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Find video protocols related to scientific articles indexed in Pubmed.
8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations.
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[Reponses of soil total organic carbon and dissolved organic carbon to simulated nitrogen deposition in temperate typical steppe in Inner Mongolia, China].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Based on a field manipulative nitrogen (N) addition experiment, the effects of atmospheric N deposition level change on the contents, inter-annual variation and profile distribution of soil total organic carbon (TOC) and dissolved organic carbon (DOC) were investigated from May, 2008 to October, 2011 in a temperate typical steppe in Inner Mongolia of China, and the relationship between TOC and DOC was also discussed. The treatments in the manipulative experiment included N additions at rates of 0, 5, 10, and 20 g x (m2 x a)(-1), representing the control (CK), low N (LN), medium N (MN), and high N (HN) treatment, respectively. The results indicated that the concentrations of soil TOC and DOC decreased progressively with soil depth in all cases except for the DOC at 10-20 cm depth in individual years. The increase of N input in typical steppe did not change the vertical distribution of soil TOC and DOC, but reduced the vertical variation of TOC and increased the vertical variation of DOC in the surface soil horizon. In addition, the contents of soil TOC and DOC at 0- 10 cm and 10- 20 cm soil layers changed insignificantly after the continuous increase in anthropogenic N input for four years. The soil organic C density of 0-20 cm soil layer for different N treatment levels varied between 3.9 kg x m(-2) and 5.6 kg x m(-2), and the soil organic C densities of fertilized treatments in the first two years were similar to or slightly lower than those of CK, while in the following two years, the increase in N deposition gradually played a positive role in increasing soil organic C density, but the differences in soil TOC and DOC contents between CK and fertilized plots were not significant (P > 0.05). The ratio of soil DOC to TOC (DOC/TOC) varied from 0.32% to 1.09%. The increase in N deposition generally lowered the proportion of DOC in soil TOC, which was conducive to the accumulation of soil organic C. The change of soil DOC was positively correlated with that of TOC (P < 0.01). The temporal variations of soil DOC in different N treatments were all far greater than those of TOC, and the soil DOC was the important sensitive indicator for predicting and evaluating the response of soil C pool to the change in atmospheric N deposition in the temperate grassland ecosystem.
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Nickel exposure is associated with the prevalence of type 2 diabetes in Chinese adults.
Int J Epidemiol
PUBLISHED: 10-18-2014
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Nickel exposure can induce hyperglycaemia in rodents, but little is known about its association with abnormal glucose metabolism in humans. We aimed to investigate the association of nickel exposure with the prevalence of type 2 diabetes in Chinese adults.
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Association of HTR2A T102C and A-1438G polymorphisms with susceptibility to major depressive disorder: a meta-analysis.
Neurol. Sci.
PUBLISHED: 09-24-2014
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Serotonin 2A receptor (HTR2A) gene was implicated to be associated with major depressive disorder (MDD) susceptibility due to its role of key neurotransmitter in many physiologic processes. A great number of related studies reported in different populations have emerged. The results of these studies, however, have been inconsistent and thereby definite conclusions are difficult to establish. With the cumulative data in recent years, it was necessary to carry out a comprehensive analysis of previous findings. Electronic databases were systematically searched for studies published before May 2013. Pooled odds ratios (OR) and 95 % confidence interval (CI) were estimated under three different genetic models. Subgroup and sensitivity analyses were also performed. A total of 21 studies, 3,299 patients and 4,092 controls, met the selection criteria. 15 studies included HTR2A T102C polymorphism (with a total of 2,409 patients and 3,130 controls), and 9 studies included HTR2A A-1438G polymorphism (with a total of 1,510 patients and 2,281 controls). Our results showed that no significant association of MDD susceptibility with T102C polymorphism was found in allelic analysis and genotypic analysis (For T vs. C: OR = 1.06, 95 % CI = 0.95-1.18, P = 0.307; For TT + TC vs. CC: OR = 1.07, 95 % CI = 0.90-1.28, P = 0.451; For TT vs. TC + CC: OR = 1.08, 95 % CI = 0.95-1.22, P = 0.235). With respect to A-1438G polymorphism, however, carriers with A allele tend to suffer from MDD (AA + AG vs. GG: OR = 1.20, 95 % CI = 1.02-1.43, P = 0.030). When stratified by race for T102C polymorphism and A-1438G polymorphism of the HTR2A, we found no significant association. In conclusions, our study suggests that the A allele of A-1438G polymorphism might play a role in susceptibility to MDD. On the contrary, T102C polymorphism does not seem to be capable of modifying MDD risk.
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Unveiling equal importance of two 14-3-3 proteins for morphogenesis, conidiation, stress tolerance and virulence of an insect pathogen.
Environ. Microbiol.
PUBLISHED: 09-11-2014
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Two conserved 14-3-3 proteins orthologous to Saccharomyces cerevisiae Bmh1/2 are poorly understood in filamentous fungi. Here we show that Bmh1 and Bmh2 contribute equally to the fundamental biology and physiology of Beauveria bassiana by targeting many sets of proteins/enzymes. Single Bmh deletion caused similar upregulation of another. Excellent knockdown (?91%) expressions of Bmh1 in ?Bmh2 and Bmh2 in ?Bmh1 resulted in equally more severe multi-phenotypic defects than the single deletions, including G2 /M transition, blastospore size, carbon/nitrogen utilization, conidiation, germination, and conidial tolerances to high osmolarity, oxidation, cell wall stress, high temperature and UV-B irradiation. All the deletion and deletion/knockdown mutants showed similar defects in blastospore yield and density, hyphal septation and cell size, hyphal responses to most chemical stresses, and virulence. All the defects were evident with altered transcripts of phenotype-related genes and well restored by each Bmh complementation. Our Bmh1- and Bmh2-specific transcriptomes generated under osmotic and oxidative stresses revealed up to 6% genes differentially expressed by at least twofold in the fungal genome. Many of those were greatly depressed or co-depressed in ?Bmh1 and ?Bmh2. Our findings provide a thorough insight into the functions and complementary effects of the two 14-3-3 proteins in the filamentous entomopathogen.
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Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.
PLoS ONE
PUBLISHED: 08-29-2014
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To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.
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An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits.
Acta Biomater
PUBLISHED: 08-27-2014
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Inflammatory factor overexpression is the major cause of cartilage and osteochondral damage. Resveratrol (Res) is known for its anti-inflammatory, antioxidant and immunmodulatory properties. However, these effects are hampered by its water insolubility and rapid metabolism in vivo. To optimize its therapeutic efficacy in this study, Res was grafted to polyacrylic acid (PAA, 1000Da) to obtain a macromolecular drug, PAA-Res, which was then incorporated into atelocollagen (Coll) hydrogels to fabricate anti-inflammatory cell-free (Coll/Res) scaffolds with improved mechanical strengths. The Coll/Res scaffolds demonstrated the ability to capture diphenylpicrylhydrazyl free radicals. Both pure Coll and Coll/Res scaffolds could maintain their original shape for 6weeks in phosphate buffered saline. The scaffolds were degraded by collagenase over several days, and the degradation rate was slowed down by Res loading. The Coll and Coll/Res scaffolds with excellent cytocompatibility were shown to promote the proliferation and maintain the normal phenotype of the seeded chondrocytes and bone marrow stromal stem cells (BMSCs). In addition, the Coll/Res scaffold exhibited the capacity to protect the chondrocytes and BMSCs against reactive oxygen species. The acellular Coll/Res scaffolds were transplanted into the rabbit osteochondral defects. After implantation for 2, 4 and 6weeks, the samples were retrieved for quantitative real-time polymerase chain reaction, and the inflammatory related genes interleukin-1?, matrix metalloproteinases-13, COX-2 and bone and cartilage related genes SOX-9, aggrecan, Coll II and Coll I were determined. Compared with the untreated defects, the inflammatory related genes were down-regulated and those bone and cartilage related genes were up-regulated by filling the defect with an anti-inflammatory scaffold. After 12weeks, the osteochondral defects were completely repaired by the Coll/Res scaffold, and the neo-cartilage integrated well with its surrounding tissue and subchondral bone. Immunohistochemical and glycosaminoglycan staining confirmed the distribution of Coll II and glycosaminoglycans in the regenerated cartilage. The anti-inflammatory acellular Coll/Res scaffolds are convenient to administer in vivo, holding a greater potential for future clinical applications.
