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Find video protocols related to scientific articles indexed in Pubmed.
Thrap3 docks on phosphoserine 273 of PPAR? and controls diabetic gene programming.
Genes Dev.
PUBLISHED: 10-14-2014
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Phosphorylation of peroxisome proliferator-activated receptor ? (PPAR?) at Ser273 by cyclin-dependent kinase 5 (CDK5) in adipose tissue stimulates insulin resistance, but the underlying molecular mechanisms are unclear. We show here that Thrap3 (thyroid hormone receptor-associated protein 3) can directly interact with PPAR? when it is phosphorylated at Ser273, and this interaction controls the diabetic gene programming mediated by the phosphorylation of PPAR?. Knockdown of Thrap3 restores most of the genes dysregulated by CDK5 action on PPAR? in cultured adipocytes. Importantly, reduced expression of Thrap3 in fat tissue by antisense oligonucleotides (ASOs) regulates a specific set of genes, including the key adipokines adiponectin and adipsin, and effectively improves hyperglycemia and insulin resistance in high-fat-fed mice without affecting body weight. These data indicate that Thrap3 plays a crucial role in controlling diabetic gene programming and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes.
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Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib-resistant non-small cell lung cancers with Met amplification.
Cancer Sci.
PUBLISHED: 09-25-2014
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Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been introduced for the treatment of non-small cell lung cancer (NSCLC), the emergence of secondary T790M mutation in EGFR or amplification of the Met proto-oncogene restrain the clinical success of EGFR-TKIs. Since heat shock protein-90 (Hsp90) stabilizes various oncoproteins including EGFR and c-Met, the inhibition of Hsp90 activity appears as a rational strategy to develop anticancer drugs. Despite preclinical efficacy of geldanamycin-anasamycin (GA)-derivatives containing benzoquinone moiety as Hsp90 inhibitors, the hepatotoxicity of these GA-derivatives restricts their therapeutic benefit. We have prepared WK-88 series of GA-derivatives, which lack the benzoquinone moiety. In this study, we have examined the anticancer effects of WK88-1 in Met-amplified- and gefitinib-resistant (HCC827GR) NSCLC cells and its parental HCC827 cells. Treatment with WK88-1 reduced the cell viability in both HCC827 and HCC827GR cells, which was associated with marked decrease in the constitutive expression of Hsp90 client proteins, such as EGFR, ErbB2, ErbB3, Met and Akt. Moreover, WK88-1 attenuated phosphorylation of these Hsp90 client proteins and reduced the anchorage-independent growth of HCC827GR cells. Administration of WK88-1 did not cause hepatotoxicity in animals and significantly reduced the growth of HCC827GR cells xenograft tumors in nude mice. Our study provides evidence that ErbB3 might be a client for Hsp90 in Met-amplified NSCLCs. In conclusion, we demonstrate that inhibition of Hsp90 dampens the activation of EGFR- or c-Met-mediated survival of Met-amplified NSCLCs and that WK88-1 as a Hsp90 inhibitor alleviates gefitinib resistance in HCC827GR cells.
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Endovascular treatment of symptomatic high-flow vertebral arteriovenous fistula as a complication after c1 screw insertion.
J Korean Neurosurg Soc
PUBLISHED: 08-08-2014
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High-flow vertebral arteriovenous fistulas (VAVF) are rare complications of cervical spine surgery and characterized by iatrogenic direct-communication of the extracranial vertebral artery (VA) to the surrounding venous plexuses. The authors describe two patients with VAVF presenting with ischemic presentation after C1 pedicle screw insertion for a treatment of C2 fracture and nontraumatic atlatoaxial subluxation. The first patient presented with drowsy consciousness with blurred vision. The diffusion MRI showed an acute infarction on bilateral cerebellum and occipital lobes. The second patient presented with pulsatile tinnitus, dysarthria and a subjective weakness and numbness of extremities. In both cases, digital subtraction angiography demonstrated high-flow direct VAVFs adjacent to C1 screws. The VAVF of the second case occurred near the left posterior inferior cerebellar artery originated from the persistent first intersegmental artery of the left VA. Both cases were successfully treated by complete occlusion of the fistulous portion and the involved segment of the left VA using endovascular coil embolization. The authors reviewed the VAVFs after the upper-cervical spine surgery including C1 screw insertion and the feasibility with the attention notes of its endovascular treatment.
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A novel non-agonist peroxisome proliferator-activated receptor ? (PPAR?) ligand UHC1 blocks PPAR? phosphorylation by cyclin-dependent kinase 5 (CDK5) and improves insulin sensitivity.
J. Biol. Chem.
PUBLISHED: 08-06-2014
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Thiazolidinedione class of anti-diabetic drugs which are known as peroxisome proliferator-activated receptor ? (PPAR?) ligands have been used to treat metabolic disorders, but thiazolidinediones can also cause several severe side effects, including congestive heart failure, fluid retention, and weight gain. In this study, we describe a novel synthetic PPAR? ligand UNIST HYUNDAI Compound 1 (UHC1) that binds tightly to PPAR? without the classical agonism and which blocks cyclin-dependent kinase 5 (CDK5)-mediated PPAR? phosphorylation. We modified the non-agonist PPAR? ligand SR1664 chemically to improve its solubility and then developed a novel PPAR? ligand, UHC1. According to our docking simulation, UHC1 occupied the ligand-binding site of PPAR? with a higher docking score than SR1664. In addition, UHC1 more potently blocked CDK5-mediated PPAR? phosphorylation at Ser-273. Surprisingly, UHC1 treatment effectively ameliorated the inflammatory response both in vitro and in high-fat diet-fed mice. Furthermore, UHC1 treatment dramatically improved insulin sensitivity in high-fat diet-fed mice without causing fluid retention and weight gain. Taken together, compared with SR1664, UHC1 exhibited greater beneficial effects on glucose and lipid metabolism by blocking CDK5-mediated PPAR? phosphorylation, and these data indicate that UHC1 could be a novel therapeutic agent for use in type 2 diabetes and related metabolic disorders.
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Renal Insufficiency in newly-diagnosed multiple myeloma: analysis according to International Myeloma Working Group consensus statement.
Anticancer Res.
PUBLISHED: 07-31-2014
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Renal impairment (RI) is one of the key clinical manifestations of symptomatic multiple myeloma. However, the incidence of RI and renal response to treatment are variable depending on their definition. A total of 379 patients newly-diagnosed and treated for symptomatic myeloma at the Samsung Medical Center between January 2000 and December 2011 were retrospectively reviewed. RI and renal response were assessed according to the recent International working group (IMWG) recommendations. Out of the 379 patients, renal insufficiency was present in 117 (30.8%) and was associated with adverse clinical parameters such as anemia, elevated beta-2 microglobulin (B2M), elevated lactate dehydrogenase (LDH), hypercalcemia, and more advanced disease by the International Staging System (ISS). Out of the 85 patients who were evaluable for renal response, 58 (68.2%) showed renal response and 46 (54%) had major renal response. Less advanced disease by the International Staging System and inclusion of high-dose dexamethasone as first-line treatment were independently predictive for major renal response. Median time-to-renal response was 5.5 months, and bortezomib-containing regimen, high-dose dexamethasone, and less advanced stage disease were associated with a more rapid renal response.
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Effects of visual display terminal works on cervical movement pattern in patients with neck pain.
J Phys Ther Sci
PUBLISHED: 07-30-2014
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[Purpose] This study examined changes in the onset of neck movement in young adults with and without mild neck pain (MNP) during visual display terminal (VDT) work. [Subjects] Ten control subjects and 10 subjects with MNP who were VDT workers were recruited. The upper (UC) and lower cervical (LC) spine angles in the sagittal plane were collected using an ultrasound-based motion analysis system during VDT work for 5?min. [Results] The MNP group had faster movement initiation in the UC and LC compared with the control group during VDT work. [Conclusion] These findings suggest that young adults with MNP should be cautious when performing VDT work while sitting.
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Comparison of the Freiburg and Charlson comorbidity indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma.
Biomed Res Int
PUBLISHED: 07-10-2014
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Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG?2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and ?4). FCI was a strong prognostic tool for OS (P>0.001) and predicted clinical outcome better than CCI (P=0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma.
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Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-?B activation through MAPK signaling pathways in MCF-7 human breast carcinoma cells.
