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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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Hydrodynamic interaction of two deformable drops in confined shear flow.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 09-16-2014
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We investigate hydrodynamic interaction between two neutrally buoyant circular drops in a confined shear flow based on a computational fluid dynamics simulation using the volume-of-fluid method. The rheological behaviors of interactive drops and the flow regimes are explored with a focus on elucidation of underlying physical mechanisms. We find that two types of drop behaviors during interaction occur, including passing-over motion and reversing motion, which are governed by the competition between the drag of passing flow and the entrainment of reversing flow in matrix fluid. With the increasing confinement, the drop behavior transits from the passing-over motion to reversing motion, because the entrainment of the reversing-flow matrix fluid turns to play the dominant role. The drag of the ambient passing flow is increased by enlarging the initial lateral separation due to the departure of the drop from the reversing flow in matrix fluid, resulting in the emergence of passing-over motion. In particular, a corresponding phase diagram is plotted to quantitatively illustrate the dependence of drop morphologies during interaction on confinement and initial lateral separation.
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[Role of zinc finger protein 1 in rat liver fibrosis and as related to TGFb expression].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-01-2014
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To determine the role of zinc finger protein 1 (ZEB 1) in liver fibrosis and in regards to expression of the tumor growth factor-beta (TGFb) signaling factor using a rat model system.
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Physiological, biochemical and proteomics analysis reveals the adaptation strategies of the alpine plant Potentilla saundersiana at altitude gradient of the Northwestern Tibetan Plateau.
J Proteomics
PUBLISHED: 08-30-2014
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This study presents an analysis of leave and rood morphology, biochemical and proteomics approach as adaptation strategies of the alpine plant Potentilla saundersiana in an altitude gradient. Several plant physiological parameter, including root and leaf architecture, leaf photosynthesis capacity, specific leaf area (SLA) and leaf nitrogen concentration, histology and microscopy, anthocyanin and proline contents, antioxidant enzyme activity assay, in-gel enzyme activity staining, H2O2 and O2(-) content, immunoblotting, auxin and strigolactone content and proteomics analysis were evaluated at five different altitudes. P. saundersiana modulated the root architecture and leaf phenotype to enhance adaptation to alpine environmental stress through mechanisms that involved hormone synthesis and signal transduction, particularly the cross-talk between auxin and strigolactone. Furthermore, an increase of antioxidant proteins and primary metabolites as a response to the alpine environment in P. saundersiana was observed. Proteins associated with the epigenetic regulation of DNA stability and post-translational protein degradation was also involved in this process. Based on these findings, P. saundersiana uses multiple strategies to adapt to the high-altitude environment of the Alpine region.
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Structural Definition of an Antibody-Dependent Cellular Cytotoxicity Response Implicated in Reduced Risk for HIV-1 Infection.
J. Virol.
PUBLISHED: 08-27-2014
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The RV144 vaccine trial implicated epitopes in the C1 region of gp120 (A32-like epitopes) as targets of potentially protective antibody-dependent cellular cytotoxicity (ADCC) responses. A32-like epitopes are highly immunogenic, as infected or vaccinated individuals frequently produce antibodies specific for these determinants. Antibody titers, as measured by enzyme-linked immunosorbent assay (ELISA) against these epitopes, however, do not consistently correlate with protection. Here, we report crystal structures of CD4-stabilized gp120 cores complexed with the Fab fragments of two nonneutralizing, A32-like monoclonal antibodies (MAbs), N5-i5 and 2.2c, that compete for antigen binding and have similar antigen-binding affinities yet exhibit a 75-fold difference in ADCC potency. We find that these MAbs recognize overlapping epitopes formed by mobile layers 1 and 2 of the gp120 inner domain, including the C1 and C2 regions, but bind gp120 at different angles via juxtaposed VH and VL contact surfaces. A comparison of structural and immunological data further showed that antibody orientation on bound antigen and the capacity to form multivalent antigen-antibody complexes on target cells were key determinants of ADCC potency, with the latter process having the greater impact. These studies provide atomic-level definition of A32-like epitopes implicated as targets of protective antibodies in RV144. Moreover, these studies establish that epitope structure and mode of antibody binding can dramatically affect the potency of Fc-mediated effector function against HIV-1. These results provide key insights for understanding, refining, and improving the outcome of HIV vaccine trials, in which relevant immune responses are facilitated by A32-like elicited responses.
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Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo.
J. Virol.
PUBLISHED: 08-20-2014
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Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody transfer would prevent HIV-1 transmission in humans. To increase the protective efficacy of such monoclonal antibodies, we employed next-generation sequencing, computational bioinformatics, and structure-guided design to enhance the neutralization potency and breadth of VRC01, an antibody that targets the CD4 binding site of the HIV-1 envelope. One variant, VRC07-523, was 5- to 8-fold more potent than VRC01, neutralized 96% of viruses tested, and displayed minimal autoreactivity. To compare its protective efficacy to that of VRC01 in vivo, we performed a series of simian-human immunodeficiency virus (SHIV) challenge experiments in nonhuman primates and calculated the doses of VRC07-523 and VRC01 that provide 50% protection (EC50). VRC07-523 prevented infection in NHPs at a 5-fold lower concentration than VRC01. These results suggest that increased neutralization potency in vitro correlates with improved protection against infection in vivo, documenting the improved functional efficacy of VRC07-523 and its potential clinical relevance for protecting against HIV-1 infection in humans.
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Salicylic acid alleviates cadmium-induced inhibition of growth and photosynthesis through upregulating antioxidant defense system in two melon cultivars (Cucumis melo L.).
Protoplasma
PUBLISHED: 08-10-2014
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Cadmium (Cd) is a widespread toxic heavy metal that usually causes deleterious effects on plant growth and development. Salicylic acid (SA), a naturally existing phenolic compound, is involved in specific responses to various environmental stresses. To explore the role of SA in the tolerance of melon (Cucumis melo L.) to Cd stress, the influence of SA application on the growth and physiological processes was compared in the two melon cultivars Hamilv (Cd-tolerant) and Xiulv (Cd-sensitive) under Cd stress. Under 400-?M Cd treatment, Hamilv showed a higher biomass accumulation, more chlorophyll (Chl), greater photosynthesis, and less oxidative damage compared to Xiulv. Foliar spraying of 0.1 mM SA dramatically alleviated Cd-induced growth inhibition in the two melon genotypes. Simultaneously, SA pretreatment attenuated the decrease in Chl content, photosynthetic capacity, and PSII photochemistry efficiency in Cd-stressed plants. Furthermore, exogenous SA significantly reduced superoxide anion production and lipid peroxidation, followed by increase in the activities of antioxidant enzyme superoxide dismutase, guaiacol peroxidase, catalase, and ascorbate peroxidase, and content of soluble protein and free proline in both the genotypes under Cd stress. The effect of SA was more conspicuous in Xiulv than Hamilv, reflected in the biomass, photosynthetic pigments, stomatal conductance, water use efficiency, and antioxidant enzymes. These results suggest that exogenous spray of SA can alleviate the adverse effects of Cd on the growth and photosynthesis of both the melon cultivars, mostly through promoting antioxidant defense capacity. It also indicates that SA-included protection against Cd damage is to a greater extent more pronounced in Cd-sensitive genotype than Cd-tolerant genotype.
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Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.
