production of photons over cosmic history and may contain faint, extended components missed in galaxy point-source surveys. Infrared EBL fluctuations have been attributed to primordial galaxies and black holes at the epoch of reionization (EOR) or, alternately, intrahalo light (IHL) from stars tidally stripped from their parent galaxies at low redshift. We report new EBL anisotropy measurements from a specialized sounding rocket experiment at 1.1 and 1.6 micrometers. The observed fluctuations exceed the amplitude from known galaxy populations, are inconsistent with EOR galaxies and black holes, and are largely explained by IHL emission. The measured fluctuations are associated with an EBL intensity that is comparable to the background from known galaxies measured through number counts and therefore a substantial contribution to the energy contained in photons in the cosmos.
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Inhibition of Secreted Frizzled-Related Protein 5 Improves Glucose Metabolism.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 11-06-2014
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Elucidating the role of secreted frizzled-related protein 5 (SFRP5) in metabolism and obesity has been complicated by contradictory findings when knock-out mice were used to determine metabolic phenotypes. By over-expressing SFRP5 in obese, pre-diabetic mice we consistently observed elevated hyperglycemia and glucose intolerance, supporting SFRP5 as a negative regulator of glucose metabolism. Accordingly, Sfrp5 mRNA expression analysis of both epididymal and subcutaneous adipose depots of mice indicated a correlation with obesity. Thus, we generated a monoclonal antibody (mAb) against SFRP5 to ascertain the effect of SFRP5 inhibition in vivo. Congruent with SFRP5 over-expression worsening blood glucose and glucose intolerance, anti-SFRP5 mAb therapy improved these phenotypes in vivo. The results from both the over-expression and the mAb inhibition studies suggest a role for SFRP5 in glucose metabolism and pancreatic beta-cell function, and thus establish use of an anti-SFRP5 mAb as a potential approach to treat Type 2 Diabetes.
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Advancing therapeutic discovery through phenotypic screening of the extracellular proteome using hydrodynamic intravascular injection.
Expert Opin. Ther. Targets
PUBLISHED: 10-07-2014
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Although the human genome encodes ? 20,000 protein-coding genes, only a very small fraction of these have been explored as potential targets for therapeutic development. The challenge of identifying and validating new protein targets has contributed to the significant reduction in the productivity of the pharmaceutical industry in the recent decade, highlighting the continued need to find new therapeutic targets.
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Haplotype Analysis of Association of the MYOC Gene with Primary Angle-Closure Glaucoma in a Han Chinese Population.
Genet Test Mol Biomarkers
PUBLISHED: 10-01-2014
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Purpose: The aim of this study is to examine whether or not myocilin (MYOC) genetic variations are associated with susceptibility to primary angle-closure glaucoma (PACG) in the Han Chinese population. Methods: Four single-nucleotide polymorphisms (SNPs)-rs235913, rs183532, rs12076134, and rs235875-in the MYOC gene were genotyped in 212 adult patients with PACG and 255 age-, sex-, and ethnic-matched healthy controls by using a polymerase chain reaction-restriction fragment length polymorphism assay. Data were analyzed by chi-square analysis. Results: The four SNPs in the MYOC gene were in the Hardy-Weinberg equilibrium in all the subjects. The frequencies of A allele rs183532 were significantly different between the PACG patients and the controls (0.238 vs. 0.169, p=0.008; OR=1.541; 95% CI: 1.117-2.127). The frequencies of the AA genotype and A allele of rs235913 were increased in PACG patients compared with controls, but the difference was not significant (p=0.037, p=0.017, respectively). A comparison of the distributions of the genotypes and alleles of rs12076134 and rs235875 showed no statistically significant differences between the PACG patients and the controls (p>0.05). Haplotype analysis indicated that the frequency of the AATG and AATA haplotypes was significantly higher for PACG patients than for control subjects (both p<0.001). However, the frequency of CGGA and CGTG haplotypes was lower for PACG patients than for control subjects (p<0.001). Conclusions: Our study suggests that rs183532 is associated with an increased risk of PACG in the Chinese Han population.
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Association between exposure to hepatitis B virus and chronic kidney disease in China.
J. Int. Med. Res.
PUBLISHED: 09-21-2014
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Hospital-based, cross-sectional study to determine whether exposure to hepatitis B virus (HBV) has an independent effect on the risk of developing chronic kidney disease (CKD).
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A randomized phase II clinical trial of nab-paclitaxel and carboplatin compared with gemcitabine and carboplatin as first-line therapy in locally advanced or metastatic squamous cell carcinoma of lung.
BMC Cancer
PUBLISHED: 09-17-2014
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Recent advances have shown that histology and genetic biomarkers are important in patient selection, which have led to significantly better outcomes for lung cancer patients. However, most new treatments only apply to adenocarcinoma or non-squamous, and in squamous carcinoma there is little breakthrough. In a phase III trial nab-paclitaxel plus carboplatin showed superior response rate over paclitaxel and carboplatin. In subgroup analysis the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment.
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Efficacy and safety of linagliptin as monotherapy or add-on treatment in Asian patients with suboptimal glycemic control: a pooled analysis.
Curr Med Res Opin
PUBLISHED: 09-13-2014
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Abstract Aims: To evaluate the efficacy and safety of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in Asian patients with type 2 diabetes mellitus (T2DM), a rapidly increasing population. Methods: Data were pooled for Asian patients receiving linagliptin orally once daily, as monotherapy or added to existing oral antidiabetes therapies, in multinational randomized placebo-controlled clinical trials. Efficacy data were taken from four pivotal trials with 24-week durations to allow for robust efficacy assessment. Safety data were pooled from a wider group of 10 trials with varying durations to capture the largest possible incidence of adverse events (AEs). The primary efficacy endpoint was change from baseline to week 24 in HbA1c. AEs were analyzed descriptively. Results: Mean baseline HbA1c (±SD) in this population was 8.2?±?0.9%. Placebo-corrected mean change in HbA1c after 24 weeks was -0.79% (95% confidence interval [CI]: -0.92 to -0.67; p?
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[Identification of metabolites of antitumor lead compound T-OA in rat urine by HPLC-HRMS].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-11-2014
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To study the major metabolites of antitumor lead compound T-OA (oleanolic acyl-3, 5, 6-trimethyl pyrazine-2-methyl ester) in rat urine, in order to preliminarily infer its metabolic mode in rats.
