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Find video protocols related to scientific articles indexed in Pubmed.
Nigrostriatal Dopamine Acting on Globus Pallidus Regulates Sleep.
Cereb. Cortex
PUBLISHED: 10-16-2014
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Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (?45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA afferents to the caudoputamen (CPu) using 6-hydroxydopamine and examined changes in sleep-wake profiles in rats. Rats with 80-90% loss of SNc neurons displayed a significant 33.7% increase in wakefulness (or sleep reduction). This increase significantly correlated with the extent of SNc DA neuron loss. Furthermore, these animals exhibited sleep-wake fragmentation and reduced diurnal variability of sleep. We then optogenetic-stimulated SNc DA terminals in the CPu and found that 20-Hz stimulation from 9 to 10 PM increased total sleep by 69% with high electroencephalograph (EEG) delta power. We finally directly optogenetic-stimulated GPe neurons and found that 20-Hz stimulation of the GPe from 9 to 10 PM increased total sleep by 66% and significantly increased EEG delta power. These findings elucidate a novel circuit for DA control of sleep and the mechanisms of abnormal sleep in BG disorders such as Parkinson's disease and Huntington's disease.
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A recessive variant of XRCC4 predisposes to non- BRCA1/2 breast cancer in chinese women and impairs the DNA damage response via dysregulated nuclear localization.
Oncotarget
PUBLISHED: 09-07-2014
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XRCC4 plays a crucial role in the non-homologous end joining pathway that maintains genome stability. In this two-stage case-control study with 1,764 non-BRCA1/2 breast cancer patients and 1,623 cancer-free controls, we investigated the contribution of genetic variants of XRCC4 to breast cancer susceptibility in Chinese women. We identified a recessive missense variant, rs3734091 (c.739G>T, p.Ala247Ser), of XRCC4 that was significantly associated with an increased risk of breast cancer (odds ratio [OR] = 3.92, P = 0.007), particularly with the risk of developing triple-negative breast cancer (OR = 18.65, P < 0.0001). This p.Ala247Ser variant disturbed the nuclear localization of XRCC4 in cells homozygous for the rs3734091-T allele but not in heterozygous cells at both the cellular and tissue levels. In heterozygous cells, wild-type XRCC4 facilitated the nuclear localization of the XRCC4A247S mutant, thus compensating for the impaired localization of XRCC4A247S. This provided a biological mechanism by which rs3734091 conferred an increased susceptibility to non-BRCA1/2 breast cancer exclusively under a recessive model. Further functional analyses revealed that p.Ala247Ser impaired the DNA damage repair capacity and ultimately perturbed genomic stability. Taken together, our findings document the role of XRCC4 in non-BRCA1/2 breast cancer predisposition and reveal its underlying biological mechanism of action.
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Intestinal stem cells and stem cell-based therapy for intestinal diseases.
Cytotechnology
PUBLISHED: 06-07-2014
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Currently, many gastrointestinal diseases are a major reason for the increased mortality rate of children and adults every year. Additionally, these patients may cope with the high cost of the parenteral nutrition (PN), which aids in the long-term survival of the patients. Other treatment options include surgical lengthening, which is not sufficient in many cases, and intestinal transplantation. However, intestinal transplantation is still accompanied by many challenges, including immune rejection and donor availability, which may limit the transplant's success. The development of more safe and promising alternative treatments for intestinal diseases is still ongoing. Stem cell-based therapy (SCT) and tissue engineering (TE) appear to be the next promising choices for the regeneration of the damaged intestine. However, suitable stem cell source is required for the SCT and TE process. Thus, in this review we discuss how intestinal stem cells (ISCs) are a promising cell source for small intestine diseases. We will also discuss the different markers were used to identify ISCs. Moreover, we discuss the dominant Wnt signaling pathway in the ISC niche and its involvement in some intestinal diseases. Additionally, we discuss ISC culture and expansion, which are critical to providing enough cells for SCT and TE. Finally, we conclude and recommend that ISC isolation, culture and expansion should be considered when SCT is a treatment option for intestinal disorders. Therefore, we believe that ISCs should be considered a cell source for SCT for many gastrointestinal diseases and should be highlighted in future clinical applications.
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Substrate-dependent modulation of 3D spheroid morphology self-assembled in mesenchymal stem cell-endothelial progenitor cell coculture.
Biomaterials
PUBLISHED: 05-06-2014
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The structural evolution of three-dimensional spheroids self-assembled from two different types of cells on selective biomaterials is demonstrated in this study. The two types of cells involved in the self-assembly are human mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). When seeded in different population ratios, they can create a variety of cellular patterns on different biomaterial substrates. When the two populations are matched in initial numbers, they are self-assembled in co-spheroids with different morphologies (i.e. randomly mixed, bumped, or concentric spheroids). The morphologies are influenced by the specific cell-substrate interaction possibly through integrin signaling, as well as a substrate-dependent regulation of heterophilic cell-cell interaction possibly through Notch signaling. In particular, the self-assembled core-shell concentric spheroids from adipose-derived MSCs and EPCs show a greater angiogenic effect in vitro. This study reveals the possibility to modulate the self-assembled morphology as well as the effect of cocultured cells by changing the cell culture substratum.
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Elevated expression of girdin in the nucleus indicates worse prognosis for patients with estrogen receptor-positive breast cancer.
Ann. Surg. Oncol.
PUBLISHED: 05-03-2014
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Girdin was identified as a novel Akt substrate that contributes to a positive feedback loop between Girdin and Akt. Although several recent studies have demonstrated that Girdin is involved in tumor metastasis, the clinical implications of Girdin in breast cancer remain unclear.
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Spatiotemporal distribution and short-term trends of particulate matter concentration over China, 2006-2010.
Environ Sci Pollut Res Int
PUBLISHED: 05-01-2014
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Air quality problems caused by atmospheric particulate have drawn broad public concern in the global scope. In the paper, the spatiotemporal distributions of fine particle (PM2.5) and inhalable particle (PM10) concentrations estimated with the artificial neural network (ANN) over China during 2006 to 2010 have been discussed. Most high PM10 concentration appears in Xinjiang, Qinghai, Gansu, Ningxia, Hubei, and parts of Inner Mongolia. The distribution of PM2.5 concentration is consistent with China's three gradient terrains. The seasonal variations of PM2.5 and PM10 concentrations both indicate that they are higher in north China in spring and winter, lowest in summer. In autumn, most provinces in south China appear high value. In particular, high PM2.5 concentration appears in the southeast coastal cities while high PM10 concentration prefers the central regions in south China. On this basis, seasonal Mann-Kendall test method is utilized to analyze the short-term trends. The results also show significant changes of PM2.5 and PM10 concentrations of China in the past 5 years, and most provinces present the tendency of reduction (3-5 ?g/m(3) for PM2.5 and 10-20 ?g/m(3) for PM10 per year) while a fraction of provinces appear the increasing trend of 8-16 ?g/m(3) (PM2.5) and 16-30 ?g/m(3) (PM10). Simultaneously, PM2.5 population exposure is discussed with the combination of population density-gridded data. Municipalities get much higher exposure level than other provinces. Shanghai suffers the highest population exposure to PM2.5, followed by Beijing and then Tianjin, Jiangsu province. Most provincial capitals, such as Guangzhou, Nanjing, Chengdu, and Wuhan, face much higher exposure level than other regions of their province. Moreover, the PM2.5 exposure situation is more serious in southeast than northwest regions for Beijing-Tianjin-Hebei region. Also, per capita PM2.5 concentration and population-weighted PM2.5 concentration are calculated. The former shows that the high-level regions distribute in Guangdong, Shanghai, and Tianjin, while the latter in Hebei, Chongqing, and Shandong provinces. Further studies may consider optimizing concentration estimation model and use it to discuss the effects of particulate matters on human health.
