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Find video protocols related to scientific articles indexed in Pubmed.
DoGSD: the dog and wolf genome SNP database.
Nucleic Acids Res.
PUBLISHED: 11-19-2014
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The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ?19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.
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Establishment of stable MRP1 knockdown by lentivirus-delivered shRNA in the mouse testis Sertoli TM4 cell line.
Toxicol. Mech. Methods
PUBLISHED: 11-19-2014
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Abstract Sertoli cells around germ cells are considered a barrier that protects spermatogenesis from harmful influences. The transporter multidrug-resistance-associated protein 1 (MRP1) is a xenobiotic efflux pump that can export glutathione S-conjugated metabolites and xenobiotics from cells. In this study, the Mrp1 gene was stably knocked down in a mouse Sertoli cell line (TM4) using lentivirus vector-mediated RNA interference (RNAi) technology. Four shRNA interference sequences were chosen and designed to screen for the most effective shRNA in candidate cells. The results indicate that lentivirus vectors with high titres were generated and successfully transfected into TM4 cells with high efficiency. Puromycin was added to the culture medium to maintain constant selection during the establishment of the stable cell lines. The expression levels of Mrp1 mRNA and MRP1 protein in stably transfected TM4 cells were significantly lower than those in the control group. Importantly, the transport activity of MRP1 to Calcein and 5-carboxyseminaptharhodafluor (SNARF-1) were significantly reduced because of MRP1 silencing. Moreover, the silencing of the Mrp1 gene in the transfected TM4 cell lines remained highly stable for more than 6 months. These results suggest that the lentivirus-based RNAi stably knocks down the expression of the Mrp1 gene in the established TM4 cell line. This transfected TM4 cell line will provide a new and powerful tool to study the underlying mechanism of MRP1-mediated drug resistance and detoxication in the reproductive system.
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Assessment of the effectiveness of antiretroviral treatment (ART) among HIV-Infected Adults: a prospective cohort study in Yunnan Province, 2004-2010.
AIDS Res. Hum. Retroviruses
PUBLISHED: 11-18-2014
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Our objective was to describe the virological and immunological responses of ART with attempt to identify the risk factors for treatment failure, and to examine rates and reasons for initial regimen modification in Yunnan Province. A total of 144 HIV-infected adults who initiated antiretroviral treatment between 2004 and 2006 of Yunnan province were recruited in this longitudinal study. The endpoints were virological failure, immunological failure, and initial regimen modification, according to World Health Organization criteria. Over the 6-year follow-up, 16(11.1%) patients demonstrated virological failure and 34 (23.6%) experienced immunological failure, for overall failure rates of 2.79 per 100 person-years (95% CI: 1.71-4.55) and 6.17 per 100 person-years (95% CI: 4.41-8.64), respectively. Male (p=0.007, HR=5.22, 95%CI of HR: 1.58-17.21) was a risk factor for immunological failure. 37.5% patients modified their initial regimen over the follow-up duration, and the most common reason for modification was adverse events. Our analysis of ART in Yunnan reveals excellent outcomes achieved over the past years. High rate of initial regimen modification should be taken seriously. Given the discordant immunological and virological responses emerged after ART initiation, viral load monitoring is urgently needed for evaluating the treatment outcomes in resource-limited settings comprehensively.
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Dihydroxanthenones from the fermentation product of an endophytic fungus Gliomastix murorum.
J Asian Nat Prod Res
PUBLISHED: 11-14-2014
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Three new dihydroxanthones, muroxanthenones A-C (1-3), together with three known dihydroxanthones (4-6) were isolated from the fermentation products of an endophytic fungus Gliomastix murorum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compound 3 showed high cytotoxicities against NB4 and PC3 cell with IC50 values of 2.2 and 2.8 ?M. The other compounds also showed moderate cytotoxicities for some tested cell lines with IC50 values between 4.1 and 9.5 ?M.
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Deficiency of Interferon-Gamma or Its Receptor Promotes Colorectal Cancer Development.
J. Interferon Cytokine Res.
PUBLISHED: 11-11-2014
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Genetic variations in interferon-gamma (IFN-?) and its receptor (IFN?R) subunits are closely associated with the risk of colorectal cancer (CRC) and survival after diagnosis. However, the role of loss of IFN-? or IFN?R function in the pathogenesis of CRC remains unclear. Here, we investigated the role of endogenous IFN-? deficiency in adenomatous polyposis coli (Apc)-mediated intestinal tumor by developing a variant of Apc(Min/+) mice. The Apc(Min/+)IFN-?(+/-) mice presented with increased number and size of adenomas, and 41.7% of these mice developed adenocarcinoma. Molecular analyses of the adenomas suggested that heterozygous deletion of IFN-? promoted EGFR/Erk1/2 and Wnt/?-catenin signaling. In vitro, IFN-? administration inhibited Apc-mutated HT-29 colon cancer cell proliferation and had no effect on the proliferation of HCT-116 colon cancer cells that express wild-type Apc. Besides, we challenged HT-29 cells with small interfering RNA targeting one of its receptor subunits IFN?R1. We found that knockdown of IFN?R1 in HT-29 cells stimulated cell proliferation and colony formation, which was also related to the regulation of EGFR/Erk1/2 and Wnt/?-catenin signaling. Thus, our results strongly support the notion that IFN-? and IFN?R1 act as a rate-limiting factor in the development of CRC, uncovering a novel role for them in cancer biology.
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Genetic Loci Associated with Circulating Levels of Very Long-Chain Saturated Fatty Acids.
J. Lipid Res.
PUBLISHED: 11-08-2014
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Very long-chain saturated fatty acids (VLSFA) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFA may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFA is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFA by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, SPTLC3 (serine palmitoyl-transferase, long-chain base subunit 3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and CERS4 (ceramide synthase 4). The SPTLC3 variant at rs680379 was associated with higher 20:0 (arachidic acid, p = 5.81x10-13). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (p = 2.65x10-40) and in analyses that adjusted for 20:0, with lower levels of 22:0 (behenic acid, p = 4.22x10-26) and 24:0 (lignoceric acid, p = 3.20x10-21). These novel associations highlight the inter-relationship of circulating VLSFA and sphingolipid synthesis.
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[Expression of bone morphogenetic protein 2 in human nonunion tissue and the clinical significance].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-31-2014
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To explore the difference of bone formation potential between hypertrophic nonunion tissue and atrophic nonunion tissue, which may be beneficial to nonunion therapy.
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[Lentivirus-mediated stable Fas gene silencing in human umbilical cord-derived mesenchymal stem cells].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 10-28-2014
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To construct a lentivirus-mediated vector for RNA interference (RNAi) of Fas and establish a human umbilical cord-derived mesenchymal stem cells (UC-MSCs) line with stable Fas gene silencing.
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Official Japanese Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale: validation against the original English version.
Mov Disord Clin Pract (Hoboken)
PUBLISHED: 10-21-2014
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The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results.
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4.0???m, high repetition rate periodically poled magnesium-oxide-doped lithium niobate mid-infrared optical parametric oscillator pumped by steep leading edge pulsed fiber laser.
Appl Opt
PUBLISHED: 10-17-2014
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A high repetition rate optical parametric oscillator (OPO) generating an idler laser with a wavelength as long as 4.0 ?m at 200 and 400 kHz was demonstrated in this paper. The OPO was pumped by a master oscillator power amplifier structure fiber laser with excellent characteristics. The pump pulse from the fiber laser had a steep leading edge, which was theoretically proved to improve the OPO's performance, compared with the Gaussian pump pulse. A homemade periodically poled magnesium-oxide-doped lithium niobate crystal with a grating period of 29 ?m was employed in our experiment. By optimizing the resonator, 2.75 and 1.67 W idler lasers were finally achieved at repetition rates as high as 200 and 400 kHz, respectively, with a wavelength as long as 4.0 ?m. The conversion efficiencies were 12.03% and 7.31%, respectively.