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[Cases of hepatitis C virus infection with 2i/2a recombination genotype in the Lanzhou area and effects of related genetic variations on interferon alpha response].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To investigate Lanzhou area cases of hepatitis C virus (H-CV) infection with a 5'-non coding region (NCR) 2i genotype and core (C), envelope protein (E) and non-structural protein (NS5) 2a genotype and the relationship with therapeutic response to interferon-alpha (IFNa).
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Fibroblast Growth Factor Receptor 4 (FGFR4) Deficiency Improves Insulin Resistance and Glucose Metabolism under Diet-induced Obesity Conditions.
J. Biol. Chem.
PUBLISHED: 09-09-2014
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The role of fibroblast growth factor receptor 4 (FGFR4) in regulating bile acid synthesis has been well defined; however, its reported role on glucose and energy metabolism remains unresolved. Here, we show that FGFR4 deficiency in mice leads to improvement in glucose metabolism, insulin sensitivity, and reduction in body weight under high fat conditions. Mechanism of action studies in FGFR4-deficient mice suggest that the effects are mediated in part by increased plasma levels of adiponectin and the endocrine FGF factors FGF21 and FGF15, the latter of which increase in response to an elevated bile acid pool. Direct actions of increased bile acids on bile acid receptors, and other potential indirect mechanisms, may also contribute to the observed metabolic changes. The results described herein suggest that FGFR4 antagonists alone, or in combination with other agents, could serve as a novel treatment for diabetes.
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Predictors for Glucose Change in Hypertensive Participants Following Short-term Treatment with Atenolol or Hydrochlorothiazide.
Pharmacotherapy
PUBLISHED: 09-09-2014
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To develop and validate a predictive model for glucose change and risk for new-onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ).
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Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sjögren's syndrome.
Chin. Med. J.
PUBLISHED: 09-06-2014
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Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sjögren's syndrome (SS). The aim of this study is to provide different treatments and services for and NMO patients combined with SS.
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Characterization of macular thickness changes in Leber's hereditary optic neuropathy by optical coherence tomography.
BMC Ophthalmol
PUBLISHED: 09-01-2014
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To characterize macular thickness (MT) changes in Leber's hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA).
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Amino Acid derivatives of ligustrazine-oleanolic Acid as new cytotoxic agents.
Molecules
PUBLISHED: 08-25-2014
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A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3?-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3?-L-lysine ester-6g not only displayed good cytotoxicity (IC50 < 3.5 ?M) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50 = 4.884 ?M) had lower nephrotoxicity than both 6g (IC50 = 2.310 ?M) and cisplatin (CDDP, IC50 = 3.691 ?M) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.
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Berberine induces hERG channel deficiency through trafficking inhibition.
Cell. Physiol. Biochem.
PUBLISHED: 08-18-2014
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The human ether-a-go-go-related gene (hERG) encodes the ? subunit of the IKr, which plays an essential role in repolarization of action potentials. hERG channels are targeted by various pro-arrhythmic drugs. Berberine (BBR) was previously found to acutely inhibit hERG currents and prolong action potential duration. The present study aimed to determine long-term effects of BBR on the expression of 135kDa/155kDa hERG and the mechanism.
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The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy.
Lipids Health Dis
PUBLISHED: 07-31-2014
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Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy.
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Early spatiotemporal characterization of microglial activation in the retinas of rats with streptozotocin-induced diabetes.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 06-30-2014
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Microglial activation has been recognized as a neuropathological feature in diabetic retinopathy. But the early spatiotemporal characterization of microglial activation in the retina and the optic nerve of diabetic animals has not been fully investigated. The purpose of this study was to investigate early sequential changes of microglia in the retinas of rats with streptozotocin-induced diabetes. Microglia in the optic nerves of rats with streptozotocin-induced diabetes were also studied.
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Population pharmacokinetic analysis of digoxin in Chinese neonates and infants.
J. Pharmacol. Sci.
PUBLISHED: 05-16-2014
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To obtain more information regarding the influence of various covariates on the disposition of digoxin in Chinese neonates and infants, routine clinical pharmacokinetic data were retrospectively collected from 131 hospitalized patients. A nonlinear mixed effects modeling (NONMEM) method was applied to the data. A one-compartment/first-order absorption model was employed to estimate the influence of total body weight (allometric power model), postnatal age, serum creatinine, gender, presence of heart congestive failure, and concomitant medications on apparent total clearance and apparent drug distribution of digoxin. Pharmacokinetic parameter estimates for CL/F and V/F were 0.147 L?h(-1)?kg(-1) and 15.7 L/kg, respectively. Total body weight and postnatal age were identified as the important factors affecting total clearance of digoxin; total body weight was the covariate identified to influence the apparent distribution volume. Both internal (bootstrap method, visual predictive checks, and normalized prediction distributed error) and external validation supported the stable and predictive performance of the final model. We concluded that the model can be used to choose an appropriate dose regimen in Chinese neonates and infants.
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Effect of quaternization degree on physiochemical and biological activities of chitosan from squid pens.
Int. J. Biol. Macromol.
PUBLISHED: 04-29-2014
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Chitosan was prepared by alkaline N-deacetylation of ?-chitin from squid pens, and N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (HTCC) derivatives, with different degrees of quaternization (DQ) ranging from 0.77 to 1.06, were synthesized. It was identified by FT-IR, 1H NMR and XRD analysis. All of the HTCC showed good water solubility in a wide pH range. The moisture absorption and retention abilities of all the HTCC were much better than that of the chitosan. The moisture absorption and retention values of all the HTCC at 43% RH for 24 h were above 49% and 92%, respectively. The scavenging ability of HTCC against hydroxyl and ABTS radicals improved with increasing concentration. The effectiveness of HTCC against hydroxyl radicals was lower than that of chitosan. These results indicated that HTCC, which has a much better moisture absorption and retention capacity, may act as a potential moisturizer in vitro.
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[Correlation of sex hormnnones and parathyroid hormone with biochemical markers of bone turnover in aged men].
Zhonghua Nan Ke Xue
PUBLISHED: 04-18-2014
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To investigate the correlation of serum sex hormones and parathyroid hormone (PTH) with the biochemical markers of bone turnover in aged men.
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Response properties of ON-OFF retinal ganglion cells to high-order stimulus statistics.
Neurosci. Lett.