J Med Food
PUBLISHED: 07-07-2014
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Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. The synthesis and secretion of MMP-9 can be stimulated by a variety of stimuli, including cytokines and phorbol 12-myristate 13-acetate (PMA), during various pathological processes, such as tumor invasion, atherosclerosis, inflammation, and rheumatoid arthritis, whereas MMP-2 is usually expressed constitutively. Delphinidin, an anthocyanidin present in pigmented fruits and vegetables, possesses potent antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we investigated the antiproliferative and antiinvasive effects of delphinidin on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells using zymography, western blotting, reverse transcription-polymerase chain reaction, and Matrigel invasion assay. Delphinidin significantly suppressed PMA-induced MMP-9 protein expression in MCF-7 human breast carcinoma cells, and it also inhibited the MMP-9 gene transcriptional activity by blocking the activation of NFkappaB (NF-?B) through MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that delphinidin reduces PMA-induced cancer cell invasion. These results suggest that delphinidin is a potential antimetastatic agent that suppresses PMA-induced cancer cell invasion through the specific inhibition of NF-?B-dependent MMP-9 gene expression.
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Surgical strategies for removal of intra- and extraforaminal dumbbell-shaped schwannomas in the subaxial cervical spine.
Eur Spine J
PUBLISHED: 07-02-2014
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Spinal dumbbell-shaped schwannoma is common neoplasm, usually occurring in the cervical spine. Posterior or anterolateral approaches are frequently used to remove this benign tumor. We analyzed how much amount of tumor could be possible to be totally removed with posterior approach.
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SB365, Pulsatilla saponin D, suppresses the growth of gefitinib-resistant NSCLC cells with Met amplification.
Oncol. Rep.
PUBLISHED: 06-04-2014
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Clinical treatment using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib has been applied in patients with non-small cell lung cancers (NSCLCs). Unfortunately, acquired drug resistance emerges in these patients due to the amplification of the Met proto-oncogene, which may be a compensatory mechanism of NSCLCs against EGFR inhibition. To overcome this resistance, identification of new small-molecule natural compounds is crucial for cancer therapeutics. In this regard, SB365, saponin D from the root of Pulsatilla koreana which has been used as a traditional medicine in Korea for several diseases, has attracted wide interest. In the present study, SB365 effectively suppressed the proliferation of gefitinib-resistant HCC827GR NSCLC cells with Met amplification. Notably, our data revealed that SB365 inhibited the phosphorylation of Met and the downstream signaling pathway required for growth and survival in the Met-amplified HCC827GR cells. Moreover, SB365 suppressed the anchorage-independent growth, migration and invasion along with induction of apoptosis in the HCC827GR cells. Therefore, these results suggest that SB365 is good candidate as a natural product for use in the treatment of Met-amplified NSCLCs.
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Catalytic transparency of hexagonal boron nitride on copper for chemical vapor deposition growth of large-area and high-quality graphene.
ACS Nano
PUBLISHED: 06-02-2014
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Graphene transferred onto h-BN has recently become a focus of research because of its excellent compatibility with large-area device applications. The requirements of scalability and clean fabrication, however, have not yet been satisfactorily addressed. The successful synthesis of graphene/h-BN on a Cu foil and DFT calculations for this system are reported, which demonstrate that a thin h-BN film on Cu foil is an excellent template for the growth of large-area and high-quality graphene. Such material can be grown on thin h-BN films that are less than 3 nm thick, as confirmed by optical microscopy and Raman spectroscopy. We have evaluated the catalytic growth mechanism and the limits on the CVD growth of high-quality and large-area graphene on h-BN film/Cu by performing Kelvin probe force microscopy and DFT calculations for various thicknesses of h-BN.
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Caffeine enhances micturition through neuronal activation in micturition centers.
Mol Med Rep
PUBLISHED: 05-28-2014
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Caffeine may promote incontinence through its diuretic effect, particularly in individuals with underlying detrusor overactivity, in addition to increasing muscle contraction of the bladder smooth muscle. Caffeine may also affect bladder function via central micturition centers, including the medial preoptic area, ventrolateral periaqueductal gray, and pontine micturition center. However, the biochemical mechanisms of caffeine in central micturition centers affecting bladder function remain unclear. In the present study, the effects of caffeine on the central micturition reflex were investigated by measuring the degree of neuronal activation, and by quantifying nerve growth factor (NGF) expression in rats. Following caffeine administration for 14 days, a urodynamic study was performed to assess the changes to bladder function. Subsequently, immunohistochemical staining to identify the expression of c?Fos and NGF in the central micturition areas was performed. Ingestion of caffeine increased bladder smooth muscle contraction pressure and time as determined by cystometry. Expression levels of c?Fos and NGF in all central micturition areas were significantly increased following the administration of caffeine. The effects on contraction pressure and time were the most potent and expression levels of c?Fos and NGF were greatest at the lowest dose of caffeine. These results suggest that caffeine facilitates bladder instability through enhancing neuronal activation in the central micturition areas.
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Cordyceptin induces apoptosis through repressing hTERT expression and inducing extranuclear export of hTERT.
J. Biosci. Bioeng.
PUBLISHED: 05-26-2014
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Cordycepin is an adenosine analog originally extracted from Cordyceps militaris that possesses many pharmacological effects including immune activation and antioxidant and antitumor effects. However, the underlying relationship between apoptosis and telomerase activity in response to cordycepin exposure has not been investigated. In this study, we found that cordycepin-induced apoptosis of human leukemia cells (H937 and THP-1 cells) was associated with inactivation of telomerase and downregulation of human telomerase reverse transcriptase (hTERT) as well as the transcription factors c-Myc and Sp1, which are required for basal transcription from the hTERT gene promoter. Cordycepin also attenuated the activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, thereby reducing phosphorylation and nuclear translocation of hTERT. We further showed that the PI3K inhibitor LY29004 significantly decreased telomerase activity in cordycepin-treated cells and increased cordycepin-induced cell death. These findings demonstrate that cordycepin is cytotoxic to human leukemia cells and suppresses telomerase activity through transcriptional and post-translational suppression of hTERT by inactivating the PI3K/Akt signaling pathway.
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Diagnosis of Leucocytozoon caulleryi infection in commercial broiler breeders in South Korea.
Avian Dis.
PUBLISHED: 04-25-2014
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This report confirms a recent outbreak of a Leucocytozoon caulleryi infection in a commercial broiler breeder flock in South Korea. Seven, 18-day-old broiler breeders (Gallus gallus) were necropsied following a history of depression, sudden death, and subcutaneous hemorrhages. On necropsy, subcutaneous hemorrhages were identified in the wings and legs, pectoral and thigh muscles, thymus, epicardium, pancreas, and kidneys. On histopathology, there were numerous schizonts and merozoits of a Leucocytozoon sp. noted in the heart, spleen, liver, kidneys, thymus, and bursa of Fabricius. Molecular analysis of the mitochondrial cytochrome oxidase b confirmed that the causative agent was Leucocytozoon caulleryi. Although L. caulleryi was diagnosed previously in South Korea, there had been no reports of L. caulleryi over the past several decades.
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Aerobic exercise affects myostatin expression in aged rat skeletal muscles: a possibility of antiaging effects of aerobic exercise related with pelvic floor muscle and urethral rhabdosphincter.
Int Neurourol J
PUBLISHED: 04-24-2014
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Aging-induced loss of muscle mass and subsequent reduction of strength is a fundamental cause of frailty, functional decline, and disability. And this may lead to muscular dysfunction, voiding dysfunction, or urinary incontinence due to pelvic muscle weakness induced by aging. Physical exercise has been recommended for the prevention and the treatment of these age-related frail states. We investigated the effects of treadmill exercise on muscle strength, myostatin mRNA and protein expression, and gastrocnemius myocytes proliferation in aged rats to investigate the possible antiaging effects of aerobic exercise on skeletal muscles such as pelvic floor muscles and urethral rhabdosphincter muscle.
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The effects of precise contraction of the pelvic floor muscle using visual feedback on the stabilization of the lumbar region.
J Phys Ther Sci
PUBLISHED: 04-23-2014
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[Purpose] The purpose of this study is to verify whether precise contraction of the pelvic floor muscle (PFM) using visual feedback actually affects the thickness of abdominal muscles. [Subjects] The subjects were 29 healthy adults in their 20s who consented to participate in this study. [Methods] This study provided visual feedback on PFM using one ultrasound device and identified changes in the transversus abdominis (TRA) using another ultrasound device. Abdominal muscle thicknesses were measured by ultrasound under three conditions (rest, PFM contraction, PFM contraction with visual feedback). [Results] There were no statistically significant differences in the external oblique (EO) and internal oblique (IO) muscles between the measurements taken at rest and during the contraction of the PFM, and between those taken at rest and during the contraction of the PFM with visual feedback. There were significant differences in the TRA. In particular, TRA thickness was highest in the order of PFM contraction, PFM contraction with visual feedback, and rest. [Conclusion] Hollowing with visual feedback is not an efficient stabilization exercise method for the PFM.
