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Find video protocols related to scientific articles indexed in Pubmed.
The Rates and Clinical Characteristics of Pneumolabyrinth in Temporal Bone Fracture.
Otol. Neurotol.
PUBLISHED: 11-20-2014
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Pneumolabyrinth is a rare inner ear clinical manifestation. To date, only about 50 cases have been reported-all as case reports. Consequently, the rate and clinical characteristics of pneumolabyrinth have not been evaluated.
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Maternal low-level somatic mosaicism of Cys155Tyr of F9 in severe hemophilia B.
Blood Coagul. Fibrinolysis
PUBLISHED: 11-18-2014
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Hemophilia B is an X-linked bleeding disorder caused by deficient coagulation factor IX from a mutation in the F9 gene. Here, we report a family with two brothers having severe hemophilia B inherited from a mother with low-level somatic mosaicism of a F9 mutation. The proband was a 2-year-old boy with severe hemophilia B from a hemizygous mutation of F9, c.464G>A (p.Cys155Tyr). He was the first child and was considered a sporadic case based on the lack of family history of bleeding diathesis. His mother was tested for carrier status and was determined to be homozygous for wild-type genotypes (noncarrier). Subsequently, however, his brother was born and also had severe hemophilia B from Cys155Tyr. This prompted us to review the chromatogram of the mother, which revealed a small peak corresponding to the mutant genotype. On suspicion of somatic low-level mosaicism in the mother, we further performed allele-specific PCR and thymine and adenine cloning, and confirmed the presence of the mutant allele in the mother. To our knowledge, this is the first case of maternal somatic mosaicism for a cytosine-phosphate-guanine transition mutation in hemophilia B. The acknowledgment of somatic mosaicism and further molecular investigation are important in sporadic hemophilia B to deliver informative genetic counseling and risk assessment.
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Sulfhydryl-Specific Probe for Monitoring Protein Redox Sensitivity.
ACS Chem. Biol.
PUBLISHED: 10-30-2014
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Reactive oxygen species (ROS) regulate various biological processes by modifying reactive cysteine residues in the proteins participating in the relevant signaling pathways. Identification of ROS target proteins requires specific reagents that identify ROS-sensitive cysteine sulfhydryls that differ from the known alkylating agents, iodoacetamide and N-ethylmaleimide, which react nonspecifically with oxidized cysteines including sulfenic and sulfinic acid. We designed and synthesized a novel reagent, methyl-3-nitro-4-(piperidin-1-ylsulfonyl)benzoate (NPSB-1), that selectively and specifically reacts with the sulfhydryl of cysteines in model compounds. We validated the specificity of this reagent by allowing it to react with recombinant proteins followed by peptide sequencing with nanoUPLC-ESI-q-TOF tandem mass spectrometry (MS/MS), and mutant studies employed it to identify cellular proteins containing redox-sensitive cysteine residues. We also obtained proteins from cells treated with various concentrations of hydrogen peroxide, labeled them with biotinylated NPSB-1 (NPSB-B), pulled them down with streptavidin beads, and identified them with MS/MS. We grouped these proteins into four families: (1) those having reactive cysteine residues easily oxidized by hydrogen peroxide, (2) those with cysteines reactive only under mild oxidative stress, (3) those with cysteines reactive only after exposure to oxidative stress, and (4) those with cysteines that are reactive regardless of oxidative stress. These results confirm that NPSBs can serve as novel chemical probes for specifically capturing reactive cysteine residues and as powerful tools for measuring their oxidative sensitivity and can help to understand the function of cysteine modifications in ROS-mediated signaling pathways.
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Factors affecting cancer screening intention and behavior of the korean elderly.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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In this study we investigated factors influencing cancer screening intention and behavior to develop measures to increase the rate of cancer screening in the Korean elderly.
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Risk factors for latent tuberculosis infection in close contacts of active tuberculosis patients in South Korea: a prospective cohort study.
BMC Infect. Dis.
PUBLISHED: 10-16-2014
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BackgroundThe diagnosis and treatment of latent tuberculosis infection (LTBI) have become mandatory to reduce the burden of tuberculosis worldwide. Close contacts of active TB patients are at high risk of both active and LTBI. The aim of this study is to identify the predominant risk factors of contracting LTBI, persons in close contact with TB patients were recruited. This study also aimed to compare the efficacy of the tuberculin skin test (TST) and QuantiFERON®-TB GOLD (QFT-G) to diagnose LTBI.MethodsClose contacts of active pulmonary TB patients visiting a hospital in South Korea were diagnosed for LTBI using TST and/or QFT-G. The association of positive TST and/or QFT-G with the following factors was estimated: age, gender, history of Bacillius Calmette-Guerin (BCG) vaccination, history of pulmonary TB, cohabitation status, the acid-fast bacilli smear status, and presence of cough in source cases.ResultsOf 308 subjects, 38.0% (116/305) were TST positive and 28.6% (59/206) were QFT-G positive. TST positivity was significantly associated with male gender (OR: 1.734; 95% CI: 1.001-3.003, p =0.049), history of pulmonary TB (OR: 4.130; 95% CI: 1.441-11.835, p =0.008) and household contact (OR: 2.130; 95% CI: 1.198-3.786, p =0.01) after adjustment for confounding variables. The degree of concordance between TST and QFT-G was fair (70.4%, ¿ =0.392).ConclusionsA prevalence of LTBI among close contacts of active pulmonary TB patients was high, and prior TB history and being a household contact were risk factors of LTBI in the study population.
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A novel nonsense mutation Tyr301* of PROS1 causing protein S deficiency.
Blood Coagul. Fibrinolysis
PUBLISHED: 09-26-2014
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Hereditary protein S deficiency is one of the natural anticoagulant deficiency causing thrombophilia. Protein S deficiency is caused by a mutation in the PROS1 gene on 3q11.2 and is typically inherited in an autosomal dominant manner. We herein describe a Korean man with protein S deficiency from a novel nonsense mutation of PROS1. The patient was a 47-year-old man with deep-vein thrombosis. No relevant family history was documented. Coagulation test results included a significantly decreased protein S activity at 30%. Molecular genetic analysis targeting PROS1 on suspicion of hereditary protein S deficiency revealed that he was heterozygous for a novel transversion mutation, c.903C>G, in the exon 9 of PROS1. The mutation was predicted to result in premature termination at the codon 301 in the laminin G-type domain (p.Tyr301) of the protein (nonsense mutation). According to a review of the literature and database, the mutation described herein is the first substitution mutation affecting the codon 301 of PROS1.
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Characterization of a GH family 8 ?-1,3-1,4-glucanase with distinctive broad substrate specificity from Paenibacillus sp. X4.