Trials
PUBLISHED: 07-31-2014
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Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis.
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Evidence for peripheral immune activation in amyotrophic lateral sclerosis.
J. Neurol. Sci.
PUBLISHED: 07-29-2014
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There is evidence of the activity of immune system in the spinal cords of patients with amyotrophic lateral sclerosis (ALS), however; few studies to date have explored the status of peripheral immune response in ALS patients. Blood samples from 284 ALS patients and 217 aged-match controls were evaluated, and parameters of T cell subset, humoral immunity, and complement system activation were observed. CD4+ T lymphocytes and circulating immune complexes (CICs) were significantly decreased, and component C3 was significantly increased in ALS patients compared with normal controls. Patients with severe or moderate impairment had a higher CD4+ T cell percentage and a lower IgG levels when compared to those with mild impairment. There was an inverse correlation between CD4 T cell percentage and both revised ALS Functional Rating Scale (ALSFRS-R) score and disease duration, but the correlation was positive between IgG level and both ALSFRS-R score and disease duration among ALS patients. These correlations were gender-specific. This investigation demonstrated the existence of peripheral immune abnormalities in ALS patients.
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Localizing seizure-susceptible brain regions associated with low-grade gliomas using voxel-based lesion-symptom mapping.
Neuro-oncology
PUBLISHED: 07-18-2014
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Patients afflicted with low-grade glioma (LGG) frequently suffer from seizures. The mechanisms of seizure initiation in these patients remain poorly understood. Tumor location has been correlated with seizure initiation. However, these correlative studies relied on dichotomized data analysis based on arbitrary lobe assignments. As a result, the lesion-symptom correlation may be incorrectly interpreted. Here, we present the first study that used a voxel-wise quantitative lesion analysis to investigate the spatial correlation between tumor location and seizure susceptibility.
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Tag SNPs of CFI contributed to the susceptibility for non-small cell lung cancer in Chinese population.
Tumour Biol.
PUBLISHED: 07-07-2014
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Complement factor I (CFI) plays an important role in the development of non-small cell lung cancer (NSCLC). This study aims to examine the association of CFI genetic variants with the risk of developing NSCLC in Chinese population. A hospital-based case-control study was conducted in 470 patients with NSCLC and 470 controls in Chinese population. Totally, 13 tag single nucleotide polymorphisms (tag SNPs) of CFI were selected by Haploview software using the HapMap database. Genotyping was performed using iPLEX Gold Genotyping Assay and Sequenom MassARRAY. The odds ratios (ORs) and 95 % confidence interval (95 % CI) were calculated by logistic regression model. Our results showed that individuals with rs6822976 GG genotype had a significant decreased risk of NSCLC (OR?=?0.64; 95 % CI?=?0.42-0.98) when compared with rs6822976 AA genotype carriers. We also found that rs7671905 TT genotype exhibited a significant decreased risk of NSCLC compared with CC genotype with OR (95 % CI) of 0.55 (0.33-0.91). There was no significant association between other selected SNPs and the risk of NSCLC. When stratified by smoking status, the decreased risk of NSCLC was observed to be associated with the genotype with at least one rs6822976 G allele among non-smokers (OR?=?0.66; 95 % CI?=?0.47-0.93), but not among smokers (OR?=?1.01; 95 % CI?=?0.67-1.53). For CFI rs7671905 polymorphism, the individuals with at least one T allele have a decreased risk of NSCLC with OR (95 % CI) of 0.71 (0.51-0.99), but not among smokers (OR?=?0.93; 95 % CI?=?0.61-1.41). When stratified by age, we found that rs7671905 TT genotype has contributed to the decreased risk of NSCLC among older subjects with OR (95 % CI) of 0.46 (0.23-0.95), but not among younger subjects with OR (95 % CI) of 0.64 (0.31-1.34) (P interaction?=?0.03). After stratifying by sex, our study showed that rs7671905 TT genotype was related to the risk of NSCLC among males (OR?=?0.53; 95 % CI?=?0.29-0.98), but not among females (OR?=?0.62; 95 % CI?=?0.25-1.57) (P interaction?=?0.03). CFI genetic variants played an important role in the development of NSCLC in Chinese population.
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[3+3] annulation of allylic phosphoryl-stabilized carbanions/phosphorus ylides and vinyl azides: a practice strategy for synthesis of polyfunctionalized anilines.
Chem. Commun. (Camb.)
PUBLISHED: 06-24-2014
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Tandem Michael addition and Witting or Horner-Wadsworth-Emmons olefination initiated [3+3] annulation between vinyl azides and allylic phosphorus ylides or allylic phosphoryl-stabilized carbanions has been developed. This one-pot protocol furnishes highly functionalized anilines in good to excellent yields under mild, room-temperature conditions. A rational mechanism is also proposed.
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MicroRNA-377 inhibited proliferation and invasion of human glioblastoma cells by directly targeting specificity protein 1.
Neuro-oncology
PUBLISHED: 06-20-2014
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Increasing evidence has indicated that microRNAs (miRNAs) are strongly implicated in the initiation and progression of glioblastoma multiforme (GBM). Here, we identi?ed a novel tumor suppressive miRNA, miR-377, and investigated its role and therapeutic effect for GBM.
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Thermal slip for liquids at rough solid surfaces.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 06-18-2014
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Molecular dynamics simulation is used to examine the thermal slip of liquids at rough solid surfaces as characterized by fractal Cantor structures. The temperature profiles, potential energy distributions, thermal slip, and interfacial thermal resistance are investigated and evaluated for a variety of surface topographies. In addition, the effects of liquid-solid interaction, surface stiffness, and boundary condition on thermal slip length are presented. Our results indicate that the presence of roughness expands the low potential energy regions in adjacent liquids, enhances the energy transfer at liquid-solid interface, and decreases the thermal slip. Interestingly, the thermal slip length and thermal resistance for liquids in contact with solid surfaces depends not only on the statistical roughness height, but also on the fractal dimension (i.e., topographical spectrum).
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A novel perspective on seed yield of broad bean (Vicia faba L.): differences resulting from pod characteristics.
Sci Rep
PUBLISHED: 06-16-2014
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Broad bean (Vicia faba L.) is an important crop worldwide. An increase in seed yield would increase both the grain reserve and the profit for farmers. Previous studies on increasing broad bean seed yield have focused mainly on increases at the whole population level. Few studies have focused on the differences in plant type within populations. In this study, we classified broad bean plants into four categories based on pod type, and then evaluated the ratio of each category in field-grown broad bean populations. We analysed the seed and pod characteristics of each category, and their contributions to total seed yield. The number of seeds per pod, and the number of pods or seeds per plant differed among the four plant categories, but the seed weight was relatively uniform. There were significant differences in seed yield per plant among the four plant categories. We calculated the effects of increasing the proportion of each plant category by 10% or to 100% on seed yield, and found that seed yield could be improved by increasing the ratio of plants with the highest seed production rate. This study provides a novel perspective on estimating the seed yield of broad bean.
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[Expression of peroxisome proliferators-activated receptor in glioma and its effect on the growth of human glioma cells].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-15-2014
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To study the expression of peroxisome proliferators-activated receptor (PPAR) in human glioma tissue and its influence on tumor growth.
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Structure and immune recognition of trimeric pre-fusion HIV-1 Env.
Nature
PUBLISHED: 06-04-2014
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The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.