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Analysis of murine B-cell epitopes on bluetongue virus 12 nonstructural protein 1.
Appl. Microbiol. Biotechnol.
PUBLISHED: 08-22-2014
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The bluetongue virus (BTV) NS1 protein is one of the major proteins synthesized during BTV infection and is responsible for the generation of virus-specific tubules. Although some functional and structural studies on the BTV NS1 protein have been reported, there have been no reports describing the linear B-cell epitopes recognized by humoral immune responses published to date. In this study, 25 BTV12 NS1-reactive monoclonal antibodies (MAbs) and polyclonal antisera (polyclonal antibodies, PAbs) were generated and analyzed. We identified 14 linear NS1 epitopes recognized by the PAbs and MAbs using NS1-derived peptides in an enzyme-linked immunosorbent assay. Moreover, we predicted 23 linear B-cell epitopes using the ABCpred online server which employs an artificial neural network. Analysis of the predicted and identified epitopes of NS1 demonstrated the feasibility of B-cell epitope prediction. Sequence alignments indicated that the epitopes recognized by MAbs are highly conserved among BTV serotypes, but not among the other members of the genus Orbivirus, such as the African horse sickness virus (AHSV), epizootic hemorrhagic disease virus (EHDV), and Chuzan disease virus (CV). Importantly, we identified specific MAbs that recognized all BTV serotypes tested as well as MAbs that recognized only BTV12, suggesting that these NS1-specific MAbs could serve as a basis for BTV diagnostic approaches. The generation and identification of NS1 protein epitopes will provide the foundation for further studies about the function and structure of NS1 and novel epitope-based vaccines.
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Expression and roles of syndecan-4 in dental epithelial cell differentiation.
Int. J. Mol. Med.
PUBLISHED: 08-19-2014
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Syndecan-4 (SDC4), a transmembrane heparan sulfate proteoglycan, acts as a signal transducer. It affects the growth and differentiation of a number of tissues and organs. However, the specific mechanisms through which SDC4 regulates the differentiation of dental epithelial cells (amelogenesis) and tooth development remains largely unknown. In the present study, to identify the SDC4-regulated processes in dental epithelial cells, the SDC4 expression pattern was examined in mouse molar and postnatal incisor tooth germs during the late bell stage of development. Small interfering RNA (siRNA) was designed for this study and used to downregulate SDC4 expression in the rat dental epithelial cell line, HAT-7. The results revealed that SDC4 was mainly present in the oral epithelium, the dental epithelial cells of enamel organs in the molars and the cervical loops in the incisors. When the inner enamel epithelial cells gave rise to ameloblasts, however, the loss of SDC4 expression was evident. SDC4 was also expressed in stratum intermedium (SI) cells in the incisors and in dental mesenchymal cells adjacent to the cervical loops in molars (E18) and postnatal incisors. Fibroblast growth factor 10 (FGF10) promoted proliferation and slightly decreased cell differentiation. The knockdown of SDC4 using specific siRNA led to a decrease in cell proliferation and a highly significant increase in amelogenin, ameloblastin, kallikrein 4 and matrix metalloproteinase 20 expression, molecules that are known to participate in the formation of enamel. These effects were attenuated by FGF10, which upregulated SDC4 expression. Taken together, these results suggest that SDC4 participates in amelogenesis, and FGF10 may modulate dental epithelial cell behaviors through the regulation of SDC4 expression.
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Label-free quantitative proteomic analysis reveals potential biomarkers and pathways in renal cell carcinoma.
Tumour Biol.
PUBLISHED: 08-12-2014
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Renal cell carcinoma (RCC) is one of the most common malignancies in adults, and there is still no acknowledged biomarker for its diagnosis, prognosis, recurrence monitoring, and treatment stratification. Besides, little is known about the post-translational modification (PTM) of proteins in RCC. Here, we performed quantitative proteomic analysis on 12 matched pairs of clear cell RCC (ccRCC) and adjacent kidney tissues using liquid chromatography-tandem mass spectrometry (nanoLCMS/MS) and Progenesis LC-MS software (label-free) to identify and quantify the dysregulated proteins. A total of 1872 and 1927 proteins were identified in ccRCC and adjacent kidney tissues, respectively. Among these proteins, 1037 proteins were quantified by Progenesis LC-MS, and 213 proteins were identified as dysregulated proteins between ccRCC and adjacent tissues. Pathway analysis using IPA, STRING, and David tools was performed, which demonstrated the enrichment of cancer-related signaling pathways and biological processes such as mitochondrial dysfunction, metabolic pathway, cell death, and acetylation. Dysregulation of two mitochondrial proteins, acetyl-CoA acetyltransferase 1 (ACAT1) and manganese superoxide dismutase (MnSOD) were selected and confirmed by Western blotting and immunohistochemistry assays using another 6 pairs of ccRCC and adjacent tissues. Further mass spectrometry analysis indicated that both ACAT1 and MnSOD had characterized acetylation at lysine residues, which is the first time to identify acetylation of ACAT1 and MnSOD in ccRCC. Collectively, these data revealed a number of dysregulated proteins and signaling pathways by label-free quantitative proteomic approach in RCC, which shed light on potential diagnostic or prognostic biomarkers and therapeutic molecular targets for clinical intervention of RCC.
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Inner ear stem cells derived feeder layer promote directional differentiation of amniotic fluid stem cells into functional neurons.
Hear. Res.
PUBLISHED: 08-11-2014
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Intact spiral ganglion neurons are required for cochlear implantation or conventional hearing amplification as an intervention for sensorineural hearing loss. Treatment strategies to replace the loss of spiral ganglion neurons are needed. Recent reports have suggested that amniotic fluid-derived stem cells are capable of differentiating into neuron-like cells in response to cytokines and are not tumorigenic. Amniotic fluid stem cells represent a potential resource for cellular therapy of neural deafness due to spiral ganglion pathology. However, the directional differentiation of amniotic fluid stem cells is undetermined in the absence of cytokines and the consequence of inner ear supporting cells from the mouse cochlea organ of Corti on the differentiation of amniotic fluid stem cells remains to be defined. In an effort to circumvent these limitations, we investigated the effect of inner ear stem cells derived feeder layer on amniotic fluid stem cells differentiation in vitro. An inner ear stem cells derived feeder layer direct contact system was established to induce differentiation of amniotic fluid stem cells. Our results showed that inner ear stem cells derived feeder layer successfully promoted directional differentiation of amniotic fluid stem cells into neurons with characteristics of functionality. Furthermore, we showed that Wnt signaling may play an essential role in triggering neurogenesis. These findings indicate the potential use of inner ear stem cells derived feeder layer as a nerve-regenerative scaffold. A reliable and effective amniotic fluid stem cell differentiation support structure provided by inner ear stem cells derived feeder layer should contribute to efforts to translate cell-based strategies to the clinic.
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The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.
Cell Reprogram
PUBLISHED: 07-29-2014
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Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
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De novo approach to classify protein-coding and noncoding transcripts based on sequence composition.
Methods Mol. Biol.