Biotechnol. Lett.
PUBLISHED: 09-25-2014
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A ?-1,3-1,4 glucanase gene of Paenibacillus sp. X4, bglc8H, was cloned and characterized. BGlc8H was predicted to be a protein of 409 amino acid residues, including a signal peptide of 31 amino acids. The mature enzyme was predicted to have 378 amino acid residues; ITS molecular mass and pI were estimated as 41,561 Da and 7.61, respectively. BGlc8H belongs to glycoside hydrolase family 8 (GH8). Site-directed mutants of Glu95 and Asp156 of BGlc8H showed a near-complete loss of activity, indicating that they are catalytically-active residues. Unlike other GH8 members, BGlc8H had broad substrate specificity and hydrolyzed barley-?-D-glucan > chitosan > carboxymethyl-cellulose > and lichenan. BGlc8H had a lower ratio of lichenase/barley-?-D-glucanase activities compared to GH16 enzymes. BGlc8H was optimally active at pH 5 and 50 °C, except for barley-?-D-glucanase (40 °C) and chitosanase (pH 7) activities. BGlc8H hydrolyzed cello-oligosaccharides (G3-G6) to G3 and G2 but not to G1. Ca(2+) increased the activity and thermostability of BGlc8H for lichenan suggesting its use for the saccharification of cellulosic biomass.
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In-house development of an optimized synthetic module for routine [11C]acetate production.
Nucl Med Commun
PUBLISHED: 09-19-2014
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[C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[F]fluoro-D-glucose in a number of cancers. Here, the optimized automatic synthesis of [C]acetate using an in-house-developed module under different conditions has been reported for routine production. [C]CO2 was produced in a 16.4?MeV PETtrace cyclotron, and methyl magnesium chloride was used for synthesis. For product purification, ion-exchange solid-phase extraction cartridges were used, connected in series. High-performance liquid chromatography and gas chromatography were used to measure radiochemical and chemical purity. The Limulus amebocyte lysate test and the fluid thioglycollate medium test were performed for quality control of [C]acetate. The total reaction time of [C]acetate was within 15?min, and the overall decay-corrected radiochemical yield was 84.33±8.85%. Radiochemical purity was greater than 98% when evaluated on an analytical high-performance liquid chromatography system. No endotoxins or anaerobic bacteria were seen on quality control checks. Optimized production of [C]acetate was achieved by the in-house module. Radiochemical and biological properties of the [C]acetate produced were appropriate for clinical PET study.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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The relationships between intra-abdominal echogenicity, cardiometabolic risk factors and physical performance in obese children.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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While the abdominal adipose tissue has been identified as an important pathomarker for the cardiometabolic syndrome in adults, the relationships between the cardiometabolic risk factors and abdominal adipose morphology or physical performance levels have not been examined in children with obesity. Therefore, the specific aim of this study was to investigate the relationships between risk factors (BMI and physical activity levels and abdominal fat layers including subcutaneous, intra-abdominal preperitoneal and mesenteric fat thickness in children with obesity. 30 children with obesity (mean ± SD = 10.0 ± 4.5 yrs; 9 girls; BMI > 20) underwent physical performance (curl-ups, sit and reach, push-ups, and a 400-m run), ultrasound measurement of thickness of fat composition of the abdomen, blood pressure, oxygen consumption. Pearson correlation analysis showed significant correlations, ranging from -0.523- 0.898 between the intra-abdominal adipose tissue thickness, cardiometabolic risk factors (BMI, blood pressure, heart rate), and the curl-up physical performance test. In conclusion, the present study provides a compelling evidence that the intra-abdominal adipose tissue morphological characteristics were associated with BMI, physical performance, and most importantly cardiometabolic risk factors (blood pressure and heart rate), which eventually contribute to the development of cardiometabolic syndrome in adulthood.
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Biopsychological traits of Sasang typology based on Sasang personality questionnaire and body mass index.
BMC Complement Altern Med
PUBLISHED: 08-26-2014
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The purpose of present study was to examine biological and psychological characteristics of people according to the Sasang typology, which is popular in Korea. We evaluated the Sasang Personality Questionnaire (SPQ) as a measure of temperament, and Body Mass Index (BMI) as a measure of the somatic properties of each Sasang type.
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Long non-coding RNA HOTAIR is associated with human cervical cancer progression.
Int. J. Oncol.
PUBLISHED: 08-20-2014
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The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.
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Changes in the gray matter volume during compensation after vestibular neuritis: A longitudinal VBM study.
Restor. Neurol. Neurosci.
PUBLISHED: 08-07-2014
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Peripheral vestibular dysfunction following vestibular neuritis (VN) often persists but functional recovery of balance can be variable. The authors compared structural changes in the brain before and after post-VN compensation and related it to the functional recovery.
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Comparison of upper extremity motor recovery of stroke patients with actual physical activity in their daily lives measured with accelerometers.
J Phys Ther Sci
PUBLISHED: 07-30-2014
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[Purpose] This study compared the upper extremity recovery of stroke patients with the amount of their upper extremity use in real life as measured by accelerometers. [Subjects] Forty inpatients who had had a stroke were recruited. [Methods] The subjects were divided into two groups by the Fugl-Meyer Assessment of Motor Function (FMA) score, a moderately recovered group and a well recovered group. The amount of upper extremity physical activity and its ratio in daily time periods were analyzed for the affected and unaffected sides. [Results] The well recovered group showed significantly higher affected arm use and use ratio than the moderately recovered group in all time periods. [Conclusion] The upper extremity recovery level of the affected side is similar to the physical activity level according to the amount of upper extremity physical activity in actual life measured with an accelerometer. Overuse of the normal side regardless of the recovery level of upper extremity proves the International Classification of Functioning (ICF) concept of differentiating between capacity and performance, and rehabilitation treatments should focus on improving performance.
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Surgical outcomes of robotic radical hysterectomy using three robotic arms versus conventional multiport laparoscopy in patients with cervical cancer.
Yonsei Med. J.
PUBLISHED: 07-23-2014
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To compare surgical outcomes of robotic radical hysterectomy (RRH) using 3 robotic arms with those of conventional laparoscopy in patients with early cervical cancer.
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Matrix metalloproteinase-8 plays a pivotal role in neuroinflammation by modulating TNF-? activation.
