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Find video protocols related to scientific articles indexed in Pubmed.
Effectiveness of a New Navigable Percutaneous Disc Decompression Device (L'DISQ) in Patients with Lumbar Discogenic Pain.
Pain Med
PUBLISHED: 11-14-2014
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This study is a pilot study to assess the clinical outcomes of percutaneous disc decompression using the L'DISQ in patients with lumbar discogenic pain.
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Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart.
FASEB J.
PUBLISHED: 11-05-2014
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The regulation of AMPK in the ischemic heart remains incompletely understood. Recent evidence implicates the role of Sestrin2 in the AMPK signaling pathway, and it is hypothesized that Sestrin2 plays an influential role during myocardial ischemia to promote AMPK activation. Sestrin2 protein was found to be expressed in adult cardiomyocytes and accumulated in the heart during ischemic conditions. Sestrin2 knockout (KO) mice were used to determine the importance of Sestrin2 during ischemia and reperfusion (I/R) injury. When wild-type (WT) and Sestrin2 KO mice were subjected to in vivo I/R, myocardial infarct size was significantly greater in Sestrin2 KO compared with WT hearts. Similarly, Langendorff perfused hearts indicated exacerbated postischemic contractile function in Sestrin2 KO hearts compared with WT. Ischemic AMPK activation was found to be impaired in the Sestrin2 KO hearts. Immunoprecipitation of Sestrin2 demonstrated an association with AMPK. Moreover, liver kinase B1 (LKB1), a major AMPK upstream kinase, was associated with the Sestrin2-AMPK complex in a time-dependent manner during ischemia, whereas this interaction was nearly abolished in Sestrin2 KO hearts. Thus, Sestrin2 plays an important role in cardioprotection against I/R injury, serving as an LKB1-AMPK scaffold to initiate AMPK activation during ischemic insults.-Morrison, A., Chen, L. Wang, J., Zhang, M., Yang, H., Ma, Y., Budanov, A., Lee, J. H., Karin, M., Li, J. Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart.
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Anti-inflammatory effects of galangin on lipopolysaccharide-activated macrophages via ERK and NF-?B pathway regulation.
Immunopharmacol Immunotoxicol
PUBLISHED: 10-01-2014
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Abstract Inflammation is the major symptom of the innate immune response to microbial infection. Macrophages, immune response-related cells, play a role in the inflammatory response. Galangin is a member of the flavonols and is found in Alpinia officinarum, galangal root and propolis. Previous studies have demonstrated that galangin has antioxidant, anticancer, and antineoplastic activities. However, the anti-inflammatory effects of galangin are still unknown. In this study, we investigated the anti-inflammatory effects of galangin on RAW 264.7 murine macrophages. Galagin was not cytotoxic to RAW 264.7 cells, and nitric oxide (NO) production induced by lipopolysaccharide (LPS)-stimulated macrophages was significantly decreased by the addition of 50??M galangin. Moreover, galangin treatment reduced mRNA levels of cytokines, including IL-1? and IL-6, and proinflammatory genes, such as iNOS in LPS-activated macrophages in a dose-dependent manner. Galangin treatment also decreased the protein expression levels of iNOS in activated macrophages. Galangin was found to elicit anti-inflammatory effects by inhibiting ERK and NF-?B-p65 phosphorylation. In addition, galangin-inhibited IL-1? production in LPS-activated macrophages. These results suggest that galangin elicits anti-inflammatory effects on LPS-activated macrophages via the inhibition of ERK, NF-?B-p65 and proinflammatory gene expression.
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The Role of Perioperative Transfusion on Long-Term Survival of Veterans Undergoing Surgery.
Ann. Surg.
PUBLISHED: 09-16-2014
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To examine the influence of perioperative blood transfusions on perioperative outcomes and late survival.
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Rapid detection of 6×-histidine-labeled recombinant proteins by immunochromatography using dye-labeled cellulose nanobeads.
Biotechnol. Lett.
PUBLISHED: 09-12-2014
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A rapid and easy immunochromatography assay using dye-labeled cellulose nanobeads (CNBs) was developed to detect proteins with hexa-histidine tag (His-tag) to characterize recombinant proteins during purification. Recombinant ATG8 protein was used as a His-tagged protein, and ATG8-conjugated CNBs (A-CNBs) were prepared. The original ATG8 in the sample solution competed with A-CNBs for anti-His-tag antibodies spotted on to the strip resulting in an inverse relationship between ATG8 concentration and the colorimetric signal. The usefulness of this method was shown by adding ATG8 to a 1 % Escherichia coli extract. In addition, this assay can be used to detect other His-tagged proteins without protein-specific antibodies. Because the identification of fractions containing His-tagged proteins by western blotting or ELISA is labor-intensive and expensive, our method provides an efficient and cheaper alternative.
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Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers.
Nat Commun
PUBLISHED: 09-05-2014
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Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding the molecular mechanism of obesity interference in autophagy, development of therapeutic strategies for correcting such defects in obese individuals is challenging. Here we show that a chronic increase of the cytosolic calcium concentration in hepatocytes during obesity and lipotoxicity attenuates autophagic flux by preventing the fusion between autophagosomes and lysosomes. As a pharmacological approach to restore cytosolic calcium homeostasis in vivo, we administered the clinically approved calcium channel blocker verapamil to obese mice. Such treatment successfully increases autophagosome-lysosome fusion in liver, preventing accumulation of protein inclusions and lipid droplets and suppressing inflammation and insulin resistance. As calcium channel blockers have been safely used in clinics for the treatment of hypertension for more than 30 years, our results suggest they may be a safe therapeutic option for restoring autophagic flux and treating metabolic pathologies in obese patients.
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Facial skin fistula as a postoperative complication related to maxillary sinus grafting: A case report.
Quintessence Int
PUBLISHED: 09-04-2014
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Maxillary sinus elevation has become an important surgical procedure in dental implant surgery. This procedure may induce a variety of postoperative complications including infection, perforation of the sinus membrane, and maxillary sinusitis. However, postoperative infections are relatively infrequent. In this report, an unusual form of infection resulting in a facial skin fistula following maxillary sinus elevation is described.
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Off-hour effect on 3-month functional outcome after acute ischemic stroke: a prospective multicenter registry.
PLoS ONE
PUBLISHED: 08-28-2014
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The time of hospital arrival may have an effect on prognosis of various vascular diseases. We examined whether off-hour admission would affect the 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals.
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Anti-inflammatory Effects of Ethanolic Extract from Sargassum horneri (Turner) C. Agardh on Lipopolysaccharide-Stimulated Macrophage Activation via NF-?B Pathway Regulation.
Immunol. Invest.