PUBLISHED: 07-25-2014
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Each day, more and more transcripts are being discovered along the genome (especially in poorly annotated species) thanks to the rapid progress of high-throughput technology such as RNA sequencing. However, this situation unravels the challenge of how to classify the newly identified transcripts into protein coding or noncoding. Here, we describe a de novo approach named coding-noncoding index (CNCI), a powerful signature tool by profiling adjoining nucleotide triplets (ANT) to effectively distinguish between protein-coding and noncoding sequences independently of known annotations. The main advantage of CNCI is its ability to accurately classify transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, which allowed it to be used for all vertebrates and invertebrates based on the training data of well-annotated species (such as human and Arabidopsis). In this chapter, we illustrate the CNCI method in detail through an example of RNA-sequencing data generated from six biological replicates of six mouse tissues. CNCI software is available at http://www.bioinfo.org/software/cnci.
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[Fermentation transformed ginsenoside by Lactobacillus plantarum].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-22-2014
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To explore ginseng fermentation process by Lactobacillus plantarum, and to make part of total saponins transformed into more reactive ginsenoside Rd.
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Relationship of Serum Heart-Type Fatty Acid-Binding Protein Levels and Cerebral Infarction: a Meta-analysis.
Mol. Neurobiol.
PUBLISHED: 06-20-2014
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Clinical scores are recommended for predicting cardiovascular and cerebrovascular risk in patients with cerebral infarction to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores, and we conducted this analysis for the purpose of interpreting the association between serum H-FABP levels and cerebral infarction. Potential relevant studies were identified covering PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM and CNKI databases. Two reviewers extracted data and assessed studies independently. Statistical analyses were conducted with the version 12.0 Stata statistical software. A total of 9 case-control papers that evaluated the correlation of serum H-FABP levels with cerebral infarction, including 1,176 subjects (patients?=?662, healthy controls?=?514) were reviewed. Positive association was detected between serum H-FABP levels and cerebral infarction (SMD?=?1.70, 95 %CI: 1.13-2.27, P?
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Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma.
BMC Cancer
PUBLISHED: 06-16-2014
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Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC.
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Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury.
Stem Cells Dev.
PUBLISHED: 06-16-2014
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Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase-polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.
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[Screening of variation in the promoter of PPARGC1A gene and study of its association with the risk of type 2 diabetes in ethnic Hans from Beijing].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-15-2014
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To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).
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rs10505474 and rs7837328 at 8q24 cumulatively confer risk of prostate cancer in Northern Han Chinese.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-13-2014
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Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese.
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Voxel model of individual cells and its implementation in microdosimetric calculations using GEANT4.
Radiat Environ Biophys
PUBLISHED: 05-11-2014
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Accurate dosimetric calculations at cellular and sub-cellular levels are crucial to obtain an increased understanding of the interactions of ionizing radiation with a cell and its nucleus and cytoplasm. Ion microbeams provide a superior opportunity to irradiate small biological samples, e.g., DNA, cells, and to compare their response to computer simulations. However, the phantoms used to simulate small biological samples at cellular levels are often simplified as simple volumes filled with water. As a first step to improve the situation in comparing measurements of cell response to ionizing radiation with model calculations, a realistic voxel model of a KB cell was constructed and used together with an already constructed geometry and tracking 4 (GEANT4) model of the horizontal microbeam line of the Centre d'Etudes Nucléaires de Bordeaux-Gradignan (CENBG) 3.5 MV Van de Graaf accelerator at the CENBG, France. The microbeam model was then implemented into GEANT4 for simulations of the average number of particles hitting an irradiated cell when a specified number of particles are produced in the beam line. The result shows that when irradiating the developed voxel model of a KB cell with 200 ? particles, with a nominal energy of 3 MeV in the beam line and 2.34 MeV at the cell entrance, 100 particles hit the cell on average. The mean specific energy is 0.209 ± 0.019 Gy in the nucleus and 0.044 ± 0.001 Gy in the cytoplasm. These results are in agreement with previously published data, which indicates that this model could act as a reference model for dosimetric calculations of radiobiological experiments, and that the proposed method could be applied to build a cell model database.
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Heat shock protein 70 from Trichinella spiralis induces protective immunity in BALB/c mice by activating dendritic cells.
Vaccine
PUBLISHED: 05-07-2014
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Trichinella spiralis heat shock protein 70 (Ts-Hsp70) is a protective antigen that induces partial protective immunity against T. spiralis infection in mice. To determine whether dendritic cells are involved in the mechanism responsible for the protection induced by Ts-Hsp70, mouse bone marrow-derived dendritic cells (DCs) were incubated with recombinant Ts-Hsp70 (rTs-Hsp70), and the DC-secreted cytokines and expressed surface markers were measured. The results demonstrated that rTs-Hsp70 activated DC maturation that was characterized by the secretion of IL-1?, IL-12p70, TNF-?, and IL-6 and the increased surface expression of CD11c, MHC II, CD40, CD80, and CD86. The rTs-Hsp70-activated DCs enabled the stimulation, proliferation and secretion of Th1/2 cytokines (i.e., INF-?, IL-2, IL-4 and IL-6) in CD4(+) T cells from T. spiralis-infected mice. The mice that received rTs-Hsp70-activated DCs exhibited a 38.4% reduction in muscle larvae upon larval challenge with T. spiralis compared to the group that received PBS-incubated DCs. This partial protection was correlated with Th1 and Th2 mixed anti-Ts-Hsp70-specific immune responses that included high titers of total IgG, IgG1 and IgG2a and increased levels of Th1/2 cytokines (i.e., IFN-?, IL-2, IL-4, IL-6). These results indicate that the rTs-Hsp70-induced protective immunity was mediated by the activation of the DCs and that rTs-Hsp70-loaded DCs could be an alternative vaccine approach against trichinellosis.
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Study of genetic variants of 8q21 and 8q24 associated with prostate cancer in Jing-Jin residents in northern China.
Clin. Lab.
PUBLISHED: 05-01-2014
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To identify the genetic risk of six genetic variants at 8q21 and 8q24 (including rs1512268, A; rs12543663, C; rs10086908, C; rs1016343, T; rs13252298, A, and rs6983561, C) associated with prostate cancer in Beijing and Tianjin (Jing-jin) area residents in northern China.
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KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates rat models of rheumatoid arthritis.
PUBLISHED: 04-26-2014
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Objective. Fibroblast-like synoviocytes (FLS) participate in joint inflammation and damage during rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi-K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy. Methods. We compared KCa1.1 expression levels in FLS from rats with the pristane-induced arthritis (PIA) model of RA and in FLS from healthy rats. We then used ex vivo functional assays combined with siRNA-induced knock-down, over-expression, and functional modulation of KCa1.1 in PIA-FLS. Finally, we determined the effectiveness of modulating KCa1.1 in two rat models of RA, moderate PIA and severe complete Freund's adjuvant collagen-induced arthritis (CFA-CIA). Results. We found that PIA-FLS express the KCa1.1 channel as their major potassium channel, as do FLS from patients with RA. In contrast, FLS from healthy rats expressed fewer of these channels. Inhibiting the function or expression of KCa1.1 ex vivo reduced the proliferation, production of proteases, and invasive properties of PIA-FLS whereas opening native KCa1.1 or over-expressing the channel enhanced the invasiveness of both PIA-FLS and FLS isolated from healthy rats. Treatment with a KCa1.1 channel blocker starting at onset of clinical signs stopped disease progression in both PIA and CFA-CIA, reduced joint and bone damage, and inhibited FLS invasiveness and proliferation. Conclusion. Our results demonstrate a critical role for KCa1.1 channels in the regulation of FLS invasiveness and suggest they represent a potential therapeutic target for RA. © 2014 American College of Rheumatology.
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Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.
Diabetologia
PUBLISHED: 04-25-2014
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Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations.
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A three-stage birandom program for unit commitment with wind power uncertainty.