J. Immunol.
PUBLISHED: 07-21-2014
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Matrix metalloproteinases (MMPs) play important roles in normal brain development and synaptic plasticity, although aberrant expression of MMPs leads to brain damage, including blood-brain barrier disruption, inflammation, demyelination, and neuronal cell death. In this article, we report that MMP-8 is upregulated in LPS-stimulated BV2 microglial cells and primary cultured microglia, and treatment of MMP-8 inhibitor (M8I) or MMP-8 short hairpin RNA suppresses proinflammatory molecules, particularly TNF-? secretion. Subsequent experiments showed that MMP-8 exhibits TNF-?-converting enzyme (TACE) activity by cleaving the prodomain of TNF-? (A(74)/Q(75), A(76)/V(77) residues) and, furthermore, that M8I inhibits TACE activity more efficiently than TAPI-0, a general TACE inhibitor. Biochemical analysis of the underlying anti-inflammatory mechanisms of M8I revealed that it inhibits MAPK phosphorylation, NF-?B/AP-1 activity, and reactive oxygen species production. Further support for the proinflammatory role of microglial MMP-8 was obtained from an in vivo animal model of neuroinflammatory disorder. MMP-8 is upregulated in septic conditions, particularly in microglia. Administration of M8I or MMP-8 short hairpin RNA significantly inhibits microglial activation and expression/secretion of TNF-? in brain tissue, serum, and cerebrospinal fluid of LPS-induced septic mice. These results demonstrate that MMP-8 critically mediates microglial activation by modulating TNF-? activity, which may explain neuroinflammation in septic mouse brain.
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Characterization of biomaterial-free cell sheets cultured from human oral mucosal epithelial cells.
J Tissue Eng Regen Med
PUBLISHED: 07-15-2014
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The purpose of this study was to report the characteristics of biomaterial-free sheets cultured from human oral mucosal epithelial cells without fibrin support, in vitro and after transplantation to limbal-deficient models. Human oral mucosal epithelial cells and limbal epithelial cells were cultured for 2 weeks, and the colony-forming efficiency (CFE) rates were compared. Markers of stem cells (p63), cell proliferation (Ki-67) and epithelial differentiation (cytokeratin; K1, K3, K4, K13) were observed in colonies and in biomaterial-free sheets. Biomaterial-free sheets which had been detached with 1% dispase or biomaterial-free sheets generated by fibrin support were transplanted to 12 limbal-deficient rabbit models. In vitro cell viability, in vivo stability and cytokeratin characteristics of biomaterial-free sheets were compared with those of sheets formed by fibrin-coated culture 1 week after transplantation. Mean CFE rate was significantly higher in human oral mucosal epithelial cells (44.8%) than in human limbal epithelial cells(17.7%). K3 and K4 were well expressed in both colonies and sheets. Biomaterial-free sheets had two to six layers of stratified cells and showed an average of 79.8% viable cells in the sheets after detachment. Cytokeratin expressions of biomaterial-free sheets were comparable to those of sheets cultured by fibrin support, in limbal-deficient models. Both p63 and Ki-67 were well expressed in colonies, isolated sheets and sheets transplanted to limbal-deficient models. Our results suggest that biomaterial-free sheets cultured from human oral mucosal epithelial cells without fibrin support can be an alternative option for cell therapy in use for the treatment of limbal-deficient diseases. Copyright © 2014 John Wiley & Sons, Ltd.
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Effect of comedication on lamotrigine clearance in Korean epilepsy patients.
Clin. Chim. Acta
PUBLISHED: 06-23-2014
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Lamotrigine (LTG) is a widely used antiepileptic-drug (AED) for the treatment of epilepsy. We investigated the effect of AED comedication on LTG clearance in Korean patients with epilepsy.
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ROSics: Chemistry and proteomics of cysteine modifications in redox biology.
Mass Spectrom Rev
PUBLISHED: 06-12-2014
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Post-translational modifications (PTMs) occurring in proteins determine their functions and regulations. Proteomic tools are available to identify PTMs and have proved invaluable to expanding the inventory of these tools of nature that hold the keys to biological processes. Cysteine (Cys), the least abundant (1-2%) of amino acid residues, are unique in that they play key roles in maintaining stability of protein structure, participating in active sites of enzymes, regulating protein function and binding to metals, among others. Cys residues are major targets of reactive oxygen species (ROS), which are important mediators and modulators of various biological processes. It is therefore necessary to identify the Cys-containing ROS target proteins, as well as the sites and species of their PTMs. Cutting edge proteomic tools which have helped identify the PTMs at reactive Cys residues, have also revealed that Cys residues are modified in numerous ways. These modifications include formation of disulfide, thiosulfinate and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and thiosulfonic acid, transformation to dehydroalanine (DHA) and serine, palmitoylation and farnesylation, formation of chemical adducts with glutathione, 4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here, a review of relevant ROS biology, possible chemical reactions of Cys residues and details of the proteomic strategies employed for rapid, efficient and sensitive identification of diverse and novel PTMs involving reactive Cys residues of redox-sensitive proteins. We propose a new name, "ROSics," for the science which describes the principles of mode of action of ROS at molecular levels. © 2014 The Authors. Mass Spectrometry Reviews published by Wiley Periodicals Inc.
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Cutoff value of pharyngeal residue in prognosis prediction after neuromuscular electrical stimulation therapy for Dysphagia in subacute stroke patients.
Ann Rehabil Med
PUBLISHED: 05-22-2014
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To determine the cutoff value of the pharyngeal residue for predicting reduction of aspiration, by measuring the residue of valleculae and pyriformis sinuses through videofluoroscopic swallowing studies (VFSS) after treatment with neuromuscular electrical stimulator (VitalStim) in stroke patients with dysphagia.
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Difference of diagnostic rates and analytical methods in the test positions of vestibular evoked myogenic potentials.
Ann Rehabil Med
PUBLISHED: 04-29-2014
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To compare the differences of diagnostic rates, of the two widely used test positions, in measuring vestibular evoked myogenic potentials (VEMP) and selecting the most appropriate analytical method for diagnostic criteria for the patients with vertigo.
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In situ recruitment of human BMSCs using chemokines for articular cartilage regeneration.
Cell Transplant
PUBLISHED: 04-25-2014
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Bone marrow-derived mesenchymal stem cells (BMSCs) are a good cell source for regeneration of cartilage as they can migrate directly to the site of cartilage injury and differentiate into articular chondrocytes. Articular cartilage defects do not heal completely due to the lack of chondrocytes or BMSCs at the site of injury. In this study, the chemotaxis of BMSCs toward chemokines, which may give rise to a complete regeneration of the articular cartilage, was investigated. CCR2, CCR4, CCR6, CXCR1, and CXCR2 were expressed in normal BMSCs and were increased significantly upon treatment with pro-inflammatory cytokines. BMSC migration was increased by MIP-3a and IL-8 more than by MCP-1 or SDF-1?. IL-8 and MIP-3? significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1?, or the PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3? significantly increased in vivo compared with that to scaffolds containing the PBS. Furthermore, IL-8- and MIP-3?-containing scaffolds enhanced tissue regeneration of ostechondral defect site formed in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3? are the candidates that induce the regeneration of damaged articular cartilage.