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Particulate matter pollution and population exposure assessment over mainland China in 2010 with remote sensing.
Int J Environ Res Public Health
PUBLISHED: 03-13-2014
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The public is increasingly concerned about particulate matter pollution caused by respirable suspended particles (PM10) and fine particles (PM2.5). In this paper, PM10 and PM2.5 concentration are estimated with remote sensing and individual air quality indexes of PM10 and PM2.5 (IPM10 and IPM2.5) over mainland China in 2010 are calculated. We find that China suffered more serious PM2.5 than PM10 pollution in 2010, and they presented a spatial differentiation. Consequently, a particulate-based air quality index (PAQI) based on a weighting method is proposed to provide a more objective assessment of the particulate pollution. The study demonstrates that, in 2010, most of mainland China faced a lightly polluted situation in PAQI case; there were three areas obviously under moderate pollution (Hubei, Sichuan-Chongqing border region and Ningxia-Inner Mongolia border region). Simultaneously, two indicators are calculated with the combination of population density gridded data to reveal Chinese population exposure to PM2.5. Comparing per capita PM2.5 concentration with population-weighted PM2.5 concentration, the former shows that the high-level regions are distributed in Guangdong, Shanghai, and Tianjin, while the latter are in Hebei, Chongqing, and Shandong. By comparison, the results demonstrate that population-weighted PM2.5 concentration is more in line with the actual situation.
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Correlation between the suppressor of cytokine signaling-1 and 3 and hepatitis B virus: possible roles in the resistance to interferon treatment.
Virol. J.
PUBLISHED: 03-06-2014
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The suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy.
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An aberrant spliced transcript of focal adhesion kinase is exclusively expressed in human breast cancer.
J Transl Med
PUBLISHED: 02-16-2014
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To clarify the roles of a new aberrantly spliced transcript of FAK that lacks exon 26 (denoted -26-exon FAK) in human breast cancers.
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Effect of Ca(2+) on the activity and structure of ?-glucosidase: inhibition kinetics and molecular dynamics simulations.
J. Biosci. Bioeng.
PUBLISHED: 01-20-2014
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Understanding the mechanism of inhibition of ?-glucosidase (EC 3.2.1.20) is clinically important because of the involvement of this enzyme in type 2 diabetes mellitus. In this study, we conducted inhibition kinetics of ?-glucosidase with Ca(2+) and 10-ns molecular dynamics simulations. We found that direct binding of Ca(2+) to the enzyme induced structural changes and inhibited enzyme activity. Ca(2+) inhibited ?-glucosidase in a mixed-type reaction (Ki = 27.0 ± 2.0 mM) and directly induced the unfolding of ?-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca(2+) ions may interact with ?-glucosidase residues and that the Ca(2+) binding sites are associated with the structural changes in ?-glucosidase. Our study provides insight into the mechanism of the Ca(2+)-induced structural changes in ?-glucosidase and the inhibition of ligand binding. These results suggest that Ca(2+) could act as a potent inhibitor of ?-glucosidase for the treatment of type 2 diabetes mellitus.
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A serum-free medium developed for in vitro expansion of murine intestinal stem cells.
Biotechnol J
PUBLISHED: 01-12-2014
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Intestinal stem cells (ISCs) are located at the base of the intestinal crypts and have the ability to self-renew as well as to differentiate into mature epithelial cells. Recently, ISCs have received much attention for the treatment of many intestinal diseases. However, many challenges face those studying ISCs because insufficient ISCs are available. Therefore, the development of a culture medium for ISC expansion is an important necessity for basic research and clinical application. In this study, we described the technique used to develop a serum-free medium for expanding ISCs in vitro. Furthermore, five serum substitutes were selected and optimized in order to maintain the long-term proliferation and enteroid-forming ability of ISCs: (i) ethanolamine; (ii) ascorbic acid phosphate; (iii) transferrin; (iv) glutathione; and (v) sodium selenite. Analysis of gene expression of Lgr5, Bmi1, Msi1 and PTEN demonstrated that our serum-free medium sustained the expression of genes involved in ISC-related functions in the expanded ISCs. Additionally, the expression intensity of surface markers, including Lgr5, CD24 and CD44, on serum-free expanded cells in crypts was greatly increased. Taken together, our results demonstrate that the number of ISCs can be expanded and their functionality maintained in our serum-free medium, indicating the suitability of this serum-free expansion medium for increasing the numbers of ICSs available for basic research and clinical applications in the future.
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Enhanced production of fumigaclavine C by ultrasound stimulation in a two-stage culture of Aspergillus fumigatus CY018.
Bioresour. Technol.
PUBLISHED: 01-07-2014
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Stimulation by physical means including ultrasound is important to cell morphology and the product yield. In this work, the effect of ultrasound on the production of fumigaclavine C (FC), a conidiation-associated alkaloid with strong anti-inflammatory activity, was investigated in a newly developed two-stage culture of Aspergillus fumigatus CY018. The optimum ultrasonication conditions consisted of exposing cultures (at 12h of growth phase) to 10-min repeated irradiation (4 times) with a 24-h interval at the fixed power (500 W). Under this condition, FC production reached 118.09 mg/L, which was 89% higher than the control and much higher than previous reported values. Morphological analysis demonstrated that mycelia morphology from ultrasonication was in the form smaller and looser pellets as compared to that of the control. In addition, conidia that is closely related to FC biosynthesis were significantly increased after ultrasound stimulation, with 3 folds of that from the control.
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Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene.
Int J Ophthalmol
PUBLISHED: 01-01-2014
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To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology.
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New insights into FAK phosphorylation based on a FAT domain-defective mutation.
PLoS ONE
PUBLISHED: 01-01-2014
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Mounting evidence suggests that the FAK N-terminal (FERM) domain controls FAK phosphorylation and function; however, little is known regarding the role of the C terminal (FAT) domain in FAK regulation. We identified a patient-derived FAK mutant, in which a 27-amino acid segment was deleted from the C-terminal FAT domain (named FAK-Del33). When FAK-Del33 was overexpressed in specific tumor cell lines, Y397 phosphorylation increased compared with that observed in cells expressing FAK-WT. Here, we attempt to unveil the mechanism of this increased phosphorylation. Using cell biology experiments, we show that FAK-Del33 is incapable of co-localizing with paxillin, and has constitutively high Y397 phosphorylation. With a kinase-dead mutation, it showed phosphorylation of FAK-Del33 has enhanced through auto-phosphorylation. It was also demonstrated that phosphorylation of FAK-Del33 is not Src dependent or enhanced intermolecular interactions, and that the hyperphosphorylation can be lowered using increasing amounts of transfected FERM domain. This result suggests that Del33 mutation disrupting of FAT's structural integrity and paxillin binding capacity leads to incapable of targeting Focal adhesions, but has gained the capacity for auto-phosphorylation in cis.
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ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Inhibitors of DNA-binding (ID) proteins are known as important modulators in the regulation of cell proliferation and differentiation. This study sought to investigate the prognostic value of ID proteins in breast cancer.
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A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.
PLoS ONE
PUBLISHED: 01-01-2014
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The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.
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Morphologic characteristics of the posterior malleolus fragment: a 3-D computer tomography based study.
Arch Orthop Trauma Surg
PUBLISHED: 12-24-2013
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The objective of this study was to evaluate the morphological characteristics of the posterior malleolus fragment (PMF) based on 3-D computed tomography scans, and evaluated the variability in different types of injuries (ankle fracture, spiral tibial shaft fracture and pilon fracture).