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Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 10-12-2014
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Smooth muscle contraction can be divided into two phases: the initial contraction determines the amount of developed force and the second phase determines how well the force is maintained. The initial phase is primarily due to activation of actomyosin interaction and is relatively well understood, whereas the second phase remains poorly understood. Force maintenance in the sustained phase can be disrupted by strains applied to the muscle; the strain causes actomyosin cross-bridges to detach and also the cytoskeletal structure to disassemble in a process known as fluidization, for which the underlying mechanism is largely unknown. In the present study we investigated the ability of airway smooth muscle to maintain force after the initial phase of contraction. Specifically, we examined the roles of Rho-kinase and protein kinase C (PKC) in force maintenance. We found that for the same degree of initial force inhibition, Rho-kinase substantially reduced the muscle's ability to sustain force under static conditions, whereas inhibition of PKC had a minimal effect on sustaining force. Under oscillatory strain, Rho-kinase inhibition caused further decline in force, but again, PKC inhibition had a minimal effect. We also found that Rho-kinase inhibition led to a decrease in the myosin filament mass in the muscle cells, suggesting that one of the functions of Rho-kinase is to stabilize myosin filaments. The results also suggest that dissolution of myosin filaments may be one of the mechanisms underlying the phenomenon of fluidization. These findings can shed light on the mechanism underlying deep inspiration induced bronchodilation.
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A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.
Open Biol
PUBLISHED: 10-10-2014
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Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.
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Antibacterial wound dressing from chitosan/polyethylene oxide nanofibers mats embedded with silver nanoparticles.
J Biomater Appl
PUBLISHED: 10-05-2014
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Novel antibacterial nanomaterials have been developed for biomedical applications. The present study involves the preparation and properties of antibacterial nanofibers from chitosan/polyethylene oxide electrospun nanofibers incorporated with silver nanoparticles. Silver nanoparticles were efficiently synthesized in situ after ultra violet (UV) with AgNO3 as precursor and chitosan/polyethylene oxide as reducing agent and protecting agent, respectively. Then the resultant solutions were electrospun into nanofibers. The formation of silver nanoparticles was confirmed with ultraviolet visible (UV-vis) and transmission electron microscopy (TEM), and the electrospun nanofibers were characterized by scanning electron microscopy and energy dispersive X-ray. The resultant fibers exhibited uniform morphology with silver nanoparticles distributed throughout the fiber. Also, the fibers showed certain tensile strength and excellent antibacterial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Sustained release of silver nanoparticles from fibers could last for over 72?h. The silver-containing chitosan/polyethylene oxide nanofibers showed excellent cytocompatibility.
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PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.
Oral Dis
PUBLISHED: 10-04-2014
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To determine the role of PRDM1, a key molecule for modulating the immune cells, in warthin tumour (WT) pathogenesis.
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Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS.
Neurology
PUBLISHED: 09-24-2014
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In the current exploratory study, we longitudinally measured immune parameters in the blood of individuals with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and investigated their relationship to disease duration and clinical and radiologic measures of CNS injury.
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Frequency, interobserver reproducibility and clinical significance of equivocal peaks in PCR clonality testing using Euroclonality/BIOMED-2 primers.
J. Clin. Pathol.
PUBLISHED: 09-22-2014
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PCR studies for lymphoid clonality are now widely employed, especially using Euroclonality/BIOMED-2 primers. Criteria for interpretation as a clonal result, however, have proven controversial. This study examines the frequency and clinical significance of equivocal amplification patterns and measures the interobserver reproducibility of clonality interpretations.
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Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer.
Ann. Surg. Oncol.
PUBLISHED: 09-21-2014
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Medullary thyroid cancer (MTC) is a rare thyroid cancer accounting for 5 % of all thyroid malignancies. The purpose of our study was to design a predictive nomogram for cancer-specific mortality (CSM) utilizing clinical, pathological, and biochemical variables in patients with MTC.
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EZH2 promotes angiogenesis through inhibition of miR-1/Endothelin-1 axis in nasopharyngeal carcinoma.
Oncotarget
PUBLISHED: 09-20-2014
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Emerging evidence clearly indicates that EZH2 plays a crucial role in tumor angiogenesis. However, the role of EZH2 in angiogenesis is still unknown in nasopharyngeal carcinoma (NPC). We here showed that the elevated EZH2 level was closely associated with an aggressive and poor prognostic phenotype, and was positively correlated with microvessel density (MVD) in NPC tissues. Functional studies showed that EZH2 upregulation promoted cell proliferation, migration and tubule formation of endothelial cells, and knockdown of EZH2 suppressed tumor growth, metastasis and angiogenesis in vivo. Mechanistic investigations revealed that EZH2 inhibited miR-1 transcription via promoter binding activity, leading to enhanced expression of Endothelin-1 (ET-1) which is suppressed by miR-1 targeting of ET-1 3'UTR. Furthermore, knockdown of EZH2 or overexpression of miR-1 exerted anti-angiogenic effect on NPC cells. More importantly, the neutralizing antibody against ET-1 significantly abrogated the pro-angiogenic effect of EZH2, and forced expression of ET-1 rescued the anti-angiogenic effect induced by EZH2 knockdown. In clinical specimens, ET-1 was widely overexpressed and associated with clinical stage and MVD. Taken together, our results identify a novel signaling pathway involved in NPC angiogenesis, and also suggest that EZH2-miR-1-ET-1 axis represents multiple potential therapeutic targets for NPC.
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High incidence of HIV and syphilis among migrant men who have sex with men in Beijing, China: a prospective cohort study.
BMJ Open
PUBLISHED: 09-18-2014
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The purpose of the study was to investigate the incidence of HIV and syphilis and their related factors, as well as to examine the predictors associated with seroconversion among migrant men who have sex with men (MSM) in Beijing, China.
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Morphology variability of radial pulse wave during exercise.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Pulse wave contains much information on a cardiovascular system. Pulse wave variability during exercise is of great significance as it reflects more information combining with pulse wave under stationary state. This paper studied the morphology variability of radial pulse wave during exercise. Radial pulse waves were collected from 30 subjects with two pressure pulse sensors worn at the wrists of the right and left hands, respectively. Electrocardiography (ECG) was also detected synchronously. After data preprocessing and feature point extraction, the variability of several parameters of pulse wave and ECG were analyzed. It is notable that pulse rate (PR) and heart rate (HR) change synchronously. During the exercise period, both systolic phase and diastolic phase of a radial pulse shorten but the latter is more obvious. The amplitude of the dicrotic notch decreases and even turns negative. Aligning the radial pulse waveforms together, the radial pulse waveforms prior to, during and after exercise coincide with each other except for some details like the tidal wave which fades away during exercise.
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Degradable/non-degradable polymer composites for in-situ tissue engineering small diameter vascular prosthesis application.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Various tissue-engineered vascular grafts have been studied in order to overcome the clinical disadvantages associated with conventional prostheses. However, previous tissue-engineered vascular grafts have possessed insufficient mechanical properties and thus have generally required either preoperative cellular manipulation or the use of bioreactors to improve their performance. In this study, we focused on the concept of in situ cellularization and developed a tissue-engineered vascular graft with degradable/non-degradable polymer composites for arterial reconstruction that would facilitate the renewal of autologous tissue without any pretreatment. Additionally, these composites are designed to improve the mechanical performance of a small-diameter vascular prosthesis scaffold that is made from a flexible membrane of poly(e-caprolactone) (PCL). The PCL scaffold was reinforced by embedding a tubular fabric that was knitted from polyethylene terephthalate (PET) yarns within the freeze-dried composite structure. Adding this knitted fabric component significantly improved the mechanical properties of the composite scaffold, such as its tensile strength and initial modulus, radial compliance, compression recovery, and suture retention force. Finally, this reinforced composite structure is a promising candidate for use as a tissue-engineered scaffold for a future small diameter vascular prosthesis.