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Mutant Enrichment with 3'-Modified Oligonucleotides (MEMO)-Quantitative PCR for Detection of NPM1 Mutations in Acute Myeloid Leukemia.
J. Clin. Lab. Anal.
PUBLISHED: 04-10-2014
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Detection of NPM1 mutations in acute myeloid leukemia (AML) is important for risk stratification, treatment decision, and therapeutic monitoring. We have designed a real-time PCR method implementing the Mutant enrichment with 3'-modified oligonucleotides (MEMO) technique to detect NPM1 mutations and validated its utility in clinical samples.
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Is There a Role for a Needle Thoracoscopic Pleural Biopsy under Local Anesthesia for Pleural Effusions?
Korean J Thorac Cardiovasc Surg
PUBLISHED: 04-10-2014
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A closed pleural biopsy is commonly performed for diagnosing patients exhibiting pleural effusion if prior thoracentesis is not diagnostic. However, the diagnostic yield of such biopsies is unsatisfactory. Instead, a thoracoscopic pleural biopsy is more useful and less painful.
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Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-09-2014
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Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes.
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Interleukin-6 induces the lineage commitment of bone marrow-derived mesenchymal multipotent cells through down-regulation of Sox2 by osteogenic transcription factors.
FASEB J.
PUBLISHED: 04-09-2014
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Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a heterogeneous population of cells that differ in size and morphology. BM-MSCs become committed to the osteogenic lineage as senescence approaches and lose multipotency. Nevertheless, little is known about the effects of cell-cell interaction between different populations on stemness loss and lineage commitment. The current study aimed to identify mechanisms by which cell-cell interactions between heterogeneous BM-MSCs affect stemness and lineage commitment of multipotent subpopulation. The lineage commitment of primitive multipotent cells was strongly induced in the presence of cytokines secreted by senescent-like cells in a cell culture insert system. Senescent-like cells secreted higher levels of interleukin-6 (IL-6) than primitive multipotent cells in a human cytokine array. IL-6 induced the lineage commitment and stemness loss in multipotent cells by decreasing Sox2 expression. Furthermore, we confirmed that IL-6 decreased the transcriptional activity of Sox2 through up-regulation of Runx2 and Dlx5. We suggest a mechanism by which IL-6 modulates the expression of Sox2, resulting in decreased multipotency and causing primitive multipotent cells to undergo osteogenic lineage commitment. This is the first study to identify mechanisms in which the cell-cell interactions between the different populations play important roles in the stemness loss and lineage commitment of multipotent populations.-Yoon, D. S., Kim, Y. H., Lee, S., Lee, K.-M., Park, K. H., Jang, Y., Lee, J. W. Interleukin-6 induces the lineage commitment of bone marrow-derived mesenchymal multipotent cells through down-regulation of Sox2 by osteogenic transcription factors.
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Psychometric properties and factor structure of an L2 reading motivation questionnaire.
Technol Health Care
PUBLISHED: 04-08-2014
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The purpose of this study is to investigate the psychometric properties and factor structure of a popular second language reading motivation questionnaire developed by Mori (2002). 550 first year high school students in Korea answered the 30-item questionnaire which consists of statements indicating different degrees of English reading motivation. Exploratory factor analysis was conducted with principal axis factoring and promax rotation, which yielded a four-factor solution. The factors included 'Intercultural and Intellectual Orientation', 'Reading Efficacy', 'Intrinsic Motivation', and 'Negative Attitudes'. The results supported the multidimensionality of the construct of L2 reading motivation, but could not replicate the nine factor structure which was originally proposed by Mori. The implications for further research on L2 reading motivation and development of a more valid L2 reading scale are discussed.
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[A comparison study using mixed methods on foreign residents' satisfaction with Korean health care services].
J Korean Acad Nurs
PUBLISHED: 03-19-2014
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This study was conducted to examine and compare satisfaction with Korean health care services for Americans, Chinese and Russians who resided in Korea.
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Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).
Eur J Med Chem
PUBLISHED: 03-18-2014
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In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain A?-lowering effect of 40 is also described.
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The anti-inflammatory role of tissue inhibitor of metalloproteinase-2 in lipopolysaccharide-stimulated microglia.
J Neuroinflammation
PUBLISHED: 03-05-2014
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Tissue inhibitors of metalloproteinases (TIMPs) are known to be endogenous inhibitors of matrix metalloproteinases (MMPs). Our preliminary study showed that TIMP-2 is constitutively expressed in microglia but significantly inhibited by lipopolysaccharide (LPS) treatment. The current study was undertaken to investigate the role of TIMP-2 in microglia.
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Ginsenoside Re and Rd enhance the expression of cholinergic markers and neuronal differentiation in Neuro-2a cells.
Biol. Pharm. Bull.
PUBLISHED: 03-05-2014
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In Alzheimer's disease (AD), extensive neuronal loss and a deficiency of the neurotransmitter acetylcholine (ACh) are the major characteristics during pathogenesis in the brain. In the present study, we aimed to investigate whether representative ginsenosides from ginseng can regulate choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are required for cholinergic neurotransmission. Our results revealed that Re and Rd induced effectively the expression of ChAT/VAChT genes in Neuro-2a cells as well as ACh elevation. Microtubule-associated protein-2 (MAP-2), nerve growth factor receptor (p75), p21, and TrkA genes and proteins were also significantly expressed. Moreover, both activated extracelullar signal-regulated protein kinase (ERK) and Akt were inhibited by K252a, a selective Trk receptor inhibitor. These findings strongly indicate that Re and Rd play an important role in neuronal differentiation and the nerve growth factor (NGF)-TrkA signaling pathway. High performance liquid chromatography analysis showed that Re and Rd administered orally were transported successfully into brain tissue and increased the level of ChAT and VAChT mRNA. The present study demonstrates that Re and Rd are selective candidates for upregulation of the expression of cholinergic markers, which may counter the symptoms and progress of AD.
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Oral administration of herbal medicines for the treatment of otitis media with effusion: protocol for a systematic review.
BMJ Open
PUBLISHED: 03-01-2014
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The purpose of this systematic review is to investigate the efficacy of the oral administration of herbal medicines for otitis media with effusion through analysing trial data.
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Expression of Heat Shock Proteins and Cytokines in Response to Ethanol Induced Damage in the Small Intestine of ICR Mice.