PUBLISHED: 08-20-2014
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Inflammation is major symptom of the innate immune response by infection of microbes. Macrophages, one of immune response related cells, play a role in inflammatory response. Recent studies reported that various natural products can regulate the activation of immune cells such as macrophage. Sargassum horneri (Turner) C. Agardh is one of brown algae. Recently, various seaweeds including brown algae have antioxidant and anti-inflammatory effects. However, anti-inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown. In this study, we investigated anti-inflammatory effects of ethanolic extract of Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with 70% ethanol and then lyophilized at -40?°C. ESH was not cytotoxic to RAW 264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage activation was significantly decreased by the addition of 200??g/mL of ESH. Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1?, and pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory effects by inhibiting ERK, p-p38 and NF-?B phosphorylation. In addition, ESH inhibited the release of IL-1? in LPS-stimulated macrophages. These results suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage activation via the inhibition of ERK, p-p38, NF-?B, and pro-inflammatory gene expression.
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Relationship of liver stiffness and controlled attenuation parameter measured by transient elastography with diabetes mellitus in patients with chronic liver disease.
J. Korean Med. Sci.
PUBLISHED: 07-30-2014
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High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
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Tauroursodeoxycholic Acid, a Bile Acid, Promotes Blood Vessel Repair by Recruiting Vasculogenic Progenitor Cells.
Stem Cells
PUBLISHED: 07-29-2014
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Although serum bile acid concentrations are ~10 ?M in healthy subjects, the cross-talk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein (FAP) via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hindlimb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hindlimb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hindlimb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells. This article is protected by copyright. All rights reserved.
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The Arabidopsis thaliana RNA-binding protein FCA regulates thermotolerance by modulating the detoxification of reactive oxygen species.
New Phytol.
PUBLISHED: 07-24-2014
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Heat stress affects various aspects of plant growth and development by generating reactive oxygen species (ROS) which cause oxidative damage to cellular components. However, the mechanisms by which plants cope with ROS accumulation during their thermotolerance response remain largely unknown. Here, we demonstrate that the RNA-binding protein FCA, a key component of flowering pathways in Arabidopsis thaliana, is required for the acquisition of thermotolerance. Transgenic plants overexpressing the FCA gene (35S:FCA) were resistant to heat stress; the FCA-defective fca-9 mutant was sensitive to heat stress, consistent with induction of the FCA gene by heat. Furthermore, total antioxidant capacity was higher in the 35S:FCA transgenic plants but lower in the fca-9 mutant compared with wild-type controls. FCA interacts with the ABA-INSENSITIVE 5 (ABI5) transcription factor, which regulates the expression of genes encoding antioxidants, including 1-CYSTEINE PEROXIREDOXIN 1 (PER1). We found that FCA is needed for proper expression of the PER1 gene by ABI5. Our observations indicate that FCA plays a role in the induction of thermotolerance by triggering antioxidant accumulation under heat stress conditions, thus providing a novel role for FCA in heat stress responses in plants.
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Bioreducible Guanidinylated Polyethylenimine for Efficient Gene Delivery.
ChemMedChem
PUBLISHED: 07-16-2014
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Cationic polymers are known to afford efficient gene transfection. However, cytotoxicity remains a problem at the molecular weight for optimal DNA delivery. As such, optimized polymeric gene delivery systems are still a sought-after research goal. A guanidinylated bioreducible branched polyethylenimine (GBPEI-SS) was synthesized by using a disulfide bond to crosslink the guanidinylated BPEI (GBPEI). GBPEI-SS showed sufficient plasmid DNA (pDNA) condensation ability. The physicochemical properties of GBPEI-SS demonstrate that it has the appropriate size (?200?nm) and surface potential (?30?mV) at a nitrogen-to-phosphorus ratio of 10. No significant toxicity was observed, possibly due to bioreducibility and to the guanidine group delocalizing the positive charge of the primary amine in BPEI. Compared with the nonguanidinylated analogue, BPEI-SS, GBPEI-SS showed enhanced transfection efficiency owing to increased cellular uptake and efficient pDNA release by cleavage of disulfide bonds. This system is very efficient for delivering pDNA into cells, thereby achieving high transfection efficiency and low cytotoxicity.
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Endopelvic fascia preservation during robot-assisted laparoscopic radical prostatectomy: Does it affect urinary incontinence?
Scand J Urol
PUBLISHED: 07-10-2014
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Abstract Objective. Urinary incontinence has a significant impact on the quality of life after radical prostatectomy. This study aimed to determine whether preserving the endopelvic fascia influences subsequent urinary incontinence. Material and methods. Consecutive patients (n = 138) who underwent robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer between October 2010 and June 2012 with a minimum of 1 year follow-up were retrospectively analysed. The subjects were divided into two groups: the non-preserved endopelvic fascia group (nPE group) and the preserved endopelvic fascia group (PE group). Continence was defined as not using any pads and having no urine leakages. Continence rates at set time-points after RALP were compared using the chi-squared test. Continence recovery rates were analysed with the Kaplan-Meier method and the log-rank test. Prognostic factors of incontinence were identified using the Cox proportional hazards model. Results. The age, body mass index, preoperative prostate-specific antigen levels, prostate volume, estimated blood loss, mean operative time, Gleason score and pathological stage were not significantly different between the two study groups. The continence rate of the nPE group and PE group was 88.4% and 97.1%, respectively, at 12 months after surgery (p = 0.049), which was also significant according to the Kaplan-Meier analysis (p < 0.001). Preservation of endopelvic fascia was the only significant prognostic factor for urinary incontinence (p = 0.002, hazard ratio = 1.867) according to the multivariate analysis. Conclusions. Endopelvic fascia preservation during RALP significantly enhances postoperative continence and is related to the speed of recovery of continence.
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Identification of endothelial progenitor cells in the corpus cavernosum in rats.
Biomed Res Int
PUBLISHED: 07-02-2014
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The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs). In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin) were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34(+)/Flk-1(+) and CD34(+)/VE-cadherin(+) positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction.
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Urethroplasty by use of turnover flaps (modified mathieu procedure) for distal hypospadias repair in adolescents: comparison with the tubularized incised plate procedure.
Korean J Urol
PUBLISHED: 06-27-2014
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The purpose of this study was to examine whether urethroplasty with a turnover flap, as an alternative method of distal hypospadias repair in adolescents, improves the outcome of surgery.
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MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification.
J Stroke
PUBLISHED: 06-25-2014
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In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC).
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Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling.
Biochem. Biophys. Res. Commun.
PUBLISHED: 06-25-2014
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Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and AKT. MMP-2 activation was also significantly increased. Specific inhibitors of p38 (SB203580) and JNK (SP600125) inhibited tube formation and wound healing, while an ERK inhibitor (PD98059) did not. MMP-2 activation and AKT phosphorylation were also attenuated and associated with the suppression of p38 and JNK phosphorylation, but not with that of ERK. These results indicate that fucoidan, in the presence of FGF-2, induces angiogenesis through AKT/MMP-2 signalling by activating p38 and JNK. These findings provide basic molecular information on the effect of fucoidan on angiogenesis in the presence of FGF-2.
