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Find video protocols related to scientific articles indexed in Pubmed.
RNAi Knockdown of Hypoxia-Inducible Factor-1? Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.
Cell Biochem. Biophys.
PUBLISHED: 11-13-2014
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The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1?). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1? inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1? was achieved by HIF-1?-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1? and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1? expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1? further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1? could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.
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Lipozyme RM IM-Catalyzed Acidolysis of Cinnamomum camphora Seed Oil with Oleic Acid To Produce Human Milk Fat Substitutes Enriched in Medium-Chain Fatty Acids.
J. Agric. Food Chem.
PUBLISHED: 10-17-2014
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In the present study, a human milk fat substitute (HMFS) enriched in medium-chain fatty acids (MCFAs) was synthesized through acidolysis reaction from Cinnamomum camphora seed oil (CCSO) with oleic acid in a solvent-free system. A commercial immobilized lipase, Lipozyme RM IM, from Rhizomucor miehei, was facilitated as a biocatalyst. Effects of different reaction conditions, including substrate molar ratio, enzyme concentration, reaction temperature, and reaction time were investigated using response surface methodology (RSM) to obtain the optimal oleic acid incorporation. After optimization, results showed that the maximal incorporation of oleic acid into HMFS was 59.68%. Compared with CCSO, medium-chain fatty acids at the sn-2 position of HMFS accounted for >70%, whereas oleic acid was occupied predominantly at the sn-1,3 position (78.69%). Meanwhile, triacylglycerol (TAG) components of OCO (23.93%), CCO (14.94%), LaCO (13.58%), OLaO (12.66%), and OOO (11.13%) were determined as the major TAG species in HMFS. The final optimal reaction conditions were carried out as follows: substrate molar ratio (oleic acid/CCSO), 5:1; enzyme concentration, 12.5% (w/w total reactants); reaction temperature, 60 °C; and reaction time, 28 h. The reusability of Lipozyme RM IM in the acidolysis reaction was also evaluated, and it was found that it could be reused up to 9 times without significant loss of activities. Urea inclusion method was used to separate and purify the synthetic product. As the ratio of HMFS/urea increased to 1:2, the acid value lowered to the minimum. In a scale-up experiment, the contents of TAG and total tocopherols in HMFS (modified CCSO) were 77.28% and 12.27 mg/100 g, respectively. All of the physicochemical indices of purified product were within food standards. Therefore, such a MCFA-enriched HMFS produced by using the acidolysis method might have potential application in the infant formula industry.
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Retroperitoneoscopic Anatomical Necrosectomy: A Modified Single-Stage Video-Assisted Retroperitoneal Approach for Treatment of Infected Necrotizing Pancreatitis.
Surg Innov
PUBLISHED: 10-16-2014
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Background. Video-assisted retroperitoneal necrosectomy is a minimally invasive surgical technique for the treatment of severe acute pancreatitis. This study evaluated the safety and feasibility of a modified single-stage video-assisted retroperitoneal necrosectomy, retroperitoneoscopic anatomical necrosectomy (REAN). Methods. Between September 2010 and May 2012, a total of 17 patients with infected necrotizing pancreatitis underwent REAN. The surgical procedures were similar to retroperitoneoscopic pancreatectomy, in which 3 trocars are utilized. Briefly, the perirenal space was entered through the posterior pararenal space. Dissection proceeded from posterior to anterior direction to expose the dorsal side of the perirenal fascia. This was opened to reach the anterior perirenal space, where the peripancreatic abscess was located. Necrotic tissue was then debrided and catheter drainage was performed in a single stage. Results. Operating time ranged from 45 to 100 minutes with minimal blood loss. All patients recovered except for one who died. Major perisurgical complications included peritoneal injury (1 patient), splenic vein injury (1 patient), retroperitoneal infection with paralytic ileus (1 patient), hydrothorax and atelectasis (2 patients), and subcutaneous cellulitis beneath the incision (3 patients). Two patients required additional percutaneous catheter drainage, and 1 patient required a laparotomy to debride the remaining necrotic tissue. Postoperative hospital stay ranged from 21 to 64 days. Conclusions. This study demonstrates that REAN, a modified single-stage video-assisted retroperitoneal approach, was safe and feasible for the treatment of infected necrotizing pancreatitis. The advantages of this procedure include direct access with shorter operating time, complete necrotic tissue debridement, easy hemostasis, simple manipulation, and easy drainage.
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Virologic Resistance Analysis From a Phase 2 Study of MK-5172 Combined With Pegylated Interferon/Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Infection.
Clin. Infect. Dis.
PUBLISHED: 09-28-2014
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?Virologic failure following treatment of hepatitis C virus (HCV) genotype 1 with direct-acting antiviral agents is often accompanied by the emergence of resistant variants. MK-5172 is an investigational once-daily protease inhibitor. We analyzed variants in treatment-naive noncirrhotic patients with virologic failure on MK-5172 (100-800 mg/day) plus pegylated interferon alfa/ribavirin (peg-IFN/RBV) during a phase 2 trial.
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[Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Chinese children: a primary study on clinical characteristics and gene mutations].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 09-26-2014
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To study the clinical features and gene mutations of EBV-HLH in Chinese children.
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[The measurement of the third-order branches of the mesenteric artery tone by microvascular ring technique].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 09-24-2014
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In our study, the function of the third-order branches of the mesentenc artery was measured by microvascular ring technique, which can be used to detect microvascular function in some disease related to microvascular dysfunction.
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Thermocapillary effect on the dynamics of viscous beads on vertical fiber.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 09-09-2014
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The gravity-driven flow of a thin liquid film down a uniformly heated vertical fiber is considered. This is an unstable open flow that exhibits rich dynamics including the formation of droplets, or beads, driven by a Rayleigh-Plateau mechanism modified by the presence of gravity as well as the variation of surface tension induced by temperature disturbance at the interface. A linear stability analysis and a nonlinear simulation are performed to investigate the dynamic of axisymmetric disturbances. The results showed that the Marangoni instability and the Rayleigh-Plateau instability reinforce each other. With the increase of the thermocapillary effect, the fiber flow has a tendency to break up into smaller droplets.
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Effect of CYP2C9-VKORC1 interaction on warfarin stable dosage and its predictive algorithm.
J Clin Pharmacol
PUBLISHED: 09-04-2014
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This study aimed to identify the effect of CYP2C9-VKORC1 interaction on warfarin dosage requirement and its predictive algorithm by investigating four populations. Generalized linear model was used to evaluate the relationship between the interaction and warfarin stable dosage (WSD), whereas multiple linear regression analysis was applied to construct the WSD predictive algorithm. To evaluate the effect of CYP2C9-VKORC1 interaction on the predictive algorithms, we compared the algorithms with and without the interaction. The interaction was significantly associated with WSD in the Chinese and White cohorts (P values?
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Effects of intravenous bolus injection of emulsified isoflurane on QTc interval of healthy volunteers in Pharmacokinetics study.
Pak J Pharm Sci
PUBLISHED: 09-02-2014
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Emulsified isoflurane is a novel intravenous anesthetic, which is a lipid emulsion of isoflurane. As some drugs have a QTc-prolongation effect which can increase a risk of arrhythmia, this study was to evaluate the effects of emulsified isoflurane on the QTc interval. This was a single-center, randomized, single-blind, non-comparative study. Subjects were randomly allocated to receive an intravenous bolus injection of 22.63, 38.26, or 49.73 mg/kg emulsified isoflurane, respectively. Standard 12-lead electrocardiograms were recorded before administration and at 28 timepoints after administration. Blood samples and the end-tidal isoflurane concentrations were collected for pharmacokinetic analysis. The primary target variable was the QTcF change from baseline at each time point. A two-sided 90% confidence interval (CI) was calculated for a QTcF change from baseline at each timepoint. The maximal 90% CIs of the mean QTcF from the baseline for 22.63, 38.26 and 49.73mg/kg emulsified isoflurane were 2.52-21.18 ms, 15.66-35.90 ms, and 17.65-40.71 ms, respectively. Non-significant relationship was observed between QTcF and the plasma concentration (or the end-tidal isoflurane concentration). Single intravenous dose of emulsified isoflurane of the anticipated therapeutic dose or supra-therapeutic doses was associated with a potential dose-dependent and non-concentration-related QTc-prolongation effect.