ScientificWorldJournal
PUBLISHED: 04-11-2014
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The integration of large-scale wind power adds a significant uncertainty to power system planning and operating. The wind forecast error is decreased with the forecast horizon, particularly when it is from one day to several hours ahead. Integrating intraday unit commitment (UC) adjustment process based on updated ultra-short term wind forecast information is one way to improve the dispatching results. A novel three-stage UC decision method, in which the day-ahead UC decisions are determined in the first stage, the intraday UC adjustment decisions of subfast start units are determined in the second stage, and the UC decisions of fast-start units and dispatching decisions are determined in the third stage is presented. Accordingly, a three-stage birandom UC model is presented, in which the intraday hours-ahead forecasted wind power is formulated as a birandom variable, and the intraday UC adjustment event is formulated as a birandom event. The equilibrium chance constraint is employed to ensure the reliability requirement. A birandom simulation based hybrid genetic algorithm is designed to solve the proposed model. Some computational results indicate that the proposed model provides UC decisions with lower expected total costs.
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An improved LC-MS/MS method for the determination of mangiferin in rat plasma and its application in nonlinear pharmacokinetics.
Pharmazie
PUBLISHED: 04-11-2014
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A rapid and sensitive LC-MS/MS method was developed and validated for the determination of mangiferin in rat plasma. After simple protein precipitation of the plasma sample (100 microL) with 120 microL acetonitrile containing the internal standard rutin (500 ng/mL), the analytes were separated on a Zorbax SB-C18 column (150 x 2.1 mm, 3.5 microm) using an eluent of acetonitrile-0.05% formic acid in water (18:82, v/v), and then detected by electrospray ionization mass spectrometry in the negative multiple reaction monitoring mode with a chromatographic run time of 3.0 min. The method was sensitive, with a lower limit of quantification of 1 ng/mL and good linearity (r > 0.998) over the range of 1-250 ng/mL. It was also specific, precise and accurate when it was used to measure mangiferin levels in plasma and to characterize the pharmacokinetic properties following oral administration of mangiferin at a single dose of 5, 15, 45 and 90 mg/kg in rats. In addition, the pharmacokinetics of mangiferin were found to be nonlinear over the above dose range, which provides insight into dose regimen design of this potent compound in new drug development.
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Internet addiction, adolescent depression, and the mediating role of life events: finding from a sample of Chinese adolescents.
Int J Psychol
PUBLISHED: 04-01-2014
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The aim of this study is to examine the mediating role of life events in the relation between Internet addiction and depression using an adolescent sample in China. A total of 3507 urban adolescent students were asked to complete the questionnaires including Young's Internet Addiction Scale, Adolescent Self-Rating Life Events Checklist, and Center for Epidemiologic Studies Depression Scale, Parent-Child Conflict Tactics Scales, and demographic characteristics. Path analyses demonstrated that life events fully mediated the relationship between Internet addiction and adolescent depression. Specificity for the mediating role of life events was demonstrated in comparison to alternative competing mediation models. The findings support our hypothesis that the effect of Internet addiction on adolescent depression is mediated by the life events. Further research is required to test the temporal relationship between Internet addiction and adolescent depression and explore mechanisms underlying the pathways leading to adolescent depression.
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[Development of the Chinese nasal obstruction symptom evaluation (NOSE) questionnaire].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 04-01-2014
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To develop the Chinese version of the nasal obstruction symptom evaluation (NOSE) questionnaire.
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Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.
Exp. Gerontol.
PUBLISHED: 03-26-2014
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The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay. In this study, we analyzed the distribution of CETP*V (rs5882) and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109) and 340 controls (aged 20-58). In addition to replicating the association of longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk against longevity and was associated with high-cholesterol (hTC) and mixed dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable-adjusted logistic regression, and nonparametric MDR analysis all suggested a significant CETP*APOE interaction associated with hTG. The unadjusted odds for hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without either (OR=4.36, P<0.001). These results provide evidence of strong independent associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as an independently non-significant variant, might interact with CETP*V resulting in an increased risk for hTG.
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Elevated plasma retinol-binding protein 4 is associated with increased risk of type 2 diabetes in middle-aged and elderly Chinese adults.
J. Nutr.
PUBLISHED: 03-19-2014
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The association between circulating retinol-binding protein 4 (RBP4) and risk of type 2 diabetes has been inconsistent in cross-sectional studies, but prospective evidence is limited. We aimed to investigate whether plasma RBP4 is associated with future development of type 2 diabetes and whether the association could be explained by iron or other risk factors. A total of 2091 Chinese adults aged 50-70 y were followed up for 6 y. Baseline dietary intakes and fasting plasma RBP4, ferritin, adiponectin, C-reactive protein (CRP), ?-glutamyltransferase, creatinine, and erythrocyte fatty acids were determined. Self-reported doctor-diagnosed diabetes, or usage of antidiabetic agents, or fasting plasma glucose concentration at the follow-up visit ?7.0 mmol/L was defined as an incident diabetes case. Plasma RBP4 concentration was significantly associated with dietary heme iron intake, plasma ferritin concentration, and other established risk factors. After multivariate adjustment for demographic and lifestyle variables, relative risk (RR) for type 2 diabetes when the extreme quartiles of RBP4 were compared was 1.75 (95% CI: 1.30, 2.37; P-trend < 0.001). This association remained significant when the extreme quartiles were compared (RR = 1.48; 95% CI: 1.06, 2.05; P-trend = 0.036) after further controlling for ferritin and dietary factors, as well as other risk factors, including body mass index, adiponectin, CRP, lipids, liver and kidney function, insulin resistance, and hypertension. A threshold effect of RBP4 concentrations on incident diabetes was suggested by restricted quadratic spline analysis (P = 0.026 for nonlinearity). Our study indicates that plasma RBP4 is independently associated with the 6-y risk of developing type 2 diabetes.
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Stereopsis impairment is associated with decreased color perception and worse motor performance in Parkinson's disease.
Eur. J. Med. Res.
PUBLISHED: 03-11-2014
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We conducted this study is to investigate the correlation between stereopsis dysfunction and color perception, as well as whether stereopsis impairment is associated with motor dysfunction in patients with Parkinson's disease (PD).
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Gender-specific DNA methylome analysis of a Han Chinese longevity population.
Biomed Res Int
PUBLISHED: 02-28-2014
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Human longevity is always a biological hotspot and so much effort has been devoted to identifying genes and genetic variations associated with longer lives. Most of the demographic studies have highlighted that females have a longer life span than males. The reasons for this are not entirely clear. In this study, we carried out a pool-based, epigenome-wide investigation of DNA methylation profiles in male and female nonagenarians/centenarians using the Illumina 450 K Methylation Beadchip assays. Although no significant difference was detected for the average methylation levels of examined CpGs (or probes) between male and female samples, a significant number of differentially methylated probes (DMPs) were identified, which appeared to be enriched in certain chromosome regions and certain parts of genes. Further analysis of DMP-containing genes (named DMGs) revealed that almost all of them are solely hypermethylated or hypomethylated. Functional enrichment analysis of these DMGs indicated that DNA hypermethylation and hypomethylation may regulate genes involved in different biological processes, such as hormone regulation, neuron projection, and disease-related pathways. This is the first effort to explore the gender-based methylome difference in nonagenarians/centenarians, which may provide new insights into the complex mechanism of longevity gender gap of human beings.
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PAR2-mediated epigenetic upregulation of ?-synuclein contributes to the pathogenesis of Parkinson?s disease.
Brain Res.