PUBLISHED: 04-04-2014
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The visual stimulus statistics are the fundamental parameters to provide the reference for studying visual coding rules. In this study, the multi-electrode extracellular recording experiments were designed and implemented on bullfrog retinal ganglion cells to explore the neural response properties to the changes in stimulus statistics. The changes in low-order stimulus statistics, such as intensity and contrast, were clearly reflected in the neuronal firing rate. However, it was difficult to distinguish the changes in high-order statistics, such as skewness and kurtosis, only based on the neuronal firing rate. The neuronal temporal filtering and sensitivity characteristics were further analyzed. We observed that the peak-to-peak amplitude of the temporal filter and the neuronal sensitivity, which were obtained from either neuronal ON spikes or OFF spikes, could exhibit significant changes when the high-order stimulus statistics were changed. These results indicate that in the retina, the neuronal response properties may be reliable and powerful in carrying some complex and subtle visual information.
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Comparison of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus.
Eur. J. Endocrinol.
PUBLISHED: 04-02-2014
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We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM).
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Alteration in fasting glucose after prolonged treatment with a thiazide diuretic.
Diabetes Res. Clin. Pract.
PUBLISHED: 03-28-2014
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Thiazide diuretics are recommended as first line antihypertensive treatment, but may contribute to new onset diabetes. We aimed to describe change in fasting glucose (FG) during prolonged thiazide treatment in an observational setting.
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Is diabetes mellitus-linked amino acid signature associated with ?-blocker-induced impaired fasting glucose?
Circ Cardiovasc Genet
PUBLISHED: 03-13-2014
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The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.
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Clinical manifestations of Parkinson disease and the onset of rapid eye movement sleep behavior disorder.
Sleep Med.
PUBLISHED: 03-06-2014
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To identify whether the presence and/or timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset were associated with differences in clinical features and sleep parameters of Parkinson disease (PD).
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2014 Eighth Joint National Committee panel recommendation for blood pressure targets revisited: results from the INVEST study.
J. Am. Coll. Cardiol.
PUBLISHED: 03-01-2014
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The 2014 Eighth Joint National Committee panel recommendations for management of high blood pressure (BP) recommend a systolic BP threshold for initiation of drug therapy and a therapeutic target of <150 mm Hg in those ?60 years of age, a departure from prior recommendations of <140 mm Hg. However, it is not known whether this is an optimal choice, especially for the large population with coronary artery disease (CAD).
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Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.
Vinicius Tragante, Michael R Barnes, Santhi K Ganesh, Matthew B Lanktree, Wei Guo, Nora Franceschini, Erin N Smith, Toby Johnson, Michael V Holmes, Sandosh Padmanabhan, Konrad J Karczewski, Berta Almoguera, John Barnard, Jens Baumert, Yen-Pei Christy Chang, Clara C Elbers, Martin Farrall, Mary E Fischer, Tom R Gaunt, Johannes M I H Gho, Christian Gieger, Anuj Goel, Yan Gong, Aaron Isaacs, Marcus E Kleber, Irene Mateo Leach, Caitrin W McDonough, Matthijs F L Meijs, Olle Melander, Christopher P Nelson, Ilja M Nolte, Nathan Pankratz, Tom S Price, Jonathan Shaffer, Sonia Shah, Maciej Tomaszewski, Peter J van der Most, Erik P A van Iperen, Judith M Vonk, Kate Witkowska, Caroline O L Wong, Li Zhang, Amber L Beitelshees, Gerald S Berenson, Deepak L Bhatt, Morris Brown, Amber Burt, Rhonda M Cooper-DeHoff, John M Connell, Karen J Cruickshanks, Sean P Curtis, George Davey-Smith, Christian Delles, Ron T Gansevoort, Xiuqing Guo, Shen Haiqing, Claire E Hastie, Marten H Hofker, G Kees Hovingh, Daniel S Kim, Susan A Kirkland, Barbara E Klein, Ronald Klein, Yun R Li, Steffi Maiwald, Christopher Newton-Cheh, Eoin T O'Brien, N Charlotte Onland-Moret, Walter Palmas, Afshin Parsa, Brenda W Penninx, Mary Pettinger, Ramachandran S Vasan, Jane E Ranchalis, Paul M Ridker, Lynda M Rose, Peter Sever, Daichi Shimbo, Laura Steele, Ronald P Stolk, Barbara Thorand, Mieke D Trip, Cornelia M van Duijn, W Monique Verschuren, Cisca Wijmenga, Sharon Wyatt, J Hunter Young, Aeilko H Zwinderman, Connie R Bezzina, Eric Boerwinkle, Juan P Casas, Mark J Caulfield, Aravinda Chakravarti, Daniel I Chasman, Karina W Davidson, Pieter A Doevendans, Anna F Dominiczak, Garret A FitzGerald, John G Gums, Myriam Fornage, Hakon Hakonarson, Indrani Halder, Hans L Hillege, Thomas Illig, Gail P Jarvik, Julie A Johnson, John J P Kastelein, Wolfgang Koenig, Meena Kumari, Winfried März, Sarah S Murray, Jeffery R O'Connell, Albertine J Oldehinkel, James S Pankow, Daniel J Rader, Susan Redline, Muredach P Reilly, Eric E Schadt, Kandice Kottke-Marchant, Harold Snieder, Michael Snyder, Alice V Stanton, Martin D Tobin, André G Uitterlinden, Pim van der Harst, Yvonne T van der Schouw, Nilesh J Samani, Hugh Watkins, Andrew D Johnson, Alex P Reiner, Xiaofeng Zhu, Paul I W de Bakker, Daniel Levy, Folkert W Asselbergs, Patricia B Munroe, Brendan J Keating.
Am. J. Hum. Genet.
PUBLISHED: 02-20-2014
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Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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Phosphorescent quantum dots/doxorubicin nanohybrids based on photoinduced electron transfer for detection of DNA.
Biosens Bioelectron
PUBLISHED: 02-16-2014
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MPA-capped Mn-doped ZnS QDs/DXR nanohybrids (MPA: 3-mercaptopropionic acid; QDs: quantum dots; DXR: cetyltrimethyl ammonium bromide) were constructed via photoinduced electron transfer (PIET) and then used as a room-temperature phosphorescence (RTP) probe for detection of DNA. DXR as a quencher will quench the RTP of Mn-doped ZnS QDs via PIET, thereby forming Mn-doped ZnS QDs/DXR nanohybrids and storing RTP. With the addition of DNA, it will be inserted into DXR and thus DXR will be competitively desorbed from the surface of Mn-doped ZnS QDs, thereby releasing the RTP of Mn-doped ZnS QDs. Based on this, a new method for DNA detection was built. The sensor for DNA has a detection limit of 0.039 mg L(-1) and a linear range from 0.1 to 14 mg L(-1). The present QDs-based RTP method does not need deoxidants or other inducers as required by conventional RTP detection methods, and avoids interference from autofluorescence and the scattering light of the matrix that are encountered in spectrofluorometry. Therefore, this method can be used to detect the DNA content in body fluid.