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A Semi-mechanistic Model for the Effects of a Novel Glucagon Receptor Antagonist on Glucagon and the Interaction Between Glucose, Glucagon, and Insulin Applied to Adaptive Phase II Design.
AAPS J
PUBLISHED: 08-27-2014
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A potent novel compound (MK-3577) was developed for the treatment of type 2 diabetes mellitus (T2DM) through blocking the glucagon receptor. A semi-mechanistic model was developed to describe the drug effect on glucagon and the interaction between glucagon, insulin, and glucose in healthy subjects (N?=?36) during a glucagon challenge study in which glucagon, octreotide (Sandostatin), and basal insulin were infused for 2 h starting from 3, 12, or 24 h postdose of a single 0-900 mg MK-3577 administration. The drug effect was modeled by using an inhibitory E max model (I max?=?0.96 and IC50?=?13.9 nM) to reduce the ability of glucagon to increase the glucose production rate (GPROD). In addition, an E max model (E max?=?0.79 and EC50?=?575 nM) to increase glucagon secretion by the drug was used to account for the increased glucagon concentrations prechallenge (via compensatory feedback). The model adequately captured the observed profiles of glucagon, glucose, and insulin pre- and postchallenge. The model was then adapted for the T2DM patient population. A linear model to correlate fasting plasma glucose (FPG) to weighted mean glucose (WMG) was developed and provided robust predictions to assist with the dose adjustment for the interim analysis of a phase IIa study.
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Medaka Oct4 is Essential for Pluripotency in Blastula Formation and ES Cell Derivation.
Stem Cell Rev
PUBLISHED: 08-21-2014
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The origin and evolution of molecular mechanisms underlying cellular pluripotency is a fundamental question in stem cell biology. The transcription factor Oct4 or Pou5f1 identified in mouse features pluripotency expression and activity in the inner cell mass and embryonic stem (ES) cells. Pou2 identified in zebrafish is the non-mammalian homolog prototype of mouse Oct4. The genes oct4 and pou2 have reportedly evolved by pou5 gene duplication in the common ancestor of vertebrates. Unlike mouse oct4, however, zebrafish pou2 lacks pluripotency expression and activity. Whether the presence of pluripotency expression and activity is specific for mammalian Oct4 or common to the ancestor of vertebrate Oct4 and Pou2 proteins has remained to be determined. Here we report that Oloct4, the medaka oct4/pou2, is essential for early embryogenesis and pluripotency maintenance. Oloct4 exists as a single copy gene and is orthologous to pou2 by sequence and chromosome synteny. Oloct4 expression occurs in early embryos, germ stem cells and ES cells like mouse oct4 but also in the brain and tail bud like zebrafish pou2. Importantly, OlOct4 depletion caused blastula lethality or blockage. We show that Oloct4 depletion abolishes ES cell derivation from midblastula embryos. Thus, Oloct4 has pluripotency expression and is essential for early embryogenesis and pluripotency maintenance. Our results demonstrate the conservation of pluripotency expression and activity in vertebrate Oct4 and Pou2 proteins. The finding that Oloct4 combines the features of mouse oct4 and zebrafish pou2 in expression and function suggests that Oloct4 might represent the ancestral prototype of vertebrate oct4 and pou2 genes.
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Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis.
J. Infect.
PUBLISHED: 08-16-2014
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Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Until recently, SFTSV-associated encephalitis remained largely uninvestigated.
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AMPK Activation Ameliorates Alzheimer's Disease-Like Pathology and Spatial Memory Impairment in a Streptozotocin-Induced Alzheimer's Disease Model in Rats.
J. Alzheimers Dis.
PUBLISHED: 08-11-2014
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Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is thought to be a convergent point of the two diseases. However, the underlying mechanisms of diabetes-associated AD are still unclear. In the current study, we investigated the roles of AMPK in diabetes-related AD-like pathologic features in models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and SIRT1 activity were decreased and the level of phosphorylated tau was increased at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats. Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial membrane potential, complex I activity, ATP level, and superoxide dismutase activity as well as an increase of reactive oxygen species production when compared with that from control rats. Meanwhile the number of apoptotic cell confirmed by cleaved caspase-3 (active type of caspase-3) staining was also stronger in ICV-STZ rats than control rats. All pathological changes including biochemistry and cognitive function could be mitigated through rescuing AMPK activity with its specific activator (AICAR) in ICV-STZ rats. Taken together, these results suggested that AMPK activation improves AD-like pathological changes via repairing mitochondrial functions in ICV-STZ rats.
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Diagnostic performance of the three-dimensional fast spin echo-Cube sequence in comparison with a conventional imaging protocol in evaluation of the lachrymal drainage system.
Eur Radiol
PUBLISHED: 08-05-2014
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To compare the three-dimensional (3D)-fast spin-echo (FSE)-Cube with a conventional imaging protocol in evaluation of dacryostenosis.
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Oxidative stress induces endothelial cell senescence via downregulation of Sirt6.
Biomed Res Int
PUBLISHED: 08-05-2014
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Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated ?-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.
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[Clinical features and outcome of eight patients with mediastinal and neck hematoma after transradial cardiac catheterization approach].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-22-2014
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The clinical features of patients with mediastinal and/or neck hematoma after transradial cardiac catheterization were reviewed and analyzed to help the clinicians to recognize this complication, and try their best to avoid the complication and treat the complication properly.
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Novel multipotent AChEI-CCB attenuates hyperhomocysteinemia-induced memory deficits and Neuropathologies in rats.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
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Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3?. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
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[Cardiac ischemia in type 2 diabetes mellitus rats induced by high sucrose and high fat diet and STZ treated].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 07-15-2014
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To build a type 2 diabetes mellitus rat model with cardiac ischemia.
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Imparting superhydrophobicity to biodegradable poly(lactide-co-glycolide) electrospun meshes.
Biomacromolecules
PUBLISHED: 06-20-2014
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The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA-PGC18) copolymers and their use as biodegradable polymer dopants is reported to enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven meshes. Solutions of PLGA are doped with PLA-PGC18 and electrospun to form meshes with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer composition influence the nonwetting nature of the meshes and alter their mechanical (tensile) properties. Contact angles as high as 160° are obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal foreign body response when implanted in mice. In summary, a general method for constructing biodegradable fibrous meshes with tunable hydrophobicity is described for use in tissue engineering and drug delivery applications.
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Decreased RGS6 expression is associated with poor prognosis in pancreatic cancer patients.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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Regulator of G-protein signaling 6 (RGS6), a member of a family of RGS proteins, has been reported to involve in multiple processes during tumor development. However, its role in pancreatic cancer has not been studied yet. In this study, we aimed to investigate the expression of RGS6 in pancreatic cancer and its role in predicting outcomes of patients with pancreatic cancer. We first measured the expression of RGS6 mRNA in 20 cases of tumor tissues and matched adjacent non-tumorous tissues by quantitative real-time PCR and examined RGS6 protein by immunohistochemistry in tissue microarrays containing 90 tumor and 90 paired adjacent non-tumor tissues. Decreased RGS6 mRNA detected in primary tumor, compared with their non-tumor counterparts. In addition, decreased RGS6 protein expression was associated with tumor differentiation (P = 0.027), pT classification (P = 0.034), smoking status (P = 0.041) and a poor survival (P = 0.007). Cox proportional hazards regression modeling analysis revealed that lymph node metastasis (P = 0.001; hazard ratio, 2.347, 95% CI, 1.387-3.972), tumor differentiation (P = 0.015; hazard ratio, 0.505, 95% CI, 0.291-0.876) and RGS6 expression (P = 0.048; hazard ratio, 0.567, 95% CI, 0.324-0.994) were three independent prognostic factors. Taken together, these date demonstrate that RGS6 decreases in tumor tissue and may serve as a novel biomarker for outcomes in pancreatic cancer patients and be a potential therapeutic target potential therapeutic target.