Intest Res
PUBLISHED: 02-24-2014
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Ethanol administration causes intestinal epithelial cell damage by increasing intestinal permeability and the translocation of endotoxins from intestinal bacterial flora. Heat shock proteins (HSPs) are associated with recovery and protection from cell damage. The aim of the current study was to investigate differences in the expression of HSPs in the small intestine and the biochemical changes attributable to ethanol-induced intestinal damage.
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Population pharmacokinetic analysis of simvastatin and its active metabolite with the characterization of atypical complex absorption kinetics.
Pharm. Res.
PUBLISHED: 02-19-2014
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The pharmacokinetics of simvastatin is complex with multiple peaks in the absorption phase, which cannot be adequately described by a conventional first order absorption model. The biotransformation of simvastatin into simvastatin acid, an active metabolite, is reversible. This study evaluated the pharmacokinetics of simvastatin and simvastatin acid, focusing on the absorption kinetics.
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Treatment and survival of patients with occult breast cancer with axillary lymph node metastasis: a nationwide retrospective study.
J Surg Oncol
PUBLISHED: 02-12-2014
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Occult breast cancer (OBC) accounts for 0.3-1.0% of all breast cancers and is a rare presentation of the disease. The present retrospective study examined the overall survival and prognostic factors associated with OBC in Korea.
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Antigen Expression Patterns of Plasma Cell Myeloma: An Association of Cytogenetic Abnormality and International Staging System (ISS) for Myeloma.
J. Clin. Lab. Anal.
PUBLISHED: 02-09-2014
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Immunophenotyping of plasma cell has become an important diagnostic tool for plasma cell myeloma. There have been a few studies for association of antigen expression and cytogenetic abnormality of plasma cell myeloma.
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Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays.
J. Radiat. Res.
PUBLISHED: 02-07-2014
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The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage.
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Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials.
Chin Med
PUBLISHED: 02-06-2014
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It was reported that 64% of tic disorder patients used complementary and alternative medicine. This review aims to evaluate the efficacy of herbal medicines in treating tic disorders.
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Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with amyotrophic lateral sclerosis.
Neurobiol. Aging
PUBLISHED: 01-29-2014
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Mutations in the UBQLN2 and SIGMAR1 genes were recently identified in X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS and/or FTD) and FTD and/or motor neuron disease, respectively. Subsequent studies, however, found that UBQLN2 mutations were rare, and the pathogenicity of SIGMAR1 mutation in FTD and/or motor neuron disease was controversial. In the present study, we analyzed mutations in the UBQLN2 and SIGMAR1 genes in a Korean cohort of 258 patients with familial ALS (n = 9) or sporadic (sALS; n = 258) ALS. One novel UBQLN2 variant (p.D314E) was observed in 2 patients with sALS and 5 of 727 controls indicating that this variant might be a rare polymorphism rather than a disease-causing mutation. A novel SIGMAR1 gene variant in the 3'-untranslated region (c.*58T>C) was found in 1 sALS and was absent in 727 control samples. Taken together, our data suggest that causative mutations in the UBQLN2 and SIGMAR1 genes are rare in Korean patients with either familial or sporadic ALS.
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Genetic and phenotypic diversity in breast tumor metastases.
Cancer Res.
PUBLISHED: 01-21-2014
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Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance, our knowledge of how cancer cell populations change during metastatic progression is limited. Here, we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer. We analyzed cellular genotypes and phenotypes at the single cell level by performing immunoFISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected before systemic therapy. We calculated the Shannon index of intratumor diversity in all cancer cells and within phenotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-naïve primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2(+) tumors compared with other subtypes and in metastases of triple-negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples could be used for the improved prognostication of patients with cancer and for the design of more effective therapies for progressive disease.
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Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats.
Nutr Res Pract
PUBLISHED: 01-16-2014
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Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause.
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Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3.
Cancer Res Treat
PUBLISHED: 01-15-2014
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Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis.
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Innovative strength training-induced neuroplasticity and increased muscle size and strength in children with spastic cerebral palsy: an experimenter-blind case study--three-month follow-up.
NeuroRehabilitation
PUBLISHED: 01-15-2014
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In children with cerebral palsy (CP), the never-learned-to-use (NLTU) effect and underutilization suppress the normal development of cortical plasticity in the paretic limb, which further inhibits its functional use and increases associated muscle weakness.
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Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes.
BMC Complement Altern Med
PUBLISHED: 01-11-2014
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Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level.
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Discrimination of Lycium chinense and Lycium barbarum by taste pattern and betaine analysis.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Lycii Fructus was used as natural products with therapeutic properties for a long time. Betaine is a natural amino acid and one of the major constituents of Lycii Fructus. It is reported that this fruit plays a role in reducing blood levels of homocysteine, a toxic byproduct of the amino acid metabolism. This study was used to establish infra based on oriental medicine through the analysis of correlation of taste, contents of betaine, %Brix and physico-chemical properties of Lycii Fructus. To investigate betaine, quantitative analysis was performed using HPLC separation system. In addition, %Brix and saccharide were estimated. Taste pattern analysis was measured using the taste sensing system, SA402B equipped with six taste sensors including newly developed sweetness sensor. Betaine quantitative analysis showed that L. barbarum 0.64 ± 0.15% (n = 6) was significantly higher than L. chinense 0.55 ± 0.1% (n = 12). And %Brix and saccharide composition of Lycii Fructus analysis showed that L. barbarum was significantly higher than L. chinense. The results of taste pattern analysis between L. barbarum and L. chinense showed a significant difference in almost every taste. In contrast, sweetness of L. barbarum was higher than L. chinense. When clustering with sweetness and bitterness, the two species are distinctly separated. In conclusion, these taste patterns, %Brix, betaine, and saccharide composition analysis could be applied to the establishment of herbal medicine marker for identification of different species in various regions.
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N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage.
PLoS ONE
PUBLISHED: 01-01-2014
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Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.
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Anti-inflammatory effects of ?-galactosylceramide analogs in activated microglia: involvement of the p38 MAPK signaling pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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Microglial activation plays a pivotal role in the development and progression of neurodegenerative diseases. Thus, anti-inflammatory agents that control microglial activation can serve as potential therapeutic agents for neurodegenerative diseases. Here, we designed and synthesized ?-galactosylceramide (?-GalCer) analogs to exert anti-inflammatory effects in activated microglia. We performed biological evaluations of 25 ?-GalCer analogs and observed an interesting preliminary structure-activity relationship in their inhibitory influence on NO release and TNF-? production in LPS-stimulated BV2 microglial cells. After identification of 4d and 4e as hit compounds, we further investigated the underlying mechanism of their anti-inflammatory effects using RT-PCR analysis. We confirmed that 4d and 4e regulate the expression of iNOS, COX-2, IL-1?, and IL-6 at the mRNA level and the expression of TNF-? at the post-transcriptional level. In addition, both 4d and 4e inhibited LPS-induced DNA binding activities of NF-?B and AP-1 and phosphorylation of p38 MAPK without affecting other MAP kinases. When we examined the anti-inflammatory effect of a p38 MAPK-specific inhibitor, SB203580, on microglial activation, we observed an identical inhibitory pattern as that of 4d and 4e, not only on NO and TNF-? production but also on the DNA binding activities of NF-?B and AP-1. Taken together, these results suggest that p38 MAPK plays an important role in the anti-inflammatory effects of 4d and 4e via the modulation of NF-?B and AP-1 activities.