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Target genes involved in antiproliferative effect of modified ginseng extracts in lung cancer A549 cells.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 04-16-2014
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Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Panax ginseng has long been used to treat cancer and other diseases worldwide. Most of the pharmacological actions of ginseng are attributed to a variety of ginsenosides, which are often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng was increased after enzymatic processing of ginseng saponin (50% inhibitory concentration, >70 ?g/ml). To elucidate the mechanism by which modified ginseng extract (MGX) induced cell death in human lung cancer cells, the gene expression profiles of A549 cells regulated by MGX were assayed using Agilent PrimeView Human Gene Expression Arrays. The expression of 17 genes involved in the regulation of cell signaling, cell metabolism, transport, and cytoskeleton-regulation was up-regulated, whereas the expression of 16 genes implicated in invasion and metastasis and cellular metabolism was down-regulated in MGX-treated A549 cells. Moreover, nuclear staining with 4',6-diamidino-2-phenylindole revealed that MGX clearly caused nuclear condensation and fragmentation which are observed in apoptosis cell. These results elucidate crucial anticancer mechanisms of MGX and provide potential new targets for the assessment of anticancer activity of MGX.
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Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of werner's syndrome protein.
Environ. Health Perspect.
PUBLISHED: 04-15-2014
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Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence.
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DJ-1 contributes to adipogenesis and obesity-induced inflammation.
Sci Rep
PUBLISHED: 04-09-2014
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Adipose tissue functions as an endocrine organ, and the development of systemic inflammation in adipose tissue is closely associated with metabolic diseases, such as obesity and insulin resistance. Accordingly, the fine regulation of the inflammatory response caused by obesity has therapeutic potential for the treatment of metabolic syndrome. In this study, we analyzed the role of DJ-1 (PARK7) in adipogenesis and inflammation related to obesity in vitro and in vivo. Many intracellular functions of DJ-1, including oxidative stress regulation, are known. However, the possibility of DJ-1 involvement in metabolic disease is largely unknown. Our results suggest that DJ-1 deficiency results in reduced adipogenesis and the down-regulation of pro-inflammatory cytokines in vitro. Furthermore, DJ-1-deficient mice show a low-level inflammatory response in the high-fat diet-induced obesity model. These results indicate previously unknown functions of DJ-1 in metabolism and therefore suggest that precise regulation of DJ-1 in adipose tissue might have a therapeutic advantage for metabolic disease treatment.
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Chicken NK-lysin is an alpha-helical cationic peptide that exerts its antibacterial activity through damage of bacterial cell membranes.
Poult. Sci.
PUBLISHED: 04-08-2014
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The antimicrobial peptides (AMP) are important elements of the first line of defense against pathogens in animals, and an important constituent of innate immunity. Antimicrobial peptides act on a broad spectrum of microbial organisms. NK-Lysin is a cationic antibacterial peptide that was originally isolated from porcine intestinal tissue based on its antibacterial activity. We synthesized peptides corresponding to each helical region of chicken NK-lysin and analyzed their secondary structures in addition to their antimicrobial activity. Circular dichroism spectroscopy of the synthetic chicken NK-lysin (cNK-78) and 4 small peptides in negatively charged liposomes demonstrated transition in the conformation of ?-helical peptides relative to the charged environment. Chicken NK-lysin inhibits the growth of a representative gram-negative bacterium, Escherichia coli. The antimicrobial activity of 2 peptides designated H23 and H34 was similar to that of mature NK-lysin, cNK-78. Microscopic analyses revealed the death of bacterium with disrupted membranes after peptide treatment, suggesting that chicken NK-lysin, an alpha-helical cationic peptide, exerts its antimicrobial activity by damaging the bacterial cell membrane.
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Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term memory by suppressing apoptosis in the hippocampus of rats.
J Exerc Rehabil
PUBLISHED: 04-01-2014
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Multiple sclerosis is one of the autoimmune diseases in the central nervous system. Multiple sclerosis occurs through multiple mechanisms, and it is also mediated in part by an apoptotic mechanism. Swimming exercise has been recommended for the prevention and treatment of chronic diseases. In the present study, we investigated the effects of swimming exercise on short-term memory in relation with apoptotic neuronal cell death in the hippocampus following induction of multiple sclerosis. For this study, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for caspase-3 were performed. The animal model of multiple sclerosis was made by bilateral intracerebral ventricle injection of ethidium bromide. The rats in the swimming exercise groups were forced to swim for 30 min once daily for 14 consecutive days, starting 3 days after induction of multiple sclerosis. In the present results, short-term memory was deteriorated in the multiple sclerosis-induced rats. The number of TUNEL-positive and caspase-3-positive cells in the hippocampal dentate gyrus was increased in the multiple sclerosis-induced rats. Swimming exercise alleviated multiple sclerosis-induced short-term memory impairment by suppressing apoptotic neuronal cell death in the hippocampus. These effects of swimming exercise may aid symptom relief in the incurable neurodegenerative diseases.
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The cytoprotective effect of sulfuretin against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2/ARE and JNK/ERK MAPK-mediated heme oxygenase-1 expression.
Int J Mol Sci
PUBLISHED: 03-26-2014
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Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury.
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Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats.
J. Biomed. Sci.
PUBLISHED: 02-28-2014
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Spinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation.
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Hsp90 inhibition by WK88-1 potently suppresses the growth of gefitinib-resistant H1975 cells harboring the T790M mutation in EGFR.
Oncol. Rep.
PUBLISHED: 02-28-2014
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Heat shock protein 90 (Hsp90) is a molecular chaperone for numerous client proteins, many of which are crucial for the pathogenesis of non-small cell lung cancers (NSCLCs). To date, therapeutic approaches using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib for the treatment of NSCLCs have been limited due to the emergence of acquired drug resistance mainly mediated by a secondary T790M mutation in EGFR. Considering this, Hsp90 inhibition seems promising as it leads to overall degradation of the oncogenic EGFR family proteins. In this regard, the present study provides the preclinical basis for a new Hsp90 inhibitor, WK88-1, for the treatment of NSCLCs harboring the T790M mutation in EGFR. Our data revealed that inhibition of Hsp90 by WK88-1 induced overall degradation of multiple oncogenic signaling molecules including EGFR, ErbB2 and ErbB3, leading to subsequent growth arrest and apoptosis in the gefitinib-resistant H1975 cell line. In addition, treatment with WK88-1 markedly inhibited proliferation, migration and invasion in H1975 cells. Moreover, an in vivo xenograft assay indicated that WK88-1 markedly suppressed tumor growth in the H1975 xenografts, highlighting the potential efficacy of WK88-1 for overcoming gefitinib resistance in NSCLCs harboring the T790M mutation in EGFR.
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Bimetallic non-alloyed NPs for improving the broadband optical absorption of thin amorphous silicon substrates.
Nanoscale Res Lett
PUBLISHED: 02-23-2014
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We propose the use of bimetallic non-alloyed nanoparticles (BNNPs) to improve the broadband optical absorption of thin amorphous silicon substrates. Isolated bimetallic NPs with uniform size distribution on glass and silicon are obtained by depositing a 10-nm Au film and annealing it at 600°C; this is followed by an 8-nm Ag film annealed at 400°C. We experimentally demonstrate that the deposition of gold (Au)-silver (Ag) bimetallic non-alloyed NPs (BNNPs) on a thin amorphous silicon (a-Si) film increases the film's average absorption and forward scattering over a broad spectrum, thus significantly reducing its total reflection performance. Experimental results show that Au-Ag BNNPs fabricated on a glass substrate exhibit resonant peaks at 437 and 540 nm and a 14-fold increase in average forward scattering over the wavelength range of 300 to 1,100 nm in comparison with bare glass. When deposited on a 100-nm-thin a-Si film, Au-Ag BNNPs increase the average absorption and forward scattering by 19.6% and 95.9% compared to those values for Au NPs on thin a-Si and plain a-Si without MNPs, respectively, over the 300- to 1,100-nm range.
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High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after radiotherapy.
Korean J Urol
PUBLISHED: 02-14-2014
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To evaluate the oncologic outcomes and postoperative complications of high-intensity focused ultrasound (HIFU) as a salvage therapy after external-beam radiotherapy (EBRT) failure in patients with prostate cancer.
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Multicenter study evaluating the impact of hypomethylating agents as bridging therapy to hematopoietic stem cell transplantation in myelodysplastic syndromes.
Int. J. Hematol.