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Nicotine Accelerates Diabetes-Induced Retinal Changes.
Curr. Eye Res.
PUBLISHED: 06-10-2014
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Abstract Purpose: To investigate the effects of nicotine on retinal alterations in early-stage diabetes in an established rodent model. Materials and Methods: Sprague-Dawley rats were examined using a combination of confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography to determine changes in retinal structure in response to nicotine exposure, diabetes and the combined effects of nicotine and diabetes. Diabetes was induced by a single injection of 65?mg/kg streptozotocin and nicotine injections were administered subcutaneously daily. Retinal thickness in the superior, inferior, nasal and temporal quadrants were determined based on the spectral domain optical coherence tomography (SD-OCT) volume scans (20°?×?20°) centered on the optic disc. Segmentation of discrete retinal layers was performed on a subset of SD-OCT cross-sections to further examine changes in each treatment group. Survival of neurons within the ganglion cell layer (GCL) was assessed by confocal morphometric imaging. Results: The control group did not experience any significant change throughout the study. The nicotine treatment group experienced an average decrease in total retinal thickness (TRT) of 9.4?µm with the majority of the loss localized within the outer nuclear layer (ONL) as determined by segmentation analysis (p?
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WWOX suppresses KLF5 expression and breast cancer cell growth.
Chin. J. Cancer Res.
PUBLISHED: 06-06-2014
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The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX's role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5-an oncogenic transcription factor-at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former's WW domains and the latter's PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.
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Two anatomical pathways for retroperitoneoscopic pancreatectomy: indications for the posterior and lateral approaches.
World J Surg
PUBLISHED: 05-29-2014
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Retroperitoneoscopic pancreatectomy (RP) is a novel surgical procedure that is safe and feasible in animal models and clinical practice. However, the optimal approach for RP has not been established.
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Single-port and multi-port laparoscopic left lateral liver sectionectomy for treating benign liver diseases: a prospective, randomized, controlled study.
World J Surg
PUBLISHED: 05-29-2014
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The use of single-port laparoscopy for left-lateral liver sectionectomy (LLLS) has been reported in the literature, but the effectiveness and safety of LLLS has not been validated in randomized, controlled trials. This prospective randomized controlled trial compared the effectiveness and safety of single-port and multi-port laparoscopic LLLS for the surgical treatment of benign liver disease.
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Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome.
World J. Gastroenterol.
PUBLISHED: 05-16-2014
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To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome (D-IBS).
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A randomized clinical trial of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy for the treatment of morbid obesity in China: a 5-year outcome.
Obes Surg
PUBLISHED: 05-16-2014
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No randomized comparative trials have presented long-term outcomes for laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). The present study was designed to compare the efficacy and safety of these two procedures.
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Presence of autoantibodies against ?1-adrenoceptor aggravates the kidney injury in rats.
Sheng Li Xue Bao
PUBLISHED: 04-30-2014
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Since the autoantibodies against the second extracellular loop of ?(1)-adrenoceptor (?(1)-AABs) have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDCM), the involvement of autoimmune mechanisms in the pathogenesis of many cardiovascular diseases has extensively been investigated. Our previous study found that urinary occult blood and protein excretion were frequently found in the rats with positive ?(1)-AABs, but the mechanisms are unclear. Therefore, we infused the ?(1)-AABs into the vein periodically in an attempt to investigate whether ?(1)-AABs could induce morphological and functional changes in the kidneys of adult and aged rats and explore the possible mechanisms. The synthetic peptide according to the sequences of the second extracellular loop of ?(1)-adrenoceptor (?(1)-AR-ECII) was used to immunize the adult rats to acquire enough ?(1)-AABs for use. Neonatal rat ventricular myocytes (NRVMs) culture was used to observe the biological effects of ?(1)-AABs on the beating rate. The purified ?(1)-AABs were transfused into the vein of rats. The sera level of blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), urinary specific gravity, protein excretion, occult blood and urinary glucose were detected at the different time points by biochemistry and urine analyzers. HE and Masson's trichrome staining were used to detect the changes in kidney structure of passively immunized rats. Enhanced green fluorescent protein (EGFP) and ?(1)-AR-EGFP plasmids were transfected into the human embryonic kidney 293 (HEK293) cells in order to observe the changes in cell injury with the treatment of ?(1)-AABs. It was found that the sera level of BUN, CR and UA increased gradually and the ratio of BUN to CR decreased progressively with the administration of ?(1)-AABs. The increasing of proteinuria, urinary occult blood and urinary glucose was detected by urine analyzer in ?(1)-AABs group. By HE and Masson's coloration, lots of mononuclear cell infiltration and collagen fibers deposition could be observed at the 24th week of immunization. After the treatment of ?(1)-AABs, the caspase-3 activity increased significantly in the HEK293 cells transfected with ?(1)-AR-EGFP plasmids, while no significant changes were observed for lactate dehydrogenase (LDH) activity. The results indicate that long-term presence of ?(1)-AABs can induce the morphological and functional damage of the kidneys in adult and aged rats.
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Do static and dynamic insulin resistance indices perform similarly in predicting pre-diabetes and type 2 diabetes?
Diabetes Res. Clin. Pract.
PUBLISHED: 04-11-2014
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We designed a study to compare the predictive power of static and dynamic insulin resistance indices for categorized pre-diabetes (PDM)/type 2 diabetes (DM).
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Changes in HIV incidence among people who inject drugs in Taiwan following introduction of a harm reduction program: a study of two cohorts.
PLoS Med.
PUBLISHED: 04-01-2014
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Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.
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Polymeric micelles with citraconic amide as pH-sensitive bond in backbone for anticancer drug delivery.
Int J Pharm
PUBLISHED: 03-21-2014
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A novel pH-sensitive polymeric micelle was reported. Methoxy poly(ethylene glycol)-b-poly(?-caprolactone) copolymer with citraconic amide as pH-sensitive bond was synthesized (mPEG-pH-PCL). The copolymers self-assembled into micelles to encapsulate anticancer drug doxorubicin (DOX). The morphology, size and size distribution, drug release profile and in vitro anticancer activity of the DOX loaded mPEG-pH-PCL micelles were studied. The results showed that the mean size of the micelles was around 120 nm, the drug loading content and encapsulation efficiency of the mPEG-pH-PCL micelles were 6.8% and 54.3%, respectively. The mean diameter and size distribution of the mPEG-pH-PCL micelles increased significantly when soaking in medium with pH 5.5. The drug release of micelles in pH 5.5 was much faster than that in pH 7.4. The confocal laser microscopy and flow cytometry measurements indicated that the weak acidity of endosomes broke the citraconic amide bonds in the copolymer backbones and triggered the fast release of DOX. The in vitro IC50 of the drug loaded mPEG-pH-PCL micelles was lower than that of drug loaded polymeric micelles without pH-sensitivity to both HepG2 and 4T1 cancer cells.
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Plasma ferritin levels, HFE polymorphisms, and risk of pancreatic cancer among Chinese Han population.
Tumour Biol.
PUBLISHED: 03-01-2014
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The etiology of pancreatic cancer (PC) remains poorly understood. High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. The aim of this study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for PC. A case-control study was conducted to examine plasma ferritin levels (n?=?1,000 cases; 1,004 controls), two hemochromatosis gene (HFE) SNPs (n?=?1,386 cases; 1,386 controls), and PC risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression. We did not observe a significant association between plasma ferritin and PC risk. However, HFE rs1799945 was significantly associated with PC risk, with each additional copy of minor allele T being associated with a 1.21-fold increased risk of PC (OR?=?1.21, 95 % CI 1.05-1.39, P?=?7.72?×?10(-3)). Overall, high iron levels do not increase the risk of PC. Our observation that HFE rs1799945 increased PC risk warrants replication in additional study populations.
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The normative range for and age and gender effects on the Sydney Swallow Questionnaire (SSQ).