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[Clinical effect of combination therapy with high-frequency oscillation ventilation, pulmonary surfactant and inhaled nitric oxide in the treatment of neonatal hypoxemic respiratory failure].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 12-18-2013
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To investigate the clinical effect of combination therapy with high-frequency oscillation ventilation (HFOV), pulmonary surfactant (PS) and inhaled nitric oxide (iNO) in the treatment of neonatal hypoxemic respiratory failure (HRF).
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Somatic mutational analysis of FAK in breast cancer: A novel gain-of-function mutation due to deletion of exon 33.
Biochem. Biophys. Res. Commun.
PUBLISHED: 11-16-2013
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Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introduced into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.
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[Promote the development of dental education via National Board Dental Examinations].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 11-16-2013
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By evaluating the data of National Board Dental Examinations over recent 3 years, the disadvantages in the present dental education were analyzed and improvement schemes were proposed.
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[Value of percentage of highly fluorescent lymphocytic cells for rapidly assessing septicemia in tumor patients].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-16-2013
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To evaluate the value of percentage of highly fluorescent lymphocytic cells (HFLC%) for rapidly assessing septicemia in tumor patients.
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Generation of patient-specific induced neuronal cells using a direct reprogramming strategy.
Stem Cells Dev.
PUBLISHED: 09-17-2013
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Direct reprogramming of human fibroblasts into functional neurons in vitro by defined factors provides an invaluable resource for regenerative medicine. However, clinical applications must consider the risk of immune rejection, thus patient-specific induced neuronal cells (iNCs) may serve as an ideal source for autologous cell replacement. In this study, we report a robust process for functional neuronal cells from the patients scalp by lentiviral gene delivery of Ascl1, Myt1l, and Sox2. These three-factor iNCs are similar to human neuronal cells in morphology, surface antigens, gene expression, and electrophysiological characteristics. Our findings might provide a source of patient-specific functional neurons for cell therapy.
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Advanced oxidation protein products induce inflammatory response in fibroblast-like synoviocytes through NADPH oxidase -dependent activation of NF-?B.
Cell. Physiol. Biochem.
PUBLISHED: 09-12-2013
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Advanced oxidation protein products (AOPPs), a marker of oxidative stress, are prevalent in many kinds of disorders. Rheumatoid arthritis (RA), mainly resulting from the dysfunction of fibroblast-like synoviocytes (FLSs), is related to oxidative stress. Although the increased levels of AOPPs in RA patients were reported, the effect of AOPPs on FLSs function still remains unclear. Therefore, our study aims to investigate whether AOPPs have an effect on the inflammatory response of FLSs in vitro.
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Enhanced production of Fumigaclavine C in liquid culture of Aspergillus fumigatus under a two-stage process.
Bioresour. Technol.
PUBLISHED: 08-23-2013
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Fumigaclavine C (FC) produced by Aspergillus fumigatus is a conidiation associated ergot alkaloid with strong anti-inflammatory activity. However, its wide application has been severely limited by low FC production from submerged culture. In this work, a novel two-stage culture process by combining shake culture with static culture was proposed to enhance the production of FC. After the process optimization, the FC production reached 62.7mg/L, which was significantly higher than ever report. For scaling up this new culture process, the gas-liquid interfacial area per unit volume (Agas-liq) was identified as the key factor. The results showed that in a combined stirred-static bioreactor system, a maximum FC production (58.97mg/L) was obtained at an Agas-liq value of 1.30cm(2)/mL. These results demonstrated that two-stage culture is an efficient strategy to enhance FC production and the information obtained will be useful to production of this powerful bioactive compound on a large scale.
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[Effect of adenovirus-mediated TXNIP overexpression on apoptosis and injury of H9C2 cardiomyocytes].
Sheng Li Xue Bao
PUBLISHED: 06-22-2013
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Adenovirus transfection technique was used in the current study to show if thioredoxin-interacting protein (TXNIP) overexpression can induce cell apoptosis and injury in H9C2 cardiomyocytes cultured in normal glucose condition. And the mechanisms were then investigated. Briefly, H9C2 cardiomyocytes in logarithmic growth phase were randomly divided into three groups: normal cultured group, empty adenovirus vector group (Ad-eGFP) and TXNIP overexpression group (Ad-TXNIP-eGFP). All cells were cultured in DMEM containing normal concentration of glucose (5 mmol/L) and lipid. 72 h after adenovirus transfection, cells and culture mediums were collected for further assay. The results showed that Ad-eGFP and Ad-TXNIP-eGFP adenovirus transfected H9C2 cells successfully, and the transfection efficiency reached the peak at 72 h. Compared with Ad-eGFP group, Ad-TXNIP-eGFP transfection significantly increased TXNIP mRNA (P < 0.05) and protein expression level (P < 0.01). TXNIP overexpression induced remarkable cell apoptosis and injury as evidenced by increased caspase-3 activity (P < 0.05), apoptotic rate (P < 0.01) and LDH activity (P < 0.01). To further analysis the mechanisms of TXNIP-induced cell apoptosis, we also determined Trx activity, Trx related free radical injury and p38 kinase activation, which are involved in free radical induced apoptosis. The results showed that, compared with those in Ad-eGFP group, Trx activity was significantly decreased (P < 0.01), while malondialdehyde (MDA), 3-nitrotyrosine contents and p38 kinase activity were significantly increased (P < 0.01) in TXNIP overexpression group. These results suggest that TXNIP overexpression alone can induce severe apoptosis and injury in H9C2 cardiomyocytes even they are cultured in normal glucose and lipid concentration conditions. The mechanism involved is that overexpressed TXNIP can bind and inhibit Trx, impairs its antioxidative and antiapoptotic function, and then increases free radical induced injury and p38 kinase dependent apoptosis.
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Investigation of medical waste management in Gansu Province, China.
Waste Manag Res
PUBLISHED: 04-08-2013
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Medical waste is a special category of waste with potential health and environment risks. The present study aimed to explore the current status of medical waste management in western China. Seventy-four healthcare facilities were selected to assess the general status of medical waste management based upon a designed questionnaire survey. The surveyed results showed that the quantities of average medical waste generation were 0.79, 0.59 and 0.61 kg bed(-1) day(-1) in tertiary, secondary and primary hospitals, respectively. The incomplete segregation of domestic and medical waste generated a higher quantity of medical waste in primary hospitals (0.61 kg bed(-1) day(-1)) than that in secondary hospitals. Furthermore, the effective implementation of the medical waste management system depended on national regulations, occupational safety, internal policies and administration and the qualifications and competence of the directors of the waste management department in the healthcare facilities. Therefore, sufficient training programmes and protective measures should be provided by healthcare facilities to all relevant personnel and adequate financial support and effective administrative monitoring should be performed by local authorities.
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Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer.
J Transl Med
PUBLISHED: 03-23-2013
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Basigin, which has four isoforms, has been demonstrated to be involved in progression of various human cancers. The aim of this study was to examine the prognostic value of basigin-2 protein expression in epithelial ovarian cancer. Furthermore, the function of basigin-2 in ovarian cancer was further investigated in cell culture models.
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Regeneration and Agrobacterium-mediated transformation of the apomictic species Eulaliopsis binata.
Appl. Biochem. Biotechnol.