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Herbal medicines for the treatment of acute otitis media: protocol for a systematic review.
BMJ Open
PUBLISHED: 12-03-2013
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The aim of this systematic review is to analyse the trial data on the efficacy of herbal medicines for acute otitis media.
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Downregulation of erythroid differentiation regulator 1 as a novel marker of skin tumors.
Int. J. Dermatol.
PUBLISHED: 10-29-2013
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Erythroid differentiation regulator 1 is decreased in malignant melanoma. However, the expression of erythroid differentiation regulator 1 has not been reported in normal epidermis, vessel, nerve, dermal adnexae, and various skin tumors.
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Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-?B/AP-1 Pathways.
Biomol Ther (Seoul)
PUBLISHED: 09-04-2013
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Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimers disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-? expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-?B and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-?B/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.
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Significance of isoagglutinin titer in ABO-incompatible kidney transplantation.
J Clin Apher
PUBLISHED: 08-14-2013
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ABO-incompatible (ABO-i) kidney transplantation (KT) has emerged for overcoming the shortage of organ donors. Although this technique initially achieved only low graft survival due to isoagglutinin, recently developed desensitization protocols have improved survival to levels that are comparable to ABO-compatible KT. However, isoagglutinin is still regarded as a major obstacle to ABO-i KT. In this study, we evaluate the impact of isoagglutinin titer on clinical outcomes as well as factors that may influence isoagglutinin titers. In total, data from 95 patients who underwent ABO-i KT were analyzed. Preoperatively, rituximab administration and plasmapheresis were performed until the titer was reduced to ?1:4. Retrospective analysis included blood group; timing and dosage of rituximab; isoagglutinin titer; number of plasmapheresis; and clinical outcomes including graft survival and serum creatinine. Graft survival was 95.8% (n?=?91) and average serum creatinine at 1- and 1.5-year post-ABOi-KT was 1.3. Three patients died of sepsis. The identified predictors of titer-rebound after transplant were short interval (<7 days) between rituximab and first plasmapheresis (P?=?0.004); high initial titer (?256) (P?=?0.023); low titer-reduction rate (P?
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Two ?-strands of RAGE participate in the recognition and transport of amyloid-? peptide across the blood brain barrier.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-08-2013
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Amyloid-? (A?) peptide is central to the development of brain pathology in Alzheimer disease (AD) patients. Association with receptors for advanced glycation end-products (RAGE) enables the transport of A? peptide from circulating blood to human brain, and also causes the activation of the NF-?B signaling pathway. Here we show that two ?-strands of RAGE participate in the interaction with A? peptide. Serial deletion analysis of the RAGE V domain indicates that the third and eighth ?-strands are required for interaction with A? peptide. Site-directed mutagenesis of amino acids located in the third and eighth ?-strands abolish the interaction of RAGE with A? peptide. Wild-type RAGE activates the NF-?B signaling pathway in response to A? peptide treatment, while a RAGE mutant defective in A? binding does not. Furthermore, use of peptide for the third ?-strand or a RAGE monoclonal antibody that targets the RAGE-A? interaction interface inhibited transport of the A? peptide across the blood brain barrier in a mice model. These results provide information crucial to the development of RAGE-derived therapeutic reagents for Alzheimer disease.
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Treatment of nevus of Ota using low fluence Q-switched Nd:YAG laser.
Int. J. Dermatol.
PUBLISHED: 07-08-2013
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Nevus of Ota, caused by dermal melanocytosis, is cosmetically troublesome in Asian patients. The destruction of dermal melanocytosis using Q-switched laser systems carries a high risk of postinflammatory hyperpigmentation/hypopigmentation.
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Extracellular signal-regulated kinase1/2-dependent changes in tight junctions after ischemic preconditioning contributes to tolerance induction after ischemic stroke.
Brain Struct Funct
PUBLISHED: 04-28-2013
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Less disruption of the blood-brain barrier (BBB) after severe ischemic stroke is one of the beneficial outcomes of ischemic preconditioning (IP). However, the effect of IP on tight junctions (TJs), which regulate paracellular permeability of the BBB, is not well understood. In the present study, we examined IP-induced changes in TJs before and after middle cerebral artery occlusion (MCAO) in mice, and the association between changes in TJs and tolerance to a subsequent insult. After IP, we found decreased levels of transmembrane TJ proteins occludin and claudin-5, and widened gaps of TJs with perivascular swelling at the ultrastructural level in the brain. An inflammatory response was also observed. These changes were reversed by inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) via the specific ERK1/2 inhibitor U0126. After MCAO, reduced brain edema and inflammatory responses were associated with altered levels of angiogenic factors and cytokines in preconditioned brains. Pretreatment with U0126 reversed the neuroprotective effects of IP against MCAO. These findings suggest that ERK1/2 activation has a pivotal role in IP-induced changes in TJs and inflammatory response, which serve to protect against BBB breakdown and inflammation after ischemic stroke.
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Effect of silane activation on shear bond strength of fiber-reinforced composite post to resin cement.
J Adv Prosthodont
PUBLISHED: 04-25-2013
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Among the surface treatment methods suggested to enhance the adhesion of resin cement to fiber-reinforced composite posts, conflicting results have been obtained with silanization. In this study, the effects of silanization, heat activation after silanization, on the bond strength between fiber-reinforced composite post and resin cement were determined.
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Effect of computer-based cognitive rehabilitation (CBCR) for people with stroke: a systematic review and meta-analysis.
NeuroRehabilitation
PUBLISHED: 03-29-2013
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We conducted a systematic review and meta-analysis to identify the effect of computer-based cognitive rehabilitation (CBCR) on improving cognitive functions in patients with stroke.
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Sequence variation data of F8 and F9 genes in functionally validated control individuals: implications on the molecular diagnosis of hemophilia.
Blood Res
PUBLISHED: 03-28-2013
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The F8 and F9 genes encode for coagulation factor VIII (FVIII) and FIX, respectively, and mutations in these genes are the genetic basis of hemophilia A/B. To determine whether a sequence variation in F8/F9 is a disease-causing mutation, frequency data from a control population is needed. This study aimed to obtain data on sequence variation in F8/F9 in a set of functionally validated control chromosomes of Korean descent.