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Quantum fluctuations and isotope effects in ab initio descriptions of water.
J Chem Phys
PUBLISHED: 09-15-2014
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Isotope substitution is extensively used to investigate the microscopic behavior of hydrogen bonded systems such as liquid water. The changes in structure and stability of these systems upon isotope substitution arise entirely from the quantum mechanical nature of the nuclei. Here, we provide a fully ab initio determination of the isotope exchange free energy and fractionation ratio of hydrogen and deuterium in water treating exactly nuclear quantum effects and explicitly modeling the quantum nature of the electrons. This allows us to assess how quantum effects in water manifest as isotope effects, and unravel how the interplay between electronic exchange and correlation and nuclear quantum fluctuations determine the structure of the hydrogen bond in water.
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[Advances in plant anthocyanin transport mechanism].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-13-2014
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Anthocyanin biosynthesis is one of the thoroughly studied enzymatic pathways in biology, but little is known about the molecular mechanisms of its final stage: the transport of the anthocyanins into the vacuole. A clear picture of the dynamic trafficking of flavonoids is only now beginning to emerge. So far four different models have been proposed to explain the transport of anthocyanins from biosynthetic sites to the central vacuole, and four types of transporters have been found associated with the transport of anthocyanins: glutathione S-transferase, multidrug resistance-associated protein, multidrug and toxic compound extrusion, bilitranslocase-homologue. The functions of these proteins and related genes have also been studied. Although different models have been proposed, cellular and subcellular information is still lacking for reconciliation of different lines of evidence in various anthocyanin sequestration studies. According to the information available, through sequence analysis, gene expression analysis, subcellular positioning and complementation experiments, the function and location of these transporters can be explored, and the anthocyanin transport mechanism can be better understood.
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Residual metallic impurities within carbon nanotubes play a dominant role in supposedly "metal-free" oxygen reduction reactions.
Chem. Commun. (Camb.)
PUBLISHED: 09-11-2014
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Oxygen reduction reactions (ORRs) are of key importance in the area of electrochemical energy production. The replacement of the Pt industrial standard with heteroatom doped metal-free carbon nanotubes was previously suggested for ORRs. Here we will show that the ORR electrocatalysis on these supposedly metal-free materials is likely in fact due to the presence of residual metallic impurities within the carbon nanotubes and that these impurities play a dominant role.
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Theoretical Sum Frequency Generation Spectroscopy of Peptides.
J Phys Chem B
PUBLISHED: 09-10-2014
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Vibrational sum frequency generation (SFG) has become a very promising technique for the study of proteins at interfaces, and it has been applied to important systems such as anti-microbial peptides, ion channel proteins, and human islet amyloid polypeptide. Moreover, so-called "chiral" SFG techniques, which rely on polarization combinations that generate strong signals primarily for chiral molecules, have proven to be particularly discriminatory of protein secondary structure. In this work, we present a theoretical strategy for calculating protein amide I SFG spectra by combining line-shape theory with molecular dynamics simulations. We then apply this method to three model peptides, demonstrating the existence of a significant chiral SFG signal for peptides with chiral centers, and providing a framework for interpreting the results on the basis of the dependence of the SFG signal on the peptide orientation. We also examine the importance of dynamical and coupling effects. Finally, we suggest a simple method for determining a chromophore's orientation relative to the surface using ratios of experimental heterodyne-detected signals with different polarizations, and test this method using theoretical spectra.
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Effects of different doses of letrozole on the incidence of early-onset ovarian hyperstimulation syndrome after oocyte retrieval.
Syst Biol Reprod Med
PUBLISHED: 09-05-2014
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Abstract We explored the effects of different doses of letrozole on the incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval during in vitro fertilization (IVF) in patients with high-risk OHSS. A total of 88 patients were randomly divided into a control group, and groups treated with 2.5?mg, 5?mg, or 7.5?mg of letrozole. We found that from the fifth day after human chorionic gonadotrophin (hCG) treatment, the E2 level decreased and there were statistical differences between the four groups (p?
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Symptom Improvement in Women After Fecal Incontinence Treatments: A Multicenter Cohort Study of the Pelvic Floor Disorders Network.
Female Pelvic Med Reconstr Surg
PUBLISHED: 09-02-2014
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The study aims were to characterize women with fecal incontinence (FI) and measure changes in FI severity and quality of life 3 and 12 months after treatment.
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Rb suppresses human cone-precursor-derived retinoblastoma tumours.
Nature
PUBLISHED: 09-01-2014
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Retinoblastoma is a childhood retinal tumour that initiates in response to biallelic RB1 inactivation and loss of functional retinoblastoma (Rb) protein. Although Rb has diverse tumour-suppressor functions and is inactivated in many cancers, germline RB1 mutations predispose to retinoblastoma far more strongly than to other malignancies. This tropism suggests that retinal cell-type-specific circuitry sensitizes to Rb loss, yet the nature of the circuitry and the cell type in which it operates have been unclear. Here we show that post-mitotic human cone precursors are uniquely sensitive to Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN and MDM2. Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation. Moreover, Rb-depleted cone precursors formed tumours in orthotopic xenografts with histological features and protein expression typical of human retinoblastoma. These findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. More generally, they demonstrate that cell-type-specific circuitry can collaborate with an initiating oncogenic mutation to enable tumorigenesis.
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Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.
Nat. Med.
PUBLISHED: 08-31-2014
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Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the clinical observation of a patient with ALK fusion-positive lung cancer who had an exceptional response to an insulin-like growth factor 1 receptor (IGF-1R)-specific antibody, we define a therapeutic synergism between ALK and IGF-1R inhibitors. Similar to IGF-1R, ALK fusion proteins bind to the adaptor insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effects of ALK inhibitors. In models of ALK TKI resistance, the IGF-1R pathway is activated, and combined ALK and IGF-1R inhibition improves therapeutic efficacy. Consistent with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients progressing on crizotinib monotherapy. Collectively these data support a role for the IGF-1R-IRS-1 pathway in both ALK TKI-sensitive and ALK TKI-resistant states and provide a biological rationale for further clinical development of dual ALK and IGF-1R inhibitors.
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Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-activatable near-infrared fluorescent probe.
Int. J. Cancer
PUBLISHED: 08-23-2014
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Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distant organ. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pHe ) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors.
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CMTM1_v17 is a novel potential therapeutic target in breast cancer.
Oncol. Rep.
PUBLISHED: 08-20-2014
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Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing 1 (CMTM1) consists of at least 23 alternatively spliced isoforms designated CMTM1_v1-v23. In the present study, we detected CMTM1_v17 expression in multiple human normal and tumor tissues and found that CMTM1_v17 was highly expressed in testis and many tumor tissues including breast tumor. The overexpression of CMTM1_v17 in the breast cancer cell line MDA-MB-231 promoted cell proliferation and resistance to tumor necrosis factor-? (TNF-?)-induced apoptosis. Moreover, siRNA-mediated silencing of CMTM1_v17 sensitized MDA-MB-231 cells to TNF-?-induced apoptosis. We propose that CMTM1_v17 may be a novel potential target for therapy in breast cancer patients. The present study provides insight into a novel mechanism by which CMTM1_v17 enhances cellular proliferation and abrogates TNF-?-induced apoptosis. These findings also have implications for clinical practice as they highlight the potential for therapeutic targeting of CMTM1_v17 for the treatment of breast and other cancers in which CMTM1_v17 impacts cellular proliferation and survival.