PUBLISHED: 02-12-2014
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Allogeneic hematopoietic stem cell transplantation (alloSCT) is currently the only curative treatment modality for myelodysplastic syndromes (MDS). The treatment paradigm for MDS has changed in recent years with the introduction of hypomethylating agents (HMAs). The present retrospective multicenter study was designed to assess the effects of pre-transplant HMA on transplant outcome and determine which patients would benefit most from this therapy. A total of 109 patients who received alloSCT at one of five institutions between 2007 and 2010 were enrolled in this study regardless of pre-transplant HMA therapy. 81 of the 109 patients enrolled were treated with HMA prior to alloSCT. 28 patients received alloSCT without HMA bridging. The distributions of WHO classification groups and IPSS scores were similar between the two groups (P = 0.752 and P = 0.265, respectively). Pre-transplant HMA did not affect OS (P = 0.244), and there were no differences in response to HMA therapy within the HMA-treated group. The cumulative incidence of NRM was not significantly different between the two groups (P = 0.500). However, for patients with a high blast count (>5 % of bone marrow at the time of diagnosis), pre-transplant HMA therapy had a NRM benefit (83.3 vs. 48.6 %, P = 0.014).
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Prognostic factor analysis in core-binding factor-positive acute myeloid leukemia.
Anticancer Res.
PUBLISHED: 02-11-2014
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Acute myeloid leukemia (AML) cases with t(8;21) or inv(16) have a favorable outcome, but the associated prognoses are heterogeneous and complicated by additional molecular aberrations.
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Changes in Shoulder External Rotator Muscle Activity during Shoulder External Rotation in Various Arm Positions in the Sagittal Plane.
J Phys Ther Sci
PUBLISHED: 02-06-2014
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[Purpose] The aim of this study was to investigate changes in electromyographic (EMG) activity of the infraspinatus and posterior deltoid muscles during shoulder external rotation under different shoulder flexion angles. [Subjects] Thirteen participants were included in this study. [Methods] The participants performed isometric shoulder external rotation at 45°, 90°, and 135° of shoulder flexion. A surface EMG system recorded the EMG activity of the infraspinatus and posterior deltoid muscles during shoulder external rotation. The changes in the muscle activity of infraspinatus and posterior deltoid and ratio of infraspinatus to posterior deltoid muscle activity were analyzed using one-way repeated-measures analysis of variance with Bonferroni's correction. [Results] The posterior deltoid activity was significantly decreased, while the ratio of the infraspinatus to posterior deltoid activity was significantly increased at 45° of shoulder flexion compared with 90° and 135° of shoulder flexion (p < 0.05). There were no significant differences in the EMG activity of the infraspinatus among the three conditions (p > 0.05). [Conclusion] These findings indicate that shoulder external rotation at 45° of shoulder flexion effectively reduced the contribution of the posterior deltoid activation to shoulder external rotation.
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Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts.
Cell Tissue Res.
PUBLISHED: 01-30-2014
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The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of ?2?1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, ?-catenin activation and GSK-3? phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-?B p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/?-catenin, MAP kinase and NF-?B pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.
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Therapeutic foam scaffolds incorporating biopolymer-shelled mesoporous nanospheres with growth factors.
Acta Biomater
PUBLISHED: 01-29-2014
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A novel therapeutic scaffolding system of engineered nanocarriers within a foam matrix for the long-term and sequential delivery of growth factors is reported. Mesoporous silica nanospheres were first functionalized to have an enlarged mesopore size (12.2nm) and aminated surface, which was then shelled by a biopolymer, poly(lactic acid) (PLA) or poly(ethylene glycol) (PEG), via electrospraying. The hybrid nanocarrier was subsequently combined with collagen to produce foam scaffolds. Bovine serum albumin (BSA), used as a model protein, was effectively loaded within the enlarged nanospheres. The biopolymer shell substantially prolonged the release period of BSA (2-3weeks from shelled nanospheres vs. within 1week from bare nanospheres), and the release rate was highly dependent on the shell composition (PEG>PLA). Collagen foam scaffolding of the shelled nanocarrier further slowed down the protein release, while enabling the incorporation of a rapidly releasing protein, which is effective for sequential protein delivery. Acidic fibroblast growth factor (aFGF), loaded onto the shelled-nanocarrier scaffolds, was released over a month at a highly sustainable rate, profiling a release pattern similar to that of BSA. The biological activity of the aFGF was evidenced by the significant proliferation of osteoblastic precursor cells in the aFGF-releasing scaffolds. Furthermore, the aFGF-delivering scaffolds implanted in rat subcutaneous tissue for 2weeks showed a substantially enhanced invasion of fibroblasts with a homogeneous population. Taken together, it is concluded that the biopolymer encapsulation of mesoporous nanospheres effectively prolongs the release of growth factors over weeks to a month, providing a nanocarrier platform for a long-term growth factor delivery. Moreover, the foam scaffolding of the nanocarrier system is a potential therapeutic three-dimensional matrix for cell culture and tissue engineering.
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Iron oxide nanotube layer fabricated with electrostatic anodization for heterogeneous Fenton like reaction.
J. Hazard. Mater.
PUBLISHED: 01-23-2014
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Iron oxide nanotubes (INT) were fabricated with potentiostatic anodization of zero valent iron foil in 1M Na2SO4 containing 0.5wt% NH4F electrolyte, holding the potential at 20, 40, and 60V for 20min, respectively. Field emission scanning electron microscopy and X-ray diffractometry were used to evaluate the morphology and crystalline structure of the INT film. The potential of 40V for 20min was observed to be optimal to produce an optimal catalytic film. Cyanide dissolved in water was degraded through the Fenton-like reaction using the INT film with hydrogen peroxide (H2O2). In case of INT-40V in the presence of H2O2 3%, the first-order rate constant was found to be 1.7×10(-2)min(-1), and 1.2×10(-2)min(-1) with commercial hematite powder. Degradation of cyanide was much less with only H2O2. Therefore, this process proposed in this work can be an excellent alternative to traditional catalysts for Fenton-like reaction.
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Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.
J. Korean Med. Sci.
PUBLISHED: 01-17-2014
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We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).
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Biointerface control of electrospun fiber scaffolds for bone regeneration: engineered protein link to mineralized surface.
Acta Biomater
PUBLISHED: 01-11-2014
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Control over the interface of biomaterials that favors the initial adhesion and subsequent differentiation of stem cells is one of the key strategies in bone tissue engineering. Here we engineer the interface of biopolymer electrospun fiber matrices with a fusion protein of fibronectin 9-10 domain (FNIII9-10) and osteocalcin (OCN), aiming to stimulate mesenchymal stem cell (MSC) functions, including initial adhesion, growth and osteogenic differentiation. In particular, a specific tethering of FNIII9-10-OCN protein was facilitated by the hydroxyapatite (HA) mineralization of the biopolymer surface through a molecular recognition of OCN to the HA crystal lattice. The FNIII9-10-OCN anchorage to the HA-mineralized fiber was observed to be highly specific and tightly bound to preserve stability over a long period. Initial cell adhesion levels, as well as the spreading shape and process, of MSCs within 24h were strikingly different between the fibers linked with and without fusion protein. Significant up-regulations in the mRNA expression of adhesion signaling molecules occurred with the fusion protein link, as analyzed by the reverse transcriptase polymerase chain reaction. The expression of a series of osteogenic-related genes at later stages, over 2-3weeks, was significantly improved in the fusion protein-tailored fiber, and the osteogenic protein levels were highly stimulated, as confirmed by immunofluorescence imaging and fluorescence-activated cell sorting analyses. In vivo study in a rat calvarium model confirmed a higher quantity of new bone formation in the fiber linked with fusion protein, and a further increase was noticed when the MSCs were tissue-engineered with the fusion protein-linked fiber. Collectively, these results indicate that FN-OCN fusion protein links via HA mineralization is a facile tool to generate a biointerface with cell-attractive and osteogenic potential, and that the engineered fibrous matrix is a potential bone regenerative scaffold.
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Differences in Muscle Activities of the Infraspinatus and Posterior Deltoid during Shoulder External Rotation in Open Kinetic Chain and Closed Kinetic Chain Exercises.