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Hizikia fusiformis fractions successfully improve atopic dermatitis indices in anti-CD3-stimulated splenocytes and 2,4-dinitrochlorobenzene-treated BALB/c mice.
J. Pharm. Pharmacol.
PUBLISHED: 03-06-2013
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In the present study, we aimed to examine whether fractions from an edible sea weed, Hizikia fusiformis, had immunomodulatory effects, particularly an anti-atopic effect, by attenuating the expression of T cell-dependent cytokines using in-vitro and in-vivo animal atopic dermatitis-like models.
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Bilateral perisylvian ulegyria: an under-recognized, surgically remediable epileptic syndrome.
Epilepsia
PUBLISHED: 02-25-2013
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Interest in the association of epilepsy and pseudobulbar palsy was rekindled since the identification through magnetic resonance imaging (MRI) of bilateral perisylvian polymicrogyria (PMG). Seizures are often intractable, but resective epilepsy surgery has not been recommended. However, a similar clinical picture can be encountered in patients with bilateral perisylvian destructive lesions, which fit the description of ulegyria (ULG). We report a series of patients with epilepsy and pseudobulbar palsy due to bilateral perisylvian ULG (BP-ULG), show that hippocampal sclerosis (HS) is often associated and highlight the fact that in this entity, unlike in malformative bilateral perisylvian PMG, seizures may be surgically treated.
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Fully coupled fluid-structure interaction model of congenital bicuspid aortic valves: effect of asymmetry on hemodynamics.
Med Biol Eng Comput
PUBLISHED: 02-25-2013
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A bicuspid aortic valve (BAV) is a congenital cardiac disorder where the valve consists of only two cusps instead of three, as in a normal tricuspid valve (TAV). Although 97 % of BAVs include asymmetric cusps, little or no prior studies have investigated the blood flow through a three-dimensional BAV and root. The aim of the present study was to characterize the effect of asymmetric BAV on the blood flow using fully coupled fluid-structure interaction (FSI) models with improved boundary conditions and tissue properties. This study presents four FSI models, including a native TAV, asymmetric BAVs with or without a raphe, and an almost symmetric BAV. Cusp tissue is composed of hyperelastic finite elements with collagen fibres embedded in the elastin matrix. A full cardiac cycle is simulated by imposing the same physiological blood pressures for all the TAV and BAV models. The latter have significantly smaller opening areas compared with the TAV. Larger stress values were found in the cusps of BAVs with fused cusps, at both the systolic and diastolic phases. The asymmetric geometry caused asymmetric vortices and much larger flow shear stress on the cusps which could be a potential initiator for early valvular calcification of BAVs.
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Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells.
Int J Mol Sci
PUBLISHED: 02-17-2013
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Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinsons disease and Alzheimers disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-? secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-?, IL-1b, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-kB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders.
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Epidemiological characteristics of imported shigellosis in Korea, 2010-2011.
Osong Public Health Res Perspect
PUBLISHED: 02-12-2013
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Shigellosis is a global disease as food poisoning by infection of Shigella spp (S. dysenteriae, S. flexneri, S. boydii and S. sonnei). In Korea, approximately 500 cases of shigellosis have reported every year since 2004, and imported shigellosis is increasing gradually from 2006 in particular. According to increase of numbers of overseas travelers, the numbers of patients diseased with imported shigellosis is also increasing. We need continuous surveillance studies network (SSN) for control of imported shigellosis. We studied epidemiological characteristic of imported shigellosis by using database of Korea Centers for Disease Control and Prevention (KCDC) from 2010 to 2011. The imported shigellosis is analyzed on correlation with variable factors such as sex, age, symptom, visited country as well as Shigella spp in the database. Total 399 patients diseased with shigellosis have been reported between 2010 and 2011, The 212 patients (53.1%) among them were disease with imported shigellosis and the 205 patients (96.7%) were diagnosed as definite shigellosis. Shigella sonnei (65.6%) and Shigella flexneri (20.3%) were isolated in order. Clinical symptoms of the shigellosis were diarrhea (96.5%), abdominal pain (54.7%), fever (52.8%), chill (31.6%), and weakness (21.7% etc) in order. Duration of diarrhea was 1 to 5 days, the number of diarrhea was mostly more than 10 times, and type of stool was almost yellow stool. Almost shigellosis was occurred in the travelers visited to Asia (98.1%). Particularly, the occurrence rate of shigellosis was highest in traveler visited to Southeast Asia which is India (21.7%), Cambodia (19.8%), Philippines (17.9%), and Vietnam (9.0%) in order. According to increase of traveler to Southeast Asia, imported Shigellosis also increased. We need to strengthen the public health and hygiene, which is infection prevention rules, eating properly-cook food, washing hands, drinking boiled water, for traveler to Asia. The quarantine and surveillance system to control imported shigellosis is need continually in Korea.
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Protection from antimycin A-induced mitochondrial dysfunction by Nelumbo nucifera seed extracts.
Environ. Toxicol. Pharmacol.
PUBLISHED: 02-07-2013
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Antimycin A (AMA) damages the mitochondria through inhibition of mitochondrial electron transport. In this study, exposure of L6 rat skeletal muscle cells to AMA induced a decrease in ATP content, followed by a decrease in mitochondrial membrane potential, leading to apoptosis. We evaluated the protective effects of water and ethanol extracts of Nelumbo nucifera seeds on L6 cells with AMA-induced oxidative stress. We found that the extracts reduced cellular apoptosis; preserved the mitochondrial membrane potential; protected mitochondrial ATP production; inhibited p53, Bax, and caspase 3 activities; and induced Bcl-2 production. Our results suggested that AMA induced apoptosis in L6 cells via impairment of mitochondrial function. N. nucifera extracts protected the cells from this mitochondria-mediated cell death.
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Hypoxia antagonizes glucose deprivation on interleukin 6 expression in an Akt dependent, but HIF-1/2? independent manner.