PUBLISHED: 02-26-2014
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Parkinson?s disease (PD) is a common neurodegenerative disorder characterized by the selective degeneration of projecting dopaminergic neurons in the substantia nigra and diminished dopamine levels in the striatum. Accumulating evidences demonstrate that the aggregation of extracellular ?-synuclein contributes to the neuroinflammation and neuronal injury in the substantia nigra in the brain of patients with PD. Proteinase-activated receptor 2 (PAR2), a G-protein coupled receptor, is expressed throughout the peripheral and central nerve system. The present study aims to investigate the involvement of PAR2-NF-?B signaling in the upregulation of ?-synuclein and motor dysfunction in the rodent model of PD. Significantly increased expression of ?-synuclein was observed in the substantia nigra of the rats injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In these rats, significantly increased nigral PAR2 was observed, and blockade of PAR2 signaling reduced the ?-synuclein synthesis in substantia nigra and recovered the motor dysfunction in the rats injected with MPTP. Furthermore, significantly increased phosphorylation of NF-?B subunit p65 was detected in these rats, which was abolished by the inhibition of PAR2 signaling. Blockade of NF-?B signaling significantly decreased histone H3 acetylation in Snca promoter region and ?-synuclein expression in substantia nigra. It also decreased the synthesis of cytokine IL-1? and TNF-? in substantia nigra and recovered the motor dysfunction in the rats injected with MPTP. These results indicated the critical involvement of PAR2-NF-?B signaling in the upregulation of ?-synuclein and motor dysfunction in the rodent model of PD, and shed light on the development of novel approaches for the treatment of patients with PD.
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[Risk and risk factors of suicide attempt after first onset of suicide ideation: findings from medical students in grades 1 and 2].
Wei Sheng Yan Jiu
PUBLISHED: 02-26-2014
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To examine transition probabilities from first onset of suicide ideation to attempt over time among medical students in grades 1 and 2 and risk factors in the transition.
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miRNA profiling reveals a potential role of milk stasis in breast carcinogenesis.
Int. J. Mol. Med.
PUBLISHED: 02-17-2014
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The tumor microenvironment plays an important role in breast carcinogenesis. Milk acts as an important microenvironment of breast cancer, but its role in breast carcinogenesis is largely unknown. Milk stasis may exist in the breast for a number of years after breastfeeding. In the present study, we reported the first microRNA (miRNA) profiling of milk from patients with milk stasis. We identified 266 known miRNAs and 271 novel miRNAs in 10 milk stasis only samples, 271 known miRNAs and 140 novel miRNAs in 10 milk stasis plus breast neoplasm samples by deep sequencing. miRNA profiles were different between the two groups. Furthermore, nine tumor suppressor miRNAs such as miR-29a, miR-146 and miR-223 were significantly downregulated, while seven oncogenic miRNAs such as miR-451, miR-486, miR-107, miR-92 and miR-10 were significantly upregulated in the milk of milk stasis plus neoplasm patients. Three of the identified miRNAs (miR-140, miR-21 and let-7a) were selected using real-time PCR, confirming that these miRNAs were highly expressed. The results also showed that the three miRNAs detected were more abundant in the milk than in the blood. In summary, the data suggested that miRNAs in milk from milk stasis patients may contribute to breast carcinogenesis and that they are more sensitive biomarkers for breast cancer than miRNAs in the blood.
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Lipopolysaccharide binding protein, obesity status and incidence of metabolic syndrome: a prospective study among middle-aged and older Chinese.
Diabetologia
PUBLISHED: 02-16-2014
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Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women.
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[Correlation of androgen receptor CAG repeats with the risks of benign prostatic hyperplasia and prostate cancer: a meta-analysis].
Zhonghua Nan Ke Xue
PUBLISHED: 02-14-2014
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To explore the association of the androgenic receptor (AR) CAG repeats with the risks of benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
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Gene-modified cell detachment on photoresponsive hydrogels strengthened through hydrogen bonding.
Acta Biomater
PUBLISHED: 02-07-2014
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Photoresponsive hydrogels are potentially useful as drug delivery and cell culture media, but there has been no report on manipulation of cell attachment/detachment and gene transfection simultaneously on the surface of this single gel. In the present study, strong light sensitive hydrogels were prepared mechanically by photoinitiated copolymerization of spiropyran-containing monomer, 2-vinyl-4,6-diamino-1,3,5-triazine, hydrogen bonding monomer, oligo(ethylene glycol) methacrylate and polyethylene glycol diacrylate (PEGDA, Mn=575). The multiple hydrogen bondings of diaminotriazine residues could contribute to the increase in compressive strengths of the photosensitive hydrogels up to 5.1MPa. UV (365nm) irradiation led to detachment of adhered cells as a result of the increased surface hydrophilicity caused by a switch from hydrophobic spiropyran to hydrophilic merocyanine form. Furthermore, selective detachment of cells could also be achieved by UV light illumination on the specified gel surface. Hydrogen bonding between diaminotriazines were shown to tightly anchor the PVDT/pDNA complex particles on the gel surface, where reverse gene transfection was achieved. Following up with UV irradiation triggered the unharmful detachment of gene-modified cells from the gel surface. It is envisioned that this photosensitive hydrogel holds potential as a versatile platform for operating gene delivery and controlled harvest of desired cells for tissue engineering.
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Fast functionalization of silver decahedral nanoparticles with aptamers for colorimetric detection of human platelet-derived growth factor-BB.
Anal. Chim. Acta
PUBLISHED: 02-06-2014
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Aptamer-silver decahedral nanoparticles (Ag10NPs-aptamer) based detection was developed for protein. Ag10NPs were synthesized by photochemical method. The advantage of Ag10NPs was its tolerance of NaCl which facilitates the functionalization of silver nanoparticles with all kinds of ssDNA. Attaching aptamers to Ag10NPs could be achieved within 2 h, much faster than traditional methods. Human platelet-derived growth factor-BB (PDGF-BB) was used as a model protein to test the binding capacity of aptamers attached on Ag10NPs. Our data showed that the aptamer-Ag10NPs conjugates were successful in detecting human PDGF-BB. Furthermore, we developed an aptamer-Ag10NPs conjugates-based colorimetric sensor to detect PDGF-BB. The results showed a linear relationship between PDGF-BB concentrations (5 ng mL(-1)-200 ng mL(-1)) and ?OD with excellent detection specificity in serum. Therefore, the sensor based on aptamer-Ag10NPs conjugates was highly effective and sensitive and had great promise for further development and applications.
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OsAAP6 functions as an important regulator of grain protein content and nutritional quality in rice.
Nat Commun
PUBLISHED: 01-29-2014
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Grains from cereals contribute an important source of protein to human food, and grain protein content (GPC) is an important determinant of nutritional quality in cereals. Here we show that the quantitative trait locus (QTL) qPC1 in rice controls GPC by regulating the synthesis and accumulation of glutelins, prolamins, globulins, albumins and starch. qPC1 encodes a putative amino acid transporter OsAAP6, which functions as a positive regulator of GPC in rice, such that higher expression of OsAAP6 is correlated with higher GPC. OsAAP6 greatly enhances root absorption of a range of amino acids and has effects on the distribution of various amino acids. Two common variations in the potential cis-regulatory elements of the OsAAP6 5'-untranslated region seem to be associated with GPC diversity mainly in indica cultivars. Our results represent the first step toward unravelling the mechanism of regulation underlying natural variation of GPC in rice.
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THADA gene polymorphism and prostate cancer risk: a meta-analysis.
Oncol Res Treat
PUBLISHED: 01-29-2014
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The single nucleotide polymorphism (SNP) rs1465618 in THADA at 2p21 has been identified as being associated with prostate cancer (PCa) risk in Europeans; however, it is not clear whether the SNP is related to PCa risk in multiple populations. We investigated the association of rs1465618 in THADA with PCa in a Chinese population and carried out a meta-analysis in multiple populations, testing the relevance of this SNP for PCa risk.
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Magnetic resonance imaging-detected inner ear hemorrhage as a potential cause of sudden sensorineural hearing loss.
Am J Otolaryngol
PUBLISHED: 01-27-2014
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The aim of this study is to assess the value of magnetic resonance imaging in identifying the etiology of sudden sensorineural hearing loss, and to correlate the high signals in the labyrinth with clinical features to identify if inner ear hemorrhage could be implicated.
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Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma.
Tumour Biol.