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The preliminary study of (18)F-FLT micro-PET/CT in predicting radiosensitivity of human nasopharyngeal carcinoma xenografts.
Ann Nucl Med
PUBLISHED: 05-28-2014
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The purpose of the preliminary study was to investigate the value of (18)F-FLT micro-PET/CT in predicting radiosensitivity of human nasopharyngeal carcinoma (NPC) xenografts in nude mice models.
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MiR-124 governs glioma growth and angiogenesis and enhances chemosensitivity by targeting R-Ras and N-Ras.
Neuro-oncology
PUBLISHED: 05-25-2014
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Glioma is one of the most aggressive and lethal human brain tumors. Accumulating evidence shows that microRNAs play important roles in cancers, including glioma. Previous studies reported that miR-124 levels were downregulated in glioma specimens. Here, we further investigate the potential role of miR-124 in glioma.
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The prevention of titanium-particle-induced osteolysis by OA-14 through the suppression of the p38 signaling pathway and inhibition of osteoclastogenesis.
Biomaterials
PUBLISHED: 05-21-2014
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Wear-particle-induced osteolysis leads to prosthesis loosening, which is one of the most common causes of joint-implant failure, a problem that must be fixed using revision surgery. Thus, a potential treatment for prosthetic loosening is focused on inhibiting osteoclastic bone resorption, which prevents wear-particle-induced osteolysis. In this study, we synthesized a compound named OA-14 (N-(3- (dodecylcarbamoyl)phenyl)-1H-indole-2-carboxamide) and examined how OA-14 affects titanium (Ti)-particle-induced osteolysis and osteoclastogenesis. We report that OA-14 treatment protected against Ti-particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of tartrate-resistant acid phosphatase-positive osteoclasts decreased after treatment with OA-14 in vivo, which suggested that OA-14 inhibits osteoclast formation. To test this hypothesis, we conducted in vitro studies, and our results revealed that OA-14 markedly diminished osteoclast differentiation and osteoclast-specific gene expression in a dose- and time-dependent manner. Moreover, OA-14 suppressed osteoclastic bone resorption and F-actin ring formation. Furthermore, we determined that OA-14 inhibited osteoclastogenesis by specifically blocking the p38-Mitf-c-fos-NFATc1 signaling cascade induced by RANKL (ligand of receptor activator of nuclear factor ?B). Collectively, our results suggest that the compound OA-14 can be safely used for treating particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
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A multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma.
Hepatology
PUBLISHED: 04-17-2014
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Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomization controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. Three hundred and sixty patients with Child-Pugh class A or B cirrhosis and one or two HCC lesions ? 4 cm, treatment naïve, without metastasis were randomly assigned to cryoablation (n=180) or RFA (n=180). The primary end-points were local tumor progression at 3 years after treatment, and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P=0.043). For lesions >3 cm in diameter, local tumor progression rate was significantly lower in cryoablation group versus RFA group (7.7% vs 18.2%, P=0.041). The 1-, 3-, and 5-year overall survival rates were 97%, 67% and 40%, for cryoablation and 97%, 66%, and 38% for RFA, respectively (P=0.747). The 1-, 3-, and 5-year tumor-free survival rates were 89%, 54%, and 35% in cryoablation group and 84%, 50%, and 34% in RFA group, respectively (P=0.628). Multivariate analyses demonstrated that Child-Pugh class B and distant intrahepatic recurrence were significant negative predictors to overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P=0.776). Conclusion: Cryoablation resulted in a significantly lower local tumor progression, although both cryoablation and RFA were equally safe and effective with similar 5-year survival rates. (Hepatology 2014;).
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An exploratory study of serum creatinine levels in patients with amyotrophic lateral sclerosis.
Neurol. Sci.
PUBLISHED: 04-16-2014
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The etiology of amyotrophic lateral sclerosis (ALS) remains unknown, but existing data argue for a role of creatinine in ALS pathophysiology. Our aim is to clarify the correlation between serum creatinine and ALS in Chinese population. A total of 512 sporadic ALS (SALS) patients and 501 age- and gender-matched healthy controls were included. Revised ALS Functional Rating Scale (ALS-FRS-R) was used to assess the motor functional status of SALS patients. Survival analysis was performed using Kaplan-Meier method. Serum creatinine levels were significantly lower in SALS patients than in controls (p < 0.001). Patients with the second, the third and highest quartiles of creatinine levels had a significantly lower presence of ALS compared to those with the lowest quartile (p for trend <0.001). However, decreased presence of ALS was not found in the highest quartiles compared with the lowest quartiles in females. Sporadic ALS patients with different site of onset have similar serum creatinine levels, but underweight patients presented lower levels of serum creatinine. Patients with low serum creatinine levels are more likely to have severe motor impairment and low body mass index (BMI) values. This study demonstrates that SALS patients have lower serum creatinine levels than well-matched controls. Higher levels of serum creatinine are less likely to be associated with the presence of ALS in Chinese populations. Low serum creatinine levels may be related to severe motor impairment in SALS patients, after adjusting the confounding factor-BMI. However, serum creatinine has no deleterious impact on survival in ALS.
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miR-622 suppresses proliferation, invasion and migration by directly targeting activating transcription factor 2 in glioma cells.
J. Neurooncol.
PUBLISHED: 04-06-2014
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Malignant gliomas are the most common and devastating primary brain tumors in adults. The rapid invasion of tumor cells into the adjacent normal brain tissues is a major cause of treatment failure, yet the mechanisms that regulate this process remain poorly understood. MicroRNAs have recently emerged as regulators of invasion and metastasis by acting on multiple signaling pathways. In this study, we found that miR-622 is significantly downregulated in glioma tissues and cell lines. Functional experiments showed that increased miR-622 expression reduced glioma cell invasion and migration, whereas decreased miR-622 expression enhanced cell invasion and migration. Moreover, activating transcription factor 2 (ATF2), an important transcription factor that regulate tumor invasion, was identified as a direct target of miR-622. Knockdown of ATF2 using small interefering RNA recapitulated the anti-invasive function of miR-622, whereas restoring the ATF2 expression attenuated the function of miR-622 in glioma cells. Furthermore, clinical data indicated that miR-622 and ATF2 were inversely expressed in glioma specimens. Our findings provide insight into the specific biological behavior of miR-622 in tumor invasion and migration. Targeting miR-622/ATF2 axis is a novel therapeutic approach for blocking glioma invasion.
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Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: regulation of Treg/Th17 cells.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-17-2014
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Liver cirrhosis is one of the major consequences of hepatitis B virus (HBV) infection, and transplantation of autologous bone marrow mesenchymal stem cells (ABMSCs) is one of promising therapies for patients with HBV-related liver cirrhosis (HBV-LC). However, the mechanism is unclear. The aim of the current study was to explore the role of Treg/Th17 cells in ABMSCs transplantation in patients with HBV-LC.
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Downregulation of osteopontin enhances the sensitivity of glioma U251 cells to temozolomide and cisplatin by targeting the NF-?B/Bcl?2 pathway.