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The effects of fibrinogen concentration on fibrin/atelocollagen composite gel: an in vitro and in vivo study in rabbit calvarial bone defect.
Clin Oral Implants Res
PUBLISHED: 06-24-2014
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This study aimed to optimize the fibrinogen concentration in fibrin and atelocollagen (AT-COL) (fibrin/AT-COL) composite gel for improving bone regeneration.
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Anti-angiogenic potential of an ethanol extract of Annona atemoya seeds in vitro and in vivo.
BMC Complement Altern Med
PUBLISHED: 06-17-2014
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Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. Therefore, many efforts have been made to develop effective anti-angiogenic agents as anticancer therapeutics. In the current study, we investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo.
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Effects of three-dimensional polymer networks in vertical alignment liquid crystal display controlled by in-plane field.
Opt Express
PUBLISHED: 06-13-2014
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Polymer network in vertical alignment liquid crystal cell driven by in-plane field (VA-IPS) is formed in three dimensions to achieve fast response time and to keep the liquid crystal alignment even when an external pressure is applied to the cell. The network formed by UV irradiation to vertically aligned liquid crystal cell with reactive mesogen does not disturb a dark state while exhibiting very fast decaying response time less than 2ms in all grey scales and almost zero pooling mura. The proposed device has a strong potential to be applicable to field sequential display owing to super-fast response time and flexible display owing to polymer network in bulk which supports a gap between two substrates.
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Myocardial contrast echocardiography for the detection of coronary artery disease in patients with global hypokinesis admitted for first-onset acute heart failure: pilot study.
J Cardiovasc Ultrasound
PUBLISHED: 05-31-2014
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The non-invasive differentiation of ischemic and nonischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether resting myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD) in patients with decreased left ventricular (LV) systolic function and global hypokinesis presenting with AHF.
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Long-term survival after surgical resection for huge hepatocellular carcinoma: comparison with transarterial chemoembolization after propensity score matching.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-28-2014
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Surgical resection (SR) and transarterial chemoembolization (TACE) have been commonly applied for patients with huge hepatocellular carcinoma (HCC). However, optimal treatment has not been established.
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TiO2/ferroelectric heterostructures as dynamic polarization-promoted catalysts for photochemical and electrochemical oxidation of water.
Phys. Rev. Lett.
PUBLISHED: 05-13-2014
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Using first-principles density functional theory calculations, we explore the chemical activity of epitaxial heterostructures of TiO2 anatase on strained polar SrTiO3 films focusing on the oxygen evolution reaction (OER), the bottleneck of water splitting. Our results show that the reactivity of the TiO2 surface is tuned by electric dipoles dynamically induced by the adsorbed species during the intermediate steps of the reaction while the initial and final steps remain unaffected. Compared to the OER on unsupported TiO2, the combined effects of the dynamically induced dipoles and epitaxial strain strongly reduce rate-limiting thermodynamic barriers and significantly improve the efficiency of the reaction.
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Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-13-2014
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Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.
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Enhanced bone healing by improved fibrin-clot formation via fibrinogen adsorption on biphasic calcium phosphate granules.
Clin Oral Implants Res
PUBLISHED: 05-03-2014
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Fibrin clots play an important role in bone tissue regeneration. This study aimed at improving the fibrin-clotting rate by coating the surface of biphasic calcium phosphate (BCP) granules with fibrinogen (FNG).
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Calcifying cystic odontogenic tumor associated with ameloblastic fibro-odontoma of the anterior mandible.
J Craniofac Surg
PUBLISHED: 05-03-2014
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Calcifying cystic odontogenic tumor, which was formerly named calcifying odontogenic cyst, is a benign odontogenic tumor containing clusters of ghost cells within ameloblastic epithelium. Calcifying cystic odontogenic tumors have been associated with other odontogenic tumors, a finding that is a rare event in other types of odontogenic cysts or tumors. This report describes a case of hybrid odontogenic tumor composed of calcifying cystic odontogenic tumor and ameloblastic fibroma-odontoma of the anterior mandible that occurred in a 4-year-old Korean girl.
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Functional capacity as a significant independent predictor of postoperative mortality for octogenarian ASA-III patients.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 04-30-2014
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The American Society of Anesthesiology's (ASA) 6-point physical status classification remains one of the most significant predictors of perioperative morbidity and mortality and is the most widely used risk stratification tool worldwide. Its utility is significantly limited for octogenarians, however, as the majority of these patients are classified as ASA-III. Thus, for patients aged 80 or older, we hypothesized that incorporating patients' functional status, defined by the ability to perform activities of daily living independently, would improve perioperative risk stratification.
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FCA mediates thermal adaptation of stem growth by attenuating auxin action in Arabidopsis.
Nat Commun
PUBLISHED: 04-29-2014
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Global warming is predicted to profoundly affect plant distribution and crop yield in the near future. Higher ambient temperature can influence diverse aspects of plant growth and development. In Arabidopsis, the basic helix-loop-helix transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) regulates temperature-induced adaptive responses by modulating auxin biosynthesis. At high temperature, PIF4 directly activates expression of YUCCA8 (YUC8), a gene encoding an auxin biosynthetic enzyme, resulting in auxin accumulation. Here we demonstrate that the RNA-binding protein FCA attenuates PIF4 activity by inducing its dissociation from the YUC8 promoter at high temperature. At 28?°C, auxin content is elevated in FCA-deficient mutants that exhibit elongated stems but reduced in FCA-overexpressing plants that exhibit reduced stem growth. We propose that the FCA-mediated regulation of YUC8 expression tunes down PIF4-induced architectural changes to achieve thermal adaptation of stem growth at high ambient temperature.
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Evaluation of soft tissue asymmetry using cone-beam computed tomography after open reduction and internal fixation of zygomaticomaxillary complex fracture.
J Korean Assoc Oral Maxillofac Surg
PUBLISHED: 04-21-2014
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In this study, we assessed soft tissue asymmetry that occurred after open reduction of unilateral zygomaticomaxillary complex (ZMC) fractures. We proposed a simple method to assess soft tissue asymmetry after reduction surgery by evaluating the symmetry between the affected and the unaffected sides. The factors affecting soft tissue contour after surgery were also analyzed.
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Safety and efficacy of intravenous recombinant tissue plasminogen activator administered in the 3- to 4.5-hour window in Korea.
J Stroke Cerebrovasc Dis
PUBLISHED: 04-11-2014
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The safety and efficacy of intravenous tissue plasminogen activator (IV-TPA) in the 3- to 4.5-hour window were largely driven from Western populations, but have not been systematically explored in Korean population.