Dysphagia
PUBLISHED: 02-26-2014
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The Sydney Swallow Questionnaire (SSQ) is a validated measure of the symptomatic severity of oral-pharyngeal dysphagia. Up until now no normative ranges have been established for the questionnaire. This is a limitation in its utility as it makes it difficult to use the tool to identify the prevalence and burden of oral-pharyngeal dysphagia in the general population or within patient populations. The study's aim was to derive the normative range of dysphagia scores for the SSQ and to determine whether, in nondysphagic individuals, there are any age or gender effects on these scores. The questionnaire was administered to 73 eligible nondysphagic individuals who had been screened for any dysphagia or conditions that might predispose them to dysphagia. The frequency distribution of SSQ scores was first examined for normality and appropriate transformations performed before determining the upper limit of normal. Of the 73 healthy participants, 45 were male, and the cohort had a mean age of 58.6 years (range = 22.0-82.1 years). No statistically significant relationship between SSQ scores and either age (r s[73] = 0.140, p = 0.239) or gender (r pb[73] = 0.021, p = 0.857) was found. The mean total SSQ score (maximum possible score = 1,700) was 59.0 (SD = 56.7; range = 2-241). The frequency distribution of scores was non-normal and markedly skewed. After a Box-Cox transformation to normalise the distribution, the calculated upper limit of the reference interval was 234 with a 90 % CI of [193, 277]. The SSQ scores in a nondysphagic population are not influenced by age or gender. These data complement the existing reliability and validation data and thereby improve the overall utility of the SSQ in the context of future studies of oral-pharyngeal dysphagia prevalence, efficacy, and outcome.
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SOX10 is a novel oncogene in hepatocellular carcinoma through Wnt/?-catenin/TCF4 cascade.
Tumour Biol.
PUBLISHED: 02-24-2014
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SOX (high mobility group) genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the function role of SOXs in the human hepatocellular carcinoma (HCC). The gene expression changes of SOXs in HCC tissues compared with those in noncancerous hepatic tissues were detected using real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry. In addition, we identified the gene SOX10 that was significantly upregulated in HCC by QRT-PCR analysis and immunohistochemistry. Furthermore, we discovered that SOX10 promoted cancer cell proliferation in vitro, and SOX10 expression correlated with elevated ?-catenin levels in HCC, and ?-catenin function was required for SOX10's oncogenic effects. Mechanistically, SOX10 facilitates TCF4 to bind to ?-catenin and form a stable SOX10/TCF4/?-catenin complex and trans-activate its downstream target gene. SOX10 mutations that disrupt the SOX10-?-catenin interaction partially prevent its function in tumor cells. All in all, SOX10 is a commonly activated tumor promoter that activates Wnt/?-catenin signaling in cancer cells of HCC.
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Randomized controlled trial: moxibustion and acupuncture for the treatment of Crohn's disease.
World J. Gastroenterol.
PUBLISHED: 02-10-2014
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To evaluate the clinical efficacy and safety of acupuncture and moxibustion for the treatment of active Crohn's disease (CD).
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RBRDetector: improved prediction of binding residues on RNA-binding protein structures using complementary feature- and template-based strategies.
Proteins
PUBLISHED: 02-02-2014
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Computational prediction of RNA-binding residues is helpful in uncovering the mechanisms underlying protein-RNA interactions. Traditional algorithms individually applied feature- or template-based prediction strategy to recognize these crucial residues, which could restrict their predictive power. To improve RNA-binding residue prediction, herein we propose the first integrative algorithm termed RBRDetector (RNA-Binding Residue Detector) by combining these two strategies. We developed a feature-based approach that is an ensemble learning predictor comprising multiple structure-based classifiers, in which well-defined evolutionary and structural features in conjunction with sequential or structural microenvironment were used as the inputs of support vector machines. Meanwhile, we constructed a template-based predictor to recognize the putative RNA-binding regions by structurally aligning the query protein to the RNA-binding proteins with known structures. The final RBRDetector algorithm is an ingenious fusion of our feature- and template-based approaches based on a piecewise function. By validating our predictors with diverse types of structural data, including bound and unbound structures, native and simulated structures, and protein structures binding to different RNA functional groups, we consistently demonstrated that RBRDetector not only had clear advantages over its component methods, but also significantly outperformed the current state-of-the-art algorithms. Nevertheless, the major limitation of our algorithm is that it performed relatively well on DNA-binding proteins and thus incorrectly predicted the DNA-binding regions as RNA-binding interfaces. Finally, we implemented the RBRDetector algorithm as a user-friendly web server, which is freely accessible at http://ibi.hzau.edu.cn/rbrdetector.
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Comparative studies on the interactions of dihydroartemisinin and artemisinin with bovine serum albumin using spectroscopic methods.
Luminescence
PUBLISHED: 01-24-2014
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The interactions of dihydroartemisinin (DHA) and artemisinin (ART) with bovine serum albumin (BSA) have been investigated using fluorescence, UV/vis absorption and Fourier transform infrared (FTIR) spectra under simulated physiological conditions. The binding characteristics of DHA/ART and BSA were determined by fluorescence emission and resonance light scattering (RLS) spectra. The quenching mechanism between BSA and DHA/ART is static. The binding constants and binding sites of DHA/ART-BSA systems were calculated at different temperatures (293, 298, 304 and 310?K). According to Förster non-radiative energy transfer theory, the binding distance of BSA to DHA/ART was calculated to be 1.54/1.65?nm. The effect of DHA/ART on the secondary structure of BSA was analyzed using UV/vis absorption, FTIR, synchronous fluorescence and 3D fluorescence spectra. In addition, the effects of common ions on the binding constants of BSA-DHA and BSA-ART systems were also discussed. Copyright © 2014 John Wiley & Sons, Ltd.
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A method for real-time measurement of respiratory rhythms in medaka (Oryzias latipes) using computer vision for water quality monitoring.
Ecotoxicol. Environ. Saf.
PUBLISHED: 01-18-2014
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The respiratory rhythms of Japanese medaka is considered to be an efficient indicator for monitoring water quality since they are sensitive to chemicals and can be measured directly from the movement of fish gill tissue generated by their breathe. However, few methods have been established to measure the feature of small free-swimming fish intuitively. In this article, a method is proposed to measure the influence of the pollution to the Japanese medaka's respiratory rhythms with computer vision technology in real time. In order to get the images which contains the complete gill tissue remotely and steadily, a special object container and an experiment platform are designed. With the aim of capturing Japanese medaka's respiratory rhythms in real time, a set of image processing algorithms such as the color distribution table, Support Vector Machine (SVM), adaptive boosting (Adaboost) and mathematical morphology are applied. Then, in order to verify the effectiveness and accuracy of the whole method, fourteen groups of Japanese medakas are respectively exposed to copper ions solutions with different concentrations of 0, 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mg/L for 48 h. The comparison between the human eyes observation and the above method indicates that the data obtained through the method is generally accurate. We found that the respiratory rate of Japanese medaka showed a downward trend initially when exposed in the copper ions solution, afterwards fluctuated repeatly arounding the lower rate, before death, the respiratory rate rised slowly for a while. With the increase of concentration, this trend will be more obvious. But the above phenomenon is absolutely different from that in the standard dilution water. Moreover, the two kinds of special respiratory rhythm of medakas poisoning were discovered. This method can be widely applied to study some toxic substances' effects on Japanese medaka's respiratory rhythms and to assess the degree of risk of the water environment.
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The dineolignan from Saururus chinensis, manassantin B, inhibits tumor-induced angiogenesis via downregulation of matrix metalloproteinases 9 in human endothelial cells.
Oncol. Rep.
PUBLISHED: 01-03-2014
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Manassantin B (MB) is a neolignan isolated from Saururus chinensis that exhibits a range of activities, including anti-inflammatory, antiseptic and antitumor activity. MB was recently found to affect cell adhesion and expression of several adhesion molecules. Based on the important roles of these adhesion molecules in angiogenesis, we evaluated a possible role for MB in tumor-induced angiogenesis in endothelial cells (ECs). In the present study, we found that MB blocked tumor-induced tube formation of ECs and significantly inhibited the invasion of ECs through the reconstituted basement membrane. MB suppressed the activity of matrix metalloproteinases (MMPs) and downregulated the expression of matrix metalloproteinases 9. Western blotting showed reduction of RUNX2 activation by MB. RUNX2 transcription factor assay and chromatin immunoprecipitation assay showed that the interaction between RUNX2 and target sequences in the matrix metalloproteinases 9 promoters was inhibited by MB. Our findings suggested that the inhibitory effects of MB on tumor-induced angiogenesis were caused by matrix metalloproteinases 9 inhibition, which was associated with the downregulation of RUNX2 transcriptional activity.