PUBLISHED: 03-17-2013
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Protocols for regeneration and Agrobacterium-mediated transformation of the apomictic species Eulaliopsis binata were developed. Initially, seeds of four genotypes of E. binata were incubated on a callus induction Murashige and Skoog (MS) basal medium supplemented with three concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D). It was found that 36.2 % of explants developed highly friable callus on medium containing 3.0 mg l(-1) 2,4-D. Based on frequency of callus induction, the genotype Neixiang was selected for regeneration and transformation. Callus incubated on MS basal medium supplemented with 0.2 mg l(-1) ?-naphthalene acetic acid and 6.0 mg l(-1) 6-furfuryl-aminopurine developed shoots. Subsequently, Agrobacterium tumefaciens strain EHA105-harboring a plasmid pCAMBIA1381 carrying a hygromycin phosphotransferase (hpt) resistance gene and a synthetic green fluorescent protein (GFP) gene, both driven by the cauliflower mosaic virus 35S promoter-was used for transformation system. Putative transgenic callus was obtained following two cycles of hygromycin selection. Expression of the transgene(s) in putative transgenic callus was analyzed using the GFP detection. Molecular identification of putative transformed shoots was performed by polymerase chain reaction and Southern blot analysis to confirm presence and integration of the hpt gene.
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Proteomic Analysis of Two Metabolic Proteins with Potential to Translocate to Plasma Membrane Associated with Tumor Metastasis Development and Drug Targets.
J. Proteome Res.
PUBLISHED: 03-14-2013
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Metastasis is the main cause for death of breast cancer patients. However, the underlying mechanism is still poorly understood. Plasma membrane (PM) proteins play a key role in various biological processes, especially for cell migration. In this study, we used a set of well-characterized mammary mouse cell lines, 67NR, 168FARN, 4T1, representing the metastatic progression, to study the differentially expressed membrane proteins. These proteins were analyzed by a linear ion trap tandem mass spectrometry (LTQ-MS/MS) following cell surface biotinylation and streptavidin purification. A total of 1667 membrane proteins were identified, out of which 472 were characterized as differentially expressed with at least 2-fold change and p-value < 0.01. Functional clustering of the 472 proteins revealed that 178 of them were metabolic proteins. Finally, we focused on two metabolic proteins, fatty acid synthase (FASN) and NAD(P)H steroid dehydrogenase-like protein (NSDHL), which were validated by Western blot and immunofluorescence. We found that FASN and NSDHL translocated to the plasma membrane from the intracellular compartment, and their expressions increased from 67NR to 4T1. This alteration of localization along with differential expressions might be necessary for metastasis development. Potentially, FASN and NSDHL could serve as drug targets in new antimetastasis therapy.
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miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma.
J. Exp. Med.
PUBLISHED: 03-11-2013
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MicroRNAs (miRNAs) play a critical role in tumor metastasis. In this study, we identified a set of 32 miRNAs involved in hepatocellular carcinoma (HCC) metastasis. Among them, miR-612 was shown for the first time to have inhibitory effects on HCC proliferation, migration, invasion, and metastasis. AKT2 was verified to be one of the direct targets of miR-612, through which the epithelial-mesenchymal transition (EMT) and metastasis were inhibited. The level of miR-612 in HCC patients was inversely associated with tumor size, stage, EMT, and metastasis. Of particular importance, miR-612 is involved in both the initial and final steps of the metastatic cascade, by suppressing local invasion and distant colonization. The pleiotropic roles of miR-612 in the HCC metastatic cascade suggest that it could be an effective target for both early and advanced HCC.
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The predictive value of anti-Mullerian hormone on embryo quality, blastocyst development, and pregnancy rate following in vitro fertilization-embryo transfer (IVF-ET).
J. Assist. Reprod. Genet.
PUBLISHED: 03-04-2013
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The objective of this study was to investigate the predictive value of anti-Mullerian hormone (AMH) on fertilization rate (FR), blastocyst development, embryo quality, the outcome of the pregnancy and the live birth rate (LBR) following in vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI).
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Androgen inhibits abdominal fat accumulation and negatively regulates the PCK1 gene in male chickens.
PLoS ONE
PUBLISHED: 02-16-2013
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Capons are male chickens whose testes have been surgically incised. Capons show a significant increase in fat accumulation compared to intact male chickens. However, while caponization leads to a significant reduction in androgen levels in roosters, little is known about the molecular mechanisms through which androgen status affects lipogenesis in avian species. Therefore, investigation of the influence of androgens on fat accumulation in the chicken will provide insights into this process. In this study, Affymetrix microarray technology was used to analyze the gene expression profiles of livers from capons and intact male chickens because the liver is the major site of lipogenesis in avian species. Through gene ontology, we found that genes involved in hepatic lipogenic biosynthesis were the most highly enriched. Interestingly, among the upregulated genes, the cytosolic form of the phosphoenolpyruvate carboxykinase (PCK1) gene showed the greatest fold change. Additionally, in conjunction with quantitative real-time PCR data, our results suggested that androgen status negatively regulated the PCK1 gene in male chickens.
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A stromal-free, serum-free system to expand ex vivo hematopoietic stem cells from mobilized peripheral blood of patients with hematologic malignancies and healthy donors.
Cytotherapy
PUBLISHED: 02-07-2013
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The number of hematopoietic stem cells (HSCs) is critical for transplantation. The ex vivo expansion of mobilized peripheral blood (MPB) HSCs is of clinical value for reconstitution to meet clinical need.
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Expression of curcin-transferrin receptor binding peptide fusion protein and its anti-tumor activity.
Protein Expr. Purif.
PUBLISHED: 01-28-2013
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Curcin can inhibit the proliferation of tumor cells and promote tumor cell apoptosis, but the cytotoxicity of curcin is not selective for tumors or normal cells. In order to enhance the targeting of the anti-tumor ability of curcin, a transferrin receptor (TfR) binding peptide, TfRBP9, was fused with curcin. The curcin-TfRBP9 gene was cloned into pQE-30 and the recombinant vector pQE-30-curcin-TfRBP9 was established. Then the recombinant vector pQE-30-curcin-TfRBP9 was transferred into Escherichia coli M15. After being induced by 0.5mM IPTG for 6h at 37°C, the expressed quantity of the recombinant protein was about 30% of the total protein. Recombinant curcin-TfRBP9 was expressed in the form of an inclusion body. After dissolution, purification and renaturation, the purity of the recombinant curcin-TfRBP9 reached 95%. Immunofluorescence analysis showed that the TfRBP9 significantly enhanced the ability of the curcin binding to HepG2, and was enriched in the cytoplasm. The curcin-TfRBP9 fusion protein had significant proliferation inhibition effects on the HepG2 cells that over-expressed transferrin receptors, had lower inhibitory effects on the SKBR-3 cells that expressed low transferrin receptors, and had the lowest inhibitory effects on the LO-2 cells that were normal human liver cells. Compared with curcin, the curcin-TfRBP9 induced higher apoptosis rates in the HepG2 cells.
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Morphological characteristics of split-depression fractures of the lateral tibial plateau (Schatzker type II): a computer-tomography-based study.
Int Orthop
PUBLISHED: 01-17-2013
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The objective of this study was to evaluate the morphological characteristics of lateral tibial plateau split-depression fractures (Schatzker type II).
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Protein arginine methyltransferase 1 interacts with and activates p38? to facilitate erythroid differentiation.