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Genistein inhibits pro?inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway.
Int. J. Mol. Med.
PUBLISHED: 04-08-2014
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Anaphylaxis is a rapidly occurring allergic reaction to any foreign substance, including venom from insects, foods and medications, which may cause fatalities. To prevent anaphylaxis, these triggers must be avoided. However, avoidance of numerous triggers is difficult. For this reason, the development of immunotherapeutic adjuvants that suppress the allergic response is important for anaphylaxis control. Mast cells are one of the major inflammatory cells involved in the inflammatory response, which secrete several inflammatory cytokines, including tumor necrosis factor (TNF)??, interleukin (IL)?6, and IL?1?, and recruits other immune cells. Mast cells are also involved in a number of diseases, such as sinusitis, rheumatoid arthritis and asthma. Genistein, a phytoestrogen, has been reported to have anti?oxidative and anti?inflammatory activities. However, the effects of genistein on the anti?inflammatory response of mast cells remain unknown. In the present study, the anti?inflammatory effects of genistein on mast cells were investigated. Genistein significantly decreased IL?6 and IL?1? mRNA levels, as well as IL?6 production in PMA/A23187?induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187?induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.
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The Arabidopsis NAC transcription factor NTL4 participates in a positive feedback loop that induces programmed cell death under heat stress conditions.
Plant Sci.
PUBLISHED: 03-31-2014
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Programmed cell death (PCD) is an integral component of plant development and adaptation under adverse environmental conditions. Reactive oxygen species (ROS) are one of the most important players that trigger PCD in plants, and ROS-generating machinery is activated in plant cells undergoing PCD. The membrane-bound NAC transcription factor NTL4 has recently been proven to facilitate ROS production in response to drought stress in Arabidopsis. In this work, we show that NTL4 participates in a positive feedback loop that bursts ROS accumulation to modulate PCD under heat stress conditions. Heat stress induces NTL4 gene transcription and NTL4 protein processing. The level of hydrogen peroxide (H2O2) was elevated in 35S:4?C transgenic plants that overexpress a transcriptionally active nuclear NTL4 form but significantly reduced in NTL4-deficient ntl4 mutants under heat stress conditions. In addition, heat stress-induced cell death was accelerated in the 35S:4?C transgenic plants but decreased in the ntl4 mutants. Notably, H2O2 triggers NTL4 gene transcription and NTL4 protein processing under heat stress conditions. On the basis of these findings, we conclude that NTL4 modulates PCD through a ROS-mediated positive feedback control under heat stress conditions, possibly providing an adaptation strategy by which plants ensure their survival under extreme heat stress conditions.
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Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1.
FEBS J.
PUBLISHED: 03-28-2014
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Autophagy is a homeostatic process that is important for degrading protein aggregates, nutrient deposits, dysfunctional organelles and several signaling molecules. p62/sequestosome-1 is a protein that binds to several autophagy substrates, such as ubiquitinated proteins, damaged mitochondria and signaling molecules such as an Nrf2 inhibitor Keap1, promoting their autophagic degradation. Sestrin2, a stress-inducible protein, has recently been shown to bind to p62 and promote autophagic degradation of such p62 targets. Because Sestrin2 is a metabolic regulator that suppresses diverse age- and obesity-associated pathologies, the autophagy-controlling function of Sestrin2 may be important for its other physiological functions. However, the molecular mechanism of how Sestrin2 can promote clearance of p62-associated proteins has been unclear. Here we show that Sestrin2 physically associates with Unc-51-like protein kinase 1 (ULK1) and p62 to form a complex in which both Sestrin2 and p62 become phosphorylated by ULK1 at multiple sites. Ser403 of p62, whose phosphorylation is known to promote autophagic degradation of p62 and its targets, is among the sites phosphorylated by ULK1. ULK1-mediated p62 phosphorylation was facilitated by Sestrin2 in cells as well as in in vitro kinase assays. Consistent with this finding, oligomycin-induced energy deprivation, which strongly activates ULK1, provoked a robust Ser403 phosphorylation of p62 in wild-type mouse embryonic fibroblasts. However, in ULK1/2- and Sestrin2-deficient mouse embryonic fibroblasts, oligomycin-induced p62 phosphorylation was dramatically attenuated, suggesting that endogenous Sestrin2-ULK1/2 mainly mediates p62 phosphorylation in response to energetic stress. Taken together, this study identifies ULK1 as a new p62 Ser403 kinase and establishes Sestrin2 as a promoter of ULK1-mediated p62 phosphorylation.
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Inhibitory Effects of Extract from G. lanceolata on LPS-Induced Production of Nitric Oxide and IL-1? via Down-regulation of MAPK in Macrophages.
Appl. Biochem. Biotechnol.
PUBLISHED: 03-24-2014
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Grateloupia lanceolata is a red alga native to coastal areas of East Asia. In this study, extract from G. lanceolata (EGL) was investigated for suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. EGL was found to have anti-inflammatory properties with the inhibition of nitric oxide (NO), pro-inflammatory cytokine production, and MAPK signaling in LPS-induced RAW 264.7 macrophages. Moreover, treatment of RAW 264.7 macrophage with EGL inhibited LPS-induced IL-1? production in a dose-dependent manner. These inhibitory effects were found with the blockage of p38 mitogen-activated protein kinases (MAPK), extracellular signal regulated kinases 1 and 2 (ERK1/2), and also c-Jun N-terminal kinases 1 and 2 (JNK1/2). These results indicated that anti-inflammatory actions of EGL in RAW 264.7 macrophages involved in the inhibition of LPS-induced p38MAPK/ERK/JNK signaling pathways. In addition, our findings suggest that EGL holds great promise for use in the treatment of various inflammatory diseases.
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Internet-based Control Recruitment for a Case-Control Study of Major Risk Factors for Stroke in Korea: Lessons from the Experience.
J Stroke Cerebrovasc Dis
PUBLISHED: 03-18-2014
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This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment.
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Effects of fibrinogen concentration on fibrin glue and bone powder scaffolds in bone regeneration.
J. Biosci. Bioeng.
PUBLISHED: 03-17-2014
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Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 80 mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6 ± 3.6%, while the compressive strength increased 1.16 ± 0.02 Mpa, when compared with the values for the 10 mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering.
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Recanalization therapy for internal carotid artery occlusion presenting as acute ischemic stroke.
J Stroke Cerebrovasc Dis
PUBLISHED: 03-14-2014
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We aimed to describe the current status and clinical outcomes of recanalization therapy for internal carotid artery occlusion (ICAO) presenting as acute ischemic stroke.
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The essential role of FoxO6 phosphorylation in aging and calorie restriction.
