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Find video protocols related to scientific articles indexed in Pubmed.
Prognostic analysis of orthostatic intolerance using survival model in children.
Chin. Med. J.
PUBLISHED: 11-11-2014
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Orthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI.
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Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings.
Nanotechnology
PUBLISHED: 10-02-2014
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Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.
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Value of qualitative research in polycystic ovary syndrome.
Chin. Med. J.
PUBLISHED: 10-01-2014
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This article aims to introduce the benefits of qualitative research and to discuss how such research can be applied to the study of polycystic ovary syndrome (PCOS).
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Complete mitochondrial genome of Clouded angelshark (Squatina nebulosa).
Mitochondrial DNA
PUBLISHED: 09-11-2014
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Abstract The complete mitochondrial genome of the Squatina nebulosa was determined first in the present study. The mitochondrial genome is 16,698 nucleotides, encoding a standard set of 13 protein-coding genes and 2 ribosomal RNA genes, 22 tRNA genes, 1 control region and 1 origin of the light strand replication. The overall base composition of Squatina nebulosa is T 31.4%, C 24.1%, A 30.7%, and G 13.8%, and the A?+?T content is higher than G?+?C content. These mitogenome sequence data will play an important role in population genetics and phylogenetic analysis of the Suqatinids.
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Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
Nat. Genet.
PUBLISHED: 09-07-2014
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To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10(-5)) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68-0.78; P = 1.00 × 10(-20)), 0.78 (0.72-0.84; P = 2.43 × 10(-15)) and 0.71 (0.65-0.77; P = 4.48 × 10(-14)), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC.
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Genome-wide Association Study of Survival in Early-stage Non-Small Cell Lung Cancer.
Ann. Surg. Oncol.
PUBLISHED: 08-22-2014
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Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers, including genetic variants, may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. To better understand the effects of molecular biomarkers on the treatment of NSCLC, we conducted a genome-wide analysis to investigate the prognostic implications of genetic variants in early-stage NSCLC patients with surgery.
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hMSH2 expression is associated with paclitaxel resistance in ovarian carcinoma, and inhibition of hMSH2 expression in vitro restores paclitaxel sensitivity.
Oncol. Rep.
PUBLISHED: 08-20-2014
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The objective of the present study was to investigate the association between paclitaxel resistance, gene copy number, and gene expression in ovarian carcinoma, and to restore paclitaxel sensitivity in a paclitaxel-resistant ovarian carcinoma cell line by using hMSH2-targeting siRNA. Paclitaxel-resistant ovarian carcinoma cell lines OC3/TAX300 and OC3/TAX50 and their parental cell lines were analyzed by comparative genomic hybridization, and the expression levels of hMSH2 in ovarian carcinoma cell lines and tissues were determined. An siRNA targeted to hMSH2 mRNA was used to transfect a paclitaxel-resistant cell line. We assessed the morphological features, proliferation, and susceptibility to apoptosis of the transfected cells after paclitaxel treatment. Chromosome 2p21 (gene locus of hMSH2) was amplified in OC3/TAX300 cells. hMSH2 was overexpressed in 93.9 and 47.6% of paclitaxel-treated and untreated ovarian carcinoma tissue samples (P=0.0001), respectively. hMSH2 was overexpressed in 93.3 and 54.2% of low-differentiated and moderate-to-highly differentiated ovarian carcinoma tissue samples (P=0.0008), respectively. hMSH2 expression was inhibited in the OC3/TAX300 cells transfected with hMSH2 siRNA. hMSH2 siRNA increased paclitaxel sensitivity, inhibited OC3/TAX300 cell proliferation (G2/M arrest), and increased susceptibility to apoptosis. hMSH2 expression was upregulated in ovarian carcinoma cell lines and tissues after paclitaxel treatment. hMSH2 overexpression is related to paclitaxel resistance and poor prognosis. Inhibition of hMSH2 expression in vitro restores paclitaxel sensitivity in paclitaxel?resistant ovarian carcinoma cell lines and indicates a new direction in adjuvant therapy for ovarian carcinoma.
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Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women.
Nat Commun
PUBLISHED: 08-19-2014
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Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.
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A genetic variant at KIF1B predicts clinical outcome of HBV-related hepatocellular carcinoma in Chinese.
Cancer Epidemiol
PUBLISHED: 08-18-2014
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Recently, a genome-wide association study conducted in Chinese reported a single nucleotide polymorphism at KIF1B, rs17401966, associated with the susceptibility of hepatitis B virus-related hepatocellular carcinoma. In this study, we aim to investigate the effect of rs17401966 on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients at intermediate or advanced stages.