PLoS ONE
PUBLISHED: 01-14-2013
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Protein arginine methylation is emerging as a pivotal posttranslational modification involved in regulating various cellular processes; however, its role in erythropoiesis is still elusive. Erythropoiesis generates circulating red blood cells which are vital for body activity. Deficiency in erythroid differentiation causes anemia which compromises the quality of life. Despite extensive studies, the molecular events regulating erythropoiesis are not fully understood. This study showed that the increase in protein arginine methyltransferase 1 (PRMT1) levels, via transfection or protein transduction, significantly promoted erythroid differentiation in the bipotent human K562 cell line as well as in human primary hematopoietic progenitor CD34(+) cells. PRMT1 expression enhanced the production of hemoglobin and the erythroid surface marker glycophorin A, and also up-regulated several key transcription factors, GATA1, NF-E2 and EKLF, which are critical for lineage-specific differentiation. The shRNA-mediated knockdown of PRMT1 suppressed erythroid differentiation. The methyltransferase activity-deficient PRMT1G80R mutant failed to stimulate differentiation, indicating the requirement of arginine methylation of target proteins. Our results further showed that a specific isoform of p38 MAPK, p38?, promoted erythroid differentiation, whereas p38? did not play a role. The stimulation of erythroid differentiation by PRMT1 was diminished in p38?- but not p38?-knockdown cells. PRMT1 appeared to act upstream of p38?, since expression of p38? still promoted erythroid differentiation in PRMT1-knockdown cells, and expression of PRMT1 enhanced the activation of p38 MAPK. Importantly, we showed for the first time that PRMT1 was associated with p38? in cells by co-immunoprecipitation and that PRMT1 directly methylated p38? in in vitro methylation assays. Taken together, our findings unveil a link between PRMT1 and p38? in regulating the erythroid differentiation program and provide evidence suggesting a novel regulatory mechanism for p38? through arginine methylation.
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A novel compound derived from danshensu inhibits apoptosis via upregulation of heme oxygenase-1 expression in SH-SY5Y cells.
Biochim. Biophys. Acta
PUBLISHED: 01-08-2013
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Heme oxygenase-1 (HO-1) has potential anti-apoptotic properties. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2- ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)] was synthesized by joining danshensu and cysteine through an appropriate linker. This study investigated if the cytoprotective properties of DSC involved the induction of HO-1.
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A novel compound DSC suppresses lipopolysaccharide-induced inflammatory responses by inhibition of Akt/NF-?B signalling in macrophages.
Eur. J. Pharmacol.
PUBLISHED: 01-07-2013
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A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from Danshensu, exerted cytoprotective effects by anti-oxidative and anti-apoptotic activities in vitro. Herein, we reported the protective effects of DSC on lipopolysaccharide (LPS)-induced inflammatory responses in murine RAW264.7 macrophages and the underlying mechanisms. We showed that DSC concentration-dependently attenuated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression with less cytotoxicity. Signal transduction studies indicated that DSC significantly inhibited LPS-induced phosphorylation of Akt, but not c-Jun N-terminal kinase 1/2, p38, or extracellular signal-regulated kinase 1/2. Meanwhile, LPS-induced nuclear translocation of nuclear factor-?B (NF-?B) p65 was decreased by DSC. Furthermore, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 significantly suppressed LPS-induced NF-?B p65 nuclear translocation, iNOS expression, and NO production, which was also mimicked by pretreatment with DSC. These results suggested that DSC attenuated LPS-induced inflammatory response in macrophages, at least in part, through suppression of PI3K/Akt signaling and NF-?B activation.
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Cordycepin Regulates GSK-3?/?-Catenin Signaling in Human Leukemia Cells.
PLoS ONE
PUBLISHED: 01-01-2013
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Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/?-catenin pathway is required for the survival and development of LSCs. Therefore, targeting ?-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates ?-catenin expression in leukemia cells.
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[Evaluation of Clonorchis sinensis PPMP I antigen Cs2 recombinant protein for immunodiagnosis of clonorchiasis].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 10-06-2011
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To develop and preliminarily evaluate two immunodiagnostic methods for clonorchiasis using Clonorchis sinensis PPMP I antigen Cs2 recombinant protein (rCs2).
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Cyclosporine, prednisone, and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen.
Chin J Cancer
PUBLISHED: 10-01-2011
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Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis with no standard therapy. Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function. All patients were examined for response, toxicity and survival. The most significant toxicities (? grade 2) were infection (16.7%), renal insufficiency (8.3%), hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection. Treatment-related death was not observed. The overall response rate was 75.0% (complete response, 33.3%; partial response, 41.7%). With a median follow-up of 25.5 months, the median duration of response was 20 months (range, 12 to 49 months) and the median progression-free survival (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%. Our findings indicate the combination of CsA, PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.
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Lysophosphatidic acid induces erythropoiesis through activating lysophosphatidic acid receptor 3.
Stem Cells
PUBLISHED: 09-15-2011
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Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through activating G protein-coupled receptors. LPA receptor 3 (LPA(3)) is a member of the endothelial differentiation gene family, which regulates differentiation and development of the circulation system. However, the relationship among the LPA receptors (LPARs) and erythropoiesis is still not clear. In this study, we found that erythroblasts expressed both LPA(1) and LPA(3), and erythropoietic defects were observed in zLPA(3) antisense morpholino oligonucleotide-injected zebrafish embryos. In human model, our results showed that LPA enhanced the erythropoiesis in the cord blood-derived human hematopoietic stem cells (hHSCs) with erythropoietin (EPO) addition in the plasma-free culture. When hHSCs were treated with Ki16425, an antagonist of LPA(1) and LPA(3), erythropoietic process of hHSCs was also blocked, as detected by mRNA and protein expressions of CD71 and GlyA. In the knockdown study, we further demonstrated that specific knockdown of LPA(3), not LPA(1), blocked the erythropoiesis. The translocation of ?-catenin into the nucleus, a downstream response of LPAR activation, was blocked by Ki16425 treatment. In addition, upregulation of erythropoiesis by LPA was also blocked by quercetin, an inhibitor of the ?-catenin/T-cell factor pathway. Furthermore, the enhancement of LPA on erythropoiesis was diminished by blocking c-Jun-activated kinase/signal transducer and activator of transcription and phosphatidylinositol 3-kinase/AKT activation, the downstream signaling pathways of EPO receptor, suggested that LPA might play a synergistic role with EPO to regulate erythropoietic process. In conclusion, we first reported that LPA participates in EPO-dependent erythropoiesis through activating LPA(3).
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Discovery of IL-18 as a novel secreted protein contributing to doxorubicin resistance by comparative secretome analysis of MCF-7 and MCF-7/Dox.
PLoS ONE
PUBLISHED: 08-18-2011
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Resistance to chemotherapy is the major cause of failure in breast cancer treatment. Recent studies suggest that secreted proteins may play important roles in chemoresistance. We sought to systematically characterize secreted proteins associated with drug resistance, which may represent potential serum biomarkers or novel drug targets.
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[Pharmacokinetics of a fusion protein for human acidic fibroblast growth factor and transcriptional activator protein in rat and its penetration across blood-brain barrier].
Yao Xue Xue Bao
PUBLISHED: 06-28-2011
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This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimers disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.
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Lectin capture strategy for effective analysis of cell secretome.
Proteomics
PUBLISHED: 06-19-2011
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Secreted proteins play important roles in physiological and pathological processes. However, effective proteomic detection of low-abundant secreted proteins is often shielded by the presence of a large amount of intracellular proteins released from unavoidable dead cells during cell culture. In the present study, we applied lectin affinity capture approach to enrich the secreted proteins in the conditioned media (CM) of three human breast cell lines (MCF-10A, MCF-7, and MDA-MB-231). Lectin capture showed efficient enrichment of the secreted proteins in CM of all three cell lines and significantly increased the number of secreted proteins detected: from 183 to 292 for MCF-10A, 196 to 325 for MCF-7, and 194 to 368 for MDA-MB-231. Based on more comprehensive profiling of the secreted proteins, we identified 92 secreted proteins which were both upregulated in MCF-7 and MDA-MB-231, with 82 only found in lectin-captured samples. It should be noted that among these 82 potential biomarkers, 59 were not reported in the previous proteomic studies of breast cancer. These data indicate that the lectin capture approach is a powerful means to move toward more comprehensive analysis and comparison of secretomes.
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Activation of Src and transformation by an RPTP? splice mutant found in human tumours.