Age (Dordr)
PUBLISHED: 03-11-2014
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Changes in the activities of FoxOs caused by phosphorylation, acetylation, or ubiquitination induce expressional changes in the genes involved in the modulation of oxidative stress by modifying histones and chromatins and can substantially alter cellular functions during aging and age-related diseases. However, the precise role that FoxO6, a novel member of the FoxO class of transcription factors, plays in the aging kidney has not been determined. The purpose of this study was to determine the role played by FoxO6 in the maintenance of redox homeostasis in HEK293T cells and aged kidney tissues isolated from ad libitum (AL)-fed and 40 % calorie restriction (CR) rats. The results obtained from AL-fed rats showed that diminished FoxO6 activity during aging was caused by FoxO6 phosphorylation, which disabled its transcriptional activity. In contrast, CR rats were found to have significantly higher FoxO6 activities and maintained redox balance. To determine the molecular mechanism responsible for FoxO6 modification by age-related oxidative stress, we examined H2O2-treated HEK293T cells in which FoxO6 was inactivated by phosphorylation and found that H2O2-induced oxidative stress promoted FoxO6 phosphorylation via PI3K/Akt signaling. The results of this study show that the protective role of FoxO6 in the aging process may in part be related to its ability to attenuate oxidative stress by upregulating catalase expression, as shown in CR. This delineation of the role of FoxO6 expands understanding of the pathological and physiological mechanisms of aging.
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The genome sequence of the Antarctic bullhead notothen reveals evolutionary adaptations to a cold environment.
Genome Biol.
PUBLISHED: 03-07-2014
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BackgroundAntarctic fish have adapted to the freezing waters of the Southern Ocean. Representative adaptations to this harsh environment include a constitutive heat shock response and the evolution of an antifreeze protein in the blood. Despite their adaptations to the cold, genome-wide studies have not yet been performed on these fish due to the lack of a sequenced genome. Notothenia coriiceps, the Antarctic bullhead notothen, is an endemic teleost fish with a circumpolar distribution and makes a good model to understand the genomic adaptations to constant sub-zero temperatures.ResultsWe provide the draft genome sequence and annotation for N. coriiceps. Comparative genome-wide analysis with other fish genomes shows that mitochondrial proteins and hemoglobin evolved rapidly. Transcriptome analysis of thermal stress responses find alternative response mechanisms for evolution strategies in a cold environment. Loss of the phosphorylation-dependent sumoylation motif in heat shock factor 1 suggests that the heat shock response evolved into a simple and rapid phosphorylation-independent regulatory mechanism. Rapidly evolved hemoglobin and the induction of a heat shock response in the blood may support the efficient supply of oxygen to cold-adapted mitochondria.ConclusionsOur data and analysis suggest that evolutionary strategies in efficient aerobic cellular respiration are controlled by hemoglobin and mitochondrial proteins, which may be important for the adaptation of Antarctic fish to their environment. The use of genome data from the Antarctic endemic fish provides an invaluable resource providing evidence of evolutionary adaptation and can be applied to other studies of Antarctic fish.
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Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition.
Cell Metab.
PUBLISHED: 02-21-2014
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Obesity can result in insulin resistance, hepatosteatosis, and nonalcoholic steatohepatitis (NASH) and increases liver cancer risk. Obesity-induced insulin resistance depends, in part, on chronic activation of mammalian target of rapamycin complex 1 (mTORC1), which also occurs in human and mouse hepatocellular carcinoma (HCC), a frequently fatal liver cancer. Correspondingly, mTORC1 inhibitors have been considered as potential NASH and HCC treatments. Using a mouse model in which high-fat diet enhances HCC induction by the hepatic carcinogen DEN, we examined whether mTORC1 inhibition attenuates liver inflammation and tumorigenesis. Notably, rapamycin treatment or hepatocyte-specific ablation of the specific mTORC1 subunit Raptor resulted in elevated interleukin-6 (IL-6) production, activation of signal transducer and activator of transcription 3 (STAT3), and enhanced HCC development, despite a transient reduction in hepatosteatosis. These results suggest that long-term rapamycin treatment, which also increases IL-6 production in humans, is unsuitable for prevention or treatment of obesity-promoted liver cancer.
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Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway.
Anticancer Res.
PUBLISHED: 02-11-2014
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Myricetin is a flavonol found in various berries, herbs, and walnuts. Previous studies have demonstrated that myricetin has anticancer effects against several types of cancer, including hepatocarcinoma, skin carcinoma, and pancreatic cancer. However, the anticancer activity of myricetin on human colon cancer has not been yet established. In the present study, we investigated the anticancer effects of myricetin on HCT-15 human colon cancer cells. We found that myricetin induces cytotoxicity and DNA condensation in human colon cancer cells in a dose-dependent manner. We also determined that myricetin increases the BCL2-associated X protein/B-cell lymphoma 2 ratio, but not cleavage of caspase-3 and -9. In addition, myricetin induced the release of apoptosis-inducing factor from mitochondria. These results suggest that myricetin induces apoptosis of HCT-15 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.
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Impact of surgical wait time on oncologic outcomes in upper urinary tract urothelial carcinoma.
J Surg Oncol
PUBLISHED: 02-10-2014
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To assess the effect of surgical wait time on the oncologic outcomes of patients with upper urinary tract urothelial carcinoma (UTUC), particularly in the ureter.
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Peritonsillar Involvement in Pyoderma Gangrenosum associated with Ulcerative Colitis.
Intest Res
PUBLISHED: 01-22-2014
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Peritonsillar abscess is a common deep throat infection. Early diagnosis and prompt, appropriate management of a peritonsillar abscess prevents mortality. A 45-year-old woman on steroids for an ulcerative colitis (UC) exacerbation presented with sore throat and multiple skin ulcers on her left forearm and right foot. Computed tomography of the neck revealed a peritonsillar abscess. Gram staining and culture of the abscess were negative, and a skin biopsy suggested pyoderma gangrenosum (PG). The final diagnosis was peritonsillar involvement of steroid-refractory PG-associated UC. The patient showed a complete response to infliximab. Here, we report a case of successful infliximab treatment for peritonsillar involvement of steroid-refractory PG-associated UC.
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Hepatoprotective role of Sestrin2 against chronic ER stress.