PUBLISHED: 01-10-2014
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Eg5 is critical for mitosis and overexpressed in various malignant tumors, which has now been identified as a promising target in cancer therapy. However, the anti-cancer activity of Eg5 inhibitor in renal cell carcinoma (RCC) remains an open issue. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking Eg5 by S-(methoxytrityl)-L-cysteine (S(MeO)TLC) in RCC both in vitro and vivo. The expression of Eg5 was examined in clinical tissue samples and various kidney cell lines, including 293T, 786-0, and OS-RC-2. The anti-proliferative activity of Eg5 inhibitors, (S)-trityl-L-cysteine (STLC) and S(MeO)TLC, was evaluated by a cell viability assay. An apoptosis assay with Hoechst nuclear staining and flow cytometry was applied to investigate the efficacy of the S(MeO)TLC, which is more potent than STLC. Immunofluorescence was used to research the possible mechanism. Furthermore, in vivo studies were performed by using subcutaneous xenograft models, which were used to confirm its role as a potential anti-neoplastic drug. The Eg5 expression was detected in kidney cell lines and RCC tissues, which was low in normal kidney samples. STLC and S(MeO)TLC exhibited their optimal anti-proliferative activity in 72 h, and cells treated with S(MeO)TLC presented characteristic monoastral spindle phenotype in 24 h and apoptotic cells in 48 h. In vivo, S(MeO)TLC effectively suppressed tumor growth in subcutaneous xenograft models. Inhibition of Eg5 represses the proliferation of RCC in vitro and in vivo. All these findings collectively demonstrate that S(MeO)TLC, a potent Eg5 inhibitor, is a promising anti-cancer agent for the treatment of RCC.
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Transcriptional regulation of abscisic acid signal core components during cucumber seed germination and under Cu²?, Zn²?, NaCl and simulated acid rain stresses.
Plant Physiol. Biochem.
PUBLISHED: 01-09-2014
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Abscisic acid (ABA) is an important phytohormone that regulates lots of physiological and biochemical processes in plant life cycle, especially in seed germination and stress responses. For exploring the transcriptional regulation of ABA signal transduction during cucumber (Cucumis sativus L.) seed germination and under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, nine CsPYLs, three group A CsPP2Cs and two subclass III CsSnRK2s were identified from cucumber genome, which respectively showed high sequence similarities and highly conserved domains with homologous genes in Arabidopsis. Based on Real-time PCR analysis, most of the tested genes' expression decreased during cucumber seed germination, which was in accordance with the ABA level variation. In addition, according to the absolute expression, CsPYL1, CsPYL3, CsPP2C5, CsABI1, CsSnRK2.3 and CsSnRK2.4 were highly expressed, indicating that they may play more important roles in ABA signaling during cucumber seed germination. Moreover, most of these highly expressed genes, except CsPYL3, were up-regulated by ABA treatment. Meanwhile, most of the tested genes' expression dramatically changed at the initial water uptake phase, indicating that this period may be critical in the regulation of ABA on seed germination. Under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, cucumber seed germination percentage decreased and ABA content increased. Meanwhile, the expression of ABA signal transduction core components genes showed specific response to a particular stress and was not always consist with ABA variation. Generally, the expression of CsPYL1, CsPYL3, CsABI1, CsSnRK2.3 and CsSnRK2.4 was sensitive to 120 mM NaCl and 0.5 mM Cu(2+) treatments.
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Poor vitamin D status is prospectively associated with greater muscle mass loss in middle-aged and elderly Chinese individuals.
J Acad Nutr Diet
PUBLISHED: 01-08-2014
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Poor vitamin D status can increase age-related muscle mass loss. However, existing prospective evidence is limited and controversial.
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Prediction of outcome following paraquat poisoning by arterial lactate concentration-time data.
Exp Ther Med
PUBLISHED: 01-08-2014
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The present study retrospectively analyzed 170 patients diagnosed with paraquat (PQ) poisoning with the aim of clarifying whether the arterial lactate-time (arterial lactate concentration × time between ingestion and arterial lactate measurement) was a good predictor of mortality in patients with acute PQ poisoning. The results indicated that there was a positive correlation between the arterial lactate-time and PQ concentration-time (?=0.485). In addition, the arterial lactate-time data exhibited a similar discriminative power to the plasma PQ concentration-time data (z=0.712; P=0.864). For the receiver operating characteristic curve analysis, the lactate-time data had an area of 0.782 with a cut-off value of 11.95 mmol/l.h (sensitivity, 64.52%; specificity, 84.42%). To calculate the predicted probability of survival for any specified time and initial arterial lactate concentration, the following formula was derived based on the logistic regression coefficients: Logit(p) = 3.066 - 0.139 × (time lag following PQ ingestion) - 0.177 × (initial arterial lactate concentration); where the probability of survivors = 1/1 + e(-logit(p)). Therefore, the arterial lactate-time data exhibited a good predictive power for evaluating the prognosis of patients with acute PQ poisoning.
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Ryanodine receptor-mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model.
Circulation
PUBLISHED: 01-07-2014
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The progression of atrial fibrillation (AF) from paroxysmal to persistent forms remains a major clinical challenge. Abnormal sarcoplasmic reticulum (SR) Ca(2+) leak via the ryanodine receptor type 2 (RyR2) has been observed as a source of ectopic activity in various AF models. However, its potential role in progression to long-lasting spontaneous AF (sAF) has never been tested. This study was designed to test the hypothesis that enhanced RyR2-mediated Ca(2+) release underlies the development of a substrate for sAF and to elucidate the underlying mechanisms.
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Interleukin-6 genotypes and serum levels in Chinese Hui population.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6.
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The effects of harvesting media on biological characteristics and repair potential of neural stem cells after traumatic brain injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Various solutions are utilized widely for the isolation, harvesting, sorting, testing and transplantation of neural stem cells (NSCs), whereas the effects of harvesting media on the biological characteristics and repair potential of NSCs remain unclear. To examine some of these effects, NSCs were isolated from cortex of E14.5 mice and exposed to the conventional harvesting media [0.9% saline (Saline), phosphate-buffered saline (PBS) or artificial cerebrospinal fluid (ACSF)] or the proliferation culture medium (PCM) for different durations at 4°C. Treated NSCs were grafted by in situ injection into the lesion sites of traumatic brain injury (TBI) mice. In vitro, harvesting media-exposed NSCs displayed time-dependent reduction of viability and proliferation. S phase entry decreased in harvesting media-exposed cells, which was associated with upregulation of p53 protein and downregulation of cyclin E1 protein. Moreover, harvesting media exposure induced the necrosis and apoptosis of NSCs. The levels of Fas-L, cleaved caspase 3 and 8 were increased, which suggests that the death receptor signaling pathway is involved in the apoptosis of NSCs. In addition, exposure to Saline did not facilitate the neuronal differentiation of NSCs, suggesting that Saline exposure may be disadvantageous for neurogenesis. In vivo, NSC-mediated functional recovery in harvesting media-exposed NSC groups was notably attenuated in comparison with the PCM-exposed NSC group. In conclusion, harvesting media exposure modulates the biological characteristics and repair potential of NSCs after TBI. Our results suggest that insight of the effects of harvesting media exposure on NSCs is critical for developing strategies to assure the successful long-term engraftment of NSCs.
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Molecular characterization and differential expression of olfactory genes in the antennae of the black cutworm moth Agrotis ipsilon.
PLoS ONE
PUBLISHED: 01-01-2014
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Insects use their sensitive and selective olfactory system to detect outside chemical odorants, such as female sex pheromones and host plant volatiles. Several groups of olfactory proteins participate in the odorant detection process, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs) and sensory neuron membrane proteins (SNMPs). The identification and functional characterization of these olfactory proteins will enhance our knowledge of the molecular basis of insect chemoreception. In this study, we report the identification and differential expression profiles of these olfactory genes in the black cutworm moth Agrotis ipsilon. In total, 33 OBPs, 12 CSPs, 42 ORs, 24 IRs, 2 SNMPs and 1 gustatory receptor (GR) were annotated from the A. ipsilon antennal transcriptomes, and further RT-PCR and RT-qPCR revealed that 22 OBPs, 3 CSPs, 35 ORs, 14 IRs and the 2 SNMPs are uniquely or primarily expressed in the male and female antennae. Furthermore, one OBP (AipsOBP6) and one CSP (AipsCSP2) were exclusively expressed in the female sex pheromone gland. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs were suggested to be responsible for pheromone and general odorant detection and thus could be meaningful target genes for us to study their biological functions in vivo and in vitro.