EMBO J.
PUBLISHED: 06-07-2011
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Receptor protein tyrosine phosphatase ? (RPTP?)-mediated Src activation is required for survival of tested human colon and oestrogen receptor-negative breast cancer cell lines. To explore whether mutated RPTP? participates in human carcinogenesis, we sequenced RPTP? cDNAs from five types of human tumours and found splice mutants in ?30% of colon, breast, and liver tumours. RPTP?245, a mutant expressed in all three tumour types, was studied further. Although it lacks any catalytic domain, RPTP?245 expression in the tumours correlated with Src tyrosine dephosphorylation, and its expression in rodent fibroblasts activated Src by a novel mechanism. This involved RPTP?245 binding to endogenous RPTP? (eRPTP?), which decreased eRPTP?-Grb2 binding and increased eRPTP? dephosphorylation of Src without increasing non-specific eRPTP? activity. RPTP?245-eRPTP? binding was blocked by Pro210 ? Leu/Pro211 ? Leu mutation, consistent with the involvement of the structural wedge that contributes to eRPTP? homodimerization. RPTP?245-induced fibroblast transformation was blocked by either Src or eRPTP? RNAi, indicating that this required the dephosphorylation of Src by eRPTP?. The transformed cells were tumourigenic in nude mice, suggesting that RPTP?245-induced activation of Src in the human tumours may have contributed to carcinogenesis.
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Association of hypoxia inducible factor-1? polymorphisms with susceptibility to non-small-cell lung cancer.
Transl Res
PUBLISHED: 05-05-2011
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Hypoxia-inducible factor-1? (HIF-1?) is a key regulator of cellular response to hypoxia and has been suggested to play an important role in tumorigenesis and metastasis. The aim of this study was to investigate the role of HIF-1?-1772 C/T (P582S) and -1790 G/A (A588T) polymorphisms in the susceptibility to and severity of non-small-cell lung cancer (NSCLC). Using a case-control study design and polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis, the allele frequencies and genotype distributions of each single nucleotide polymorphism in 285 NSCLC cases and 300 gender-matched controls were compared. The distribution of the genotype frequencies of HIF-1?-1772 C/T and -1790 G/A were significantly different between the NSCLC and the controls. Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were observed for individuals with HIF-1?-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1?-1790 A/A genotype against GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001). There were no relationship between HIF-1?-1772 C/T or -1790 G/A allele distribution and disease severity of NSCLC (P > 0.05). However, those patients carrying a HIF-1?-1772 T/T genotype or a HIF-1?-1790 A/A had a tendency toward inferior prognosis compared with other patients.
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Protective effects of early hypoxic post-conditioning in cultured cortical neurons.
Brain Inj
PUBLISHED: 05-04-2011
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Recent evidence suggests that delayed hypoxic post-conditioning is neuroprotective. The aim of the present study was to test whether early post-conditioning applied immediately after hypoxia could protect cultured neurons from hypoxia/reoxygenation (H/R)-induced injuries.
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[A method of obtaining vibrational dephasing time of molecular multi-vibrational modes simultaneously].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 04-23-2011
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In the present paper, the authors used the time-resolved coherent anti-Stokes Raman scattering (CARS) spectroscopy based on supercontinuum developed by ourselves to acquire simultaneously the molecular vibration spectrum and vibrational dephasing time of the molecular various vibrational modes. Using benzonitrile as the sample, the authors measured its vibrational relaxation processes at its five typical vibrational modes and obtained their vibrational dephasing time respectively. In the experiment, the authors also found the phenomenon that oscillations appear in the vibrational dephasing of plane bending vibration mode of benzene ring in benzonitrile, which was caused by superposition of the two adjacent normal vibrational modes excited simultaneously. After mixing benzonitrile with anhydrous ethanol, the authors also measured their vibrational dephasing time. This method is capable of monitoring the changes of the molecular characteristics and its micro-environment, therefore it will find widespread applications in biology, chemistry and materials science.
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Treatment of HCV patients before and after renal transplantation.
Hepat Mon
PUBLISHED: 04-11-2011
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Patients with end-stage renal disease can easily acquire a hepatitis C virus (HCV) infection via several ways. An HCV infection is difficult to treat after renal transplantation due to the conflicting actions of immunosuppressant therapy to maintain the function of the transplanted kidney and viricidal interferon (IFN) or ribavirin (RBV) treatment. Antiviral therapy requires great caution to avoid the complex and potentially fatal pharmacological effects. In this review, we examined clinical challenges and potential solutions for this specific scenario.
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LRRK2 Pro755Leu variant in ethnic Chinese population with Parkinsons disease.
Neurosci. Lett.
PUBLISHED: 03-02-2011
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Parkinsons disease (PD) is a common neurodegenerative disease resulting from complex interaction involving genetic and environmental risk factors on background of aging. In terms of genetic risk factors, recent studies provided a growing number of evidence for the idea that certain polymorphisms in familiar Parkinsonism genes may contribute to risk for sporadic PD in populations of specific ethnic backgrounds. To address this issue, a case-control study was conducted to determine the prevalence of LRRK2 Pro755Leu variant in 401 patients with sporadic PD and 398 unrelated healthy controls in Han population from mainland China. Heterozygous LRRK2 Pro755Leu variant was found in four patients and two healthy controls, but no statistical differences in genotypic or allelic frequencies between PD and control groups (genotype: P=0.686; allele: P=0.687) were detected. Furthermore, to evaluate its role in ethnic Chinese population, a meta-analysis was performed on Pro755Leu in population of Chinese ancestry throughout Asia. And it was detected at a similar frequency in PD and control cohort (Z=0.48, P=0.63, odds ratio=1.44, 95% CI: 0.32-6.40). Given these findings, it was quite reasonable to suppose that LRRK2 Pro755Leu variant rarely increased risk for PD in ethnic Chinese population in Asia.
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Association of genetic polymorphisms of CXCL12/SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer.
Lung Cancer
PUBLISHED: 02-02-2011
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The aim of this study was to evaluate the relations of chemokine CXCL12, previously known as stromal cell-derived factor-1 (SDF1), and its receptor, CXCR4, gene variants on non-small cell lung cancer (NSCLC) risk and disease severity.
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Identifying conserved DR1501-restricted CD4(+) T-cell epitopes in avian H5N1 hemagglutinin proteins.
Viral Immunol.
PUBLISHED: 12-15-2010
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Highly pathogenic avian influenza H5N1 viruses are capable of causing poultry epidemics and human mortality. Vaccines that induce protective neutralizing antibodies can prevent outbreaks and decrease the potential for influenza A pandemics. Identifying unique H5N1 virus-specific HLA class II-restricted epitopes is essential for monitoring cellular strain-specific immunity. Our results indicate that 80% of the 30 study participants who were inoculated with an H5N1 vaccine produced neutralizing antibodies. We used intracellular cytokine staining (ICS) to screen and identify six DR1501-restricted H5N1 virus epitopes: H5HA(148-162), H5HA(155-169), H5HA(253-267), H5HA(260-274), H5HA(267-281) and H5HA(309-323.) Tetramer staining results confirmed that two immunodominant epitopes were DR1501-restricted: H5HA(155-169) and H5HA(267-281). Both are located at the HA surface and are highly conserved in currently circulating H5N1 clades. These results suggest that a combination of ICS and tetramer staining can be used as a T-cell epitope-mapping platform, and the identified epitopes may serve as markers for monitoring vaccine efficacy.
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Evaluation of serum autoantibody levels in the diagnosis of ovarian endometrioma.