Nat Commun
PUBLISHED: 01-21-2014
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Upon prolonged endoplasmic reticulum (ER) stress, cells attenuate protein translation to prevent accumulation of unfolded proteins. Here we show that Sestrin2 is critical for this process. Sestrin2 expression is induced by an ER stress-activated transcription factor CCAAT-enhancer-binding protein beta (c/EBP?). Once induced, Sestrin2 halts protein synthesis by inhibiting mammalian target of rapamycin complex 1 (mTORC1). As Sestrin2-deficient cells continue to translate a large amount of proteins during ER stress, they are highly susceptible to ER stress-associated cell death. Accordingly, dietary or genetically induced obesity, which does not lead to any pathological indication other than simple fat accumulation in the liver of wild-type (WT) mice, can provoke Sestrin2-deficient mice to develop severe ER stress-associated liver pathologies such as extensive liver damage, steatohepatitis and fibrosis. These pathologies are suppressed by liver-specific Sestrin2 reconstitution, mTORC1 inhibition or chemical chaperone administration. The Sestrin2-mediated unfolded protein response (UPR) may be a general protective mechanism against ER stress-associated diseases.
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Characterization of multiwalled carbon nanotube-reinforced hydroxyapatite composites consolidated by spark plasma sintering.
Biomed Res Int
PUBLISHED: 01-18-2014
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Pure HA and 1, 3, 5, and 10?vol% multiwalled carbon nanotube- (MWNT-) reinforced hydroxyapatite (HA) were consolidated using a spark plasma sintering (SPS) technique. The relative density of pure HA increased with increasing sintering temperature, but that of the MWNT/HA composite reached almost full density at 900°C, and then decreased with further increases in sintering temperature. The relative density of the MWNT/HA composites increased with increasing MWNT content due to the excellent thermal conductivity of MWNTs. The grain size of MWNT/HA composites decreased with increasing MWNT content and increased with increasing sintering temperature. Pull-out toughening of the MWNTs of the MWNT/HA composites was observed in the fractured surface, which can be used to predict the improvement of the mechanical properties. On the other hand, the existence of undispersed or agglomerate MWNTs in the MWNT/HA composites accompanied large pores. The formation of large pores increased with increasing sintering temperature and MWNT content. The addition of MWNT in HA increased the hardness and fracture toughness by approximately 3~4 times, despite the presence of large pores produced by un-dispersed MWNTs. This provides strong evidence as to why the MWNTs are good candidates as reinforcements for strengthening the ceramic matrix. The MWNT/HA composites did not decompose during SPS sintering. The MWNT-reinforced HA composites were non-toxic and showed a good cell affinity and morphology in vitro for 1 day.
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Beyond ubiquitination: proteolytic and nonproteolytic roles of HOS1.
Trends Plant Sci.
PUBLISHED: 01-16-2014
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The E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) functions as a cold signaling attenuator by degrading the INDUCER OF CBF EXPRESSION 1 transcription factor, which is a key regulator of the cold-induced transcriptome and freezing tolerance in plants. Recent studies demonstrate that HOS1 also plays nonproteolytic roles in gene expression regulation. HOS1 acts as a chromatin remodeling factor that modulates FLOWERING LOCUS C chromatin in cold regulation of flowering time. It associates with the nuclear pore complex to facilitate nucleocytoplasmic mRNA export to maintain circadian periodicity over a range of light and temperature conditions. In this review, we summarize recent advances in molecular mechanisms underlying HOS1 function during plant development in response to fluctuating environmental conditions.
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Symptomatic steno-occlusion in patients with acute cerebral infarction: prevalence, distribution, and functional outcome.
J Stroke
PUBLISHED: 01-13-2014
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Symptomatic steno-occlusion (SYSO) in acute ischemic stroke has a significant impact on treatment options and prognosis. However, the prevalence, distribution, clinical characteristics, and outcome of SYSO are not well known.
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Down-regulation of oxidative stress and COX-2 and iNOS expressions by dimethyl lithospermate in aged rat kidney.
Arch. Pharm. Res.
PUBLISHED: 01-07-2014
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Oxidative stress has been proposed to be a major cause of aging and many age-related diseases. Peroxynitrite (ONOO(-)), formed from the reaction of superoxide ((•)O2 (-)) and nitric oxide (NO), is a cytotoxic species that can oxidize various cellular components, such as proteins, lipids, and DNA. The present study investigated whether dimethyl lithospermate (DML), isolated from Salvia miltiorrhiza, modulates age-related increases of ONOO(-), NO, and reactive species (RS) levels and expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). For this study, 20-month-old rats were intraperitoneally injected with 5 or 10 mg/kg/day of DML, and 6-month-old rats were used as young control animals. Our results indicated that DML reduces ONOO(-) levels in a dose-dependent manner. The data also revealed that DML has significant inhibitory effects on NO metabolites and RS generation in a dose-dependent manner during aging. Furthermore, the results of Western blot analysis revealed that DML treatment reduces age-associated increases in COX-2 and iNOS expressions. Thus, this study found that DML caused the decrease of renal oxidative stress and COX-2 and iNOS expressions in aged rats. The significance of the present study is the finding of DML in its potential application against the aging process.
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Genistein promotes endothelial colony-forming cell (ECFC) bioactivities and cardiac regeneration in myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Although stem cell-mediated treatment of ischemic diseases offers significant therapeutic promise, the limitation in the therapeutic efficacy of transplanted stem cells in vivo because of poor engraftment remains a challenge. Several strategies aimed at improving survival and engraftment of stem cells in the ischemic myocardium have been developed, such as cell transplantation in combination with growth factor delivery, genetic modification of stem cells, and/or cell therapy using scaffolds. To improve therapeutic efficacy, we investigated the effects of genistein on the engraftment of transplanted ECFCs in an acute myocardial ischemia model. Results: We found that genistein treatment enhanced ECFCs' migration and proliferation, which was accompanied by increases in the expression of ILK, ?-parvin, F-actin, and phospholylation of ERK 1/2 signaling. Transplantation of genistein-stimulates ECFCs (GS-ECFCs) into myocardial ischemic sites in vivo induced cellular proliferation and secretion of angiogenic cytokines at the ischemic sites and thereby enhanced neovascularization and decreased myocardial fibrosis as well as improved cardiac function, as shown by echocardiography. Taken together, these data suggest that pretreatment of ECFCs with genistein prior to transplantation can improve the regenerative potential in ischemic tissues, providing a novel strategy in adult stem cell therapy for ischemic diseases.
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RNA-sequencing from single nuclei.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-18-2013
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It has recently been established that synthesis of double-stranded cDNA can be done from a single cell for use in DNA sequencing. Global gene expression can be quantified from the number of reads mapping to each gene, and mutations and mRNA splicing variants determined from the sequence reads. Here we demonstrate that this method of transcriptomic analysis can be done using the extremely low levels of mRNA in a single nucleus, isolated from a mouse neural progenitor cell line and from dissected hippocampal tissue. This method is characterized by excellent coverage and technical reproducibility. On average, more than 16,000 of the 24,057 mouse protein-coding genes were detected from single nuclei, and the amount of gene-expression variation was similar when measured between single nuclei and single cells. Several major advantages of the method exist: first, nuclei, compared with whole cells, have the advantage of being easily isolated from complex tissues and organs, such as those in the CNS. Second, the method can be widely applied to eukaryotic species, including those of different kingdoms. The method also provides insight into regulatory mechanisms specific to the nucleus. Finally, the method enables dissection of regulatory events at the single-cell level; pooling of 10 nuclei or 10 cells obscures some of the variability measured in transcript levels, implying that single nuclei and cells will be extremely useful in revealing the physiological state and interconnectedness of gene regulation in a manner that avoids the masking inherent to conventional transcriptomics using bulk cells or tissues.