J Phys Ther Sci
PUBLISHED: 01-07-2014
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[Purpose] This study investigated the changes in electromyographic (EMG) activities of the infraspinatus and posterior deltoid muscles during shoulder external rotation under open kinetic chain (OKC) and closed kinetic chain (CKC) exercise conditions. [Subjects] In total, 15 healthy males participated in this study. [Methods] Subjects performed shoulder external rotations under CKC and OKC conditions while standing with and without weight support provided by a height-adjustable table. Pressure biofeedback was used to ensure a constant amount of weight support. The activities of the infraspinatus and posterior deltoid muscles during shoulder external rotation were measured using a wireless surface EMG system. The paired t-test was used to compare the EMG activities of the infraspinatus and the posterior deltoid muscles and the ratio of the infraspinatus to the posterior deltoid during shoulder external rotation under OKC and CKC conditions. [Results] The EMG activity of the infraspinatus and the ratio of the infraspinatus to the posterior deltoid activities were significantly increased, whereas the posterior deltoid activity was significantly decreased under the CKC condition compared to the OKC condition. [Conclusion] Clinicians should consider the CKC shoulder external rotation exercise when they wish to selectively strengthen the infraspinatus.
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Chaperonin CCT-mediated AIB1 folding promotes the growth of ER?-positive breast cancer cells on hard substrates.
PLoS ONE
PUBLISHED: 01-01-2014
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Clinical observations have revealed a strong association between estrogen receptor alpha (ER?)-positive tumors and the development of bone metastases, however, the mechanism underlying this association remains unknown. We cultured MCF-7 (ER?-positive) on different rigidity substrates. Compared with cells grown on more rigid substrates (100 kPa), cells grown on soft substrates (10 kPa) exhibited reduced spreading ability, a lower ratio of cells in the S and G2/M cell cycle phases, and a decreased proliferation rate. Using stable isotope labeling by amino acids (SILAC), we further compared the whole proteome of MCF-7 cells grown on substrates of different rigidity (10 and 100 kPa), and found that the expression of eight members of chaperonin CCT increased by at least 2-fold in the harder substrate. CCT folding activity was increased in the hard substrate compared with the soft substrates. Amplified in breast cancer 1 (AIB1), was identified in CCT immunoprecipitates. CCT folding ability of AIB1 increased on 100-kPa substrate compared with 10- and 30-kPa substrates. Moreover, using mammalian two-hybrid protein-protein interaction assays, we found that the polyglutamine repeat sequence of the AIB1 protein was essential for interaction between CCT? and AIB1. CCT?-mediated AIB1 folding affects the cell area spreading, growth rate, and cell cycle. The expressions of the c-myc, cyclin D1, and PgR genes were higher on hard substrates than on soft substrate in both MCF-7 and T47D cells. ER? and AIB1 could up-regulate the mRNA and protein expression levels of the c-myc, cyclin D1, and PgR genes, and that 17 ?-estradiol could enhance this effects. Conversely, 4-hydroxytamoxifen, could inhibit these effects. Taken together, our studies demonstrate that some ER?-positive breast cancer cells preferentially grow on more rigid substrates. CCT-mediated AIB1 folding appears to be involved in the rigidity response of breast cancer cells, which provides novel insight into the mechanisms of bone metastasis.
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Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial.
Trials
PUBLISHED: 12-04-2013
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Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity.
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Cross-protective immune responses elicited by a Korean variant of infectious bronchitis virus.
Avian Dis.
PUBLISHED: 11-29-2013
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Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide. IBVs continuously evolve by developing mutations in antigenic sites; therefore, an IBV vaccine that provides broad cross-protection can be a highly relevant and practical method in IBV control strategies. Although some IBV vaccine strains are known to provide protection against multiple IBV serotypes, in general commercially available IBV vaccine strains provide protection against antigenically related viruses but not distinct heterologous viruses. In the present study we characterized the Korean variant IBV K40/09 strain with regard to its immunogenicity and protective efficacy against seven currently circulating IBV serotypes. Three-week-old specific-pathogen-free chickens were intraocularly immunized with the IBV K40/09 strain at 10(3.5) 50% egg infective dose (EID50). Three weeks after immunization all the birds were challenged with seven different strains at 10(4.5) EID50. Chickens immunized with the IBV K40/09 strain showed significantly high levels of protection against all challenge viruses at the trachea and kidney levels. Our results suggest that IBV K40/09 could be useful to ensure IBV vaccine effectiveness owing to its cross-protective ability. Therefore, the IBV K40/09 strain merits consideration as a vaccine candidate to prevent infection as well as the spread of new IBV strains and many IBV variants that have been reported worldwide.
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The Primary Extra-gastrointestinal Stromal Tumor of Pleura: A Case Report and a Literature Review.
Jpn. J. Clin. Oncol.
PUBLISHED: 10-29-2013
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The gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. The gastrointestinal stromal tumor universally expresses KIT and DOG-1 and frequently harbors oncogenic mutations in the KIT gene. While the gastrointestinal stromal tumor usually arises in the alimentary tract, it is rarely found in the extragastrointestinal area. When it is, it is called an extragastrointestinal stromal tumor. Although the pathogenesis, prognostic factors and outcomes of gastrointestinal stromal tumors are well known, those of extragastrointestinal stromal tumors have not been fully studied. We report, herein, a unique primary extragastrointestinal stromal tumor from the pleura in a 73-year-old woman who presented with pleural mass. The extragastrointestinal stromal tumor was surgically resected and confirmed by means of an immunohistochemical study and a molecular analysis.
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Nonalcoholic Fatty Liver Disease: Intravoxel Incoherent Motion Diffusion-weighted MR Imaging-An Experimental Study in a Rabbit Model.
Radiology
PUBLISHED: 10-29-2013
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Purpose To evaluate the feasibility of using intravoxel incoherent motion (IVIM) diffusion-weighted imaging with multiple b values for the noninvasive diagnosis of nonalcoholic fatty liver disease (NAFLD). Materials and Methods This study was approved by the institutional animal care and use committee. Twenty-seven 8-week-old rabbits were fed a variety of diets (from a standard diet to a high-fat, high-cholesterol diet) before IVIM diffusion-weighted imaging was performed with seven b values by using a 3-T magnetic resonance (MR) imaging unit. At histologic analysis of the animals, livers were categorized by NAFLD severity as normal, NAFLD, borderline nonalcoholic steatohepatitis (NASH), or NASH. The apparent diffusion coefficient and IVIM-derived parameters including true diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction of the liver parenchyma were measured. Each parameter was correlated with NAFLD severity, and optimal cutoff values were determined by means of receiver operating characteristics analysis. Results Perfusion fraction was significantly lower in rabbits with NAFLD than in those with a normal liver, and it decreased further as severity of NAFLD increased, with medians of 22.2%, 14.8%, 11.3%, and 9.5% in the rabbits in the normal, NAFLD, borderline, and NASH groups, respectively (? = -0.83, P < .001). Apparent diffusion coefficient, true diffusion coefficient, and pseudodiffusion coefficient were not significantly different between the NAFLD severity groups. In terms of the diagnostic performance of perfusion fraction, area under the curve values were 0.984 (normal vs NAFLD or more severe disease), 0.959 (NAFLD or less severe vs borderline or more severe disease), and 0.903 (borderline or less severe vs NASH) with optimal cutoff values of 15.2%, 13.2%, and 11.0%, respectively. Conclusion Perfusion fractions extracted from IVIM diffusion-weighted imaging may help in the differentiation of early stage NASH from simple steatosis. © RSNA, 2013.
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Construction of a bifunctional enzyme fusion for the combined determination of biogenic amines in foods.
J. Agric. Food Chem.
PUBLISHED: 09-13-2013
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Biogenic amines (BAs) are a group of low-molecular-mass organic bases derived from free amino acids. Due to the undesirable effects of BAs on human health, amine oxidase-based detection methods for BAs in foods have been developed. Here, we developed a bifunctional enzyme fusion (MAPO) using a Cu(2+)-containing monoamine oxidase (AMAO2) and a flavin adenine dinucleotide-containing putrescine oxidase (APUO) from Arthrobacter aurescens. It was necessary to activate MAPO with supplementary Cu(2+) ions, leading to a 6- to 12-fold improvement in catalytic efficiency (kcat/KM) for monoamines. The optimal temperatures of Cu(2+)-activated MAPO (cMAPO) for both tyramine and putrescine were 50 °C, and the optimal pH values for tyramine and putrescine were pH 7.0 and pH 8.0, respectively, consistent with those of AMAO2 and APUO, respectively. The cMAPO showed relative specific activities of 100, 99, 32, and 32 for 2-phenylethylamine, tyramine, histamine, and putrescine, respectively. The tyramine-equivalent BA contents of fermented soybean pastes by cMAPO were more than 90% of the total BA determined by HPLC. In conclusion, cMAPO is fully bifunctional toward biogenic monoamines and putrescine, allowing the combined determination of multiple BAs in foods. This colorimetric determination method could be useful for point-of-care testing to screen safety-guaranteed products prior to instrumental analyses.