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Circulating tumor cells in the central and peripheral venous compartment - assessing hematogenous dissemination after transarterial chemoembolization of hepatocellular carcinoma.
Onco Targets Ther
PUBLISHED: 01-01-2014
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The aims of this study were to assess the effect of transarterial chemoembolization (TACE) on circulating tumor cells (CTCs) in the peripheral blood and right atrium of patients with HCC and to evaluate whether perioperative shedding of CTCs affects time to progression of HCC. Before and after TACE, peripheral and right atrial blood samples (7.5 mL) were collected from 42 patients with HCC. CTCs were enriched using EpCAM antibody-conjugated magnetic beads. The number of CTCs was 0-30 and 0-54 in peripheral blood before and after TACE, respectively (P=0.166), and 0-65 and 0-98 in the right atrium before and after TACE, respectively (P=0.102). The number of CTCs was significantly different between the two samples both before (P=0.007) and after (P=0.021) TACE. There was no difference in time to progression between patients with and without an increase in the number of CTCs after TACE in either sample (P>0.05 for both). There were more CTCs in right atrial blood than in peripheral blood. The numbers of CTCs in both samples remained unchanged after TACE. Shedding of tumor cells did not affect time to progression of disease in patients with HCC.
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Effects of interface pressure distribution on human sleep quality.
PLoS ONE
PUBLISHED: 01-01-2014
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High sleep quality promotes efficient performance in the following day. Sleep quality is influenced by environmental factors, such as temperature, light, sound and smell. Here, we investigated whether differences in the interface pressure distribution on healthy individuals during sleep influenced sleep quality. We defined four types of pressure models by differences in the area distribution and the subjective feelings that occurred when participants slept on the mattresses. One type of model was showed "over-concentrated" distribution of pressure; one was displayed "over-evenly" distributed interface pressure while the other two models were displayed intermediate distribution of pressure. A polysomnography analysis demonstrated an increase in duration and proportion of non-rapid-eye-movement sleep stages 3 and 4, as well as decreased number of micro-arousals, in subjects sleeping on models with pressure intermediately distributed compared to models with over-concentrated or over-even distribution of pressure. Similarly, higher scores of self-reported sleep quality were obtained in subjects sleeping on the two models with intermediate pressure distribution. Thus, pressure distribution, at least to some degree, influences sleep quality and self-reported feelings of sleep-related events, though the underlying mechanisms remain unknown. The regulation of pressure models imposed by external sleep environment may be a new direction for improving sleep quality. Only an appropriate interface pressure distribution is beneficial for improving sleep quality, over-concentrated or -even distribution of pressure do not help for good sleep.
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Discrimination of Adulterated Milk Based on Two-Dimensional Correlation Spectroscopy (2D-COS) Combined with Kernel Orthogonal Projection to Latent Structure (K-OPLS).
Appl Spectrosc
PUBLISHED: 12-24-2013
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A new method for discrimination analysis of adulterated milk and pure milk is proposed by combining two-dimensional correlation spectroscopy (2D-COS) with kernel orthogonal projection to latent structure (K-OPLS). Three adulteration types of milk with urea, melamine, and glucose were prepared, respectively. The synchronous 2D spectra of adulterated milk and pure milk samples were calculated. Based on the characteristics of 2D correlation spectra of adulterated milk and pure milk, a discriminant model of urea-tainted milk, melamine-tainted milk, glucose-tainted milk, and pure milk was built by K-OPLS. The classification accuracy rates of unknown samples were 85.7, 92.3, 100, and 87.5%, respectively. The results show that this method has great potential in the rapid discrimination analysis of adulterated milk and pure milk.
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Toxicity Mechanisms in Escherichia coli Vary for Silver Nanoparticles and Differ from Ionic Silver.
ACS Nano
PUBLISHED: 12-24-2013
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Silver nanoparticles (Ag NPs) are commonly added to various consumer products and materials to impair bacterial growth. Recent studies suggested that the primary mechanism of antibacterial action of silver nanoparticles is release of silver ion (Ag(+)) and that particle-specific activity of silver nanoparticles is negligible. Here, we used a genome-wide library of Escherichia coli consisting of ?4000 single gene deletion mutants to elucidate which physiological pathways are involved in how E. coli responds to different Ag NPs. The nanoparticles studied herein varied in both size and surface charge. AgNO3 was used as a control for soluble silver ions. Within a series of differently sized citrate-coated Ag NPs, smaller size resulted in higher Ag ion dissolution and toxicity. Nanoparticles functionalized with cationic, branched polyethylene imine (BPEI) exhibited equal toxicity with AgNO3. When we used a genome-wide approach to investigate the pathways involved in the response of E. coli to different toxicants, we found that only one of the particles (Ag-cit10) exhibited a pattern of response that was statistically similar to that of silver ion. By contrast, the pathways involved in E. coli response to Ag-BPEI particles were more similar to those observed for another cationic nanoparticle that did not contain Ag. Overall, we found that the pathways involved in bacterial responses to Ag nanoparticles are highly dependent on physicochemical properties of the nanoparticles, particularly the surface characteristics. These results have important implications for the regulation and testing of silver nanoparticles.
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Influence study of solving correction forces caused by fitting errors for thin meniscus mirror.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 12-11-2013
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The actuator influence functions of a thin meniscus mirror can be expanded in Zernike polynomials. And the correctness of influence functions has a great effect on solving the correction forces. The Zernike coefficients are applied as parameters in the all-floating support system. We analyze the main interferential factors when different deformation modes are corrected. The influence caused by fitting errors is studied in this paper. A preferable result can be obtained after eliminating the interferential factors. The method can obtain useful correction forces. Comparing the peak-to-valley and root mean square values among the results calculated by different accuracy influence functions, we find that there is a limited convergence property when the accuracy increases.
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Diagnosis of Fanconi anemia in children with atypical clinical features: a primary study.
Chin. Med. J.
PUBLISHED: 11-30-2013
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Fanconi anemia is a severe congenital disorder associated with mutations in a cluster of genes responsible for DNA repair. Arriving at an accurate and timely diagnosis can be difficult in cases of Fanconi anemia with atypical clinical features. It is very important to increase the rate of accurate diagnosis for such cases in a clinical setting. The purpose of this study is to explore the clinical diagnosis of Fanconi anemia in children with atypical clinical features.
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Effect of cytotoxic T-lymphocyte-associated protein 4 on CD4(+)CD25(+) regulatory T cells in murine Schistosomiasis japonica.
Exp. Parasitol.
PUBLISHED: 11-11-2013
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In a previous study we demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) contributed to the escape of Schistosoma japonicum (S. japonicum) from the hosts immune responses. In this paper, we studied the effect of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on CD4(+)CD25(+) Tregs in murine Schistosomiasis japonica and its corresponding role in the immune evasion of S. japonicum in mice. The results showed substantial reductions of worm burden and egg production in worm groups treated with anti-CD25 or anti-CTLA-4 monoclonal antibodies (mAb) compared to an infected but untreated control. The reduction effect was even enhanced in an experimental group co-treated with both mAbs. Compared to the control group, the percentage of CD4(+)CD25(+) Tregs was very much lower in the anti-CD25 mAb group as determined by FACS analyses and higher in the anti-CTLA-4 mAb group. ELISA analyses showed that both the anti-CTLA-4 mAb and the co-treated groups had higher levels of cytokines compared to the control group as well as larger egg granuloma sizes as determined by microscopical analyses of liver sections of infected mice. These results suggest that treatment with an anti-CTLA-4 mAb allows the host to clear S. japonicum, but at the cost of elevated pathological damage. The latter indicated a role of CTLA-4 in granuloma formation. Moreover, CD4(+)CD25(+) Tregs and CTLA-4 may exert synergistic effects during immune evasion processes by enhancing Th1-type immune response.