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Bioactive Compounds from the Roots of Asiasarum heterotropoides.
Molecules
PUBLISHED: 11-14-2013
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A new tetrahydrofuran lignan, (7S,8R,7S,8S)-3-methoxy-3,4-methylenedioxy-7,9-epoxylignane-4,7,9-triol (1), and 21 known compounds 2-22 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 1-22 were elucidated by spectroscopic analysis including 1D- and 2D-NMR. Fourteen of these compounds (1-3, 7, 10, 12-17, 19, 21, and 22) were isolated from this species in this study for the first time. All of the isolates were evaluated for their anticancer activities using in vitro assays. Among the 22 tested compounds, two (compounds 5 and 7) induced the downregulation of NO production, FOXP3 expression, and HIF-1? transcriptional activity.
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Cytochalasin H, an Active Anti-Angiogenic Constituent of the Ethanol Extract of Gleditsia sinensis Thorns.
Biol. Pharm. Bull.
PUBLISHED: 10-29-2013
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Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.
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Gender differences in the age-stratified prevalence of risk factors in Korean ischemic stroke patients: a nationwide stroke registry-based cross-sectional study.
Int J Stroke
PUBLISHED: 10-22-2013
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Although ethnic or cultural differences affect prevalence of cardiovascular risk factors, limited information is available about the age- and gender-stratified prevalence of the risk factors in Asian stroke population.
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Successful endoscopic mucosal resection of a low esophageal carcinoid tumor.
Clin Endosc
PUBLISHED: 09-30-2013
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Esophageal carcinoid tumors remain some of the rarest of all carcinoid tumors, with only several cases previously reported in the literature. The endoscopic mucosal resection of selected carcinoid tumors has been shown to be a valid, safe, and effective method of treatment. Endoscopic ultrasonography is the technique of choice to select patients eligible for endoscopic resection. Here, we report successful endoscopic mucosal resection of a low esophageal carcinoid tumor and review the relevant literature. The present case is the first reported case of esophageal carcinoid tumor in Korea.
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Magnolol suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting Ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways.
Nutr Cancer
PUBLISHED: 09-25-2013
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Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to possess anticancer activity. Recent studies have also demonstrated that magnolol inhibits cell growth and induces the apoptosis of cancer cells. However, the effects of magnolol on vascular endothelial growth factor (VEGF)-induced angiogenesis in endothelial cells have not been studied. In the present study, we have used human umbilical vein endothelial cells (HUVECs) to investigate the antiangiogenic effect and molecular mechanism of magnolol. Magnolol inhibited the VEGF-induced proliferation, chemotactic motility and tube formation of HUVECs in vitro as well as the vessel sprouting of the aorta ex vivo. Furthermore, magnolol inhibited VEGF-induced Ras activation and subsequently suppressed extracellular signal-regulated kinase (ERK), phosphatidylinositol-3-kinase (PI3K)/Akt and p38, but not Src and focal adhesion kinase (FAK). Interestingly, the knockdown of Ras by short interfering RNA produced inhibitory effects that were similar to the effects of magnolol on VEGF-induced angiogenic signaling events, such as ERK and Akt/eNOS activation, and resulted in the inhibition of proliferation, migration, and vessel sprouting in HUVECs. In combination, these results demonstrate that magnolol is an inhibitor of angiogenesis and suggest that this compound could be a potential candidate in the treatment of angiogenesis-related diseases.
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Red herring vaginal discharge.
BMJ Case Rep
PUBLISHED: 09-20-2013
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Labial hair tourniquet syndrome is a rare condition that can be easily misdiagnosed and ultimately lead to irreversible damage. An 11-year-old premenarche girl presented with a 5-day history of pain and swelling in the labia with associated vaginal discharge. The general practitioner treated her with clotrimazole without improvement. On examination, there was an oedematous swelling of the right labia with a proximal hair tourniquet. Local anaesthetic was applied and the hair removed with forceps. There was instant relief of pain and the discharge stopped within 24 h. The patient was sent home with a course of antibiotics.
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Sestrins orchestrate cellular metabolism to attenuate aging.
Cell Metab.
PUBLISHED: 09-19-2013
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The Sestrins constitute a family of evolutionarily conserved stress-inducible proteins that suppress oxidative stress and regulate AMP-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis. Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction, and muscle degeneration, that resemble accelerated tissue aging. Likewise, Sestrin deficiencies in mice led to accelerated diabetic progression upon obesity. Further investigation of Sestrin function and regulation should provide new insights into age-associated metabolic diseases, such as diabetes, myopathies, and cancer.
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Submucosal tumor-like early-stage mucinous gastric carcinoma: a case study.
Korean J Gastroenterol
PUBLISHED: 08-29-2013
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Mucinous gastric carcinoma (MGC) is an unusual histologic subtype, and early detection of MGC is very rare. Early-stage MGC appears as an elevated lesion resembling a submucosal tumor (SMT) due to abundant mucin pools in the submucosa or mucosa. We report a rare case of SMT-like early-stage MGC. Tumor type was predicted preoperatively based on characteristic endoscopic findings, in which an SMT-like mass was observed at the gastric fundus. The tumor was covered by nearly normal mucosa, but with an opening allowing for the passage of copious mucus discharge. A total gastrectomy with Roux-en-Y esophagojejunostomy was subsequently performed. Histopathology of the tumor revealed early-stage (lamina propria) mucinous adenocarcinoma.
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[How should azathioprine be dosed in Crohns disease? a novel strategy of maximum dose-titration based on the lower limit of leukocyte count and tolerability].
Korean J Gastroenterol
PUBLISHED: 08-29-2013
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Although general guidelines have suggested weight-based dosing of azathioprine (AZA, 2.5 mg/kg/day) for Crohns disease (CD), a substantial number of patients develop bone marrow suppression. The aim of this study was to evaluate the maximum dose of AZA not based on weight but titrated according to the lower limit of leukocyte count for maintaining remission in patients with CD.
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Reversible dilated cardiomyopathy caused by idiopathic hypoparathyroidism.
Korean J. Intern. Med.
PUBLISHED: 08-14-2013
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Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.
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Endoscopic ultrasound-guided fine needle aspiration of solid pseudopapillary tumors of the pancreas: a report of three cases.
Korean J. Intern. Med.