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Gene expression and DNA methylation status of chicken primordial germ cells.
Mol. Biotechnol.
PUBLISHED: 09-12-2013
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DNA methylation reprogramming of primordial germ cells (PGCs) in mammals establishes monoallelic expression of imprinting genes, maintains retrotransposons in an inactive state, inactivates one of the two X chromosomes, and suppresses gene expression. However, the roles of DNA methylation in chickens PGCs are unknown. In this study, we found a 1.5-fold or greater difference in the expression of 261 transcripts when comparing PGCs and chicken embryonic fibroblasts (CEFs) using an Affymetrix GeneChip Chicken Genome Array. In addition, we analyzed the methylation patterns of the regions ~5-kb upstream of 261 sorted genes, 51 of which were imprinting homologous loci and 49 of which were X-linked homologous loci in chicken using the MeDIP Array by Roche NimbleGen. Seven hypomethylated and five hypermethylated regions within the 5-kb upstream regions of 261 genes were found in PGCs when compared with CEFs. These differentially methylated regions were restrictively matched to differentially expressed genes in PGCs. We also detected 203 differentially methylated regions within imprinting and X-linked homologous regions between male PGCs and female PGCs. These differentially methylated regions may be directly or indirectly associated with gene expression during early embryonic development, and the epigenetic difference could be evolutionally conserved between mammals and birds.
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DCEP for relapsed or refractory multiple myeloma after therapy with novel agents.
Ann. Hematol.
PUBLISHED: 09-03-2013
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Multiple myeloma remains incurable despite the use of novel agents. Dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) is one of the salvage options, but there has been a lack of data on salvage DCEP in patients with previous exposure to novel agents. A total of 59 patients who received DCEP chemotherapy between 2006 and 2013 were retrospectively reviewed. The patients who had been exposed to thalidomide, lenalidomide, or bortezomib prior to DCEP were eligible. The median age at DCEP was 58 years, and DCEP treatment was initiated at a median of 34.9 months from diagnosis. Before DCEP, patients exposed to a median of three lines of treatment and 55 patients (81.4 %) had undergone autohematopoietic stem cell transplantation. Among 51 patients with data available for response assessment, response rate was 45.1 % (1 with complete response, 1 with very good partial response, and 21 with partial response); an additional 18 patients benefited from this regimen (8 with minor response and 10 stable diseases). Grade ?3 neutropenia was observed in 91.5 %. Treatment-related mortality (TRM) was reported in eight patients (14.8 %), and seven of eight deaths were related to febrile neutropenia. Median overall survival and progression-free survival were estimated at 8.0 and 3.7 months, respectively. DCEP is an effective salvage treatment options for relapsed or refractory multiple myeloma in the setting of previous use of novel agents. However, hematologic toxicities and TRM were substantial, and concurrent use of prophylactic granulocyte-colony stimulating factor is warranted.
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Recovery and local-variation of Dirac cones in oxygen-intercalated graphene on Ru(0001) studied using scanning tunneling microscopy and spectroscopy.
Phys Chem Chem Phys
PUBLISHED: 08-20-2013
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Methods to decouple epitaxial graphene from metal substrates have been extensively studied, with anticipation of observing unperturbed Dirac cone properties, but its local electronic structures were rarely studied. Here, we investigated the local variations of Dirac cones recovered using oxygen intercalation applied to epitaxial graphene on Ru(0001) using scanning tunneling microscopy and spectroscopy (STM and STS). New V-shaped features, which appear in the STS data at the oxygen-intercalated graphene regions, are attributed to the signatures of recovered Dirac cones. The Dirac point energy was observed at 0.48 eV below the Fermi level, different from previous photoemission results because of different oxygen coverages. The observed spatial variations of Dirac point energy were explained by the weakly protruding network structures caused by a small net strain in graphene. Our study shows that oxygen-intercalated graphene provides an excellent platform for further graphene research at the nano-meter scale with unperturbed Dirac cones.
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Transmission electron microscopy characterization of thermomechanically treated Al?Ti-(8, 10, 15)% Cr intermetallics.
Microsc. Microanal.
PUBLISHED: 08-08-2013
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The ordered L1?-type Al?Ti-(8, 10, 15)% Cr intermetallic compounds, namely, Al??Ti??Cr?, Al??Ti??Cr??, and Al??Ti??Cr??, were prepared by induction melting followed by thermomechanical treatment. Their microstructure, compositional variation, and crystal structure were characterized using X-ray diffraction, optical microscopy, and scanning and transmission electron microscopy equipped with energy-dispersive spectroscopy. The Al??Ti??Cr? alloy consisted of the L1?-Al?Ti matrix and precipitates of ??-Ti?Al, D0??-Al?Ti, and ?-TiAl. The Al??Ti??Cr?? and Al??Ti??Cr?? alloys consisted of the L1?-Al?Ti matrix and grains of ?-TiAl and ?-Cr.
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Cation location in microporous zeolite, SSZ-13, probed with xenon adsorption measurement and 129Xe NMR spectrum.
J Nanosci Nanotechnol
PUBLISHED: 07-19-2013
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The location of metal ion, Ag2+, Ca2+, Cu2+ and Y3+ in the SSZ-13 has been investigated with xenon adsorption measurement and 129Xe NMR spectrum. It was referred that the location of the metal ion varies depending on the corresponding charge. The ion-exchanged Ag ion was located in the alpha-cage to interact directly with xenon. Others multivalent cation contributed little with xenon because these were present near the six membered rings where xenon cannot access.
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Discovery of hybrid Hsp90 inhibitors and their anti-neoplastic effects against gefitinib-resistant non-small cell lung cancer (NSCLC).
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-11-2013
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Heat shock protein 90 (Hsp90) represents an attractive cancer therapeutic target due to its role in the stabilization and maturation of many oncogenic proteins. We have designed a series of hybrid Hsp90 inhibitors by connecting the resorcinol ring of VER-49009 (2) and the trimethoxyphenyl ring of PU3 (3) using structure-based approach. Subsequent testing established that compound 1f inhibited gefitinib-resistant H1975 cell proliferation, brought about the degradation of Hsp90 client proteins including EGFR, Met, Her2 and Akt and induced the expression of Hsp70. The design, synthesis, and evaluation of 1f are described herein.
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Korean guideline for iron chelation therapy in transfusion-induced iron overload.
J. Korean Med. Sci.
PUBLISHED: 06-15-2013
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Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.
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High-resolution crystal structure of Streptococcus pyogenes ?-NAD? glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface.
J Synchrotron Radiat
PUBLISHED: 06-08-2013
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One of the virulence factors produced by Streptococcus pyogenes is ?-NAD(+) glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38-451) and the full-length IFS (residues 1-161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPNct-IFS complex, which consists of the SPN C-terminal domain (SPNct; residues 193-451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPNct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.
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Identification of Target Genes Involved in the Antiproliferative Effect of Enzyme-Modified Ginseng Extract in HepG2 Hepatocarcinoma Cell.
Evid Based Complement Alternat Med
PUBLISHED: 06-01-2013
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Ginsenosides are ginseng saponins, which are the major biologically active components of Panax ginseng, often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng increased after enzymatic processing of ginseng saponin (50% inhibitory concentration [IC50], >30? ? g/mL), which may be the result of the accumulation of minor saponins, such as Rh1, Rg3, compound K, and PPT constituents in ginseng saponin. Using the Agilent PrimeView Human Gene Expression Array, we found that the expression of several genes involved in apoptosis (caspase-4, Annexin A2, HSPA9, AIFM1, UQCRC2, and caspase-7) were increased in HepG2 human hepatocarcinoma cells after their treatment with enzyme-modified ginseng extract (EMGE). Furthermore, several genes implicated in cell cycle progression (CDCA3, CDCA8, CABLES2, CDC25B, CNNM3, and CCNK) showed decreased expression in HepG2 cells treated with EMGE. Finally, from flow cytometric analysis, we found that EMGE-treated HepG2 cells showed increased apoptotic sub-G1 population (24%), compared with that observed in DMSO-treated control cells (1.6%). Taken together, our results suggest that EMGE induces anticancer activity through the induction of apoptosis-related genes and cell cycle arrest via decreased expression of cell cycle regulatory genes.
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Fullerene embedded shape memory nanolens array.