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CTLA4 variants and haplotype contribute genetic susceptibility to myasthenia gravis in northern Chinese population.
PLoS ONE
PUBLISHED: 01-01-2014
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Cytotoxic T lymphocyte-associated antigen-4 (CTLA4), a critical negative regulator of the T-cell response, has been considered a candidate for many autoimmune diseases. Evidence from Caucasians supported a genetic predisposition of CTLA4 to myasthenia gravis (MG), but the contribution in East Asians has not been established.
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Identification of susceptibility variants in ADIPOR1 gene associated with type 2 diabetes, coronary artery disease and the comorbidity of type 2 diabetes and coronary artery disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Adiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the "common soil" hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population.
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What lies beyond the eye: the molecular mechanisms regulating tomato fruit weight and shape.
Front Plant Sci
PUBLISHED: 01-01-2014
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Domestication of fruit and vegetables resulted in a huge diversity of shapes and sizes of the produce. Selections that took place over thousands of years of alleles that increased fruit weight and altered shape for specific culinary uses provide a wealth of resources to study the molecular bases of this diversity. Tomato (Solanum lycopersicum) evolved from a wild ancestor (S. pimpinellifolium) bearing small and round edible fruit. Molecular genetic studies led to the identification of two genes selected for fruit weight: FW2.2 encoding a member of the Cell Number Regulator family; and FW3.2 encoding a P450 enzyme and the ortholog of KLUH. Four genes were identified that were selected for fruit shape: SUN encoding a member of the IQD family of calmodulin-binding proteins leading to fruit elongation; OVATE encoding a member of the OVATE family proteins involved in transcriptional repression leading to fruit elongation; LC encoding most likely the ortholog of WUSCHEL controlling meristem size and locule number; FAS encoding a member in the YABBY family controlling locule number leading to flat or oxheart shape. For this article, we will provide an overview of the putative function of the known genes, when during floral and fruit development they are hypothesized to act and their potential importance in regulating morphological diversity in other fruit and vegetable crops.
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Development of a new risk score for incident type 2 diabetes using updated diagnostic criteria in middle-aged and older chinese.
PLoS ONE
PUBLISHED: 01-01-2014
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Type 2 diabetes mellitus (T2DM) reaches an epidemic proportion among adults in China. However, no simple score has been created for the prediction of T2DM incidence diagnosed by updated criteria with hemoglobin A1c (HbA1c) ? 6.5% included in Chinese. In a 6-year follow-up cohort in Beijing and Shanghai, China, we recruited a total of 2529 adults aged 50-70 years in 2005 and followed them up in 2011. Fasting plasma glucose (FPG), HbA1c, and C-reactive protein (CRP) were measured and incident diabetes was identified by the recently updated criteria. Of the 1912 participants without T2DM at baseline, 924 were identified as having T2DM at follow-up, and most of them (72.4%) were diagnosed using the HbA1c criterion. Baseline body mass index, FPG, HbA1c, CRP, hypertension, and female gender were all significantly associated with incident T2DM. Based upon these risk factors, a simple score was developed with an estimated area under the receiver operating characteristic curve of 0.714 (95% confidence interval: 0.691, 0.737), which performed better than most of existing risk score models developed for eastern Asian populations. This simple, newly constructed score of six parameters may be useful in predicting T2DM in middle-aged and older Chinese.
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Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a Chinese Han population.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent large-scale genome-wide association studies have identified multiple loci robustly associated with BMI, predominantly in European ancestry (EA) populations. However, associations of these loci with obesity and related traits have not been well described in Chinese Hans. This study aimed to investigate whether BMI-associated loci are, individually and collectively, associated with adiposity-related traits and obesity in Chinese Hans and whether these associations are modified by physical activity (PA).
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Hsp90-dependent assembly of the DBC2/RhoBTB2-Cullin3 E3-ligase complex.
PLoS ONE
PUBLISHED: 01-01-2014
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The expression of the wild-type tumor-suppressor gene DBC2 (Deleted-in-Breast Cancer 2, a.k.a RhoBTB2) is suppressed in many cancers, in addition to breast cancer. In a screen for Cdc37-associated proteins, DBC2 was identified to be a potential client protein of the 90 kDa heat shock protein (Hsp90) chaperone machine. Pull down assays of ectopically expressed DBC2 confirmed that DBC2 associated with Hsp90 and its co-chaperone components in reticulocyte lysate and MCF7 cells. Similar to other atypical Rho GTPases, DBC2 was found to have retained the capacity to bind GTP. The ability of DBC2 to bind GTP was modulated by the Hsp90 ATPase cycle, as demonstrated through the use of the Hsp90 chemical inhibitors, geldanamycin and molybdate. The binding of full length DBC2 to GTP was suppressed in the presence of geldanamycin, while it was enhanced in the presence of molybdate. Furthermore, assembly of DBC2-Cullin3-COP9 E3 ligase complexes was Hsp90-dependent. The data suggest a new paradigm for Hsp90-modulated assembly of a Cul3/DBC2 E3 ubiquitin ligase complex that may extend to other E3 ligase complexes.
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Association between APOC1 polymorphism and Alzheimer's disease: a case-control study and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer's disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations.
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SORL1 genetic variants modulate risk of amnestic mild cognitive impairment in northern Han Chinese.
Int. J. Neurosci.
PUBLISHED: 11-07-2013
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The neuronal sortilin-related receptor (SORL1) has been reported to modulate the risk of Alzheimers disease (AD) in a variety of populations, but replication studies have been inconsistent. Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. However, the relationship between SORL1 and aMCI remains unclear. This study aimed to investigate the relationship between SORL1 genetic variation and aMCI in the Han Chinese population. We conducted a case-control study using a single-nucleotide polymorphism (SNP), rs668387 (SNP8), in the 5 region of SORL1, and three SNPs [rs2070045 (SNP19), rs3824968 (SNP23), rs2282649 (SNP24)] in the 3 region of SORL1, along with a haplotype analysis, in 139 aMCI patients and 213 cognitively-healthy controls from a northern Han Chinese population. We observed that SNP19 had a significantly different allele frequency between aMCI patients and controls (p = 0.006). Moreover, the GAT haplotype at SNPs 19-23-24 was associated with an increased risk of aMCI [odds ratio (OR) 1.377], while the TTC haplotype at SNPs 19-23-24 was associated with a decreased risk (OR 0.708). These results indicated that the SNPs in the 3 region of SORL1 are associated with aMCI in northern Han Chinese.
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[Quality of life and related factors among family members of tuberculosis patients].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-30-2013
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Objective: To understand the quality of life and related factors among family members of tuberculosis patients and provide a reference for the improvement of their quality of life. Methods: A total of 222 family members of tuberculosis patients at 4 tuberculosis hospitals in Changsha and 327 healthy controls were surveyed with structured questionnaire, the short version of the WHO quality of life scale (WHOQOL-BREF). Results: The mean score of the family members of tuberculosis patients in the psychological domain, physical domain and environmental domains was lower than that of the control group (P<0.01). Multiple linear regression showed that gender, age, monthly income, educational level, patient condition and knowledge of tuberculosis prevention and treatment were the factors affecting their quality of life. Conclusion: The quality of life of the family members of tuberculosis patients is lower than that of the control group.
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Formation of fused-ring 2-deoxycytidine adducts from 1-chloro-3-buten-2-one, an in vitro 1,3-butadiene metabolite, under in vitro physiological conditions.
Chem. Res. Toxicol.