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Temperature-dependent photoluminescence in light-emitting diodes.
Sci Rep
PUBLISHED: 08-20-2014
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Temperature-dependent photoluminescence (TDPL), one of the most effective and powerful optical characterisation methods, is widely used to investigate carrier transport and localized states in semiconductor materials. Resonant excitation and non-resonant excitation are the two primary methods of researching this issue. In this study, the application ranges of the different excitation modes are confirmed by analysing the TDPL characteristics of GaN-based light-emitting diodes. For resonant excitation, the carriers are generated only in the quantum wells, and the TDPL features effectively reflect the intrinsic photoluminescence characteristics within the wells and offer certain advantages in characterising localized states and the quality of the wells. For non-resonant excitation, both the wells and barriers are excited, and the carriers that drift from the barriers can contribute to the luminescence under the driving force of the built-in field, which causes the existing equations to become inapplicable. Thus, non-resonant excitation is more suitable than resonant excitation for studying carrier transport dynamics and evaluating the internal quantum efficiency. The experimental technique described herein provides fundamental new insights into the selection of the most appropriate excitation mode for the experimental analysis of carrier transport and localized states in p-n junction devices.
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Hepatitis C virus infection in China: an emerging public health issue.
J. Viral Hepat.
PUBLISHED: 08-18-2014
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Hepatitis C virus now represents a global viral pandemic and is the fourth most commonly reported infectious disease in China. Information on China's national HCV epidemic was limited to cross -sectional seroprevalence studies of special populations, and a national surveillance effort had been launched to inform prevention and control. We analysed novel data from two national databases: (i) China's national medical HCV case report system and (ii) the national disease sentinel surveillance system. Between 1997 and 2012, reporting incidence of medical cases for HCV infection rose from 0.7 to 15.0 cases per 100 000 with the largest burden of disease concentrated among individuals over 35 years of age, rural residents and those tested as part of routine screening. Between 2010 and 2012, disease sentinel surveillance identified the highest HCV seropositive rates among persons who use drugs and haemodialysis patients, with far lower but not negligible rates among sexually active population. The concentration of cases among older age groups is consistent with past studies of age-specific prevalence rates in Asia. Differences across regions and testing modes suggest diverse biological and social forces driving the spread of HCV in China. Surveillance data show ongoing transmission, particularly among persons who use drugs and persons undergoing invasive medical treatments, particularly haemodialysis. Improvements in case detection and data reporting systems will be critical for understanding current drivers of transmission and identifying key areas for prevention.
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Activated microglia contribute to neuronal apoptosis in Toxoplasmic encephalitis.
Parasit Vectors
PUBLISHED: 08-15-2014
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A plethora of evidence shows that activated microglia play a critical role in the pathogenesis of the central nervous system (CNS). Toxoplasmic encephalitis (TE) frequently occurs in HIV/AIDS patients. However, knowledge remains limited on the contributions of activated microglia to the pathogenesis of TE.
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Applicability of the Chinese version of the 16-item Prodromal Questionnaire (CPQ-16) for identifying attenuated psychosis syndrome in a college population.
Early Interv Psychiatry
PUBLISHED: 08-12-2014
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The aim of this study was to examine the reliability, validity, sensitivity and specificity of the Chinese version of the 16-item Prodromal Questionnaire (CPQ-16) for identifying attenuated psychosis syndrome (APS) in a college population.
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Incidence and risk factors for AIDS-related mortality in HIV patients in China: a cross-sectional study.
BMC Public Health
PUBLISHED: 08-11-2014
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To estimate the incidence and risk factors for mortality in HIV-1-infected patients in China.
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Highly sensitive room-temperature surface acoustic wave (SAW) ammonia sensors based on Co?O?/SiO? composite films.
J. Hazard. Mater.
PUBLISHED: 08-10-2014
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Surface acoustic wave (SAW) sensors based on Co3O4/SiO2 composite sensing films for ammonia detection were investigated at room temperature. The Co3O4/SiO2 composite films were deposited onto ST-cut quartz SAW resonators by a sol-gel method. SEM and AFM characterizations showed that the films had porous structures. The existence of SiO2 was found to enhance the ammonia sensing property of the sensor significantly. The sensor based on a Co3O4/SiO2 composite film, with 50% Co3O4 loading, which had the highest RMS value (3.72), showed the best sensing property. It exhibited a positive frequency shift of 3500 Hz to 1 ppm ammonia as well as excellent selectivity, stability and reproducibility at room temperature. Moreover, a 37% decrease in the conductance of the composite film as well as a positive frequency shift of 12,500 Hz were observed when the sensor was exposed to 20 ppm ammonia, indicating the positive frequency shift was derived from the decrease in film conductance.
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Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis.
Cancer Lett.
PUBLISHED: 08-07-2014
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Interferon regulatory factor 8 (IRF8), as a central element of IFN-?-signaling, plays a critical role in tumor suppression. However, its expression and underlying molecular mechanism remain elusive in renal cell carcinoma (RCC). Here, we examined IRF8 expression and methylation in RCC cell lines and primary tumors, and further assessed its tumor suppressive functions. We found that IRF8 was widely expressed in human normal tissues including kidney, but frequently downregulated by promoter methylation in RCC cell lines. IRF8 methylation was detected in 25% of primary tumors, but not in adjacent non-malignant renal tissues, and associated with higher tumor nuclear grade of RCC. Ectopic expression of IRF8 inhibited colony formation and migration abilities of RCC cells, through inducing cell cycle G2/M arrest and apoptosis. IFN-? could induce IRF8 expression in RCC cells, together with increased cleaved-PARP. We further found that IRF8 inhibited expression of oncogenes YAP1 and Survivin, as well as upregulated expression of tumor suppressor genes CASP1, p21 and PTEN. Collectively, our data demonstrate that IRF8 as a functional tumor suppressor is frequently methylated in RCC, and IRF8-mediated interferon signaling is involved in RCC pathogenesis.
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Genetic convergence in the adaptation of dogs and humans to the high-altitude environment of the tibetan plateau.
Genome Biol Evol
PUBLISHED: 08-06-2014
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The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau.
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Highly confined water: two-dimensional ice, amorphous ice, and clathrate hydrates.
Acc. Chem. Res.