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MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4.
Mol. Cell. Biochem.
PUBLISHED: 02-15-2014
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Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.
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Prediction of nonrecurrent laryngeal nerve before thyroid surgery--experience with 1825 cases.
J. Surg. Res.
PUBLISHED: 02-07-2014
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Nonrecurrent laryngeal nerve (NRLN) is a rare anatomic anomaly, which often co-occurs with aberrant right subclavian artery (ARSA). With this large case series, we present our experience of predicting the presence of NRLN by the means of chest X-ray film, thoracic computed tomography (CT), and ultrasonography.
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Cytochrome P450 2C8 ?3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 01-23-2014
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Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ?3-long-chain polyunsaturated fatty acids (?3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown.
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Effects of hydroxypropyl degree on physiochemical activities of chitosan from squid pens.
Int. J. Biol. Macromol.
PUBLISHED: 01-16-2014
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Chitosan was prepared by alkaline N-deacetylation of ?-chitin and hydroxypropyl derivatives with different degrees of substitution (DS) were synthesized. It was characterized by Fourier transform infrared (FT-IR) and elemental analysis. The DS of hydroxypropyl chitosan (HPCS) calculated by an element analyzer were 0.42, 0.75, 1.20, 1.82 and 2.25. HPCS showed better foam capacity and stability than that of chitosan, and the effectiveness correlated well with the DS of HPCS. The highest bile acid-binding capacity of all five HPCS reached 56.02 mg/g, which was 4.0-fold higher than that of chitosan. The scavenging ability of HPCS against hydroxyl and ABTS radicals improved with increasing concentration. The correlation between the hydroxypropyl content (DS) of HPCS and scavenging ABTS radical ability was positive. The hydroxyl radicals scavenging activity of HPCS correlated well with its increasing concentration, and EC50 values were below 12.5 mg/mL. These results indicated that hydroxypropylation is a possible approach to obtain chitosan derivatives with desirable physiochemical properties.
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Leber's Hereditary Optic Neuropathy is Associated with Compound Primary Mutations of Mitochondrial ND1 m.3635G?>?A and ND6 m.14502 T?>?C.
Ophthalmic Genet.
PUBLISHED: 01-15-2014
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Abstract Purpose: To describe the clinical and molecular characteristics of a Chinese Leber hereditary optic neuropathy (LHON) pedigree with compound mitochondrial DNA (mtDNA) mutations of m.3635G?>?A and m.14502T?>?C. Methods: A total of 22 individuals (2 affected, 20 unaffected) from a five-generation Chinese family with LHON underwent comprehensive ophthalmic examination, including visual acuity, slit lamp examination, fundoscopy, visual field examination and visual evoked potentials (VEP). The complete mtDNA genome of the two patients were amplified by polymerase chain reaction, sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an ABI 3700XL Genetic Analyzer. Results: Two LHON patients in the family presented typical features of LHON: painless and progressive deterioration of bilateral vision, bilateral optic atrophy, centrocecal scotomata in both eyes and significant prolonged P100 latency and low amplitude potential in VEP. Compound primary mtDNA mutations of m.3635G?>?A and m.14502T?>?C were identified in these two patients and another 12 living matrilineal members of the pedigree. Haplogroup analysis showed the patients in this LHON family belonged to the N9b1 haplogroup. Modeled mutant structure showed the mutations altered the molecular local space conformation on the surface of ND1 and ND6. Conclusions: Compound mtDNA mutations of m.3635G?>?A and m.14502T?>?C presented with low penetration, and the patients with these compound mutations exhibited mild visual impairment. The biological information analysis suggested that m.14502T?>?C might play a protective role in LHON associated with m.3635G?>?A. The haplogroup analysis indicated that the mtDNA haplogroup might be an important factor affecting the expression of LHON associated with m.3635G?>?A and/or m.14502T?>?C.
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The effects of nesfatin-1 in the paraventricular nucleus on gastric motility and its potential regulation by the lateral hypothalamic area in rats.
J. Neurochem.
PUBLISHED: 01-14-2014
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The current study investigated the effects of nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) on gastric motility and the regulation of the lateral hypothalamic area (LHA). Using single unit recordings in the PVN, we show that nesfatin-1 inhibited the majority of the gastric distention (GD)-excitatory neurons and excited more than half of the GD-inhibitory (GD-I) neurons in the PVN, which were weakened by oxytocin receptor antagonist H4928. Gastric motility experiments showed that administration of nesfatin-1 in the PVN decreased gastric motility, which was also partly prevented by H4928. The nesfatin-1 concentration producing a half-maximal response (EC50) in the PVN was lower than the value in the dorsomedial hypothalamic nucleus, while nesfatin-1 in the reuniens thalamic nucleus had no effect on gastric motility. Retrograde tracing and immunofluorescent staining showed that nucleobindin-2/nesfatin-1 and fluorogold double-labeled neurons were observed in the LHA. Electrical LHA stimulation changed the firing rate of GD-responsive neurons in the PVN. Pre-administration of an anti- nucleobindin-2/nesfatin-1 antibody in the PVN strengthened gastric motility and decreased the discharging of the GD-I neurons induced by electrical stimulation of the LHA. These results demonstrate that nesfatin-1 in the PVN could serve as an inhibitory factor to inhibit gastric motility, which might be regulated by the LHA. Nesfatin-1 regulated the gastric distension (GD)-responsive neurons and reduced gastric motility in the paraventricular nucleus (PVN), which were partly blocked by H4928. Electrical stimulation of the lateral hypothalamic area (LHA) increased the firing activities of GD-responsive neurons in the PVN and promoted the gastric motility. NUCB2/nesfatin-1/fluorogold double-labeled neurons were identified in the LHA, indicating that nesfatin-1 in the PVN could play a pivotal role in the central control of gastric motility and the LHA may participate in the regulatory process. NUCB2 = nucleobindin-2.
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Role of Lutein Supplementation in the Management of Age-Related Macular Degeneration: Meta-Analysis of Randomized Controlled Trials.