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Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma.
Tumour Biol.
PUBLISHED: 08-16-2014
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Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC). Herein, we report that the combinatorial therapy of sorafenib and anti-programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) can be implemented with good results for HCC. Cancer mouse models were used to evaluate therapeutic efficacy and examine the immunologic mechanisms of the sorafenib/anti-PD-L1 mAb therapy. The combined administration of sorafenib and anti-PD-L1 mAb into tumor-bearing mice generated potent immune responses resulting in the complete eradication or remarkable reduction of tumor growth. In some instances, the sorafenib/anti-PD-L1 mAb therapy induced long-lasting protection against tumor rechallenges. The results indicate that NK cells but not CD4T cells or CD8 cells mediated the therapeutic efficacy of this combinatorial therapy. The overall results suggest that immunotherapy consisting of the combination of sorafenib/anti-PD-L1 mAb could be a promising new approach for treating patients with HCC.
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Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in a Chinese population.
Breast Cancer Res.
PUBLISHED: 08-14-2014
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IntroductionSeveral genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) at 6q25.1 that are associated with breast cancer susceptibility. However, the exact causal variant(s) in this region has not been clarified.MethodsIn the present study, we genotyped six potentially functional SNPs within CCDC170 and ESR1 gene regions at 6q25.1 and accessed their associations with risk of breast cancer in a study of 1,064 cases and 1,073 cancer-free controls in Chinese women. Biological function of the risk variant was further evaluated by laboratory experiments.ResultsBreast cancer risk was significantly associated with three SNPs located at 6q25.1: rs9383935 in CCDC170 and rs2228480 and rs3798758 in ESR1, with variant-allele attributed odds ratio (OR) of 1.38 (95% confidence interval (CI): 1.20 - 1.57, P¿=¿2.21¿×¿10¿6), 0.84 (95% CI: 0.72 - 0.98, P¿=¿0.025) and 1.19 (95% CI: 1.04-1.37, P¿=¿0.013), respectively. The functional variant rs9383935 is in high linkage disequilibrium (LD) with GWAS-reported top-hit SNP (rs2046210), but only rs9383935 showed a strong independent effect in conditional regression analysis. The rs9383935 risk allele A showed a decreased activity of reporter gene in both MCF-7 and BT-474 breast cancer cell lines, which might be due to an altered binding capacity of miR-27a to the 3¿untranslated region (3¿UTR) sequence of CCDC170. Real-time quantitative reverse transcription PCR confirmed the correlation between rs9383935 genotypes and CCDC170 expression levels.ConclusionsThis study suggests that the functional variant rs9383935, located at the 3¿UTR of CCDC170, may be one candidate of the causal variants at 6q25.1 that modulate risk of breast cancer.
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High mobility group box 1 release from cholangiocytes in patients with acute-on-chronic liver failure.
Exp Ther Med
PUBLISHED: 08-13-2014
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High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in a number of inflammatory disorders, but little is known about its role in acute-on-chronic liver failure (ACLF). To elucidate the role of HMGB1 in ACLF, the expression of HMGB1 in liver specimens from patients with ACLF was investigated. Immunohistochemical staining was performed to confirm the expression and subcellular localization of HMGB1 in liver specimens obtained from 13 patients with ACLF caused by hepatitis B virus (HBV) infection, 20 patients with chronic viral hepatitis B and 20 healthy controls. In addition, TFK-1 cells (human cholangiocarcinoma cell line) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-?. The extracellular level of HMGB1 in the culture medium was then determined by ELISA, and cell viability was also examined. In patients with ACLF caused by HBV infection, HMGB1 was found mainly in the cholangiocytes, and cytoplasmic translocation was observed in the cholangiocytes in the liver specimens. In the TFK-1 cell cultures, HMGB1 levels gradually increased from as early as 4 h after stimulation with LPS or TNF-? until the end of the stimulation. LPS and TNF-? actively induced the cytoplasmic translocation of the HMGB1 protein in TFK-1 cells. These data suggest that HMGB1 plays a critical role in the systemic inflammation associated with ACLF.
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Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.
Cancer Biol. Ther.