PUBLISHED: 08-04-2014
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Understanding phase behavior of highly confined water, ice, amorphous ice, and clathrate hydrates (or gas hydrates), not only enriches our view of phase transitions and structures of quasi-two-dimensional (Q2D) solids not seen in the bulk phases but also has important implications for diverse phenomena at the intersection between physical chemistry, cell biology, chemical engineering, and nanoscience. Relevant examples include, among others, boundary lubrication in nanofluidic and lab-on-a-chip devices, synthesis of antifreeze proteins for ice-growth inhibition, rapid cooling of biological suspensions or quenching emulsified water under high pressure, and storage of H2 and CO2 in gas hydrates. Classical molecular simulation (MD) is an indispensable tool to explore states and properties of highly confined water and ice. It also has the advantage of precisely monitoring the time and spatial domains in the sub-picosecond and sub-nanometer scales, which are difficult to control in laboratory experiments, and yet allows relatively long simulation at the 10(2) ns time scale that is impractical with ab initio molecular dynamics simulations. In this Account, we present an overview of our MD simulation studies of the structures and phase behaviors of highly confined water, ice, amorphous ice, and clathrate, in slit graphene nanopores. We survey six crystalline phases of monolayer (ML) ice revealed from MD simulations, including one low-density, one mid-density, and four high-density ML ices. We show additional supporting evidence on the structural stabilities of the four high-density ML ices in the vacuum (without the graphene confinement), for the first time, through quantum density-functional theory optimization of their free-standing structures at zero temperature. In addition, we summarize various low-density, high-density, and very-high-density Q2D bilayer (BL) ice and amorphous ice structures revealed from MD simulations. These simulations reinforce the notion that the nanoscale confinement not only can disrupt the hydrogen bonding network in bulk water but also can allow satisfaction of the ice rule for low-density and high-density Q2D crystalline structures. Highly confined water can serve as a generic model system for understanding a variety of Q2D materials science phenomena, for example, liquid-solid, solid-solid, solid-amorphous, and amorphous-amorphous transitions in real time, as well as the Ostwald staging during these transitions. Our simulations also bring new molecular insights into the formation of gas hydrate from a gas and water mixture at low temperature.
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Pre-exposure prophylaxis of HIV: A right way to go or a long way to go?
Artif Cells Nanomed Biotechnol
PUBLISHED: 08-01-2014
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Antiretroviral drugs are being tried as candidates for the pre-exposure prophylaxis (PrEP) against HIV for a considerable period, due to their potential for immediate inhibition of viral replication. Discrepancies in the findings called for a critical review of the relevant efforts and their outcomes. A systematic literature search identified 143 eligible articles of which only 5 reported complete findings while another 11 were still on-going. Observed moderate efficacy and good safety profile seemed to identify PrEP as a promising step for minimizing the spread of HIV to relatively unaffected population and controlling the epidemic among high risk population groups. But the duration of this efficacy was found to depend heavily on the availability, adherence and other related issues like cost, political commitment, ethical consideration etc. To prevent potential cultural and behavioral modifications, proper pre-administration counseling also seemed critical for the success of PrEP as a cost-effective intervention with adequate coverage.
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Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients.
Oncol. Rep.
PUBLISHED: 07-14-2014
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Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Cigarette smoking is the number one risk factor which is attributed to more than four out of five cases of lung cancers. The prognostic impact of cell cycle regulation-associated tumor suppressors including p53 and p21 for NSCLC is still controversial. In the present study, we examined p53 and p21 expression using immunoblotting in tumor and adjacent non-cancerous tissues from NSCLC patients. Moreover, tissue microarrays (TMAs) including 150 specimens was used to examine p53 and p21 expression by immunohistochemical staining (IHC). The association between p53/p21 and various clinicopathological characteristics was evaluated. Kaplan-Meier overall survival was used to analyze the association between p53/p21 expression and prognosis of NSCLC patients, as well as the association of cigarette smoking with p53/p21 expression and prognosis. The results of the immunoblotting showed that expression of p53 and p21 in tumor tissues was significantly higher than that in the matched adjacent non-cancerous tissues (P<0.001 and P<0.05, respectively). The IHC results showed that 50.67% of the cases had high expression of p21; however, the percentage of patients having high expression of p53 was 31.3%. Univariate and Cox regression models were used to evaluate the factors related to prognosis with p53 and p21 expression. Multivariate analysis indicated that p53 expression was an independent prognostic factor for NSCLC (P=0.005), while p21 could not serve as an independent prognostic factor (P=0.123). In addition, smoking history was closely related to lung cancer risk (P=0.041), but could not be an independent assessment factor (P=0.740). In this study, we further demonstrated the association of p53/p21 expression and cigarette smoking. Our results suggest that cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis. The combination of p53/p21 expression and smoking history may be a useful biomarker for tumor progression and prognosis of NSCLC patients.
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The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response.
Dis. Markers
PUBLISHED: 07-10-2014
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Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254-3.393; P = 0.004) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411-0.928; P = 0.020) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (P = 0.021). Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings.
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Inhibiting effect of electroacupuncture at zusanli on early inflammatory factor levels formed by postoperative abdominal adhesions.
Evid Based Complement Alternat Med
PUBLISHED: 07-07-2014
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We observed the inhibitive effect of electroacupuncture (EA) at Zusanli on inflammatory mediators of postoperative intra-abdominal adhesions to find out the relationship between EA and the cholinergic anti-inflammatory pathway. Sixty-four rats were divided into 8 groups (A-H, each = 8): A = sham control; B = abdominal adhesions model; C = abdominal adhesions plus EA; D = sham acupoint control; E = abdominal adhesions plus vagotomy; F = abdominal adhesions plus EA after vagotomy; G = abdominal adhesions plus ?-bungarotoxin (BGT); and H = abdominal adhesions plus EA after ?-BGT. ?-BGT (1??g/kg) was injected into the abdominal cavity after surgery, and the bilateral celiac vagotomy was done during the surgery. On the third day the levels of inflammatory mediators (TNF-?, nitric oxide (NO), and nitric oxide synthase (NOS)) in tissues were evaluated. The abdominal adhesion groups developed obvious edema. Compared with sham control, the abdominal adhesion resulted in a significant elevation of inflammatory mediators. EA lowered the elevated levels of inflammatory mediators significantly; EA plus ?-BGT and vagotomy showed less anti-inflammatory effects. The activation of the cholinergic anti-inflammatory pathway might be one of the mechanisms of EA at Zusanli acupoints to exert the anti-inflammatory effects.
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Allelic variation within the S-adenosyl-L-homocysteine hydrolase gene family is associated with wood properties in Chinese white poplar (Populus tomentosa).
BMC Genet.
PUBLISHED: 06-20-2014
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S-adenosyl-l-homocysteine hydrolase (SAHH) is the only eukaryotic enzyme capable of S-adenosyl-l-homocysteine (SAH) catabolism for the maintenance of cellular transmethylation potential. Recently, biochemical and genetic studies in herbaceous species have obtained important discoveries in the function of SAHH, and an extensive characterization of SAHH family in even one tree species is essential, but currently lacking.
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RNA activation: Promise as a new weapon against cancer.
Cancer Lett.
PUBLISHED: 06-19-2014
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RNA activation (RNAa) is a novel mechanism in which short RNA duplexes, referred to as small activating RNAs (saRNAs), enable sequence-specific gene activation capable of lasting up to 2 weeks. RNAa was named in contrast to RNA interference (RNAi). Although many mysteries remain, increasing evidence demonstrates that RNAa not only provides a novel mechanism for the study of gene function and regulation, but also holds exciting potential for clinical translation to therapeutic modality against cancers. In this review, we will focus on the potential applications of RNAa in cancer studies and therapeutics.
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Molecular cloning and expression analysis of tea plant aquaporin (AQP) gene family.
Plant Physiol. Biochem.
PUBLISHED: 06-13-2014
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The role of aquaporin proteins (AQPs) has been extensively studied in plants. However, the information of AQPs in the tea plant (Camellia sinensis) is unclear. In this manuscript, we isolated 20 full-length AQP cDNAs from the tea plant, and these sequences were classified into five subfamilies. The genes in these subfamilies displayed differential expression profiles in the studied tissues. The CsAQP expression patterns correlated with flower development and opening (FDO) and bud endodormancy (BED). To better understand the short-term expression patterns of CsAQPs in response to abiotic stress, tea plants were treated with abscisic acid (ABA), cold, salt or drought. ABA treatment down-regulated the expression of various CsAQPs. Salt up-regulated the transcription of most CsAQP genes. Cold treatment resulted in a complicated transcriptional regulation pattern for various CsAQPs. The expression of CsAQPs, especially plasma membrane intrinsic proteins (CsPIPs) and tonoplast intrinsic proteins (CsTIPs), was induced by drought and remained relatively high after rehydration in leaves, whereas almost all the CsAQPs were repressed in roots. Our results highlighted the diversity of CsAQPs in the tea plant and demonstrated that the CsPIP and CsTIP genes play a vital role in the stress response as well as in FDO and BED. Furthermore, certain CsSIPs (small basic intrinsic proteins), CsNIPs (NOD26-like intrinsic proteins) and CsXIPs (X intrinsic proteins) may regulate BED and FDO.