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[Application of kernel orthogonal projection to latent structure discriminant analysis in the discrimination of adulterated milk].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-29-2013
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Based on the method of kernet Orthogonal Projection to Latent Structure Discriminant Analysis, discrimination models for adulterated milk were established in the present paper. Forty adulterated milk samples with melamine (0.01-3 g x L(-1)) and 40 adulterated milk samples with urea (1-20 g x L(-1)) were prepared, respectively. Then the near-infrared absorption spectra of all samples were measured. The spectra in the range of 4 200-4 800 cm(-1) were selected to construct the KOPLS-DA models for milk adulterated with melamine, milk adulterated with urea and milk adulterated with both melamine and urea. The results showed that, compared with PLS-DA and OPLS-DA models, KOPLS-DA model had better discriminant ability for the adulterated milk, and its classification accuracy rate (CAR) for milk adulterated with melamine, milk adulterated with urea and milk adulterated with both melamine and urea were 95%, 100% and 97.5%, respectively.
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Adaptive power projection method for accumulative EEG classification.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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For the dynamic classification of motor imagery mind states in the brain-computer interface (BCI), we propose a power projection based feature extraction method to classify the electroencephalogram (EEG) signals by combining information accumulative posterior Bayesian approach. This method improves the classification accuracy by maximizing the average projection energy difference of the two types of signals. The experimental results on two BCI competition datasets show that the classification accuracy is about 90%. The results of the classification accuracy and mutual information demonstrate the effectiveness of this method.
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Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination.
Stem Cells Dev.
PUBLISHED: 09-26-2013
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Multiple sclerosis (MS) is an irreversible and demyelinating disease of the central nervous system, in part influenced by chronic inflammation. There is no proven effective therapy to stop the pathological progression of MS, although suppressing the immune system to control the inflammatory response may improve the clinical performance acutely. Here, we found that mesenchymal stem cells from human umbilical cord (hUC-MSCs) could restore behavioral functions and attenuate the histopathological deficits of experimental autoimmune encephalomyelitis mice over the long term (i.e., 50 days) by suppression of perivascular immune cell infiltrations and reduction in both demyelination and axonal injury in the spinal cord. These findings suggest that transplantation of hUC-MSCs may be a potential therapy for MS.
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Increased metastatic potential of residual carcinoma after transarterial embolization in rat with McA?RH7777 hepatoma.
Oncol. Rep.
PUBLISHED: 09-09-2013
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Transarterial chemoembolization represents a first-line non-curative therapy for hepatocellular carcinoma (HCC), although the biological changes in the remaining cancer after embolization are not completely understood. In the present study, we examined whether transarterial embolization (TAE) enhances the metastatic potential of residual HCC and investigated the mechanisms underlying embolization. The hepatoma cell line McA-RH7777, which is marked by green fluorescent protein (GFP), was used in the study. The invasion of cells cultured under hypoxia and normoxia was observed using the Transwell assay. Twenty male buffalo rats were implanted with GFP transfected McA-RH7777 tumors in the left lateral lobe of the liver. After laparotomy and retrograde placement of a catheter into the gastroduodenal artery (on the 14th day after implantation), TAE using lipiodol (0.2 ml/kg) was performed. Tumor volumes were measured before and after treatment using magnetic resonance imaging (MRI). Lung metastases were observed using fluorescence imaging, and the molecular changes of residual tumor cells were evaluated by western blotting or immunohistochemistry. The invasion assays indicated that the number of invading hypoxic cells was significantly higher than that of normoxic cells (30.2±2.46 vs. 20.4±1.89, P=0.013). Accompanying an increase in hypoxia-inducible factor-1? (HIF-1?) expression, the metastatic potential of tumor cells following hypoxia or TAE was enhanced. This enhanced metastatic potential was indicated by a significant reduction in the expression of E-cadherin and an upregulation of N-cadherin and vimentin expression. The number of lung metastases in the TAE group was 19.20±1.76, whereas this number was 11.30±1.54 in the control group, which represented a statistically significant difference (P=0.003). In conclusion, hypoxia in the residual tumor after TAE can increase the invasiveness and metastatic potential of HCC and may be responsible for the failure of TAE.
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Discovery of MK-8742: An HCV NS5A Inhibitor with Broad Genotype Activity.
ChemMedChem
PUBLISHED: 08-22-2013
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The NS5A protein plays a critical role in the replication of HCV and has been the focus of numerous research efforts over the past few years. NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays, making them attractive components for inclusion in all oral combination regimens. Early work in the NS5A arena led to the discovery of our first clinical candidate, MK-4882 [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical proof-of-concept studies in HCV-infected chimpanzees harboring chronic genotype?1 infections resulted in significant decreases in viral load after both single- and multiple-dose treatments, viral breakthrough proved to be a concern, thus necessitating the development of compounds with increased potency against a number of genotypes and NS5A resistance mutations. Modification of the MK-4882 core scaffold by introduction of a cyclic constraint afforded a series of tetracyclic inhibitors, which showed improved virologic profiles. Herein we describe the research efforts that led to the discovery of MK-8742, a tetracyclic indole-based NS5A inhibitor, which is currently in phase?2b clinical trials as part of an all-oral, interferon-free regimen for the treatment of HCV infection.
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[Deconvolution of overlapped peaks in total ion chromatogram of essential oil from citri reticulatae pericarpium viride by automated mass spectral deconvolution & identification system].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-17-2013
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This experiment shows how to use the automated mass spectral deconvolution & identification system (AMDIS) to deconvolve the overlapped peaks in the total ion chromatogram (TIC) of volatile oil from Chineses materia medica (CMM). The essential oil was obtained by steam distillation. Its TIC was gotten by GC-MS, and the superimposed peaks in TIC were deconvolved by AMDIS. First, AMDIS can detect the number of components in TIC through the run function. Then, by analyzing the extracted spectrum of corresponding scan point of detected component and the original spectrum of this scan point, and their counterparts spectra in the referred MS Library, researchers can ascertain the components structure accurately or deny some compounds, which dont exist in nature. Furthermore, through examining the changeability of characteristic fragment ion peaks of identified compounds, the previous outcome can be affirmed again. The result demonstrated that AMDIS could efficiently deconvolve the overlapped peaks in TIC by taking out the spectrum of matching scan point of discerned component, which led to exact identification of the components structure.
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Expression of Ku86 and Presence of Ku86 Antibody as Biomarkers of Hepatitis B Virus Related Hepatocellular Carcinoma.
Dig. Dis. Sci.
PUBLISHED: 08-08-2013
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Hepatocellular carcinoma (HCC) is a common disease and the third leading cause of cancer-related deaths worldwide. Level of the 82-kDa ATP-dependent DNA helicase II (Ku86) increases in some tumors, but its clinical use as a marker for HCC is rare.
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The RNA/DNA-binding protein PSF relocates to cell membrane and contributes cells sensitivity to antitumor drug, doxorubicin.
Cytometry A
PUBLISHED: 07-28-2013
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Cell surface proteins play an important role in multidrug resistance (MDR). However, the identification involving chemoresistant features for cell surface proteins is a challenge. To identify potential cell membrane markers in hematologic cancer MDR, we used a cell- and antibody-based strategy of subtractive immunization coupled with cell surface comparative screening of leukemia cell lines from sensitive HL60 and resistant HL60/DOX cells. Fifty one antibodies that recognized the cell surface proteins expressed differently between the two cell lines were generated. One of them, the McAb-5D12 not only recognizes its antigen but also block its function. Comparative analysis of immunofluorescence, flow cytometry, and mass spectrum analysis validated that the membrane antigen of McAb-5D12 is a nucleoprotein-polypyrimidine tract binding protein associated splicing factor, PSF. Our results identified that PSF overexpressed on the membrane of sensitive cells compared with resistant cells and its relocation from the nuclear to the cell surface was common in hematological malignancy cell lines and marrow of leukemia patients. Furthermore, we found that cell surface PSF contributed to cell sensitivity by inhibiting cell proliferation. The results represent a novel and potentially useful biomarker for MDR prediction. The strategy enables the correlation of expression levels and functions of cell surface protein with some cell-drug response traits by using antibodies. © 2013 International Society for Advancement of Cytometry.