PUBLISHED: 06-27-2014
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MicroRNAs (miRNAs) represent a class of evolutionarily conserved, non-coding small RNAs (18-25 nt) that have emerged as master regulators of several biological processes. Recently, circulating miRNAs have also been reported to be promising biomarkers for various pathological conditions. In the present study, we report the comparative expression profiling of microRNA-101 (miR-101) in serum and tissue samples from chronic hepatitis B (CHB), HBV-associated liver cirrhosis (HBV-LC), and HBV-associated hepatocellular carcinoma (HBV-HCC) patients and healthy controls. The serum miR-101 levels were found to be significantly downregulated in the HBV-HCC patients compared with the HBV-LC patients (P<0.001), CHB patients (P<0.001) and healthy controls but were upregulated in the HBV-LC patients compared with the CHB patients (P<0.001) and healthy controls (P<0.001). Consistent with the serum data, the expression of miR-101 was also upregulated and downregulated in the HBV-LC and HBV-HCC tissue samples, respectively. A receiver operating characteristic (ROC) analysis of serum miR-101 yielded an area under the ROC curve (AUC) of 0.976 with 95.5% sensitivity and 90.2% specificity when differentiating between HBV-HCC and HBV-LC. Our results suggest that the serum miR-101 level can serve as a potential non-invasive biomarker to differentiate HBV-HCC from HBV-LC.
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Cloning, expression, and purification of a new antimicrobial peptide gene from Musca domestica larva.
Gene
PUBLISHED: 06-09-2014
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Musca domestica (Diptera: Muscidae), the housefly, exhibits unique immune defences and can produce antimicrobial peptides upon stimulation with bacteria. Based on the cDNA library constructed using the suppression subtractive hybridization (SSH) method, a 198-bp antimicrobial peptide gene, which we named MDAP-2, was amplified by rapid amplification of cDNA ends (RACE) from M. domestica larvae stimulated with Salmonella pullorum (Enterobacteriaceae: Salmonella). In the present study, the full-length MDAP-2 gene was cloned and inserted into a His-tagged Escherichia coli prokaryotic expression system to enable production of the recombinant peptide. The recombinant MDAP-2 peptide was purified using Ni-NTA HisTrap FF crude column chromatography. The bacteriostatic activity of the recombinant purified MDAP-2 protein was assessed. The results indicated that MDAP-2 had in vitro antibacterial activity against all of the tested Gram- bacteria from clinical isolates, including E. coli (Enterobacteriaceae: Escherichia), one strain of S. pullorum (Enterobacteriaceae: Salmonella), and one strain of Pasteurella multocida. DNA sequencing and BLAST analysis showed that the MDAP-2 antimicrobial peptide gene was not homologous to any other antimicrobial peptide genes in GenBank. The antibacterial mechanisms of the newly discovered MDAP-2 peptide warrant further study.
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Early Second-Trimester Serum MicroRNAs as Potential Biomarker for Nondiabetic Macrosomia.
Biomed Res Int
PUBLISHED: 05-21-2014
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Background. Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. Methods. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. Results. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P = 0.048 for miR-194 and P = 0.018 for miR-376a, resp.). Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P = 0.032). Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity = 96.7% and specificity = 40.0%). Conclusions. Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.
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[Study on RNA interference silencing hMSH2 induces the reversal chemo-resistance of ovarian carcinoma cell line OC3/TAX300].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 05-14-2014
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To investigate the reversal effect of hMSH2 small interference RNA(siRNA) on chemo-resistance of ovarian carcinoma cell line OC3/TAX300, explore the clinical significance.
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A novel fluorescence probing strategy for the determination of parathion-methyl.
Talanta
PUBLISHED: 05-13-2014
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A sensitive fluorescence probing strategy for parathion-methyl (PM) detection was developed based on electron transfer (ET) between p-nitrophenol (the hydrolysate of PM) and CdTe quantum dots (QDs) in cetyltrimethylammonium bromide (CTAB). PM was hydrolyzed by organophosphorus hydrolase (OPH) to form p-nitrophenol. P-nitrophenol is a typically electron-deficient compound due to the strong electron-withdrawing effect of the nitro groups. The positive charge of CTAB which make it assemble with electronegative mercaptopropionic acid-capped QDs, could be used as an absorbent for p-nitrophenol due to the strong hydrophobic interaction between the long alkyl chain of CTAB and aromatic ring of p-nitrophenol. Thus, the fluorescence intensity of CdTe QDs/CTAB probe could be quenched by p-nitrophenol due to the ET mechanism. The fluorescence intensity of the QD/CTAB system was proportional to PM concentration in the range of 25-3000 ng mL(-1), with a detection limit of 18 ng mL(-1). Furthermore, the proposed method was simple in design and fast in operation, and has been successfully used for PM detection in environmental and agricultural samples with satisfactory recovery.