J. Clin. Lab. Anal.
PUBLISHED: 09-28-2010
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We analyzed autoantibodies against tumor-associated antigens (TAAs) in the serum of patients with endometrioma and healthy controls to determine whether autoantibodies can be accurate biomarkers for the diagnosis of ovarian endometrioma.
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Enterovirus 71 infection of monocytes with antibody-dependent enhancement.
Clin. Vaccine Immunol.
PUBLISHED: 08-04-2010
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Enterovirus (EV) is an RNA virus that has circulated with different serotypes and genotypes worldwide. Enterovirus 71 (EV71) is a major neurotropic virus that causes severe brain stem encephalitis (BE) in infants and young children. The most vulnerable age for fatal infection is 6 to 11 months. This is associated with the coincident decline in maternal antibodies. The current report describes our finding that EV71 can infect human peripheral blood monocytes. We were able to show that EV71 infection is enhanced in the monocytic cell line THP-1 by the presence of subneutralizing concentrations of anti-EV71 antibodies. We also found that antibody-dependent enhancement (ADE) is mediated in part by Fc? receptors. These observations support the concept that ADE augments the infectivity of EV71 for human monocytes and contributes to the age-dependent pathogenesis of EV71-induced disease. The ADE phenomenon must be considered during the development of an EV71 vaccine.
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Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold.
Cytotechnology
PUBLISHED: 06-29-2010
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The feasibility of using genipin cross-linked type II collagen scaffold with rabbit bone marrow mesenchymal stem cells (RBMSCs) to repair cartilage defect was herein studied. Induction of RBMSCs into chondrocytic phenotype on type II collagen scaffold in vitro was conducted using TGF-? 3 containing medium. After 3-weeks of induction, chondrocytic behavior, including marker genes expression and specific extracellular matrix (ECM) secretion, was observed. In the in vivo evaluation experiment, the scaffolds containing RBMSCs without prior induction were autologous implanted into the articular cartilage defects made by subchondral drilling. The repairing ability was evaluated. After 2 months, chondrocyte-like cells with lacuna structure and corresponding ECM were found in the repaired sites without apparent inflammation. After 24 weeks, we could easily find cartilage structure the same with normal cartilage in the repair site. In conclusion, it was shown that the scaffolds in combination of in vivo conditions can induce RBMSCs into chondrocytes in repaired area and would be a possible method for articular cartilage repair in clinic and cartilage tissue engineering.
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PtSVP, an SVP homolog from trifoliate orange (Poncirus trifoliata L. Raf.), shows seasonal periodicity of meristem determination and affects flower development in transgenic Arabidopsis and tobacco plants.
Plant Mol. Biol.
PUBLISHED: 06-21-2010
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A MADS-box gene was isolated using the suppressive subtractive hybridization library between early-flowering mutant and wild-type trifoliate orange (Poncirus trifoliata L. Raf.). This gene is highly homologous with Arabidopsis SHORT VEGETATIVE PHASE (SVP). Based on real-time PCR and in situ hybridization during bud differentiation, PtSVP was expressed intensively in dormant tissue and vegetative meristems. PtSVP transcripts were detected in apical meristems before floral transition, then down-regulated during the transition. PtSVP expression was higher in differentiated (flower primordium) than in undifferentiated cells (apical meristems). The PtSVP expression pattern during apical meristem determination suggested that its function is not to depress flower initiation but to maintain meristem development. Transcription of PtSVP in Arabidopsis svp-41 showed partially rescued SVP function. Ectopic overexpression of PtSVP in wild-type Arabidopsis induced late flowering similar to the phenotypes induced by other SVP/StMADS-11-like genes, but transformants produced additional trichomes and floral defects, such as flower-like structures instead of carpels. Ectopic expression of PtSVP in tobacco also caused additional florets. Overexpression of PtSVP in tobacco inhibited early transition of the coflorescence and prolonged coflorescence development, thus causing additional florets at the later stage. A yeast two-hybrid assay indicated that PtSVP significantly interacted with PtAP1, a homolog of Arabidopsis APETALA1 (AP1). These findings suggest that citrus SVP homolog genes are involved in flowering time regulation and may influence inflorescence meristem identity in some conditions or genetic backgrounds. SVP homologs might have evolved among plant species, but the protein functions are conserved between Arabidopsis and citrus.
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Association of polymorphisms in the genes of the urokinase plasminogen activation system with susceptibility to and severity of non-small cell lung cancer.
Clin. Chim. Acta
PUBLISHED: 06-20-2010
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Urokinase plasminogen activating (uPA) system is implicated in neoplastic progression. High tissue levels of uPA system components correlate with a poor prognosis in lung cancer. The present study examined the single nucleotide polymorphisms (SNPs) of uPA and the corresponding receptor, uPAR, for exploring their roles in non-small cell lung cancer (NSCLC).
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Compare the effects of chondrogenesis by culture of human mesenchymal stem cells with various type of the chondroitin sulfate C.
J. Biosci. Bioeng.
PUBLISHED: 05-24-2010
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Chondroitin sulfate C (CSC) is a kind of glycosaminoglycans (GAGs) with molecular weights of 10,000 to 50,000 Da and a high charge density. GAGs are major components in extracellular matrix (ECM), which play important role in the regulation of cell proliferation, migration, and differentiation. In this study, we studied the effects of chondroitin sulfate C (CSC) on the differentiation of human mesenchymal stem cells (MSCs) toward the chondrocyte lineage. The MSCs were either cultured on type II collagen (COL II) scaffolds with high molecular weight CSC addition in the medium (free CSC) or with free oligosaccharide CSC. Special attention was given to the effects of MSCs cultured on CSC cross-linked type II scaffolds (cross-linked CSC). According to the analysis of histology stain, gene expression, and ECM secretion, our results showed that MSCs cultured with free CSC, free oligosaccharides CSC, and on the cross-linked CSC scaffolds all would be induced into chondrocytes. Moreover, free oligosaccharide CSC present in the microenvironment could significantly up-regulate MSC chondrogenesis gene expression and stimulate cartilage ECM accumulation more than free CSC with high molecular weight after 3-week induction. Importantly, cross-linked CSC had the most excellent effects on the MSC chondrogenesis. Thus, we believed that cross-linked CSC in the scaffold would play the similar roles with free oligosaccharide CSC in the medium. Cross-linked CSC would be a potential candidate for cartilage repair in the cell therapy and tissue engineering.
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Detection of swine-origin influenza A (H1N1) viruses using a localized surface plasmon coupled fluorescence fiber-optic biosensor.
Biosens Bioelectron
PUBLISHED: 05-18-2010
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Swine-origin influenza A (H1N1) virus (S-OIV) was identified as a new reassortant strain of influenza A virus in April 2009 and led to an influenza pandemic. Accurate and timely diagnoses are crucial for the control of influenza disease. We developed a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB) which combines a sandwich immunoassay with the LSP technique using antibodies against the hemagglutinin (HA) proteins of S-OIVs. The detection limit of the LSPCF-FOB for recombinant S-OIV H1 protein detection was estimated at 13.9 pg/mL, which is 10(3)-fold better than that of conventional capture ELISA when using the same capture antibodies. For clinical S-OIV isolates measurement, meanwhile, the detection limit of the LSPCF-FOB platform was calculated to be 8.25 × 10(4)copies/mL, compared with 2.06 × 10(6)copies/mL using conventional capture ELISA. Furthermore, in comparison with the influenza A/B rapid test, the detection limit of the LSPCF-FOB for S-OIV was almost 50-fold in PBS solution and 25-fold lower in mimic solution, which used nasal mucosa from healthy donors as the diluent. The findings of this study therefore indicate that the high detection sensitivity and specificity of the LSPCF-FOB make it a potentially effective diagnostic tool for clinical S-OIV infection and this technique has the potential to be applied to the development of other clinical microbe detection platforms.