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The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism and ischemic stroke in Chinese population: a meta-analysis.
Gene
PUBLISHED: 07-27-2013
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Previous studies have indicated that the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism is associated with risk of ischemic stroke (IS), but the results remain inconclusive even in Chinese population. A meta-analysis of 10 case-control studies was conducted on the relationship between ALOX5AP SG13S114 polymorphism and susceptibility to IS in Chinese population published domestically and abroad from September 2007 to December 2012. Data were extracted by two authors and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Meta-analysis results showed that the significant association between SG13S114 variant and IS was found under the allelic (OR=0.87, 95% CI: 0.80-0.96, P=0.004), dominant (OR=0.75, 95% CI: 0.62-0.92, P=0.005), and recessive (OR=0.89, 95% CI: 0.82-0.97, P=0.005) genetic models in Chinese population. In subgroup meta-analysis, SG13S114 variant and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the allelic (OR=0.86, 95% CI: 0.80-0.92, P<0.0001), dominant (OR=0.72, 95% CI: 0.57-0.91, P=0.006), and recessive (OR=0.86, 95% CI: 0.78-0.95, P=0.002) models. ALOX5AP SG13S114 polymorphism is associated with susceptibility to IS in Chinese population.
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Enhanced external counterpulsation improves cerebral blood flow following cardiopulmonary resuscitation.
Am J Emerg Med
PUBLISHED: 06-24-2013
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To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation.
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[The up-regulation of hypoxia inducible factor-1? by hypoxic postconditioning reduces hypoxia/reoxygenation-induced injury in heart-derived H9c2 cells].
Sheng Li Xue Bao
PUBLISHED: 06-22-2013
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The aim of the present study was to explore the effects of hypoxic postconditioning (PostC) on heart-derived H9c2 cells injury induced by hypoxia/reoxygenation (H/R) and the expression of hypoxia inducible factor-1? (HIF-1?), and to analyze the relationship between them. Cultured H9c2 cardiac muscle cells were subjected to 3-hour hypoxia and 2-hour reoxygenation to simulate ischemia and reperfusion, or underwent 3 cycles of 5-min reoxygenation and 5-min hypoxia preceding the long reoxygenation to simulate ischemic postconditioning. Cell viability, lactate dehydrogenase (LDH) activity, and caspase-3 activity were detected respectively to investigate the cell injury induced by H/R. The level of HIF-1? mRNA was measured by real-time PCR. Western blot was used to determine HIF-1? protein level. The results showed that postconditioning significantly increased H9c2 cell viability, reduced the activity of LDH and caspase-3. Simultaneously, postconditioning up-regulated the HIF-1? protein level. Moreover, after DMOG, an inhibitor of proline hydroxylase (PHD) which targeted to HIF-1? degradation, was used to stabilize HIF-1? protein level, the reduction of H9c2 cells injury was comparable to that by postconditioning. There was a significant linear positive relationship between HIF-1? protein level and cell viability (r = 0.743, P < 0.01). After HIF-1? gene was silenced by siRNA, the cardio-protective effects of postconditioning was significantly weakened. These data suggest that up-regulation of HIF-1? plays an important role in the cardio-protection of postconditioning.
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Smart Nanovehicles Based on pH-Triggered Disassembly of Supramolecular Peptide-Amphiphiles for Efficient Intracellular Drug Delivery.
Small
PUBLISHED: 06-19-2013
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A novel type of nanovehicle (NV) based on stimuli-responsive supramolecular peptide-amphiphiles (SPAs, dendritic poly (L-lysine) non-covalently linked poly (L-leucine)) is developed for intracellular drug delivery. To determine the pH-dependent mechanism, the supramolecular peptide-amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH-triggered disassembly of SPAS can be attributed to the disappearance of non-covalent interactions within SPAs around the isoelectric point of poly (L-leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH-dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX-loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence-activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.
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Maternal preconception body mass index and offspring cord blood DNA methylation: Exploration of early life origins of disease.
Environ. Mol. Mutagen.
PUBLISHED: 06-10-2013
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Maternal obesity is associated with a variety of common diseases in the offspring. One possible underlying mechanism could be maternal obesity induced alterations in DNA methylation. However, this hypothesis is yet to be tested. We performed epigenomic mapping of cord blood among 308 Black mother-infant pairs delivered at term at the Boston Medical Center using the Illumina HumanMethylation27 BeadChip. Linear regression and pathway analyses were conducted to evaluate the associations between DNA methylation levels and prepregnancy maternal BMI (<25, 25-30, ?30 kg/m(2) ). The methylation levels of 20 CpG sites were associated with maternal BMI at a significance level of P-value <10(-4) in the overall sample, and boys and girls, separately. One CpG site remained statistically significant after correction for multiple comparisons (FDR corrected P-value = 0.04) and was annotated to a potential cancer gene, ZCCHC10. Some of the other CpG site annotated genes appear to be critical to the development of cancers and cardiovascular diseases (i.e., WNT16, C18orf8, ANGPTL2, SAPCD2, ADCY3, PRR16, ERBB2, DOK2, PLAC1). Significant findings from pathway analysis, such as infectious and inflammatory and lipid metabolism pathways, lends support for the potential impact of maternal BMI on the above stated disorders. This study demonstrates that prepregnancy maternal BMI might lead to alterations in offspring DNA methylation in genes relevant to the development of a range of complex chronic diseases, providing evidence of trans-generational influence on disease susceptibility via epigenetic mechanism. Environ. Mol. Mutagen., 2013. © 2013 Wiley Periodicals, Inc.
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The interaction between cepharanthine and two serum albumins: multiple spectroscopic and chemometric investigations.
Luminescence
PUBLISHED: 05-29-2013
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The binding modes of cepharanthine (CEPT) with bovine serum albumin (BSA) and human serum albumin (HSA) have been established by reproducing physiological conditions, which is very important to understand the pharmacokinetics and toxicity of CEPT. These spectral data were further analyzed by the multivariate curve resolution-alternating least squares method. Moreover, the concentration profiles and pure spectra of three species (BSA/HSA, CEPT and CEPT-BSA/HSA) and the apparent equilibrium constants Kapp were evaluated. The experimental results showed that CEPT could quench the fluorescence intensity of BSA/HSA by a combined quenching (static and dynamic) procedure. The binding constant (K), the thermodynamic parameters (?G, ?H and ?S) and binding subdomain were measured, and indicated that CEPT could spontaneously bind to BSA/HSA on subdomain IIA through the hydrophobic interactions. The effect of CEPT on the secondary structure of proteins has been analyzed by circular dichroism, 3D fluorescence and Fourier transform infrared spectra. The binding distance between CEPT and tryptophan of BSA/HSA was 2.305/1.749?nm, which is based on the Förster resonance energy transfer theory. Copyright © 2013 John Wiley & Sons, Ltd.
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The Chinese version of the world health organization quality of life instrument-older adults module (WHOQOL-OLD): psychometric evaluation.
Health Qual Life Outcomes
PUBLISHED: 05-08-2013
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Under the circumstance of global population aging, the issue on how to facilitate the quality of life (QOL) for older people brings us grand challenge. On the way to solve this problem, it is inextricable to measure QOL for older people accurately at onset. This study is aimed at evaluating the reliability and validity of the Chinese version of the World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD).
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Knockdown of CRM1 inhibits the nuclear export of p27(Kip1) phosphorylated at serine 10 and plays a role in the pathogenesis of epithelial ovarian cancer.
Cancer Lett.
PUBLISHED: 04-09-2013
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In a previous study, the nuclear export protein chromosomal region maintenance (CRM1) was correlated with p27(Kip1) in glioma. The aims of the present study were to investigate the expression of CRM1 and pSer10p27 and their functional roles in epithelial ovarian cancer (EOC) tissues. Using immunohistochemical analysis, CRM1 and pSer10p27 expression levels were shown to be associated with histologic stage and grade (P<0.05). High CRM1 and pSer10p27 expression levels were prognostic indicators of overall survival (P<0.05). Knockdown of CRM1 and pSer10p27 expression arrested cell cycle progression and inhibited the proliferation of SKOV3 cells both in vitro and in vivo. These data support the idea that pSer10p27 and CRM1 play cooperative roles in EOC.