PUBLISHED: 08-14-2013
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The solid pseudopapillary tumor (SPT) of the pancreas is a rare but low-grade malignant tumor with a good prognosis after surgical excision. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is a minimally invasive, safe and reliable way of diagnosing SPT by providing characteristic cytological and immunochemical specimens. Definitive preoperative diagnosis leads to targeted and minimally invasive surgical resection. In this study, we report three cases of SPTs that were diagnosed through EUS-FNA and underwent successful laparoscopic surgery.
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The Arabidopsis Floral Repressor BFT Delays Flowering by Competing with FT for FD Binding under High Salinity.
Mol Plant
PUBLISHED: 08-10-2013
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Soil salinity is one of the most serious agricultural problems that significantly reduce crop yields in the arid and semi-arid regions. It influences various phases of plant growth and developmental processes, such as seed germination, leaf and stem growth, and reproductive propagation. Salt stress delays the onset of flowering in many plant species. We have previously reported that the Arabidopsis BROTHER OF FT AND TFL1 (BFT) acts as a floral repressor under salt stress. However, the molecular mechanisms underlying the BFT function in the salt regulation of flowering induction is unknown. In this work, we found that BFT delays flowering under high salinity by competing with FLOWERING LOCUS T (FT) for binding to the FD transcription factor. The flowering time of FD-deficient fd-2 mutant was insensitive to high salinity. BFT interacts with FD in the nucleus via the C-terminal domain of FD, which is also required for the interaction of FD with FT, and interferes with the FT-FD interaction. These observations indicate that BFT constitutes a distinct salt stress signaling pathway that modulates the function of the FT-FD module and possibly provides an adaptation strategy that fine-tunes photoperiodic flowering under high salinity.
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ABCB1 haplotype influences the sirolimus dose requirements in Chinese renal transplant recipients.
Biopharm Drug Dispos
PUBLISHED: 08-09-2013
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Sirolimus, an immunosuppressive drug used to prevent organ rejection after renal transplantation, has a narrow therapeutic index and a large inter-individual variability of pharmacokinetics. The aim of this study was to analyse the dose-normalized trough blood concentrations (C0 /D ratio) of sirolimus in patients with different genotypes and attempt to investigate the possible associations between ABCB1/CYP3A5 genotypes and sirolimus dose requirements in Chinese renal transplant recipients. Blood samples were collected from 85 Chinese renal transplant recipients who were treated with sirolimus for at least 3?months and polymorphisms of the ABCB1 and CYP3A5 were determined by the SNaPShot multiplex assay. The blood concentrations of sirolimus were determined with HPLC. A significant allele-dependent effect was observed between the CYP3A5*3 polymorphism and the C0 /D ratio of sirolimus. The patients bearing at least one CYP3A5*1 allele had a lower sirolimus C0 /D ratio compared with those with a homozygous CYP3A5*3 genotype (p?T, 2677G>T/A and 3435C>T genotype groups. However, haplotype analysis including ABCB1 1236C>T, 2677G>T/A and 3435C>T SNPs showed that the mean sirolimus C0 /D of subjects carrying the CGC/CGC diplotype was about 30% lower compared with those carrying the CGC/TTT or TTT/TTT diplotype, whether or not they expressed the CYP3A5 (p?
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High throughput ultralong (20 cm) nanowire fabrication using a wafer-scale nanograting template.
Nano Lett.
PUBLISHED: 08-09-2013
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Nanowires are being actively explored as promising nanostructured materials for high performance flexible electronics, biochemical sensors, photonic applications, solar cells, and secondary batteries. In particular, ultralong (centimeter-long) nanowires are highly attractive from the perspective of electronic performance, device throughput (or productivity), and the possibility of novel applications. However, most previous works on ultralong nanowires have issues related to limited length, productivity, difficult alignment, and deploying onto the planar substrate complying with well-matured device fabrication technologies. Here, we demonstrate a highly ordered ultralong (up to 20 cm) nanowire array, with a diameter of 50 nm (aspect ratio of up to 4,000,000:1), in an unprecedented large (8 in.) scale (2,000,000 strands on a wafer). We first devised a perfectly connected ultralong nanograting master template on the whole area of an 8 in. substrate using a top-down approach, with a density equivalent to that achieved with e-beam lithography (100 nm). Using this large-area, ultralong, high-density nanograting template, we developed a fast and effective method for fabricating up to 20 cm long nanowire arrays on a plastic substrate, composed of metal, dielectric, oxide, and ferroelectric materials. As a suggestion of practical application, a prototype of a large-area aluminum wire grid polarizer was demonstrated.
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A polycaprolactone/cuttlefish bone-derived hydroxyapatite composite porous scaffold for bone tissue engineering.
J. Biomed. Mater. Res. Part B Appl. Biomater.
PUBLISHED: 08-08-2013
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Cuttlefish bone (CB) is an attractive natural biomaterial source to obtain hydroxyapatite (HAp). In this study, a porous polycaprolactone (PCL) scaffold incorporating CB-derived HAp (CB-HAp) powder was fabricated using the solvent casting and particulate leaching method. The presence of CB-HAp in PCL/CB-HAp scaffold was confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM) and porosity analysis showed that the average pore dimension of the fabricated scaffold was approximately 200-300 ?m, with ?85% porosity, and that the compressive modulus increased after addition of CB-HAp powders. In vitro tests such as cell proliferation assay, cytotoxicity analysis, cell attachment observations, and alkaline phosphatase activity assays showed that the PCL/CB-HAp scaffold could improve the proliferation, viability, adherence, and osteoblast differentiation rate of MG-63 cells. When surgically implanted into rabbit calvarial bone defects, consistent with the in vitro results, PCL/CB-HAp scaffold implantation resulted in significantly higher new bone formation than did implantation of PCL alone. These findings suggest that addition of CB-HAp powder to the PCL scaffold can improve cellular response and that the PCL/CB-HAp composite scaffold has great potential for use in bone tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
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Hypoxia inhibits cellular senescence to restore the therapeutic potential of old human endothelial progenitor cells via the hypoxia-inducible factor-1?-TWIST-p21 axis.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 08-08-2013
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Endothelial progenitor cells (EPCs) can significantly improve tissue repair by providing regeneration potential within injured cardiovascular tissue; however, it is challenging to obtain a sufficient amount of functional EPCs from aged patients for autologous stem cell therapy. To overcome this issue, we aimed to establish adequate ex vivo expansion protocols and identify repair modulators of cellular senescence. The senescence repair circuit of hypoxia-preconditioned senescent EPCs (hyp-old EPCs) was examined in an effort to enhance their regenerative potential.
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Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.
Exp. Biol. Med. (Maywood)
PUBLISHED: 08-07-2013
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Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon 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.

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

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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.