Ophthalmic Res.
PUBLISHED: 01-11-2014
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Objective: The conduct of this meta-analysis aimed at examining the individual role of lutein as a dietary supplement in improving conditions of age-related macular degeneration (AMD) from the data generated from randomized controlled trials (RCTs). Method: The literature search was made in multiple electronic databases. Eligibility criteria were RCTs that recruited AMD patients or individuals at risk and evaluated lutein supplementation efficacy against placebo. The quality of the trials was assessed by using the Jadad scale. The meta-analysis was conducted under the fixed effect model with RevMan software by calculating the mean differences of the changes from baseline of both lutein and placebo groups. Parameters of interest were macular pigment optical density (MPOD) and visual acuity (VA) in logMAR (minimum angle of resolution). Heterogeneity was determined by ?(2) and I(2) and publication bias was assessed by visual examination of funnel plots. Results: After following predetermined inclusion and exclusion criteria, five RCTs that recruited 445 participants were selected for the meta-analysis. It has been found that lutein treatment was associated with a significant improvement in MPOD, with mean differences between lutein and placebo groups in the changes from baseline of 0.09 (95% CI: 0.06, 0.12; p < 0.00001). VA also improved with a mean difference between lutein and placebo groups in the changes from baseline of -0.04 (95% CI-0.07, 0.00; p = 0.05). Statistical heterogeneity was not apparent. Conclusion: A statistically highly significant effect of lutein supplementation has been observed for improving the MPOD, whereas the improvement in VA was milder. A daily dose of 10 mg was found as effective as higher doses in this meta-analysis. However, the number of input studies is not adequate for conclusive evidence. © 2014 S. Karger AG, Basel.
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Optimization of total polysaccharide extraction from Herba Lophatheri using RSM and antioxidant activities.
Int. J. Biol. Macromol.
PUBLISHED: 01-11-2014
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Effects of extraction temperature, extraction time and ratio of water to material as well as their interactions on the yield of total polysaccharide from Herba lophatheri were studied by response surface methodology (RSM). The optimal conditions for the extraction of polysaccharides were determined to be the ratio of liquid to solid of 39.01, extraction time of 2.11h and extraction temperature of 97.09°C. Under these optimal conditions, the yield of polysaccharides obtained was 5.73±0.10%, which was well matched with the value predicted by the model. In vitro antioxidant assays showed that the polysaccharides HLP possessed significant inhibitory effects on superoxide radical. It also exhibited strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities, hydroxyl radical scavenging activities and its reducing power, ferrous ions chelating effect was also strong. These results suggested that H. lophatheri polysaccharides could be a suitable natural antioxidant and may be the functional foods for humans.
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Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography.
Exp Ther Med
PUBLISHED: 01-08-2014
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In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber's hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ?3 months; group 2, 4-6 months; group 3, 7-9 months; group 4, 10-12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.
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A multicenter phase II study of sorafenib monotherapy in clinically selected patients with advanced lung adenocarcinoma after failure of EGFR-TKI therapy (Chinese Thoracic Oncology Group, CTONG 0805).
Lung Cancer
PUBLISHED: 01-05-2014
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Aim of the study was to investigate efficacy and safety of sorafenib in patients with advanced lung adenocarcinoma after failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy.
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Baseline predictors of central aortic blood pressure: a PEAR substudy.
J Am Soc Hypertens
PUBLISHED: 01-03-2014
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Elevated central systolic blood pressure (BP) increases the risk of cardiovascular events and appears superior to peripheral BP for long term risk prediction. The objective of this study was to identify demographic and clinical factors associated with central pressures in patients with uncomplicated hypertension. We prospectively examined peripheral BP, central aortic BP, and arterial wall properties and wave reflection in 57 subjects with uncomplicated essential hypertension in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study. Significant predictors of central SBP included height, smoking status, heart rate (HR), and peripheral systolic BP (SBP), while central diastolic BP (DBP) was explained by peripheral DBP and HR. These variables accounted for nearly all of the variability in central SBP and central DBP (R(2) = 0.94 and R(2) = 0.98, respectively). Central pulse pressure variability was largely explained by gender, ex-smoking status, HR, peripheral SBP, and peripheral DBP (R(2) = 0.94). Central augmented pressure had a direct relationship with smoking status, peripheral SBP, and duration of hypertension, whereas it was indirectly related to height, HR, and peripheral DBP. Easily obtainable demographic and clinical factors are associated with central pressures in essential hypertensive persons. These relationships should be considered in future studies to improve assessment of BP to reduce cardiovascular risk and mortality.
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Up-regulation of miR-335 predicts a favorable prognosis in esophageal squamous cell carcinoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-335 has recently been identified to be involved in tumorigenesis of several cancers such as ovarian cancer and gastric cancer. However, the regulation of miR-335 in esophageal squamous cell carcinoma (ESCC) has not been reported yet.
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Cadmium Telluride Quantum Dots (CdTe-QDs) and Enhanced Ultraviolet-B (UV-B) Radiation Trigger Antioxidant Enzyme Metabolism and Programmed Cell Death in Wheat Seedlings.
PLoS ONE
PUBLISHED: 01-01-2014
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Nanoparticles (NPs) are becoming increasingly widespread in the environment. Free cadmium ions released from commonly used NPs under ultraviolet-B (UV-B) radiation are potentially toxic to living organisms. With increasing levels of UV-B radiation at the Earth's surface due to the depletion of the ozone layer, the potential additive effect of NPs and UV-B radiation on plants is of concern. In this study, we investigated the synergistic effect of CdTe quantum dots (CdTe-QDs), a common form of NP, and UV-B radiation on wheat seedlings. Graded doses of CdTe-QDs and UV-B radiation were tested, either alone or in combination, based on physical characteristics of 5-day-old seedlings. Treatments of wheat seedlings with either CdTe-QDs (200 mg/L) or UV-B radiation (10 KJ/m2/d) induced the activation of wheat antioxidant enzymes. CdTe-QDs accumulation in plant root cells resulted in programmed cell death as detected by DNA laddering. CdTe-QDs and UV-B radiation inhibited root and shoot growth, respectively. Additive inhibitory effects were observed in the combined treatment group. This research described the effects of UV-B and CdTe-QDs on plant growth. Furthermore, the finding that CdTe-QDs accumulate during the life cycle of plants highlights the need for sustained assessments of these interactions.