Sci Rep
PUBLISHED: 05-29-2013
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Securing fragile nanostructures against external impact is indispensable for offering sufficiently long lifetime in service to nanoengineering products, especially when coming in contact with other substances. Indeed, this problem still remains a challenging task, which may be resolved with the help of smart materials such as shape memory and self-healing materials. Here, we demonstrate a shape memory nanostructure that can recover its shape by absorbing electromagnetic energy. Fullerenes were embedded into the fabricated nanolens array. Beside the energy absorption, such addition enables a remarkable enhancement in mechanical properties of shape memory polymer. The shape memory nanolens was numerically modeled to impart more in-depth understanding on the physics regarding shape recovery behavior of the fabricated nanolens. We anticipate that our strategy of combining the shape memory property with the microwave irradiation feature can provide a new pathway for nanostructured systems able to ensure a long-term durability.
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Recent progress in voice-based sasang constitutional medicine: improving stability of diagnosis.
Evid Based Complement Alternat Med
PUBLISHED: 05-02-2013
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Sasang constitutional medicine is a unique form of tailored medicine in traditional Korean medicine. Voice features have been regarded as an important cue to diagnose Sasang constitution types. Many studies tried to extract quantitative voice features and standardize diagnosis methods; however, they had flaws, such as unstable voice features which vary a lot for the same individual, limited data collected from only few sites, and low diagnosis accuracy. In this paper, we propose a stable diagnosis model that has a good repeatability for the same individual. None of the past studies evaluated the repeatability of their diagnosis models. Although many previous studies used voice features calculated by averaging feature values from all valid frames in monotonic utterance like vowels, we analyse every single feature value from each frame of a sentence voice signal. Gaussian mixture model is employed to deal with a lot of voice features from each frame. Total 15 Gaussian models are used to represent voice characteristics for each constitution. To evaluate repeatability of the proposed diagnosis model, we introduce a test dataset consisting of 10 individuals voice recordings with 50 recordings per each individual. Our result shows that the proposed method has better repeatability than the previous study which used averaged features from vowels and the sentence.
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RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species.
Carcinogenesis
PUBLISHED: 04-30-2013
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Cell survival signaling is important for the malignant phenotypes of cancer cells. Although the role of receptor-interacting protein 1 (RIP1) in cell survival signaling is well documented, whether RIP1 is directly involved in cancer development has never been studied. In this report, we found that RIP1 expression is substantially increased in human non-small cell lung cancer and mouse lung tumor tissues. RIP1 expression was remarkably increased in cigarette smoke-exposed mouse lung. In human bronchial epithelial cells (HBECs), RIP1 was significantly induced by cigarette smoke extract or benzo[a]pyrene diol epoxide (BPDE), the active form of the tobacco-specific carcinogen benzo(a)pyrene. In RIP1 knockdown HBECs, BPDE-induced cytotoxicity was significantly increased, which was associated with induction of cellular reactive oxygen species (ROS) and activation of mitogen-activated protein kinases (MAPKs), including c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38. Scavenging ROS suppressed BPDE-induced MAPK activation and inhibiting ROS or MAPKs substantially blocked BPDE-induced cytotoxicity, suggesting ROS-mediated MAPK activation is involved in BPDE-induced cell death. The ROS-reducing enzyme catalase is destabilized in an ERK- and JNK-dependent manner in RIP1 knockdown HBECs and application of catalase effectively blocked BPDE-induced ROS accumulation and cytotoxicity. Importantly, BPDE-induced transformation of HBECs was significantly reduced when RIP1 expression was suppressed. Altogether, these results strongly suggest an oncogenic role for RIP1, which promotes malignant transformation through protecting DNA-damaged cells against carcinogen-induced cytotoxicity associated with excessive ROS production.
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Impact of heparin-binding domain of recombinant human osteocalcin-fibronectinIII9-14 on the osteoblastic cell response.
Biotechnol. Lett.
PUBLISHED: 04-18-2013
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Fibronectin (FN) containing a heparin-binding domain (HBD) and an Arg-Gly-Asp (RGD) domain can promote cell adhesion and proliferation compared to FN that contained only RGD. Here, we have engineered recombinant human osteocalcin (rhOC) with FN type III9-14 (rhOC-FNIII9-14) containing RGD and HBD to promote the cellular activity of MC3T3-E1 cells, including adhesion, proliferation, and differentiation. RhOC-FNIII9-14 significantly increased cell adhesion and proliferation of MC3T3-E1 cells compared to rhOC-FNIII9-10 (P < 0.05). Moreover, rhOC-FNIII9-14 showed osteogenic differentiation of MC3T3-E1 cells in mineralization activity and osteogenic gene expression.
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Clinical significance of SF3B1 mutations in Korean patients with myelodysplastic syndromes and myelodysplasia/myeloproliferative neoplasms with ring sideroblasts.
Ann. Hematol.
PUBLISHED: 04-16-2013
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Somatic mutations in the SF3B1 gene, a gene encoding the splicing factor 3B subunit 1, were recently reported in myelodysplastic syndromes (MDS), particularly in the presence of ring sideroblasts (RS). The authors investigated the prevalence and clinical significance of SF3B1 mutations in Korean patients with myeloid neoplasms with RS. The study subjects were 43 Korean patients with myeloid neoplasms. Twenty-nine patients (67 %) had 15 % or more RS (high-count RS [HC-RS]), and 14 (33 %) had RS less than 15 % (low-count RS [LC-RS]). Molecular genetic tests were performed to detect SF3B1 mutations by direct sequencing on bone marrow samples of the patients. SF3B1 mutations were detected in 55 % (16/29) of the HC-RS group: 3 RARS (3/3), 8 RCMD (8/16), 3 RARS-t (3/4), 1 RAEB (1/4), and 1 MDS-U (1/1). All mutations were previously reported mutations with K700E being the most common (63 % of mutation-positive cases). On the other hand, none (0 %) of the LC-RS group had SF3B1 mutation. The patients with SF3B1 mutations had higher platelet counts (p?=?0.023), higher proportions of RS (p?=?0.003), and lower proportions of bone marrow blasts (p?=?0.026) than those without SF3B1 mutations. SF3B1 mutations showed a favorable survival implication (p?=?0.025), but not in multivariate analysis (p?=?0.178). This study confirmed that SF3B1 mutation is highly specific to the HC-RS phenotype in Korean patients with myeloid neoplasms with similar frequencies and distributions in previous findings and is associated with distinct hematologic features.
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Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action.
Evid Based Complement Alternat Med
PUBLISHED: 03-30-2013
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Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in an in vitro and in vivo model of Parkinsons disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factor ? (TNF- ? ), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50?mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.
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Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.
Free Radic. Biol. Med.
PUBLISHED: 03-29-2013
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Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (?H2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated ?H2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs.
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Use of azacitidine for myelodysplastic syndromes: controversial issues and practical recommendations.
Blood Res
PUBLISHED: 03-28-2013
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Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology.
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Kaposi?s sarcoma-associated herpesvirus ORF36 protein induces chromosome condensation and phosphorylation of histone H3.
Acta Virol.
PUBLISHED: 03-28-2013
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Kaposi?s sarcoma-associated herpesvirus (KSHV) has been known as an agent causing Kaposi?s sarcoma, primary effusion lymphoma, and multicentric Castleman?s disease. In the lytic phase of the virus cycle, various viral genes are expressed, which causes host cell dysregulation. Among the lytic genes, viral protein kinase (vPK) encoded by ORF36 is a member of serine/threonine protein kinase (CHPK) family, which is involved in viral gene expression, viral DNA replication and encapsidation, and nuclear egress of virions. Recent studies have shown that the BGLF4 protein of Epstein-Barr virus (EBV), a member of the CHPK family, alters the host cell chromatin structure through phosphorylation of its key regulators. The role of KSHV ORF36 in cellular mitotic events, however, is not yet understood. In the current study, we showed that KSHV ORF36 induced chromosome condensation and phosphorylation of histone H3 on Ser 10, which are known as cellular mitosis markers. These processes have occurred in a kinase activity-dependent manner.
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Molecular characteristics of cancer stem-like cells derived from human breast cancer cells.
Anticancer Res.
PUBLISHED: 03-14-2013
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We characterized the cellular properties of cancer stem-like cells (CSLCs) isolated from immortalized MDA-MB453 human breast cancer cells in culture. We showed that although the expression of Octamer-binding transcription factor-4 (OCT4) correlates to stemness in these CSLCs, OCT4 knockdown does not induce their differentiation. Our results suggest that the differentiation program in MDA-MB453 CSLCs is blocked at a step upstream of the transcription of the OCT4 promoter, allowing CSLCs to maintain their population through asymmetric cell division during many repeated passages. Comparative expression analysis indicates that only a subset of genes and signaling pathways known to be associated with survival and maintenance of CSCs are selectively expressed in CSLCs, as compared with non-CSLCs fractionated from the same parental MDA-MB453 cells. These results suggest that selective expression of a limited number of genes may be sufficient for establishment and maintenance of CSLCs with high tumorigenicity.