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Volumetric-modulated arc therapy for oropharyngeal carcinoma: A dosimetric and delivery efficiency comparison with static-field IMRT.
Phys Med
PUBLISHED: 06-04-2014
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The purpose of this study is to evaluate the treatment plan adequacy and delivery efficiency among volumetric-modulated arc therapy (VMAT) with one or two arcs and the conventional static-field dynamic multileaf collimator (dMLC) intensity-modulated radiation therapy (IMRT) in patients undergoing oropharyngeal carcinoma. Fifteen patient cases were included in this investigation. Each of the cases was planned using step-and-shoot IMRT, VMAT with a single arc (Arc1) and VMAT with double arcs (Arc2). A two-dose level prescription for planning target volumes (PTVs) was delivered with 70 Gy/56 Gy in 30 fractions. Comparisons were performed of the dose-volume histograms (DVH) for PTVs, the DVH for organs at risk (OARs), the monitor units per fraction (MU/fx), and delivery time. IMRT and Arc2 achieved similar target coverage, but superior to Arc1. Apart from the oral cavity, Arc1 showed no advantage in sparing of OARs compared with IMRT, while Arc2 obtained equivalent or better sparing of OARs among the three techniques. VMAT reduced MU/fx and shortened delivery time remarkably compared with IMRT. Our results demonstrated that for oropharyngeal cases, Arc2 can achieve superior target coverage and normal tissue sparing, as well as a significant reduction in treatment time.
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Meta-analyses of the effect of CYP1A1 and CYP2D6 polymorphisms on the risk of head and neck squamous cell carcinoma.
Oncol Res Treat
PUBLISHED: 05-30-2014
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CYP1A1 and CYP2D6 are important genes encoding enzymes involved in the metabolism of toxic chemicals and carcinogens. However, inconclusive results for the association between CYP1A1 and CYP2D6 polymorphisms and the risk of head and neck squamous cell carcinoma (HNSCC) have been reported. We conducted a meta-analysis to evaluate the association of CYP1A1 and CYP2D6 polymorphisms with the risk of HNSCC.
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Differential diagnosis between hepatic metastases and benign focal lesions using DWI with parallel acquisition technique: a meta-analysis.
Tumour Biol.
PUBLISHED: 05-24-2014
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We aim to investigate the diagnostic capability of diffusion-weighted imaging using parallel acquisition technique for the differentiation between hepatic metastases and benign focal lesions with a meta-analysis. The meta-analysis included a total of 858 hepatic metastases and 440 benign liver lesions from nine studies. The pooled sensitivity and specificity of diffusion-weighted imaging (DWI) were 0.87 (95 % CI, 0.84-0.89) and 0.90 (95 % CI, 0.87-0.93), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 8.50 (95 % CI, 4.97-14.52) and 0.17 (95 % CI, 0.11-0.26), respectively. The P value for ? (2) heterogeneity for all pooled estimates was <0.05. From the fitted summary receiver operating characteristics (SROC), the area under the curve (AUC) and Q* index were 0.95 and 0.88, respectively. Publication bias is not present (t?=?-0.76, P?=?0.471). The meta-regression analysis indicated that evaluated covariates included patient number, patient population, mean age, maximum of b factor, number of cysts, number of hemangiomas, and field were not sources of heterogeneity (all P value >0.05). Diffusion-weighted imaging was useful for differentiation between hepatic metastases and benign focal lesions. The diffusion characteristics of the benign hepatocellular lesions, including cases of focal nodular hyperplasia (FNH) and adenoma, have rarely been reported and need further studies. The diagnostic capability of DWI with parallel acquisition technique for differentiation between metastases and benign hepatic focal lesions might be overestimated.
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Acupuncture Point Laterality: Investigation of Acute Effects of Quchi (LI11) in Patients with Hypertension Using Heart Rate Variability.
Evid Based Complement Alternat Med
PUBLISHED: 05-12-2014
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Hypertension is one of the major risk factors for cardiovascular disease worldwide. Over 70% of the patients use antihypertensive drugs, so nonpharmacological treatments in addition to the medication are important. Our goal was to investigate acupuncture treatment on the Quchi acupoint using heart rate (HR) and heart rate variability (HRV) and to find out whether there is a laterality in acute effects. Sixty hypertensive patients (36 female, 24 male; mean age ±?SD?55.8?±?9.7 years) were randomly assigned to two manual needle acupuncture groups (group A: left Quchi (LI11) acupoint, group B: right Quchi acupoint). There was a significant (P < 0.05) decrease in HR immediately after inserting and stimulating the needle at the left and the right Quchi acupuncture point. In contrast, total HRV increased immediately after inserting the needle, but this increase was significant only towards the end of the stimulation phase and after removing the needle. There were some differences between stimulation of the left and right Quchi acupoint, but they remained insignificant. This study provides evidence that there is a beneficial effect on heart rate variability in patients with hypertension and that there are some effects of laterality of the acupoint Quchi.
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Multiresidue analysis of over 200 pesticides in cereals using a QuEChERS and gas chromatography-tandem mass spectrometry-based method.
Food Chem
PUBLISHED: 05-08-2014
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A simple and high-throughput multiresidue pesticide analysis method was developed and validated for 219 pesticides in cereals (corn, wheat flour and rice) based on QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure combined with gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). Different buffer system (acetate- and citrate-buffered) and sample to solvent ratios (sample amount) were compared in the modified QuEChERS procedure to get better recovery and clean-up results. The limits of quantification (LOQ) ranged between 5 and 50?gkg(-)(1), and for the majority of the pesticides the LOQ were 5?gkg(-)(1), which were below the regulatory maximum residue limits. The coefficient of determination (r(2)) was >0.99 within the calibration linearity range of 2-200?gkg(-)(1) for the majority of the pesticides. Most recoveries at 5, 10, 20, 50, 100 and 200?gkg(-)(1) were in the range 70-120% (n=6) with associated RSDs<20% indicating satisfactory accuracy.
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Frequent KIT mutations in human gastrointestinal stromal tumors.
Sci Rep
PUBLISHED: 05-07-2014
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Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.
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Mouse calvarial defect Model: An approach for the micro-tomographic evaluation of polymer scaffolds.
Microsc. Res. Tech.
PUBLISHED: 04-18-2014
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The ability of bone repair scaffolds to form bone is traditionally evaluated using cell culture and animal experiments. Mouse calvarial organ culture maintains the natural cell-to-cell and cell-to-matrix relationships as well as the anatomical order, and this model has been used to study the biological behavior of intramembranous bones. The aim of this study was to evaluate the potential of mouse calvarial organ culture to be used as an in vitro model to study the bone regenerative ability of bone repair polymer scaffolds. Critical size defects (CSD) were created in the parietal bones. Electrospun poly(?-caprolactone) scaffolds were placed into one group of defects. The remaining defects served as a control. The bones were cultured for 38 days and analyzed with ?CT, phase-contrast microscopy, dissecting microscopy, scanning electron microscopy, and energy-dispersive X-ray analyses. This organ culture technique is easily available and could permit researchers to quickly establish a valuable database of candidate bone repair scaffolds. Microsc. Res. Tech., 2014. © 2014 Wiley Periodicals, Inc.