Mol Med Rep
PUBLISHED: 02-25-2014
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Glioma is resistant to the apoptotic effects of chemotherapy and the mechanism underlying its chemoresistance is not currently understood. In a previous study, we reported that osteopontin (OPN) was overexpressed in glioma tissues and had an important anti?apoptotic effect. Furthermore, overexpression of OPN was observed following chemotherapy. To elucidate whether OPN plays a role in chemotherapy resistance and to investigate its downstream signaling pathway, this study used small interfering RNA (siRNA) to silence the expression of OPN in U251 human neuronal glioma astrocytoma cells. OPN downregulation in U251 cells enhanced the apoptotic effects induced by temozolomide (TMZ) and cisplatin (DDP). Furthermore, OPN siRNA suppressed the nuclear factor ??light?chain?enhancer of activated B cells (NF??B) activation and B cell lymphoma 2 (Bcl?2) expression that was induced by chemotherapy. Taken together, these results demonstrated that the expression levels of OPN are involved in glioma chemoresistance. Knockdown of OPN through siRNA enhanced the effects of TMZ and DDP chemotherapy by targeting the NF??B/Bcl?2 pathway.
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Spastin mutation screening in Chinese patients with pure hereditary spastic paraplegia.
Parkinsonism Relat. Disord.
PUBLISHED: 02-20-2014
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Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPAST) gene are the most common cause of pure HSP. However, few data are available regarding the clinical and genetic spectrum of HSP among Chinese patients.
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Bioinspired multicompartmental microfibers from microfluidics.
Adv. Mater. Weinheim
PUBLISHED: 02-19-2014
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Bioinspired multicompartmental microfibers are generated by novel capillary microfluidics. The resultant microfibers possess multicompartment body-and-shell compositions with specifically designed geometries. Potential use of these microfibers for tissue-engineering applications is demonstrated by creating multifunctional fibers with a spatially controlled encapsulation of cells.
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Is 18F-FDG PET/CT more reliable than 99mTc-MDP planar bone scintigraphy in detecting bone metastasis in nasopharyngeal carcinoma?
Ann Nucl Med
PUBLISHED: 02-19-2014
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Bone metastasis occurs frequently in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to compare the clinical value of 18F-FDG PET/CT with that of 99mTc-MDP planar bone scintigraphy (PBS) for detecting bone metastasis in NPC patients.
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Clinical value of [(18)F]FDG-PET/CT in the detection of metastatic medullary thyroid cancer.
Clin Imaging
PUBLISHED: 02-10-2014
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To evaluate the value of fluorine-18 2-deoxy-2-d-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) in the detection of metastatic medullary thyroid cancer.
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Posterior reversible encephalopathy syndrome in acute intermittent porphyria.
Pediatr. Neurol.
PUBLISHED: 02-09-2014
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Acute intermittent porphyria is an inherited disease that is rarely diagnosed in prepubertal children. It can affect the autonomic, peripheral, and central nervous system. Posterior reversible encephalopathy syndrome is a clinicoradiological entity characterized by headache, seizures, altered consciousness, and visual disorder associated with potentially reversible neuroradiological abnormalities predominantly in the parieto-occipital lobes. We report a child with acute intermittent porphyria who presented with radiological manifestations suggestive of posterior reversible encephalopathy syndrome.
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Parkinson?s disease-related modulation of functional connectivity associated with the striatum in the resting state in a nonhuman primate model.
Brain Res.
PUBLISHED: 01-26-2014
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The goal of this study was to describe Parkinson?s disease (PD)-related modulation of functional connectivity (FC) associated with the striatum in the resting state in a nonhuman primate model of early-stage PD. Weekly intravenous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (0.5 mg/kg body weight) were performed until parkinsonian motor symptoms developed in four macaques. After 13 weeks of MPTP treatment, all monkeys displayed parkinsonian symptoms. During the course of the experiment, each animal underwent four magnetic resonance imaging scans and four positron emission tomography (PET) scans with the vesicular monoamine transporter 2 (VMAT2)-selective ligand 9-[(18)F] fluoropropyl-(+)-dihydrotetrabenazine, performed prior to the beginning of MPTP administration as well as after 4, 9, and 13 MPTP injections. The FC profile of the striatum was evaluated using a seed voxel correlation approach and post hoc region of interest analysis on resting-state functional magnetic resonance imaging data. The PET images were subjected to region of interest analysis to examine brain regional reductions in VMAT2 density in the PD model. Significant reductions in the connectivity pattern of the striatal regions were observed: limbic striatum and left hippocampus; caudate nucleus/associative and brain regions, including the right pre-supplementary motor area and bilateral dorsolateral prefrontal cortex; putamen/associative region and left inferior temporal gyrus or right orbital and medial prefrontal cortex; and putamen/motor and cortical structures, including the right superior temporal gyrus and bilateral postcentral gyrus. Subsequent PET studies showed the progressive loss of striatal VMAT2 in the striatum with the presentation of parkinsonism. Significant differences between the specific uptake ratio reductions in each striatal subdivision were not found. By using a long-term, low-dose MPTP-lesioned nonhuman primate model, this study demonstrated PD-related decreased corticostriatal FC in a resting state; moreover, altered sensorimotor integration was also found in early-stage PD.
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TPM3, a strong prognosis predictor, is involved in malignant progression through MMP family members and EMT-like activators in gliomas.
Tumour Biol.
PUBLISHED: 01-25-2014
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Recent studies have shown that many molecular mechanisms, such as the EGFR, AKT, STAT3, and beta-catenin pathways, are involved in glioma. However, the prognosis of the disease remains poor. Explorations of the underlying mechanisms of glioma and identification of effective markers for early diagnosis and accurate prognostication remain important today. In this study, we employed survival analysis to determine that TPM3 overexpression was significantly associated with high-grade gliomas and higher mortality. Using microarray combined with Pearson correlation analysis, we found that TPM3 was positively correlated with the expression of MMP family members and EMT-like activators. Reduction of TPM3 (via TPM3-siRNA) inhibited cellular invasion and migration and decreased MMP-9 and SNAI1 levels in glioma cells. To the best of our knowledge, our work is the first to show that TPM3 plays a critical role in the progression of gliomas and provides novel insights into the key roles of MMP family members and EMT-like activators that mediate TPM3 functional signaling for glioma regulation.
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The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease: a meta-analysis.
Neuromolecular Med.
PUBLISHED: 01-24-2014
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Previous studies have reported an association between human sirtuins' single-nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) susceptibility in the apolipoprotein E (APOE) ?4-negative population, although the findings are inconsistent. To obtain a more precise estimation of this relationship, we conducted a meta-analysis to assess the association between the rs10410544 C/T polymorphism of SIRT2 and the risk of AD with APOE ?4 status. We searched all relevant PubMed publications and included three studies in our meta-analysis involving a total of 1,794 patients and 2,054 control subjects. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to evaluate the association of the SIRT2 SNP with AD susceptibility, and we analyzed the extracted data stratified by the APOE ?4-carrying status. Overall, the results show that the SIRT2 SNP is associated with human AD risk in the comparison models (T vs. C: OR 1.140, 95% CI 1.034-1.258; TC vs. CC: OR 1.178, 95% CI 1.019-1.361; TT + TC vs. CC: OR 1.197, 95% CI 1.043-1.373). In the stratified analyses, the European population had a significantly increased risk of AD (T vs. C: OR 1.110, 95% CI 1.002-1.229), and we also observed a significant association in the APOE ?4-negative population (T vs. C: OR 1.165, 95% CI 1.025-1.324; TT + TC vs. CC: OR 1.222, 95% CI 1.022-1.461). This meta-analysis indicates that the presence of the SIRT2 SNP with APOE ?4-negative status contributes to the development of AD in humans Epidemiological studies of larger sample sizes are warranted to confirm this hypothesis.