PUBLISHED: 09-25-2013
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1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic and genotoxic in human liver cells in culture with CBO being approximately 100-fold more potent than CHB. In the present study, CBO was shown to react readily with 2-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 °C) to form four dC adducts with the CBO moieties forming fused rings with the N3 and N(4) atoms of dC. The four products were structurally characterized as 2-hydroxy-2-hydroxymethyl-7-(2-deoxy-?-d-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-?-d-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-?-d-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4). Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH 7.4, 37 °C, and 6 h) and existed in equilibrium as indicated by HPLC analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 ± 0.36 and 1.7 ± 0.06 h, respectively. Decomposition of dC-4 produced both dC-1 and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 °C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H, respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the characterized CBO-dC adducts could be mutagenic and play a role in the cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC adducts may also be used as standards to characterize CBO-DNA adducts and to develop potential biomarkers for CBO formation in vivo.
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Dairy consumption, type 2 diabetes, and changes in cardiometabolic traits: a prospective cohort study of middle-aged and older chinese in beijing and shanghai.
Diabetes Care
PUBLISHED: 09-11-2013
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OBJECTIVE To prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19-1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5-1 serving/day and >1 serving/day were 0.70 (95% CI 0.55-0.88) and 0.65 (0.49-0.85), respectively, after multivariate adjustment (Ptrend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65-1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.
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The EDA-containing cellular fibronectin induces epithelial-mesenchymal transition in lung cancer cells through integrin ?9?1-mediated activation of PI3-K/AKT and Erk1/2.
Carcinogenesis
PUBLISHED: 08-08-2013
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Cellular fibronectin (cFN) is one of the main components of tissue extracellular matrices and is involved in multiple physiologic and pathologic processes such as embryogenesis, wound healing, inflammation and tumor progression. The function of fibronectin in regulating normal cell adhesion and migration is well documented, but its function in cancer progression is only partially unraveled. We have reported previously that fibronectin stimulates the proliferation and survival of non-small lung carcinoma cells through upregulation of pro-oncogenic signals related to cyclooxygenase-2/phosphatidylinositol-3-kinase/protein kinase B (COX-2/PI3-K/AKT)/mammalian target of rapamycin triggered by activation of the integrin ?5?1. Here, we extend these studies by showing that fibronectin promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. We found that cFN, but not plasma fibronectin or type 1 collagen, induces lung carcinoma cell scattering in vitro, promotes cell migration and invasion of Matrigel and stimulates the expression of the mesenchymal marker ?-smooth muscle actin while decreasing the expression of the epithelial marker E-cadherin through PI3-K and Erk pathways. Interestingly, the extra domain A (EDA) within cFN was found to be crucial for this process, as confirmed by testing cells overexpressing EDA or cells exposed to EDA-containing matrices. We found that the integrin ?9, but not ?5, mediated cFN-induced EMT as silencing integrin ?9 neutralized cFN-induced EMT. Overall, our findings show that the EDA domain within cFN induces EMT in lung carcinoma cells through integrin ?9-mediated activation of PI3-K and Erk.
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Elevated plasma ferritin is associated with increased incidence of type 2 diabetes in middle-aged and elderly Chinese adults.
J. Nutr.
PUBLISHED: 07-31-2013
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Epidemiological studies suggest that elevated circulating ferritin is associated with heightened incident diabetes in mainly Western populations, although the results were not entirely consistent. We aimed to prospectively investigate the ferritin-diabetes association in an Asian population for the first time, to our knowledge, and also to examine this association with an updated meta-analysis. Our prospective study included 2198 community-living Chinese between 50 and 70 y of age in 2005. All individuals participated in a 6-y follow-up survey in 2011. Fasting plasma ferritin, high-sensitivity C-reactive protein (hsCRP), adiponectin, and ?-glutamyltransferase (GGT) were measured at baseline. A total of 538 incident diabetes cases were documented by self-reports and/or fasting glucose ?7.0 mmol/L at the follow-up survey. After multiple adjustments, the RR of type 2 diabetes was 1.90 (95% CI: 1.37, 2.65) when comparing the highest with the lowest sex-specific ferritin quintile. The association remained significant after further controlling for BMI, hsCRP, adiponectin, and GGT. To update the evidence reported in previous meta-analyses, we searched all prospective studies evaluating the association between blood ferritin and incident diabetes on PubMed prior to October 24, 2012. Besides our prospective study, 9 additional studies were also included. The pooled RR was 1.60 (95% CI: 1.25, 2.04) when comparing the highest with the lowest category of ferritin with a moderate heterogeneity (I(2) = 49.0%; P = 0.03). A significant linear dose-response relationship was detected in this meta-analysis. Overall, our results indicate an independent and significant positive association between higher plasma ferritin, a marker of elevated body iron stores, and increased risk of developing type 2 diabetes in middle-aged and elderly Chinese adults, which is similar to Western populations.
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Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts.
Nucleic Acids Res.
PUBLISHED: 07-27-2013
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It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense-antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci.
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The impact of prophylactic intravenous lidocaine on opioid-induced cough: a meta-analysis of randomized controlled trials.
J Anesth
PUBLISHED: 07-21-2013
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Opioids are commonly used for general anesthesia, but reflex cough can occur after an intravenous injection. We have performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effectiveness and safety of prophylactic lidocaine administered intravenously (IV) on opioid-induced cough (OIC) during induction in patients undergoing general anesthesia.
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In vitro three-dimensional development of mouse molar tooth germs in a rotary cell culture system.
Int J Paediatr Dent
PUBLISHED: 07-19-2013
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In vitro tooth germ cultivation is an effective method to explore the mechanism of odontogenesis. The three-dimensional rotary cell culture system (RCCS) is typically used to culture simulated organs such as cartilage, skin, and bone. In this study, we established an in vitro tooth germ culture model using RCCS to investigate whether RCCS could provide an appropriate environment for tooth germ development in vitro.
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Multilayered molecular profiling supported the monoclonal origin of metastatic renal cell carcinoma.
Int. J. Cancer
PUBLISHED: 07-10-2013
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Primary renal cell carcinomas (pRCCs) have a high degree of intratumoral heterogeneity and are composed of multiple distinct subclones. However, it remains largely unknown that whether metastatic renal cell carcinomas (mRCCs) also have startling intratumoral heterogeneity or whether development of mRCCs is due to early dissemination or late diagnosis. To decipher the evolution of mRCC, we analyzed the multilayered molecular profiles of pRCC, local invasion of the vena cava (IVC), and distant metastasis to the brain (MB) from the same patient using whole-genome sequencing, whole-exome sequencing, DNA methylome profiling, and transcriptome sequencing. We found that mRCC had a lower degree of heterogeneity than pRCC and was likely to result from recent clonal expansion of a rare, advantageous subclone. Consequently, some key pathways that are targeted by clinically available drugs showed distinct expression patterns between pRCC and mRCC. From the genetic distances between different tumor subclones, we estimated that the progeny subclone giving rise to distant metastasis took over half a decade to acquire the full potential of metastasis since the birth of the subclone that evolved into IVC. Our evidence supported that mRCC was monoclonal and distant metastasis occurred late during renal cancer progression. Thus, there was a broad window for early detection of circulating tumor cells and future targeted treatments for patients with mRCCs should rely on the molecular profiles of metastases.
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Susceptibility loci associations with prostate cancer risk in northern Chinese men.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-28-2013
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KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy.
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Associations of erythrocyte fatty acids in the de novo lipogenesis pathway with risk of metabolic syndrome in a cohort study of middle-aged and older Chinese.
Am. J. Clin. Nutr.
PUBLISHED: 06-26-2013
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Experimental studies suggest that elevated de novo lipogenesis (DNL) might be involved in the pathogenesis of metabolic disorders. Few prospective studies have been conducted, especially among populations with a high carbohydrate intake, to determine whether DNL fatty acids are associated with the risk of the metabolic syndrome (MetS).
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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.