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The Cyp2c44 Epoxygenase Regulates Epithelial Sodium Channel Activity and the Blood Pressure Responses to Increased Dietary Salt.
J. Biol. Chem.
PUBLISHED: 12-24-2013
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Hypertension is a major risk factor for cerebral, cardiovascular, and renal disease and its prevalence and devastating consequences raises a need for new strategies for its early diagnosis and treatment. We show here that lack of a Cyp2c44 epoxygenase causes dietary salt sensitive hypertension, a common form of the human disease. Cyp2c44(-/-) mice on normal salt diets are normotensive but become hypertensive when fed high salt. Hypertensive Cyp2c44(-/-) mice show a hyperactive kidney epithelial sodium channel (ENaC) and reductions in ERK1/2 and ENaC subunit phosphorylation. The demonstration that Amiloride, an ENaC inhibitor, lowers the blood pressures of hypertensive Cyp2c44(-/-) mice identifies a role for the channel in the animals hypertensive phenotype. These studies: a) identify an anti-hypertensive role for the kidney Cyp2c44 epoxygenase, and for its epoxyeicosatrienoic acids (EETs) metabolites in the in vivo control of ENaC activity, and the activation of mitogenic kinase pathways, b) provide evidence for a Cyp2c44 epoxygenase, EET-mediated, mechanism of ENaC regulation involving an ERK1/2-catalyzed threonine phosphorylation of the channel gamma subunit, and c) characterize a common scientific platform that could explain the seemingly unrelated biological activities attributed to the epoxygenase metabolites in cell proliferation, angiogenesis, channel activity, and blood pressure control. It is expected that these results will serve as a basis for the development of novel strategies for the early diagnosis and treatment of hypertension and of pathophysiologies associated with dysfunctional mitogenic signaling.
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[Clinical characteristics in Parkinsons disease patients with cognitive impairment and effects of cognitive impairment on sleep].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-24-2013
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To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinsons disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep.
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Gene-centric meta-analyses for central adiposity traits in up to 57,412 individuals of European descent confirm known loci and reveal several novel associations.
Hum. Mol. Genet.
PUBLISHED: 12-17-2013
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Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes, and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57,412 individuals of European descent from 22 cohorts collaborating with the NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20 to 80. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ?50,000 cosmopolitan tagged SNPs across ?2,100 cardiovascular-related genes. Each trait was modeled as a function of age, study site, and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P<2.4x10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (?±SE,0.048±0.008, P=7.7x10(-9)) as was rs7302703-G in HOXC10 (?=0.044±0.008, P=2.9x10(-7)) and rs936108-C in PEMT (?=0.035±0.007, P=1.9x10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A near SHC1 (?=0.10±0.02, P=1.9x10(-6)), and rs1037575-A in ATBDB4 (?=0.046±0.01, P=2.2x10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.
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Association analysis of USF1 gene polymorphisms and total unstable carotid plaque area in atherosclerotic stroke patients.
J. Thromb. Thrombolysis
PUBLISHED: 12-16-2013
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Polymorphisms of the upstream stimulatory factor 1 (USF1) have been associated with carotid artery intima-media thickness and coronary atherosclerotic lesions. Unstable carotid plaque is an atherosclerotic change of vascular morphology that has been correlated with cerebrovascular ischemic symptoms. Associations of three single nucleotide polymorphisms of the USF1 gene with total unstable carotid plaque area (CPA) were investigated in Chinese atherosclerotic stroke patients. We recruited 668 atherosclerotic stroke patients and 602 controls. Total unstable CPA values were measured by ultrasound. Genotypes were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) or mismatched PCR-RFLP. A significant difference in total unstable CPA was found for rs2516838 and rs2516839 genotypes (P = 0.039 and 0.046, respectively) in atherosclerotic stroke patients with unstable carotid plaque. Furthermore, in multiple logistic regression analysis adjusted by age, sex, BMI, hypertension, smoking status, glucose, total cholesterol, triglycerides, high-density lipoprotein-cholesterols, low-density lipoprotein-cholesterols and high-sensitivity C-reactive protein, significant associations were seen between the total unstable CPA values and genotypes of the rs2516838 or the rs2516839 in these patients. The rare allele C of rs2516838 or rare allele A of rs2516839 could predict relative low total unstable CPA values. The rs2516838 and rs2516839 polymorphisms of USF1 influence total unstable CPA in atherosclerotic stroke patients, which might be new markers to predict the risk of recurrence for this disease.
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[Study on the effect of ursolic acid (UA) on the myocardial fibrosis of experimental diabetic mice].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 11-02-2013
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To investigate the effect of ursolic acid (UA) on the alloxan-induced myocardial fibrosis in mice and discuss the possible mechanism.
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Impact of TCF7L2 single nucleotide polymorphisms on hydrochlorothiazide-induced diabetes.
Pharmacogenet. Genomics
PUBLISHED: 10-17-2013
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Thiazide diuretics have been associated with increased risk for new onset diabetes (NOD), but pharmacogenetic markers of thiazide-induced NOD are not well studied. Single nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 gene (TCF7L2) represent the strongest and most reproducible genetic associations with diabetes. We investigated the association of tag SNPs in TCF7L2 with thiazide-induced NOD.
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PROX1 Gene Variant is Associated with Fasting Glucose Change After Antihypertensive Treatment.
Pharmacotherapy
PUBLISHED: 10-09-2013
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To assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome-wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes.
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[Effects of ozone exposure on percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells and mRNA expression of Foxp3 in asthmatic rats].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 09-26-2013
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To investigate the effects of low-concentration ozone exposure on the percentage of CD4(+)CD25(high)Foxp(3+) regulatory T cells and the mRNA expression of transcription factor Foxp3 in asthmatic rats.
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[Application of polarized Raman spectroscopy in the research on molecule conformation].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 09-25-2013
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In the present paper, the carbon tetrachloride (CCl4) is the main object of study. According to the calculation of the degree of depolarization, the authors can understand CCl4 crystal vibration. With the comparison between the calculated theoretical value and the experimental value, we are sure that our work is accurate.
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Jiaotai pill enhances insulin signaling through phosphatidylinositol 3-kinase pathway in skeletal muscle of diabetic rats.
Chin J Integr Med
PUBLISHED: 08-24-2013
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To investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats.
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Simple integer risk score to determine prognosis of patients with hypertension and chronic stable coronary artery disease.