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Association analysis of four candidate genetic variants with sporadic amyotrophic lateral sclerosis in a Chinese population.
Neurol. Sci.
PUBLISHED: 01-23-2014
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Recently, four single nucleotide polymorphisms (SNPs), including rs2814707 in the 9p21, rs12608932 in the UNC13A gene, rs13048019 in the TIMA1 gene, and rs2228576 in the SCNN1A gene have been reported to be associated with the risk for developing amyotrophic lateral sclerosis (ALS) in Caucasian population. However, this association is not consistent among different studies and yet to be tested in ALS patients in Mainland China. This study included 397 sporadic ALS (SALS) patients and 287 unrelated Chinese healthy controls from Southwest China. Four SNPs listed above were genotyped by using Sequenom's iPLEX assay. No significant differences in the genotype distributions or minor allele frequencies in all SNPs were found between ALS group and control group, between the spinal-onset group and bulbar-onset group, and between the early-onset group and the late-onset group. Our results suggest that these SNPs are unlikely to be common cause of SALS in Chinese population.
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Dicke-type phase transition in a spin-orbit-coupled Bose-Einstein condensate.
Nat Commun
PUBLISHED: 01-16-2014
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Spin-orbit-coupled Bose-Einstein condensates (BECs) provide a powerful tool to investigate interesting gauge field-related phenomena. Here we study the ground state properties of such a system and show that it can be mapped to the well-known Dicke model in quantum optics, which describes the interactions between an ensemble of atoms and an optical field. A central prediction of the Dicke model is a quantum phase transition between a superradiant phase and a normal phase. We detect this transition in a spin-orbit-coupled BEC by measuring various physical quantities across the phase transition. These quantities include the spin polarization, the relative occupation of the nearly degenerate single-particle states, the quantity analogous to the photon field occupation and the period of a collective oscillation (quadrupole mode). The applicability of the Dicke model to spin-orbit-coupled BECs may lead to interesting applications in quantum optics and quantum information science.
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Prevalence and risk of cancer of incidental uptake in prostate identified by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.
Clin Imaging
PUBLISHED: 01-16-2014
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The objective was to investigate the prevalence of incidental fluorine-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography/computed tomography.
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Identification of intrinsic subtype-specific prognostic microRNAs in primary glioblastoma.
J. Exp. Clin. Cancer Res.
PUBLISHED: 01-13-2014
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Glioblastoma multiforme (GBM) is the most malignant type of glioma. Integrated classification based on mRNA expression microarrays and whole-genome methylation subdivides GBM into five subtypes: Classical, Mesenchymal, Neural, Proneural-CpG island methylator phenotype (G-CIMP) and Proneural-non G-CIMP. Biomarkers that can be used to predict prognosis in each subtype have not been systematically investigated.
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Comparative physiological and proteomic analyses of poplar (Populus yunnanensis) plantlets exposed to high temperature and drought.
PLoS ONE
PUBLISHED: 01-01-2014
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Plantlets of Populus yunnanensis Dode were examined in a greenhouse for 48 h to analyze their physiological and proteomic responses to sustained heat, drought, and combined heat and drought. Compared with the application of a single stress, simultaneous treatment with both stresses damaged the plantlets more heavily. The plantlets experienced two apparent response stages under sustained heat and drought. During the first stage, malondialdehyde and reactive oxygen species (ROS) contents were induced by heat, but many protective substances, including antioxidant enzymes, proline, abscisic acid (ABA), dehydrin, and small heat shock proteins (sHSPs), were also stimulated. The plants thus actively defended themselves against stress and exhibited few pathological morphological features, most likely because a new cellular homeostasis was established through the collaborative operation of physiological and proteomic responses. During the second stage, ROS homeostasis was overwhelmed by substantial ROS production and a sharp decline in antioxidant enzyme activities, while the synthesis of some protective elements, such as proline and ABA, was suppressed. As a result, photosynthetic levels in P. yunnanensis decreased sharply and buds began to die, despite continued accumulation of sHSPs and dehydrin. This study supplies important information about the effects of extreme abiotic environments on woody plants.
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An axis involving SNAI1, microRNA-128 and SP1 modulates glioma progression.
PLoS ONE
PUBLISHED: 01-01-2014
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Glioblastoma is an extraordinarily aggressive disease that requires more effective therapeutic options. Snail family zinc finger 1, dysregulated in many neoplasms, has been reported to be involved in gliomas. However, the biological mechanisms underlying SNAI1 function in gliomas need further investigation.
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Prevalence and clinicopathologic characteristics of the molecular subtypes in malignant glioma: a multi-institutional analysis of 941 cases.
PLoS ONE
PUBLISHED: 01-01-2014
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Glioblastoma can be classified into four distinct molecular subtypes (Proneural, Neural, Classical and Mesenchymal), based on gene expression profiling. This study aimed to investigate the prevalence, clinicopathologic features and overall survival (OS) of the four molecular subtypes among all malignant gliomas.
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Serum uric acid levels in patients with Alzheimer's disease: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting.
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Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675.
PLoS ONE
PUBLISHED: 01-01-2014
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H19 RNA has been characterized as an oncogenic long non-coding RNA (lncRNA) in breast and colon cancer. However, the role and function of lncRNA H19 in glioma development remain unclear. In this study, we identified that H19/miR-675 signaling was critical for glioma progression. By analyzing glioma gene expression data sets, we found increased H19 in high grade gliomas. H19 depletion via siRNA inhibited invasion in glioma cells. Further, we found H19 positively correlated with its derivate miR-675 expression and reduction of H19 inhibited miR-675 expression. Bioinformatics and luciferase reporter assays showed that miR-675 modulated Cadherin 13 expression by directly targeting the binding site within the 3' UTR. Finally, introduction of miR-675 abrogated H19 knockdown-induced cell invasion inhibition in glioma cells. To our knowledge, it is first time to demonstrate that H19 regulates glioma development by deriving miR-675 and provide important clues for understanding the key roles of lncRNA-miRNA functional network in glioma.
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Libraries from Libraries: A Series of Sulfonamide Linked Heterocycles Derived from the Same Scaffold.
Tetrahedron Lett.
PUBLISHED: 12-24-2013
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A libraries from libraries approach is described for the synthesis of five different sulfonamide linked scaffolds. Four of the scaffolds are sulfonamides linked to heterocycles; piperazine, thiourea, cyclic guanidine, and dimethyl cyclic guanidine. The fifth scaffold is a polyamine linked sulfonamide. Three different diversity positions were effectively incorporated into each scaffold providing a number of different compounds with good yields and purity.
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Scaffold Ranking and Positional Scanning Utilized in the Discovery of nAChR-Selective Compounds Suitable for Optimization Studies.
J. Med. Chem.
PUBLISHED: 12-12-2013
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Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The ?4?2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid discovery of a series of ?4?2 nAChR selective compounds. Further chemistry optimization provided compound 301, which was characterized as a selective ?4?2 nAChR antagonist. This compound displayed no agonist activity but blocked nicotine-induced depolarization of HEK cells with an IC50 of approximately 430 nM. 301 demonstrated nearly 500-fold selectivity for binding and 40-fold functional selectivity for ?4?2 over ?3?4 nAChR. In total over 5 million compounds were assessed through the use of just 170 samples in order to identify a series of structural analogues suitable for future optimization toward the goal of developing clinically relevant smoking cessation medications.