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[Effects of multi-genes for reproductive traits in Tibet pig].
Yi Chuan
PUBLISHED: 05-15-2010
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Tibet pig is a unique native breed in the plateau of China, which has good adaptation to the harsh climate of high land and resistance to diseases and crude feeding. However, its reproductive rate is low. The objectives of this study were to search for the polymorphisms of estrogen receptor (ESR), follicle-stimulating hormone (FSHb), prolactin receptor (PRLR), and retinol binding protein 4 (RBP4) in Tibet pig and to analyze the effects of these variants and their combination genotypes on reproductive traits. The results showed that the effects of FSHb, ESR, and PRLR genes were significant in the Tibet pig population, and the effective genotypes of the three genes for reproductive traits were BB, BB, and AA, respectively. There were two genotypes for RBP4 gene in Tibet pig, which did not have significant effect on the reproductive traits. The optical genotype of FSHb-ESR-PRLR is BB-BB-AA, which is more effective on reproductive traits than any single gene in Tibet pig.
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[Predictors of peri-operative mortality in patients with aortic dissection].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-09-2010
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To analyze the peri-operative risk factors of mortality in patients with aortic dissection (AD).
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Protein-arginine methyltransferase 1 suppresses megakaryocytic differentiation via modulation of the p38 MAPK pathway in K562 cells.
J. Biol. Chem.
PUBLISHED: 05-04-2010
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Protein-arginine methyltransferase 1 (PRMT1) plays pivotal roles in various cellular processes. However, its role in megakaryocytic differentiation has yet to be investigated. Human leukemia K562 cells have been used as a model to study hematopoietic differentiation. In this study, we report that ectopic expression of HA-PRMT1 in K562 cells suppressed phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation as demonstrated by changes in cytological characteristics, adhesive properties, and CD41 expression, whereas knockdown of PRMT1 by small interference RNA promoted differentiation. Impairment of the methyltransferase activity of PRMT1 diminished the suppressive effect. These results provide evidence for a novel role of PRMT1 in negative regulation of megakaryocytic differentiation. Activation of ERK MAPK has been shown to be essential for megakaryocytic differentiation, although the role of p38 MAPK is still poorly understood. We show that knockdown of p38alpha MAPK or treatment with the p38 inhibitor SB203580 significantly enhanced PMA-induced megakaryocytic differentiation. Further investigation revealed that PRMT1 promotes activation of p38 MAPK without inhibiting activation of ERK MAPK. In p38alpha knockdown cells, PRMT1 could no longer suppress differentiation. In contrast, enforced expression of p38alpha MAPK suppressed PMA-induced megakaryocytic differentiation of parental K562 as well as PRMT1-knockdown cells. We propose modulation of the p38 MAPK pathway by PRMT1 as a novel mechanism regulating megakaryocytic differentiation. This study thus provides a new perspective on the promotion of megakaryopoiesis.
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Screening for two SNPs of LINGO1 gene in patients with essential tremor or sporadic Parkinsons disease in Chinese population.
Neurosci. Lett.
PUBLISHED: 03-23-2010
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Two markers rs9652490 and rs11856808 both located in intron 3 of the LINGO1 gene have been nominated recently to be associated with essential tremor (ET). Although ET and Parkinsons disease (PD) are considered as different entities, they have many overlapping clinical and pathological features. We aimed to evaluate the role of rs9652490 and rs11856808 in the development of ET and PD. To this point, we sequenced the region involving the two markers in 109 ET cases, 425 sporadic Parkinsons disease (SPD) cases and 430 controls in Chinese population. After stratification by age, the rs9652490G allele suggested protective role in the early onset PD (EOPD, age at onset < or =50 years) group compared with age matched controls (OR=0.56, 95% CI: 0.35-0.90, p=0.015). No other significant association was found. We concluded that the two markers rs9652490 and rs11856808 were not strongly related to the development of ET or late onset SPD, but the rs9652490G allele might be a protective factor for EOPD in Chinese population.
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Childhood incident asthma and traffic-related air pollution at home and school.
Environ. Health Perspect.
PUBLISHED: 03-22-2010
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Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma.
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Establishment of immortalized mesenchymal stromal cells with red fluorescence protein expression for in vivo transplantation and tracing in the rat model with traumatic brain injury.
Cytotherapy
PUBLISHED: 03-17-2010
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Human mesenchymal stromal cells (hMSC) play a crucial role in tissue engineering and regenerative medicine, and have important clinical potential for cell therapy. However, many hMSC studies have been restricted by limited cell numbers and difficult detection in vivo. To expand the lifespan, hMSC are usually immortalized by virus-mediated gene transfer. However, these genetically modified cells easily lose critical phenotypes and stable genotypes because of insertional mutagenesis.
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Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3beta-dependent opening of mPTP.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 02-12-2010
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Hydrogen sulfide (H(2)S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H(2)S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 mumol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3beta at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3beta (Ser9) at a dose of 30 mumol/kg. In conclusion, the H(2)S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3beta (Ser9) and subsequent inhibition of mPTP opening.
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Glucocerebrosidase gene L444P mutation is a risk factor for Parkinsons disease in Chinese population.
Mov. Disord.
PUBLISHED: 02-05-2010
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An association between mutations in the glucocerebrosidase (GBA) gene and Parkinsons disease (PD) has been reported in several populations. We searched for four common GBA mutations (L444P, F213I, R353W, and N370S) in 402 Chinese PD patients and 413 age- and sex-matched controls. In the PD cohort, 11 patients were found carrying a heterozygous GBA mutation and all of them had the L444P mutation. Heterozygous GBA mutations were detected none in controls. The GBA gene L444P mutation was detected at a significantly higher frequency among PD patients (11/402 = 2.74%), when compared with the control group (0/413): P = 0.0007. To evaluate the possible role of the GBA gene L444P mutation in PD in Ashkenazi Jewish and non-Jewish populations, we conducted a meta-analysis on the topic. In the Chinese population, the GBA gene L444P mutation was detected at a significantly higher frequency among PD patients, when compared with the control group: Z = 3.83, P = 0.0001, OR = 8.42, confidence interval = 95%, 2.83-25.06. In the non-Jewish populations, the difference was obviously significant: Z = 5.76, P < 0.00001, OR = 8.82, confidence interval = 95%, 4.21-18.48. The results suggest that the GBA gene L444P mutation appears to be a risk factor for PD in Chinese population.
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Expression and ultrastructural localization of Mint2 in the spinal cord of rats.
Mol. Biol. Rep.
PUBLISHED: 01-22-2010
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Mint protein family, as adaptor molecules, contains three members, Mint1, Mint2 and Mint3. Although Mint3 is ubiquitously expressed, Mint1 and Mint2 have been reported to express specifically in neuron. Here we demonstrated Mint1 and Mint2 expression pattern in rat spinal cord. The protein level of Mint2 was found to be higher than that of Mint1 in rat spinal by western blot. In an attempt to know Mint2 distribution in the spinal cord of rat, in situ hybridization was carried out, Mint2 mRNA was showed to be ubiquitously distributed in cervical, thoracic and lumbar sections of rat spinal cord, and high intensive signal was detected in motor neurons. These were further confirmed by fluorescent immunohistochemistry, Mint2 was also found to exist throughout gray matter especially motor neurons where Mint2 was mainly located in perikaryon, however, Mint1 was showed to be relatively lower. By electron microscope, Mint2 was found to be mainly located in vesicles in perikaryon in motor neuron of lumbar section, and at the same time Mint2 was located in axons in myelin and presynaptic terminals. These data suggest that Mint2 may play more important role in spinal cord than the other two family members.
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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.