J Am Heart Assoc
PUBLISHED: 08-17-2013
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It is difficult to accurately determine prognosis of patients with hypertension and chronic stable coronary artery disease (CAD). Our aim was to construct a risk score for predicting important adverse events in this population.
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[Application of preformed orbital titanium mesh in reconstruction of orbital fracture].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 07-31-2013
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To assess the effect of preformed orbital titanium mesh in the reconstruction of orbital fracture.
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Night Blood Pressure Responses to Atenolol and Hydrochlorothiazide in Black and White Patients With Essential Hypertension.
Am. J. Hypertens.
PUBLISHED: 07-25-2013
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Night blood pressure (BP) predicts patient outcomes. Variables associated with night BP response to antihypertensive agents have not been fully evaluated in essential hypertension.
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Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide.
Hypertension
PUBLISHED: 06-10-2013
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To identify novel genes influencing blood pressure response to thiazide diuretic therapy for hypertension, we conducted genome-wide association meta-analyses of ?1.1 million single-nucleotide polymorphisms in a combined sample of 424 European Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=228) and the Genetic Epidemiology of Responses to Antihypertensive study (n=196). Polymorphisms associated with blood pressure response at P<10(-5) were tested for replication of the associations in independent samples of hydrochlorothiazide-treated European hypertensives. The rs16960228 polymorphism in protein kinase C, ? replicated for same-direction association with diastolic blood pressure response in the Nordic Diltiazem study (n=420) and the Genetics of Drug Responsiveness in Essential Hypertension study (n=206), and the combined 4-study meta-analysis P value achieved genome-wide significance (P=3.3 × 10(-8)). Systolic or diastolic blood pressure responses were consistently greater in carriers of the rs16960228 A allele than in GG homozygotes (>4/4 mm Hg) across study samples. The rs2273359 polymorphism in the GNAS-EDN3 region also replicated for same-direction association with systolic blood pressure response in the Nordic Diltiazem study, and the combined 3-study meta-analysis P value approached genome-wide significance (P=5.5 × 10(-8)). The findings document clinically important effects of genetic variation at novel loci on blood pressure response to a thiazide diuretic, which may be a basis for individualization of antihypertensive drug therapy and identification of new drug targets.
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Efficacy and safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinical trial.
Curr Med Res Opin
PUBLISHED: 06-04-2013
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To evaluate the efficacy and safety of linagliptin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin and sulphonylurea.
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Cloning, expression of a feruloyl esterase from Aspergillus usamii E001 and its applicability in generating ferulic acid from wheat bran.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 05-25-2013
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A cDNA gene (AufaeA), which encodes a mature polypeptide of the type-A feruloyl esterase from Aspergillus usamii E001 (abbreviated to AuFaeA), was cloned and heterologously expressed in Pichia pastoris GS115. One transformant, labeled as P. pastoris GSFaeA4-8, expressing the highest recombinant AuFaeA (reAuFaeA) activity of 10.76 U/ml was selected by the flask expression test. The expressed reAuFaeA was purified to homogeneity with an apparent molecular weight of 36.0 kDa by SDS-PAGE analysis, and characterized using the model substrate of methyl ferulate (MFA). The purified reAuFaeA was optimally active at pH 5.0 and 45 °C, and highly stable at pH 4.0-6.5 and 45 °C or below. Its activity was not significantly affected by metal ions tested and EDTA. The K m and V max of reAuFaeA towards MFA were 4.64 mM and 115.5 U/mg, respectively. High-performance liquid chromatography analysis showed that only 9.7 % of total alkali-extractable ferulic acid (FA) was released from destarched wheat bran by reAuFaeA alone. The released FA increased to 36.5 % when reAuFaeA was used together with a recombinant Aspergillus usamii GH family 11 xylanase A, indicating a synergistic interaction between them.
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Pharmacogenomic association of nonsynonymous SNPs in SIGLEC12, A1BG, and the selectin region and cardiovascular outcomes.
Hypertension
PUBLISHED: 05-20-2013
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We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a ?-blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)×treatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.
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Central nesfatin-1 influences the excitability of ghrelin-responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats.
Eur. J. Neurosci.
PUBLISHED: 05-17-2013
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Although the novel satiety peptide nesfatin-1 has been shown to regulate gastric motility, the underlying mechanisms have yet to be elucidated. The study aimed to explore the effects of nesfatin-1 on ghrelin-responsive gastric distension (GD) neurons in the arcuate nucleus (Arc), and potential regulation mechanisms of gastric motility by the paraventricular nucleus (PVN). Single-unit discharges in the Arc were recorded extracellularly, and gastric motility in conscious rats was monitored during the administration of nesfatin-1 to the Arc or electrical stimulation of the PVN. Retrograde tracing and fluo-immunohistochemistry staining were used to determine NUCB2/nesfatin-1 neuronal projections. Nesfatin-1 inhibited most of the ghrelin-responsive GD-excitatory neurons, but excited ghrelin-responsive GD-inhibitory neurons in the Arc. Gastric motility was significantly reduced by nesfatin-1 administration to the Arc in a dose-dependent manner. The firing activity in the Arc and changes to gastric motility were partly reduced by SHU9119, an antagonist of melanocortin 3/4 receptors. Electrical stimulation of PVN excited most of the ghrelin-responsive GD neurons in the Arc and promoted gastric motility. Nonetheless, pretreatment with an anti-NUCB2/nesfatin-1 antibody in the Arc further increased the firing rate of most of the ghrelin-responsive GD-excitatory neurons and decreased the ghrelin-responsive GD-inhibitory neurons following electrical stimulation of the PVN. Gastric motility was enhanced by pretreatment with an anti-NUCB2/nesfatin-1 antibody in the Arc following PVN stimulation. Furthermore, NUCB2/nesfatin-1/fluorogold double-labeled neurons were detected in the PVN. These results suggest that nesfatin-1 could serve as an inhibitory factor in the Arc to regulate gastric motility via the melanocortin pathway. The PVN could be involved in the regulation of the Arc in gastric activity.
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Self-assembly of manganese doped zinc sulfide quantum dots/CTAB nanohybrids for detection of rutin.