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A practical approach to Sasang constitutional diagnosis using vocal features.
BMC Complement Altern Med
PUBLISHED: 03-11-2013
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Sasang constitutional medicine (SCM) is a type of tailored medicine that divides human beings into four Sasang constitutional (SC) types. Diagnosis of SC types is crucial to proper treatment in SCM. Voice characteristics have been used as an essential clue for diagnosing SC types. In the past, many studies tried to extract quantitative vocal features to make diagnosis models; however, these studies were flawed by limited data collected from one or a few sites, long recording time, and low accuracy. We propose a practical diagnosis model having only a few variables, which decreases model complexity. This in turn, makes our model appropriate for clinical applications.
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The concept of sasang health index and constitution-based health assessment: an integrative model with computerized four diagnosis methods.
Evid Based Complement Alternat Med
PUBLISHED: 03-09-2013
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SASANG CONSTITUTIONAL MEDICINE (SCM) SHARES ITS PHILOSOPHY WITH THAT OF PERSONALIZED MEDICINE: it provides constitution-specific treatment and healthcare individualized for each patient. In this work, we propose the concept of the Sasang Health Index (SHI) as an attempt to assess the individualized health status in the framework of SCM. From the target population of females in their fifties and older, we recruited 298 subjects and collected their physiological data, including complexion, radial pulse, and voice, and their questionnaire responses. The health status of each subject was evaluated by two Korean medical doctors independently, and the SHI model was obtained by combining all the integrative features of the phenotype data using a regression technique. As a result, most subjects belonged to either the healthy, subhealthy, or slightly diseased group, and the intraclass correlation coefficient between the two doctors health scoring reached 0.95. We obtained an SHI model for each constitution type with adjusted R-squares of 0.50, 0.56, and 0.30, for the TE, SE, and SY constitution types, respectively. In the proposed SHI model, the significant characteristics used in the health assessment consisted of constitution-specific features in accordance with the classic literature and features common to all the constitution types.
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Supramolecular Cl???H and O???H interactions in self-assembled 1,5-dichloroanthraquinone layers on Au(111).
Chemphyschem
PUBLISHED: 03-04-2013
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The role of halogen bonds in self-assembled networks for systems with Br and I ligands has recently been studied with scanning tunneling microscopy (STM), which provides physical insight at the atomic scale. Here, we study the supramolecular interactions of 1,5-dichloroanthraquinone molecules on Au(111), including Cl ligands, by using STM. Two different molecular structures of chevron and square networks are observed, and their molecular models are proposed. Both molecular structures are stabilized by intermolecular Cl???H and O???H hydrogen bonds with marginal contributions from Cl-related halogen bonds, as revealed by density functional theory calculations. Our study shows that, in contrast to Br- and I-related halogen bonds, Cl-related halogen bonds weakly contribute to the molecular structure due to a modest positive potential (? hole) of the Cl ligands.
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Therapy-related myeloid neoplasms in 39 Korean patients: a single institution experience.
Ann Lab Med
PUBLISHED: 02-21-2013
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Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea.
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Analysis of muscle fatigue of erect spinae caused by treatment table height in ultrasound therapy.
J Phys Ther Sci
PUBLISHED: 02-19-2013
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[Purpose] The objective of this study was to propose a work environment that could reduce musculoskeletal workload. Accordingly, spinal muscle fatigue caused by ultrasound therapy at various treatment table heights was examined and compared. [Subjects and Methods] Twenty-five healthy subjects participated in this experiment. The table height was set to 100%, 125%, and 150% of the stool height (45?cm). The electromyographic signals of the erector spinae at the thoracic (T10, T12) and lumbar (L2, L4) levels were collected by an electromyography (EMG) system during the performance of ultrasound therapy. The median frequencies were then calculated and compared. [Results] The lower the table height was, the smaller the median frequencies of thoracic and lumbar erector spinae on both sides were. The T10 and T12 levels on both sides and the left L2 region showed significant differences among the table heights. At every spinal level, the median frequency of the left erector spinae was lower than that of the right: T10, T12, L2, and L4 at 100%, L4 at 125%, and T10, T12, L2, and L4 at 150% showed significant differences. [Conclusion] During ultrasound therapy muscle fatigue increased at higher table heights and the muscle fatigue of the left erector spinae was greater than that of the right side. To reduce muscle fatigue, we recommend the table height work is raised to an appropriate height, and that is shared between left and right arms.
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An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells.
J. Cell. Physiol.
PUBLISHED: 02-15-2013
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Mesenchymal stem cells (MSCs) are multipotent adult stem cells capable of differentiating along the osteoblast, adipocyte, and chondrocyte lineages. Regulation of MSCs differentiation may be a useful tool for regenerative medicine and cell-based therapy. The discovery of small molecule that activates the osteogenic differentiation of MSCs could aid in the development of a new anabolic drug for osteoporosis treatment. We identified CW008, a derivative of pyrazole-pyridine, that stimulates osteoblast differentiation of human MSCs and increases bone formation in ovariectomized mice. CW008 promotes osteogenesis by activating cAMP/PKA/CREB signaling pathway and inhibiting leptin secretion. These results suggest that CW008 is an agonist of cAMP/PKA/CREB pathway in osteogenic differentiation and that application of CW008 may be useful for the treatment of bone-related diseases and for the study of bone biology.
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Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory.
Eur. Heart J.
PUBLISHED: 02-08-2013
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Maximal hyperaemia is a key element of invasive physiological studies and adenosine is the most commonly used agent. However, infusion of adenosine requires additional venous access and can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction block. The aim of this study was to evaluate the feasibility and efficacy of intracoronary (IC) nicorandil as a novel hyperaemic agent for invasive physiological studies.
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Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide?stimulated BV2 microglial cells.
Int. J. Mol. Med.
PUBLISHED: 02-07-2013
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Radix platycodi is the root of Platycodon grandiflorus A. DC, which has been widely used as a food material and for the treatment of a number of chronic inflammatory diseases in traditional oriental medicine. In this study, the anti?inflammatory effects of the saponins isolated from radix platycodi (PGS) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells were examined. We also investigated the effects of PGS on LPS?induced nuclear factor??B (NF-?B) activation and phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Following stimulation with LPS, elevated nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokine production was detected in the BV2 microglial cells. However, PGS significantly inhibited the excessive production of NO, PGE2 and pro?inflammatory cytokines, including interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) in a concentration-dependent manner without causing any cytotoxic effects. In addition, PGS suppressed NF-?B translocation and inhibited the LPS-induced phosphorylation of AKT and MAPKs. Our results indicate that the inhibitory effect of PGS on LPS-stimulated inflammatory response in BV2 microglial cells is associated with the suppression of NF-?B activation and the PI3K/AKT and MAPK signaling pathways. Therefore, these findings suggest that PGS may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory responses in activated microglial cells.
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Positive Correlation between Baseline PET or PET/CT Findings and Clinical Parameters in Multiple Myeloma Patients.
Acta Haematol.
PUBLISHED: 02-06-2013
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Recently, positron emission tomography (PET) has been incorporated into a series of prospective studies as a predictor of outcomes in multiple myeloma (MM), and the number of (18)F-fluorodeoxuglucose (FDG)-avid focal lesions (FLs) and the intensity of tumor metabolism have been designated as important surrogate markers for predicting prognosis. Here, we compared initial clinical characteristics of MM patients with baseline PET parameters: the number of FLs and the maximum standardized uptake value (SUVmax). A total of 59 patients diagnosed with MM between August 2004 and February 2012 were reviewed. At diagnosis, 23 patients (40.0%) had ?3 FLs, 11 patients (18.6%) 4-9 FLs, and 25 patients (42.4%) ?10 FLs. The median SUVmax was 5.3 (range 0-24.3), and 40 patients (67.8%) showed a SUVmax >4. No clinical characteristics were significantly different between groups with a SUVmax ?4 and a SUVmax >4. However, there were significant differences in several clinical indices between the FLs ?3 and FLs >3 groups; elevated ?2-microglobulin, elevated lactate dehydrogenase, anemia and more advanced disease by the Durie-Salmon stage corresponded to FLs >3 at baseline PET. Adverse baseline PET findings are positively correlated with prognostically relevant clinical parameters. Regarding PET parameters, FLs are more likely to be well correlated with disease aggressiveness and pathophysiology compared to SUVmax. © 2013 S. Karger AG, Basel.
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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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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.