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Structural Basis for HIV-1 Neutralization by 2F5-like Antibodies m66 and m66.6.
J. Virol.
PUBLISHED: 12-11-2013
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Antibodies m66.6 and 2F5 are the only effective human HIV-1-neutralizing antibodies identified thus far that recognize the N-terminal region of the membrane-proximal external region (MPER) of the gp41 subunit of the HIV-1 viral spike. Although 2F5 has been extensively characterized, much less is known about antibody m66.6 or antibody m66, a closely related light-chain variant. Here, we report the crystal structure of m66 in complex with its gp41 epitope, along with unbound structures of m66 and m66.6. We employed mutational and binding analyses to decipher antibody elements critical for recognition of their gp41 epitopes, and determined the molecular basis that underlies their neutralization of HIV-1. When bound by m66, the N-terminal region of the gp41 MPER adopts a conformation comprising a helix followed by an extended loop. Comparison of gp41-bound m66 with unbound m66.6 identified three light chain residues of m66.6 that were confirmed through mutagenesis to underlie the superior breadth and potency of m66.6-mediated virus neutralization. Recognition of gp41 by m66 also revealed similarities to antibody 2F5 both in the conformation of crucial epitope residues as well as in the angles of antibody approach. Aromatic residues at the tip of the m66.6-heavy chain third complementarity-determining region, as in the case of 2F5, were determined to be critical for virus neutralization in a manner that correlated with antibody recognition of the MPER in a lipid context. Antibodies m66, m66.6, and 2F5 thus utilize similar mechanistic elements to recognize a common gp41-MPER epitope and neutralize HIV-1.
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One-Pot Three-Component Approach to the Synthesis of Polyfunctional Pyrazoles.
Org. Lett.
PUBLISHED: 11-20-2013
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A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed.
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Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.
Chem. Biol. Interact.
PUBLISHED: 10-28-2013
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Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3? (HNF 3?) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM.
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Proliferation of parenchymal microglia is the main source of microgliosis after ischaemic stroke.
Brain
PUBLISHED: 10-22-2013
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Stroke induces rapid activation and expansion of microglia, but the main source of microgliosis is controversial. Here we investigated the formation of microgliosis and infiltration of circulating cells in a photothrombosis stroke model by taking advantage of parabiosis and two-photon microscopy. We found that a small population of blood-derived CX3CR1(GFP/+) cells infiltrated the cerebral parenchyma, but these cells did not proliferate and were phenotypically distinguishable from resident microglia. CX3CR1(GFP/+) infiltrating cells also displayed different kinetics from reactive microglia. The number of CX3CR1(GFP/+) infiltrating cells peaked on Day 5 after stroke and then decreased. The decline of these infiltrating cells was associated with an active apoptotic process. In contrast, reactive microglia were recruited to the ischaemic area continuously during the first week after stroke induction. Immunohistology and in vivo two-photon imaging revealed that cells involved in the process of microgliosis were mainly derived from proliferating resident microglia. Expansion of microglia exhibited a consistent pattern and our in vivo data demonstrated for the first time that microglia underwent active division in regions surrounding the ischaemic core. Together, these results indicated that CX3CR1(GFP/+) infiltrating cells and reactive microglia represented two distinct populations of cells with different functions and therapeutic potentials for the treatment of stroke.
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SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis.
Neurobiol. Aging
PUBLISHED: 07-25-2013
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Mutations in the sequestosome 1 gene (SQSTM1) have recently been identified in patients with amyotrophic lateral sclerosis, accounting for 1.11%-4.92% of familial ALS and 2.42%-4.37% of sporadic amyotrophic lateral sclerosis (SALS). The mutation spectrum of SQSTM1 in Chinese patients with SALS remains unknown. Three hundred and six patients with SALS from the Department of Neurology, West China Hospital of Sichuan University were recruited for this study. From the same region, 350 healthy individuals were recruited as a control group. The encoding regions of SQSTM1 were screened by direct sequencing. Three novel nonsynonymous mutations- p. I99L, p. D337E, and p. L341V-were identified in 3 patients with SALS, none of which were found in healthy controls. The male patient carrying mutation p. I99L presented limb symptom at age of 34 and died in 34 months. Two late-onset patients carrying D337E and p. L341V mutations had bulbar and limb onset, respectively. Moreover, a c.1166-14_1166-11delTACT mutation in the intron 7 was found in a living male patient with limb onset at age of 62. None of the patients carrying SQSTM1 mutation showed clinical evidence of concomitant Paget disease of bone or mutation of the valosin-containing protein gene. The mutation frequency of SQSTM1 was 0.98% in Chinese patients with SALS, which was lower than those in other racial populations.
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Parallel Synthesis of 1,6-Disubstituted-1,2,4-triazin-3-ones on Solid-Phase.
ACS Comb Sci
PUBLISHED: 06-13-2013
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A parallel solid-phase synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones from MBHA resin is described. The reduction of resin-bound nitrosamino acids provides hydrazines efficiently without affecting the amide bond. The trityl protected hydrazine is then reduced with borane, and cyclized with 1,1-carbonyldiimidazole. The desired products are cleaved from their solid support and obtained in good yield and purity. This methodology is of value for the rapid parallel preparation of these potentially bioactive molecules.
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[Expression of FOS protein in glioma and its effect on the growth of human glioma cells].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-08-2013
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To study the expression of FOS protein in human glioma tissues and its effect on tumor growth.
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Characterizing optical properties of nano contrast agents by using cross-referencing OCT imaging.
Biomed Opt Express
PUBLISHED: 06-01-2013
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We report a cross-referencing method to quickly and accurately characterize the optical properties of nanoparticles including the extinction, scattering, absorption and backscattering cross sections by using an OCT system alone. Among other applications, such a method is particularly useful for developing nanoparticle-based OCT imaging contrast agents. The method involves comparing two depth-dependent OCT intensity signals collected from two samples (with one having and the other not having the nanoparticles), to extract the extinction and backscattering coefficient, from which the absorption coefficient can be further deduced (with the help of the established scattering theories for predicting the ratio of the backscattering to total scattering cross section). The method has been experimentally validated using test nanoparticles and was then applied to characterizing gold nanocages. With the aid of this method, we were able to successfully synthesize scattering dominant gold nanocages for the first time and demonstrated the highest contrast enhancement ever achieved by the gold nanocages (and by any nanoparticles of a similar size and concentration) in an in vivo mouse tumor model. This method also enables quantitative analysis of contrast enhancement and provides a general guideline on choosing the optimal concentration and optical properties for the nanoparticle-based OCT contrast agents.
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Camptocormia in Chinese patients with Parkinsons disease.
J. Neurol. Sci.
PUBLISHED: 05-24-2013
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To investigate the frequency and clinical characteristics of camptocormia in Chinese PD patients, we included 705 patients with PD and studied the clinical features and prevalence of camptocormia. Forty-six (6.5%) patients presented with camptocormia at the time of evaluation. The mean disease duration of PD patients with camptocormia was significantly longer than that without camptocormia (P<0.01). After adjusted for age and disease duration, compared with patients without camptocormia, PD patients with camptocormia presented with higher score of UPDRS part III (P<0.01), higher H&Y stage (P<0.01), higher score of Non-Motor Symptoms Scale (P<0.01) and lower score of Mini-Mental Status Examination (P<0.01). Binary logistic regression models indicated that camptocormia is associated with higher H&Y stage and UPDRS part III score. Camptocormia is not rare (6.5%) with the disease progression of PD in Chinese PD population and is associated with more advanced PD.