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Gold(I)-catalyzed furan-yne cyclizations involving 1,2-rearrangement: efficient synthesis of functionalized 1-naphthols and its application to the synthesis of wailupemycin?G.
Chemistry
PUBLISHED: 04-16-2014
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Gold-catalyzed cascade cyclization/1,2-rearrangement of 1-(2-furanyl)phenyl propargyl alcohols has been developed, which provides a rapid and efficient access to multisubstituted 1-naphthols bearing an enal or enone moiety with high stereoselectivity. The (Z)- or (E)-stereochemistry can be easily controlled by choosing protected- or non-protected substrates. The utility of the methodology has been illustrated in the first total synthesis of wailupemycin?G.
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Quantification of endogenous brassinosteroids in sub-gram plant tissues by in-line matrix solid-phase dispersion-tandem solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry.
J Chromatogr A
PUBLISHED: 04-15-2014
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A matrix solid-phase dispersion (MSPD)-tandem mixed mode anion exchange (MAX)-mixed mode cation exchange (MCX) solid phase extraction-high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for quantification of six endogenous brassinosteroids (BRs) (24-epibrassinolide, 24-epicastasterone, 6-deoxo-24-epicastasterone, dolichosterone, teasterone and typhasterol) in rice plant tissues. Non-polar interferences were removed effectively by C8 dispersant used in MSPD, while the following tandem MAX-MCX process facilitated the elimination of polar and ionizable compounds. The weak reversed-phase retention feature of MAX-MCX leaded to good compatibility of the elution solvents in the in-line coupled MSPD-MAX-MCX system. This system was optimized for extraction and purification of BRs in plant samples. The effects of the type of solid phase, the elution solvent, the extraction temperature and the clean-up material were studied. Before HPLC separation, BRs purified were derivatized by m-aminophenylboronic acid to enhance the sensitivity of MS/MS to BRs. Compared with traditional liquid-liquid extraction and solid phase extraction (LLE-SPE), the proposed MSPD-MAX-MCX method showed higher extraction efficiency, lower matrix effect, and advantages of easy manipulation and time-saving. The in-line MSPD-MAX-MCX coupled with HPLC-MS/MS method provided a linear response over two orders of magnitude of BRs concentration with correlation coefficients above 0.9982, limits of detection between 0.008 and 0.04ngmL(-1), relative standard deviations (RSDs) below 29.4%, and recoveries above 77.8%. The proposed method has been successfully applied to analysis of endogenous BRs in rice plant at booting stage and maturity stage.
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MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma.
Mol. Cancer
PUBLISHED: 04-05-2014
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The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown.
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Electrocardiogram characteristics prior to in-hospital cardiac arrest.
J Clin Monit Comput
PUBLISHED: 04-02-2014
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Survival after in-hospital cardiac arrest (I-HCA) remains < 30 %. There is very limited literature exploring the electrocardiogram changes prior to I-HCA. The purpose of the study was to determine demographics and electrocardiographic predictors prior to I-HCA. A retrospective study was conducted among 39 cardiovascular subjects who had cardiopulmonary resuscitation from I-HCA with initial rhythms of pulseless electrical activity (PEA) and asystole. Demographics including medical history, ejection fraction, laboratory values, and medications were examined. Electrocardiogram (ECG) parameters from telemetry were studied to identify changes in heart rate, QRS duration and morphology, and time of occurrence and location of ST segment changes prior to I-HCA. Increased age was significantly associated with failure to survive to discharge (p < 0.05). Significant change was observed in heart rate including a downtrend of heart rate within 15 min prior to I-HCA (p < 0.05). There was a significant difference in heart rate and QRS duration during the last hour prior to I-HCA compared to the previous hours (p < 0.05). Inferior ECG leads showed the most significant changes in QRS morphology and ST segments prior to I-HCA (p < 0.05). Subjects with an initial rhythm of asystole demonstrated significantly greater ECG changes including QRS morphology and ST segment changes compared to the subjects with initial rhythms of PEA (p < 0.05). Diagnostic ECG trends can be identified prior to I-HCA due to PEA and asystole and can be further utilized for training a predictive machine learning model for I-HCA.
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Sequential expression of long noncoding RNA as mRNA gene expression in specific stages of mouse spermatogenesis.
Sci Rep
PUBLISHED: 04-02-2014
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Many long noncoding RNA (lncRNA) species have been identified in gametes. However, the biogenesis and function of other categories of lncRNAs in gametes is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in spermatogonial stem cells (SSC), type A spermatogonia (A), pachytene spermatocytes (PS) and round spermatids (RS) by microarray analysis. We analyze the total expression of lncRNA/mRNA in these four germ cells and found that the maximum number of lncRNAs expression is in A (22127), and the minimum is in PS (14456). Also, the maximum number of mRNAs is in A (19923), and the minimum is in PS (13941). Furthermore, the trend in the number of specific lncRNAs was similar to the number of specific mRNAs in each type of germ cells (e.g., maximum in A and minimum in PS). The trend in the number of lncRNAs was similar to the number of mRNAs in two continued types of germ cells (e.g., maximum in SSC to A and minimum in PS to RS). The correlation analysis showed a high correlation coefficient of lncRNAs/mRNAs expression (R = 0.992). The results suggested that the sequential expression of long noncoding RNA as mRNA gene expression exhibits coordinated changes in male spermatogenesis.
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Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid ?-peptide in rats.
Neurosci Bull
PUBLISHED: 03-19-2014
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Amyloid ?-peptide (A?) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of A?. However, the mechanism(s) by which HN exerts its neuroprotection against A?-induced ADlike pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre- and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by A?1-42. HN also attenuated A?1-42-induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by A?1-42. These findings provide novel mechanisms of action for the ability of HN to protect against A?1-42-induced AD-like pathological changes and memory deficits.
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Controlled-release naringin nanoscaffold for osteoporotic bone healing.
Dent Mater
PUBLISHED: 03-01-2014
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Osteoporosis is one of the most common bone diseases in the world and results from an imbalance of bone cell functions. In the process of guided bone regeneration, osteoporosis weakens the bonding strength between scaffold and bone. Naringin is evidenced to be effective for the treatment of osteoporosis and bone resorption and the aim was to explore methods and benefits of its incorporation.
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The characteristics of coarse particulate matter air pollution associated with alterations in blood pressure and heart rate during controlled exposures.
J Expo Sci Environ Epidemiol
PUBLISHED: 02-28-2014
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Although fine particulate matter (PM) air pollution <2.5??m in aerodynamic diameter (PM2.5) is a leading cause of global morbidity and mortality, the potential health effects of coarse PM (2.5-10??m in aerodynamic diameter; PM10-2.5) remain less clearly understood. We aimed to elucidate the components within coarse PM most likely responsible for mediating these hemodynamic alterations. Thirty-two healthy adults (25.9±6.6 years) were exposed to concentrated ambient coarse PM (CAP) (76.2±51.5??g/m(3)) and filtered air (FA) for 2?h in a rural location in a randomized double-blind crossover study. The particle constituents (24 individual elements, organic and elemental carbon) were analyzed from filter samples and associated with the blood pressure (BP) and heart rate (HR) changes occurring throughout CAP and FA exposures in mixed model analyses. Total coarse PM mass along with most of the measured elements were positively associated with similar degrees of elevations in both systolic BP and HR. Conversely, total PM mass was unrelated, whereas only two elements (Cu and Mo) were positively associated with and Zn was inversely related to diastolic BP changes during exposures. Inhalation of coarse PM from a rural location rapidly elevates systolic BP and HR in a concentration-responsive manner, whereas the particulate composition does not appear to be an important determinant of these responses. Conversely, exposure to certain PM elements may be necessary to trigger a concomitant increase in diastolic BP. These findings suggest that particulate mass may be an adequate metric of exposure to predict some, but not all, hemodynamic alterations induced by coarse PM mass.Journal of Exposure Science and Environmental Epidemiology advance online publication, 17 September 2014; doi:10.1038/jes.2014.62.