PLoS ONE
PUBLISHED: 02-07-2013
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Although both glucose deprivation and hypoxia have been reported to promote cascades of biological alterations that lead to induction of inflammatory mediators, we hypothesized that glucose deprivation and hypoxia might show neutral, synergistic or antagonistic effects to each other on gene expression of inflammatory mediators depending on the regulatory components in their promoters. Gene expression of interleukin 6 (IL-6) was analyzed by real-time PCR, ELISA, or Western blot. Effects of glucose deprivation and/or hypoxia on activation of signaling pathways were analyzed by time-dependent phosphorylation patterns of signaling molecules. We demonstrate that hypoxia antagonized the effects of glucose deprivation on induction of IL-6 gene expression in microglia, macrophages, and monocytes. Hypoxia also antagonized thapsigargin-induced IL-6 gene expression. Hypoxia enhanced phosphorylation of Akt, and inhibition of Akt was able to reverse the effects of hypoxia on IL-6 gene expression. However, inhibition of HIF-1/2? did not reverse the effects of hypoxia on IL-6 gene expression. In addition, phosphorylation of p38, but not JNK, was responsible for the effects of glucose deprivation on IL-6 gene expression.
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Dosimetric effect of CT contrast agent in CyberKnife treatment plans.
Radiat Oncol
PUBLISHED: 02-05-2013
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To investigate the effect of computed tomography (CT) contrast enhancement (CE) on the 3D dose distributions of non-coplanar small field beams in the CyberKnife (CK) treatment planning system (TPS) for the stereotactic ablative radiotherapy (SABR).
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Inhibition of endoplasmic reticulum stress alleviates lipopolysaccharide-induced lung inflammation through modulation of NF-?B/HIF-1? signaling pathway.
Sci Rep
PUBLISHED: 01-28-2013
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Lipopolysaccharide (LPS) is involved in a variety of inflammatory disorders. Under stress conditions, endoplasmic reticulum (ER) loses the homeostasis in its functions, which is defined as ER stress. Little is known how ER stress is implicated in LPS-induced lung inflammation. In this study, effects of inhibition of ER stress on LPS-induced lung inflammation and transcriptional regulation were examined. An ER stress regulator, 4-phenylbutyrate (PBA) reduced LPS-induced increases of various ER stress markers in the lung. Furthermore, inhibition of ER stress reduced the LPS-induced lung inflammation. Moreover, LPS-induced increases of NF-?B and HIF-1? activity were lowered by inhibition of ER stress. These results suggest that inhibition of ER stress ameliorates LPS-induced lung inflammation through modulation of NF-?B/I?B and HIF-1? signaling pathway.
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Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells.
Neurochem. Int.
PUBLISHED: 01-24-2013
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Malignant gliomas are the most common and fatal brain tumors in adults. In particular, the strong invasiveness of glioma cells into the normal brain tissue makes eradication of glioma very difficult. Matrix metalloproteinases (MMPs) play a pivotal role in glioma invasion, and thus controlling MMP expression has been suggested as an important therapeutic target for brain tumors. In the present study, we investigated the effect of protopanaxatriol ginsenoside Rh1 on MMP expressions in human astroglioma U87MG and U373MG cells. RT-PCR analysis showed that Rh1 inhibits the mRNA expressions of MMP-1, -3, and -9 in PMA-stimulated U87MG and U373MG cells. Rh1 also suppressed the promoter activities of MMP-1, -3 and -9. The ELISA, Western blot, and zymographic analyses revealed that Rh1 inhibits the protein expression and/or enzymatic activity of MMP-1, -3 and -9. In accordance with the strong inhibitory effects of Rh1 on MMPs, Rh1 efficiently inhibited the invasion and migration of U87MG and U373MG glioma cells as demonstrated by Matrigel invasion assay and wound healing assay. Further mechanistic studies revealed that Rh1 inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-?B and AP-1, which play an important role in MMP gene expressions. The data collectively suggest that ginsenoside Rh1 may have a therapeutic potential for malignant gliomas.
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Anti-inflammatory mechanism of exogenous C2 ceramide in lipopolysaccharide-stimulated microglia.
Biochim. Biophys. Acta
PUBLISHED: 01-17-2013
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Ceramide is a major molecule among the sphingolipid metabolites which are produced in the brain and other organs and act as intracellular second messengers. Although a variety of physiological roles of ceramide have been reported in the periphery and central nervous systems, the role of ceramide in microglial activation has not been clearly demonstrated. In the present study, we examined the effects of exogenous cell permeable short chain ceramides on microglial activation in vitro and in vivo. We found that C2, C6, and C8 ceramide and C8 ceramide-1-phosphate inhibited iNOS and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. In addition, the administration of C2 ceramide suppressed microglial activation in the brains of LPS-exposed mice. By HPLC and LC/MS/MS analyses, we found that C2 ceramide on its own, rather than its modified form (i.e. ceramide-1-phosphate or long chain ceramides), mainly work by penetrating into microglial cells. Further mechanistic studies by using the most effective C2 ceramide among the short chain ceramides tested, revealed that C2 ceramide exerts anti-inflammatory effects via inhibition of the ROS, MAPKs, PI3K/Akt, and Jak/STAT pathways with upregulation of PKA and hemeoxygenase-1 expressions. Interestingly, we found that C2 ceramide inhibits TLR4 signaling by interfering with LPS and TLR4 interactions. Therefore, our data collectively suggests the therapeutic potential of short chain ceramides such as C2 for neuroinflammatory disorders such as Alzheimers disease and Parkinsons disease.
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The utility of sperm DNA damage assay using toluidine blue and aniline blue staining in routine semen analysis.
Clin Exp Reprod Med
PUBLISHED: 01-16-2013
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The aim of the present study was to examine the relationship among male age, strict morphology, and sperm chromatin structure and condensation.
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Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-10-2013
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Microglial activation plays an important role in neurodegenerative diseases. Thus, controlling microglial activation is considered to be a promising therapeutic target for neurodegenerative diseases. In the present study, we found that lancemaside A, a triterpenoid saponin isolated from Codonopsislanceolata, inhibited iNOS and proinflammatory cytokines in LPS-stimulated BV2 microglial cells. By analyzing molecular mechanisms underlying the anti-inflammatory effects of lancemaside A, we found that lancemaside A selectively inhibited LPS-induced JNK phosphorylation among the three types of MAP kinases. A JNK-specific inhibitor, SP600125, like lancemaside A, significantly inhibited not only NO, TNF-?, and IL-6 productions, but also NF-?B and AP-1 activities, suggesting that JNK inhibition is largely involved in the anti-inflammatory mechanism of lancemaside A. Interestingly, both the lancemaside A and SP600125 inhibited ROS production by suppressing the expression and/or phosphorylation of NADPH oxidase subunit proteins, such as p47(phox), p67(phox), and gp91(phox). The antioxidant effects of lancemaside A and SP600125 appear to be related with an increase of hemeoxygenase-1 expression by both agents. Finally, we demonstrated the neuroprotective effects of lancemaside A and SP600125 in microglia-neuron coculture systems. Collectively, our data suggest that JNK pathway plays a key role mediating anti-inflammatory effects of lancemaside A in LPS-stimulated microglia.
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