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Increased (18)F-fluoroestradiol uptake in radiation pneumonia.
Ann Nucl Med
PUBLISHED: 05-15-2013
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A 54-year-old metastatic breast cancer patient who had undergone chemotherapy and radiotherapy was transferred to our hospital for further treatment. We utilized (18)F-fluoroestradiol (FES) to assess the estrogen receptor (ER) status of metastatic lesions. Interestingly, high accumulation of (18)F-FES in pneumonia caused by radiation was detected. Hence, this draws oncologists attention to the possible false-positive result of (18)F-FES, which may lead to inappropriate endocrine therapy.
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[SIRT1 expression and activity are up-regulated in the brain tissue of epileptic patients and rat models].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 05-07-2013
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To investigate the expression and activity of silent information regulator 1 (SIRT1) in the temporal lobe of epileptic patients and rat models and explore its role in the occurrence and progression of epilepsy.
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The hepatoprotective effect of fraxetin on carbon tetrachloride induced hepatic fibrosis by antioxidative activities in rats.
Int. Immunopharmacol.
PUBLISHED: 04-29-2013
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The aim of the study was to investigate the potentially protective effects of fraxetin on carbon tetrachloride (CCl4) induced oxidative stress and hepatic fibrosis in Sprague-Dawley rats. In this study, rats were divided into five groups, including normal controls, model, silymarin as the positive control, fraxetin 20 mg/kg and fraxetin 50 mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked. The levels of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and antioxidant enzymes such as catalase, SOD and glutathione peroxidase (GSH-Px) were determined after fraxetin administration. The hydroxyproline levels and histopathologic examinations of hepatocyte fibrosis were also determined. We found that fraxetin at doses of 20 and 50 mg/kg for 8 weeks significantly reduced the levels of TBARS and protein carbonyls compared with CCl4 group. Fraxetin significantly increased the activities of catalase, SOD and GSH-Px in the liver. We also found that fraxetin prevented CCl4 induced hepatic fibrosis by histological observations. These results indicate that fraxetin exhibits potent protective effects against CCl4 induced oxidative stress and hepatic fibrosis.
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Involvement of FOS-mediated miR-181b/miR-21 signalling in the progression of malignant gliomas.
Eur. J. Cancer
PUBLISHED: 04-26-2013
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Recently, a group of microRNAs (miRNAs) were shown to be dysregulated in gliomas, and involved in glioma development. However, the effect of miRNA-miRNA functional networks on gliomas is poorly understood. In this study, we identified that FBJ murine osteosarcoma viral oncogene homolog (FOS)-mediated miR-181b/miR-21 signalling was critical for glioma progression. Using microarrays and quantitative RT-PCR (qRT-PCR), we found increased FOS in high grade gliomas. FOS depletion (via FOS-shRNA), inhibited invasion and promoted apoptosis in glioma cells. Using microarrays, combined with Pearson correlation analysis, we found FOS positively correlated with miR-21 expression. Reduction of FOS inhibited miR-21 expression by binding to the miR-21 promoter using luciferase reporter assays. Introduction of miR-21 abrogated FOS knockdown-induced cell invasion and apoptosis. Moreover, bioinformatics and luciferase reporter assays showed that miR-181b modulated FOS expression by directly targeting the binding site within the 3UTR. Expression of FOS with a FOS cDNA lacking 3UTR overrided miR-181b-induced miR-21 expression and cell function. Finally, immunohistochemistry (IHC) and in situ hybridisation (ISH) analysis revealed a significant correlation in miR-181b, FOS and miR-21 expression in nude mouse tumour xenograft and human glioma tissues. To our knowledge, it is the first time to demonstrate that miR-181b/FOS/miR-21 signalling plays a critical role in the progression of gliomas, providing important clues for understanding the key roles of transcription factor mediated miRNA-miRNA functional network in the regulation of gliomas.
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18F-FLT PET/CT imaging is not competent for the pretreatment evaluation of metastatic gastric cancer: a comparison with 18F-FDG PET/CT imaging.
Nucl Med Commun
PUBLISHED: 04-23-2013
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The aim of this study was to evaluate the utility of 3-deoxy-3-F-fluorothymidine (F-FLT) PET/computed tomography (CT) imaging in the pretreatment evaluation of metastatic gastric cancer in comparison with F-fluorodeoxyglucose (F-FDG) PET/CT imaging.
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Tunable spin-orbit coupling and quantum phase transition in a trapped Bose-Einstein condensate.
Sci Rep
PUBLISHED: 04-18-2013
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Spin-orbit coupling (SOC), the intrinsic interaction between a particle spin and its motion, is responsible for various important phenomena, ranging from atomic fine structure to topological condensed matter physics. The recent experimental breakthrough on the realization of SOC for ultra-cold atoms provides a completely new platform for exploring spin-orbit coupled superfluid physics. However, the SOC strength in the experiment is not tunable. In this report, we propose a scheme for tuning the SOC strength through a fast and coherent modulation of the laser intensities. We show that the many-body interaction between atoms, together with the tunable SOC, can drive a quantum phase transition (QPT) from spin-balanced to spin-polarized ground states in a harmonic trapped Bose-Einstein condensate (BEC), which resembles the long-sought Dicke QPT. We characterize the QPT using the periods of collective oscillations of the BEC, which show pronounced peaks and damping around the quantum critical point.
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Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.
Cancer Lett.
PUBLISHED: 03-05-2013
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Activating B-Raf mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. Although B-Raf(V600E) induces increased Mps1 protein contributing to centrosome amplification and chromosome instability, the regulatory mechanisms of Mps1 in melanoma cells is not fully understood. Here, we report that Mps1/AKT and B-Raf(WT)/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells; notably, oncogenic B-Raf(V600E) abrogates the negative feedback loop, contributing the aberrant Mps1 functions and tumorigenesis. Our findings raise the possibility that targeting the oncogenic B-Raf and Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment.
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18F-fluoromisonidazole PET/CT: a potential tool for predicting primary endocrine therapy resistance in breast cancer.
J. Nucl. Med.
PUBLISHED: 02-11-2013
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Although endocrine therapy is an effective method to treat estrogen receptor (ER)-positive breast cancer, approximately 30%-40% of all hormone receptor-positive tumors display de novo resistance. The aim of our current study was to analyze whether (18)F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [(18)F-FMISO]) PET/CT could predict primary resistance to hormonal therapy in ER-positive breast cancer.
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Can fluorine-18 fluoroestradiol positron emission tomography-computed tomography demonstrate the heterogeneity of breast cancer in vivo?
Clin. Breast Cancer
PUBLISHED: 02-04-2013
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Our study was to investigate the heterogeneity of estrogen receptor (ER) expression among tumor sites by using fluorine-18 ((18)F) fluoroestradiol (FES) positron-emission tomography-computed tomography (PET-CT) imaging.