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An organic thin film photodiode as a portable photodetector for the detection of alkylphenol polyethoxylates by a flow fluorescence-immunoassay on magnetic microbeads in a microchannel.
Talanta
PUBLISHED: 04-03-2013
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An organic thin film photodiode (OPD) was successfully employed as a portable photodetector in a competitive enzyme-linked immunosorbent assay (ELISA) of a class of nonionic surfactants, namely alkylphenol polyethoxylates (APnEOs) which are an environmental pollutant. Microbeads that were chemically immobilized with an anti-APnEOs antibody were used in the assay. The OPD consisted of a layer of copper phthalocyanine (CuPc), C60 and a second layer of bathocuproine (BCP) with a bulk heterojunction composed of CuPc and C60 prepared by a vapor deposition method on an indium-tin oxide coated glass substrate. The OPD showed an incident photon-current efficiency (IPCE) of approximately 19% for light at a wavelength of 585 nm. This relatively high IPCE at 585 nm makes it suitable for detecting the fluorescence of resorufin (?em=585 nm), the product of the competitive ELISA, produced through the enzymatic reaction of Amplex Red with horseradish peroxidase (HRP) and H2O2. A fluorometric detector was assembled on a microchip by combining the fabricated OPD and a commercial LED as a photodetector and a light source, respectively. The photocurrent of the OPD due to the fluorescence of resorufin was proportional to the concentration of resorufin in the concentration range from 0 to 8 ?M. When the fabricated OPD was used as a portable photodetector, the competitive ELISA of APnEOs using HRP labeled APnEOs (HRP-APnEOs) was performed on magnetic microbeads on which surface an anti-APnEOs antibody had been immobilized. A typical sigmoidal calibration curve was obtained and the data were in good agreement with a numerical simulation, where the photocurrent of the OPD was plotted against the concentration of APnEOs, determined via the competitive ELISA. The detection limit of the immunoassay for APnEOs was approximately 2 and 4 ppb in batch and flow system, respectively.
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RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through targeting p21Waf1/Cip1 for ubiquitin-mediated degradation.
Neoplasia
PUBLISHED: 03-21-2013
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The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor ? (ER?)-positive breast tumors and to promote breast cell proliferation; however, its mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two ER?-positive breast cancer cell lines, MCF-7 and T47D, decreases cell proliferation and increases the protein levels of the cyclin-dependent kinase inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ER?-positive breast cancer cell proliferation at least partially through downregulating the expression of p21.
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Serum agonistic autoantibodies against type-1 angiotensin II receptor titer in patients with epithelial ovarian cancer: a potential role in tumor cell migration and angiogenesis.
J Ovarian Res
PUBLISHED: 03-03-2013
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Although agonistic autoantibodies against type-1 angiotensin-II receptor (AT1-AA) are frequently detected in women with preeclampsia, the clinical significance of AT1-AA in association with epithelial ovarian cancer (EOC) has not been identified.
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Warming Moxibustion Relieves Chronic Visceral Hyperalgesia in Rats: Relations to Spinal Dynorphin and Orphanin-FQ System.
Evid Based Complement Alternat Med
PUBLISHED: 01-25-2013
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As a twin therapy of acupuncture in traditional Chinese medicine, moxibustion has shown its effects in relieving abdominal pain in irritable bowel syndrome (IBS) patients and IBS rat models, but its mechanisms are largely unknown. In this paper, we determined the role of spinal dynorphin and orphanin-FQ system in analgesic effect of warming moxibustion (WM) on chronic visceral hyperalgesia (CVH) in IBS-like rat model. Here, we show that (1) repeated WM at bilateral ST25 and ST37 acupoints markedly attenuated the abdominal withdrawal reflex scores in CVH rats; (2) intrathecal administration of ? receptor antagonist prior to WM significantly attenuated the WM analgesia and dynorphinA (1-17) enhanced the WM analgesia. WM significantly reinforced the upregulation of spinal dynorphin mRNA/protein and ? receptor mRNA levels in CVH rats; (3) intrathecal administration of orphanin-FQ receptor antagonist prior to WM significantly attenuated the WM analgesia and orphanin-FQ enhanced the WM analgesia. WM reinforced the upregulation of spinal orphanin-FQ mRNA/protein and orphanin-FQ receptor mRNA levels in CVH rats. These results suggest that moxibustion may relieve CVH at least in part by activating spinal dynorphin and orphanin-FQ system.
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Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in tibet minipigs.
PLoS ONE
PUBLISHED: 01-01-2013
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The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies.
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Transcatheter arterial embolization promotes liver tumor metastasis by increasing the population of circulating tumor cells.
Onco Targets Ther
PUBLISHED: 01-01-2013
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Transcatheter arterial embolization (TAE) is widely used as an effective palliative treatment for hepatocellular carcinoma (HCC), and can prolong survival time. However, the high incidence of tumor recurrence and metastasis after TAE is still a major problem. Recent studies demonstrated that circulating tumor cells (CTCs) contribute to tumor metastasis. In this study, we tried to clarify whether the residual HCC after TAE can increase metastasis by increasing the number of CTCs. An orthotopic liver tumor model in the Buffalo rat was established using green fluorescent protein (GFP)-transfected HCC cell line, McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent TAE treatment from the gastroduodenal artery. Iodized oil or saline was injected intra-arterially. Blood samples were taken on day 0, 1, 3, 7, 14, and 21 for detection of CTCs after TAE treatment. We analyzed the number of CTCs and assessed the metastatic potential of surviving tumor cells in rats between TAE and control groups. Our results demonstrated that the metastatic colonies in the lung were significantly increased by TAE treatment. The number of CTCs was also significantly increased by TAE treatment from day 7 to day 21. The expression of hypoxia-inducible factor (HIF)-1? and epithelial-mesenchymal transition (EMT) marker proteins (N-cadherin and vimentin) was upregulated, but E-cadherin was downregulated after TAE treatment. In conclusion, the metastatic potential of residual HCC can be induced by TAE treatment in a rat liver tumor model, which involves the acquisition of EMT features and an increased number of CTCs.
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Prevalence of asthenopia and its risk factors in Chinese college students.
Int J Ophthalmol
PUBLISHED: 01-01-2013
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To determine the prevalence of asthenopia and identify any associated risk factors in the college students in Xian, China.
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Complications after pancreaticoduodenectomy for pancreatic cancer: a retrospective study.
Int Surg
PUBLISHED: 12-08-2011
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Postoperative complications, such as pancreatic fistulae, after pancreaticoduodenectomy for pancreatic cancers are associated with surgical outcomes of patients with pancreatic cancers. A total of 160 patients with pancreatic cancers undergoing pancreaticoduodenectomy were retrospectively analyzed. Patients were grouped into a fistulae group (n = 34) and a nonfistulae group (n = 126). The fistulae group had a significantly higher morbidity rate than the nonfistulae group (P < 0.0001), but hospital mortality was not different in both groups (P = 0.481). There was a higher incidence of intra-abdominal hemorrhage in patients with pancreatic fistulae than in those without fistulae. Two patients in fistulae group underwent reoperation. Patients with pancreatic fistulae had significantly longer hospital stay than those without fistulae. Pancreatic duct diameter, smoking, years of tobaccos consumption, preoperative jaundice, and surgical hours were associated with risk of fistulae on univariate analysis. In a multivariate analysis, diameter of pancreatic duct, surgical hours, and preoperative jaundice were independent risk factors of pancreatic fistulae. Incidence of pancreatic fistulae after pancreaticoduodenectomy is significantly influenced by the size of pancreatic duct diameter, surgical time, and preoperative jaundice. Early postoperative hemorrhage could be cautiously prevented. The survival is not significantly impacted by pancreatic fistulae.
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