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Pentacyclic Triterpenoids from Spikes of Prunella vulgaris L. Inhibit Glycogen Phosphorylase and Improve Insulin Sensitivity in 3T3-L1 Adipocytes.
Phytother Res
PUBLISHED: 02-19-2014
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Phytochemical investigation of methanol extract from the spikes of Prunella vulgaris L. led to the isolation of two new pentacyclic triterpenoid glycosides Vulgasides I (1) and II (2) along with 13 known compounds (3-15). Their structures were established on the basis of nuclear magnetic resonance (1D and 2D) and mass spectroscopic data analysis. All the isolated compounds were screened for glycogen phosphorylase inhibitory activity and also evaluated for their effect on insulin sensitivity in 3T3-L1 adipocytes. Two new compounds (1, 2) did not demonstrate the glycogen phosphorylase inhibitory activity, but other compounds (3-11) exhibited varying degrees of glycogen phosphorylase inhibitory activity with IC50 values in the range from 30.69 to 68.85??M. Compounds 3, 6, 7, 11, and 13 demonstrated markedly increased insulin-mediated glucose consumption in 3T3-L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd.
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Elevated p53 expression levels correlate with tumor progression and poor prognosis in patients exhibiting esophageal squamous cell carcinoma.
Oncol Lett
PUBLISHED: 01-26-2014
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Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer and one of the most aggressive types of malignancy, with a high rate of mortality. Early diagnosis and treatment may improve the prognosis of ESCC and, thus, survival rates. As a significant tumor suppressor, p53 is closely associated with apoptosis and the differentiation of cancer cells. The present study evaluated the expression levels of the p53 protein and the clinical significance in patients presenting with ESCC. The p53 protein expression level of 64 paired ESCC and tumor-adjacent normal tissues was evaluated using western blot analysis. In addition, immunohistochemistry (IHC) was performed to detect the p53 expression level in specimens from 118 paraffin-embedded cancerous tissues. The correlation of the p53 expression level with the clinicopathological parameters and prognosis of the ESCC patients was also analyzed. The p53 protein was identified to be highly expressed in the ESCC tissue, with western blot analysis demonstrating that the expression level of p53 in the cancerous tissue was 1.89 times that of the tumor-adjacent normal tissue (P<0.001); furthermore, IHC indicated that there was a marked positive expression of p53 in the ESCC tissue (49.15%). The expression level of p53 protein was identified to be significantly correlated with the tumor grade (P<0.001), N stage (P=0.010). Additionally, the higher level of p53 expression was found to be associated with a poor survival rate in the ESCC patients (P=0.0404). The univariate analysis showed that the survival time of patients was significantly correlated with the T stage (RR=3.886, P<0.001), N stage (lymph node metastasis; RR=3.620, P<0.001) and TNM stage (RR=3.576, P<0.001). Furthermore, the multivariate analysis revealed that the T stage (RR=3.988, P<0.001) and N stage (RR=4.240, P=0.004) significantly influenced the overall survival of the ESCC patients.
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On-line coupling of macroporous resin column chromatography with direct analysis in real time mass spectrometry utilizing a surface flowing mode sample holder.
Anal. Chim. Acta
PUBLISHED: 01-25-2014
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A surface flowing mode sample holder was designed as an alternative sampling strategy for direct analysis in real time mass spectrometry (DART-MS). With the sample holder, the on-line coupling of macroporous resin column chromatography with DART-MS was explored and the new system was employed to monitor the column chromatography elution process of Panax notoginseng. The effluent from macroporous resin column was first diluted and mixed with a derivatization reagent on-line, and the mixture was then directly transferred into the ionization region of DART-MS by the sample holder. Notoginsenosides were methylated and ionized in a metastable helium gas stream, and was introduced into MS for detection. The on-line system showed reasonable repeatability with a relative standard deviation of 12.3% for the peak area. Three notoginsenosides, i.e. notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1, were simultaneously determined during the eluting process. The alteration of the chemical composition in the effluent was accurately identified in 9 min, agreeing well with the off-line analysis. The presented technique is more convenient compared to the traditional UPLC method. These results suggest that the surface flowing mode DART-MS has a good potential for the on-line process monitoring in the pharmaceutical industry.
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Qualitative and quantitative analysis of enantiomers by mass spectrometry: application of a simple chiral chloride probe via rapid in-situ reaction.
Anal. Chim. Acta
PUBLISHED: 01-15-2014
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A tandem mass spectrometry method for high-sensitivity qualitative and quantitative discrimination of chiral amino compounds is conducted. The method is based on a chemical derivation process that uses a simple reagent, L-1-(phenylsulfonyl)pyrrolidine-carbonyl chloride, as the probe. The method is applicable in both organic solutions and biological conditions. Twenty-one pairs of enantiomer containing amino acids, amino alcohols, and amines are used to produce diastereomers using the probe via in situ reaction for 20 s at room temperature. The resulting diastereomers are successfully recognized based on the relative peak intensities of their fragments in positive mode, with the chiral recognition ability values ranging from 0.35 to 3.83. The L/D ratio of Pro spiked at different concentrations (enantiomeric excess) in both acetonitrile and dog plasma is determined by establishing calibration curves. This method achieves a lower limit of quantification of 50 pmol in analyzing amino acids using an extract ion chromatograph. The relative standard deviation for both qualitative and quantitative results is <5%. Thus, the present method is demonstrated as a new and practical technique of rapidly and sensitively determining enantiomers of amino compounds.
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De qi, a threshold of the stimulus intensity, elicits the specific response of acupoints and intrinsic change of human brain to acupuncture.
Evid Based Complement Alternat Med
PUBLISHED: 01-12-2014
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Objectives.??De qi is the subjective constellation of sensations perceived by the acupuncturists and patients as described in several literatures, but the absence of quantitative evaluation methods in de qi restricts the use of acupuncture treatment widely in the world. In the present study, we tried to investigate the intrinsic property of de qi is and how evaluate it quantitatively. Methods. 30 healthy adult volunteers were determined to investigate intrinsic changes in the human body after acupuncture with de qi. Results. Acupuncture treatment with de qi apparently increased acupoint blood flow, tissue displacement, and the amplitude of myoelectricity after de qi on acupoints. Furthermore, acupuncture treatment induced fMRI signal increase/decrease in different brain regions although no significant change in electroencephalography. Interpretation. The intrinsic change of the subjects representing the specific response of acupoints and human brain to acupuncture indicated that de qi might be evaluated quantitatively by those above aspects, which facilitated the confirmation in validity and propagation of this treatment modality widely in the world.
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Spatial analysis on hepatitis C virus infection in mainland china: from 2005 to 2011.
PLoS ONE
PUBLISHED: 01-01-2014
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The burden of Hepatitis C virus (HCV) has become more and more considerable in China. A macroscopic spatial analysis of HCV infection that can provide scientific information for further intervention and disease control is lacking.
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Tumor-associated macrophages promote tumor cell proliferation in nasopharyngeal NK/T-cell lymphoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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To explore the relationship between the number of tumor-associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T-cell lymphoma.
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