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Altered intrinsic brain activity in patients with paroxysmal kinesigenic dyskinesia by PRRT2 mutation: altered brain activity by PRRT2 mutation.
Neurol. Sci.
PUBLISHED: 02-04-2013
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The proline-rich transmembrane protein 2 (PRRT2) gene has been recently identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with an insertion mutation c.649_650insC (p.P217fsX7) reported as the most common mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains largely unknown. Resting-state functional magnetic resonance imaging is a promising approach to assess cerebral function and reveals underlying functional changes. Resting-state functional magnetic resonance imaging was performed in 4 Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the mutation, and 10 healthy control subjects. Voxel-based analysis was used to characterize alterations in the amplitude of low-frequency fluctuation (ALFF). When compared with the healthy control subjects, both groups of PKD patients showed alterations in spontaneous brain activities within cortical-basal ganglia circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited increased ALFF in the right postcenral gyrus and right rolandic operculum area, while the alteration of ALFF in group of patients without the mutation additionally involved the middle orbitofrontal cortex. Direct comparative analysis between these two patient groups revealed significantly increased ALFF in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased spontaneous brain activity in the cortical-basal ganglia circuitry, especially in the motor preparation areas, is a common pathophysiology in PKD. Differences in the spatial patterns of increased ALFF between patients with and those without the mutation might reflect the distinct pathological mechanism resulting from PRRT2 mutation.
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Dissociative adsorption of 3-chloropropyne on Si(111)-(7 × 7): binding and structure.
Langmuir
PUBLISHED: 01-28-2013
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To achieve silicon functionalization for the development of hybrid devices, multifunctional molecules may be employed to attach to the silicon surfaces. It is important to get a fundamental understanding about the molecule/silicon interface chemistry and the binding configuration. The surface chemistry of 3-chloropropyne (HC?C-CH(2)Cl) on the Si(111)-(7 × 7) surface, as a model system for understanding the interaction of the multifunctional molecules with a silicon surface, was studied by X-ray photoelectron spectroscopy (XPS), high-resolution electron energy loss spectroscopy (HREELS), and density functional theory (DFT). The 3-chloropropyne adsorbs molecularly on the silicon surface at 110 K. A chemical reaction clearly occurs such that 3-choloropropyne bonds onto the Si(111)-(7 × 7) surface at room temperature by forming C-Si linkage through the cleavage of C-Cl bond, and preserving the ethyne C?C triple bond. This functionalized silicon surface may act as an intermediate for the growth of multiple organic layers by further attaching other functional molecules.
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Association of the Val66Met polymorphism of the BDNF gene with primary cranial-cervical dystonia patients from South-west China.
Parkinsonism Relat. Disord.
PUBLISHED: 01-24-2013
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The etiology of primary dystonia remains unclear. Recent genetic studies suggest that the Val66Met polymorphism of the BDNF gene is a genetic modifier in cranial-cervical dystonia in Caucasians. However, the finding is not consistent.
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PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis.
Neurobiol. Aging
PUBLISHED: 01-06-2013
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown pathophysiological mechanisms. Profilin 1 gene (PFN1) has been identified as a causative gene, which accounts for 1% to 2% of familial ALS. In this study, we investigated the mutation spectrum of PFN1 in Chinese patients with ALS. A total of 550 ALS patients (including 540 sporadic ALS [SALS] and 10 familial ALS) from the Department of Neurology, West China Hospital of Sichuan University, were recruited for the study. From the same region, 545 healthy control individuals (HC) were recruited as a control group. The encoding regions of the PFN1 gene were screened by direct sequencing. Novel candidate mutations or variations were confirmed by polymerase chain reaction-restriction fragment length polymorphism. A novel nonsynonymous p.R136W mutation was identified in an early-onset SALS female patient. A novel synonymous mutation p.L88L detected in a late-onset SALS female patient was considered nonpathogenic, as it was also detected in a control subject. No mutations were found in 10 familial ALS patients. Moreover, we found a significant difference in the genotype distribution of reported rs13204 (p.L112L) between SALS patients and HC (p = 0.0030). The frequency of minor allele T of rs13204 in the SALS group was significantly lower than that in HC (p = 0.0040, OR = 0.7270, 95% CI = 0.5848-0.9039). Our results suggest that PFN1 mutation is an uncommon cause of ALS in the Han Chinese population. The SNP rs13204 of the PFN1 gene may have an important function in ALS development. The phenotype of ALS patients with mutantPFN1 gene varies among different genetic backgrounds.
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Emulsion droplet formation in coflowing liquid streams.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 01-03-2013
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We investigate emulsion droplet formation in coflowing liquid streams based on a computational fluid dynamics simulation using the volume-of-fluid method to track the interface motion with a focus on the dynamics of the dripping and jetting regimes. The simulations reproduce dripping, widening jetting and narrowing jetting simultaneously in a coflowing microchannel in agreement with the experimental observations in this work. The result indicates that the dripping regime, rather than the jetting regime, is a favorable way to producing monodisperse emulsions. We find that, in dripping and widening jetting regimes, the breakup of a drop is induced by higher pressure in the neck which squeezes liquid into the lower-pressure region in subsequent and primary droplets, while the breakup in the narrowing jetting regime is due to slow velocity at the back end of the trough with respect to the leading end of the trough. In addition, the capillary number of the outer fluid and the Weber number of the inner fluid not only determine the drop diameter and generation rate but also the regime of emulsification.
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Monocytes loaded with indocyanine green as active homing contrast agents permit optical differentiation of infectious and non-infectious inflammation.
PLoS ONE
PUBLISHED: 01-01-2013
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Distinguishing cutaneous infection from sterile inflammation is a diagnostic challenge and currently relies upon subjective interpretation of clinical parameters, microbiological data, and nonspecific imaging. Assessing characteristic variations in leukocytic infiltration may provide more specific information. In this study, we demonstrate that homing of systemically administered monocytes tagged using indocyanine green (ICG), an FDA-approved near infrared dye, may be assessed non-invasively using clinically-applicable laser angiography systems to investigate cutaneous inflammatory processes. RAW 264.7 mouse monocytes co-incubated with ICG fluoresce brightly in the near infrared range. In vitro, the loaded cells retained the ability to chemotax toward monocyte chemotactic protein-1. Following intravascular injection of loaded cells into BALB/c mice with induced sterile inflammation (Complete Freunds Adjuvant inoculation) or infection (Group A Streptococcus inoculation) of the hind limb, non-invasive whole animal imaging revealed local fluorescence at the inoculation site. There was significantly higher fluorescence of the inoculation site in the infection model than in the inflammation model as early as 2 hours after injection (p<0.05). Microscopic examination of bacterial inoculation site tissue revealed points of near infrared fluorescence, suggesting the presence of ICG-loaded cells. Development of a non-invasive technique to rapidly image inflammatory states without radiation may lead to new tools to distinguish infectious conditions from sterile inflammatory conditions at the bedside.
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Can positron emission tomography/computed tomography with the dual tracers fluorine-18 fluoroestradiol and fluorodeoxyglucose predict neoadjuvant chemotherapy response of breast cancer? ----a pilot study.
PLoS ONE
PUBLISHED: 01-01-2013
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To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) (18)F-fluoroestradiol ((18)F-FES) and (18)F-fluorodeoxyglucose ((18)F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer.
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What is Visualize?

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

How does it work?

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

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.