Biosens Bioelectron
PUBLISHED: 05-15-2013
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Quantum dots (QDs) nanohybrids are an effective route to obtain new property of materials, and are very significant for developing specific materials and improving the performance of existing QDs materials. The objectives of this work are to prepare MPA-capped Mn-doped ZnS QDs/CTAB nanohybrids (MPA: 3-mercaptopropionic acid; CTAB: cetyltrimethyl ammonium bromide) through electrostatic self-assembly, to investigate the formation mechanism and the Room-Temperature Phosphorescenee (RTP) changes, and to explore the possibility of their application in detection of rutin. As a result, MPA-capped Mn-doped ZnS QDs/CTAB nanohybrids greatly improve the rutin detection ability of QDs and provide an important method for developing more convenient and effective rutin detection sensor. The sensor for rutin gave a detection limit of 0.037 mg L(-1) and two linear ranges from 0.05 to 0.5 mg L(-1) and from 0.5 to 5 mg L(-1), and thus can be expanded to selective detection of other substances. Since the present QDs-based RTP method does not need deoxidants or other inducers as conventional RTP detection methods, and avoids interference from autofluorescence and the scattering light of the matrix that are encountered in spectrofluorometry, this method can be used to detect the content of rutin in body fluid.
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[Amelioration of icariin for the epididymis impairment induced by streptozocin (STZ) in rats].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 05-14-2013
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To investigate the effects of icariin on the streptozocin (STZ)-induced epididymis impair in rats.
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Impact of adjuvant chemotherapy cycles on prognosis of resectable stomach cancer: a retrospective analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 03-29-2013
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The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis.
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Sprouty4 regulates endothelial cell migration via modulating integrin ?3 stability through c-Src.
Angiogenesis
PUBLISHED: 03-27-2013
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Angiogenesis is mediated by signaling through receptor tyrosine kinases (RTKs), Src family kinases and adhesion receptors such as integrins, yet the mechanism how these signaling pathways regulate one another remains incompletely understood. The RTK modulator, Sprouty4 (Spry4) inhibits endothelial cell functions and angiogenesis, but the mechanisms remain to be fully elucidated. In this study, we demonstrate that Spry4 regulates angiogenesis in part by regulating endothelial cell migration. Overexpression of Spry4 in human endothelial cells inhibited migration and adhesion on vitronectin (VTN), whereas knockdown of Spry4 enhanced these behaviors. These activities were shown to be c-Src-dependent and Ras-independent. Spry4 disrupted the crosstalk between vascular endothelial growth factor-2 and integrin ?V?3, the receptor for VTN. Spry4 overexpression resulted in decreased integrin ?3 protein levels in a post-transcriptional manner in part by modulating its tyrosine phosphorylation by c-Src. Conversely, knockdown of Spry4 resulted in increased integrin ?3 protein levels and tyrosine phosphorylation. Moreover, in vivo analysis revealed that Spry4 regulated integrin ?3 levels in murine embryos and yolk sacs. Our findings identify an unanticipated role for Spry4 in regulating c-Src activity and integrin ?3 protein levels, which contributes to the regulation of migration and adhesion of endothelial cells. Thus, targeting Spry4 may be exploited as a target in anti-angiogenesis therapies.
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Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials.
Cardiovasc Diabetol
PUBLISHED: 03-27-2013
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In patients with type 2 diabetes mellitus (T2DM), hypertension and microalbuminuria are predictive markers for increased renal and cardiovascular risk. This post hoc analysis of data from a global development program aimed to evaluate the efficacy and safety of linagliptin in a population with joint prevalence of these two vascular risk factors.
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Mortality implications of angina and blood pressure in hypertensive patients with coronary artery disease: New data from extended follow-up of the International Verapamil/Trandolapril Study (INVEST).
Clin Cardiol
PUBLISHED: 03-07-2013
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Angina and hypertension are common in patients with coronary artery disease (CAD); however, the effect on mortality is unclear. We conducted this prespecified analysis of the International Verapamil/Trandolapril Study (INVEST) to assess relationships between angina, blood pressure (BP), and mortality among elderly, hypertensive CAD patients.
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Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: pooled analysis of data from three placebo-controlled phase III trials.
J. Diabetes Complicat.
PUBLISHED: 02-09-2013
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To evaluate the efficacy/safety of dipeptidyl peptidase-4 inhibitor, linagliptin, in subjects with insufficiently controlled type 2 diabetes mellitus (T2DM), and factors influencing treatment response.
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Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes.
Circ Cardiovasc Genet
PUBLISHED: 02-07-2013
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BACKGROUND- Aspirin or dual antiplatelet therapy with aspirin and clopidogrel is a standard therapy for patients who are at increased risk for cardiovascular events. However, the genetic determinants of variable response to aspirin (alone and in combination with clopidogrel) are not known. METHODS AND RESULTS- We measured ex vivo platelet aggregation before and after dual antiplatelet therapy in individuals (n=565) from the Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and conducted a genome-wide association study of drug response. Significant findings were extended by examining genotype and cardiovascular outcomes in 2 independent aspirin-treated cohorts: 227 percutaneous coronary intervention patients and 1000 patients of the International Verapamil SR/Trandolapril Study (INVEST) Genetic Substudy (INVEST-GENES). Results from the genome-wide association study revealed a strong association between single-nucleotide polymorphisms on chromosome 1q23 and post-dual antiplatelet therapyplatelet aggregation. Further genotyping revealed rs12041331 in the platelet endothelial aggregation receptor-1 (PEAR1) gene to be most strongly associated with dual antiplatelet therapy response (P=7.66×10(-9)). In white and black patients undergoing percutaneous coronary intervention, A-allele carriers of rs12041331 were more likely to experience a cardiovascular event or death compared with GG homozygotes (hazard ratio, 2.62; 95% confidence interval, 0.96-7.10; P=0.059; and hazard ratio, 3.97; 95% confidence interval, 1.10-14.31; P=0.035, respectively). In aspirin-treated INVEST-GENES patients, rs12041331 A-allele carriers had significantly increased risk of myocardial infarction compared with GG homozygotes (odds ratio, 2.03; 95% confidence interval, 1.01-4.09; P=0.048). CONCLUSION- Common genetic variation in PEAR1 may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00799396 and NCT00370045.
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Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling.
PLoS ONE
PUBLISHED: 02-05-2013
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Changes in the vascular smooth muscle cell (VSMC) contractile phenotype occur in pathological states such as restenosis and atherosclerosis. Multiple cytokines, signaling through receptor tyrosine kinases (RTK) and PI3K/Akt and MAPK/ERK pathways, regulate these phenotypic transitions. The Spry proteins are feedback modulators of RTK signaling, but their specific roles in VSMC have not been established.
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