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Dual effects of amiodarone on pacemaker currents in hypertrophied ventricular myocytes isolated from spontaneously hypertensive rats.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 05-13-2014
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The pacemaker current If conducted by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels plays a critical role in the regulation of cardiac automaticity, with If density increased in hypertrophied ventricular myocytes. Amiodarone, a highly effective anti-arrhythmic agent, blocks human HCN currents and native If under normal conditions. To determine the effects of amiodarone under pathological conditions, we monitored If under after both acute (0.01, 0.1, 1, 10 and 100 ?mol/L) and chronic (10 ?mol/L) amiodarone treatment in ventricular myocytes from spontaneously hypertensive rats (SHR) with left ventricular hypertrophy using the whole-cell patch-clamp technique. The If current density was significantly greater in SHR ventricular myocytes than in cells from healthy normotensive control Wistar-Kyoto (WKY) rats. Acute application of amiodarone significantly decreased If density in myocytes from both SHR and WKY rats. The inhibition was concentration dependent with an IC50 of 4.9 ± 1.2 and 6.9 ± 1.3 ?mol/L in myocytes from SHR and WKY rats, respectively. Amiodarone increased the activation and deactivation times of If in myocytes from SHR, although it did not alter the relationship of voltage-dependent activation and the reversal potential of If in myocytes from SHR. Chronic exposure of myocytes from SHR to amiodarone potently inhibited If and downregulated HCN2 and HCN4, the major channel subtypes underlying native If , at both the mRNA and protein level. These findings indicate that amiodarone inhibits If under hypertrophied conditions through dual mechanisms: (i) direct channel blockade of If currents; and (ii) indirect suppression via negative regulation of HCN channel gene expression. These unique properties of amiodarone may contribute to its anti-arrhythmic properties under pathological conditions.
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Characterization and expression analysis of two distinct neuropeptide Ya paralogues in Jian carp (Cyprinus carpio var. Jian).
Fish Physiol. Biochem.
PUBLISHED: 05-06-2014
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Two distinct neuropeptide Ya paralogues (jlNPYa1 and jlNPYa2) were cloned and characterized in Jian carp (Cyprinus carpio var. Jian), with a highly conserved organization encoded by four exons and three introns. The cDNAs for jlNPYa1 and jlNPYa2 were 693 and 730 bp in size, respectively. jlNPYa1 and jlNPYa2 both encoded a 96-amino acid protein, which shared 97.9 % identity. Phylogenetic tree showed that it has two NPYa genes, called jlNPYa1 and jlNPYa2, that presumably resulted from the tetraploidization event in the carp lineage. Analysis of expression profiles of jlNPYa1 and jlNPYa2 showed that the two NPY genes had a broad tissue distribution but expressed primarily in the forebrain, hypothalamus, testis and liver. The expression pattern was different in juvenile and adult (female and male) Jian carp. In juvenile, the highest expression level of jlNPYa1 and jlNPYa2 was detected in the testis. In adult, it was detected in the forebrain. In female hypothalamus, the expression level of jlNPYa1 was significantly higher than that of jlNPYa2. However, the opposite was true in male hypothalamus. The differing distribution patterns of the two NPY genes suggested that jlNPYa1 and jlNPYa2 might play different roles in Jian carp.
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Psychological stress induced hippocampus zinc dyshomeostasis and depression-like behavior in rats.
Behav. Brain Res.
PUBLISHED: 05-04-2014
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There are strong evidences showed that psychological stress (PS) could result in depression. Recently, many attentions were paid to the roles of corticosterone (CORT) and zinc dyshomeostasis in the development of depression. In this study, we investigated the zinc level in rat hippocampus after exposure to PS and accompanied behavior change. Male SD rats were randomly divided into the control and PS groups. Each group had two subgroups: 7-d group and 14-d group. A communication box was used to produce the PS model in rats. Compared to control group, the PS-treated group showed decreased total zinc levels and increased free zinc levels observed by TSQ staining in hippocampus. Meanwhile, there were significant decreases in mRNA expressions of zinc transporters including ZnT1, ZnT3 and ZIP1 and metallothionein (MT) contents in hippocampus. Moreover, the increased immobility time in forced swim test (FST), lower movement time and total movement distance and longer immobile time in spontaneous activity test were demonstrated in rats after PS exposure. These results suggested that the depression-like behavior in PS-treated rats might be correlated with zinc dyshomeostasis including decreased zinc contents and increased free zinc in hippocampus which was related to changes in zinc transporters and MT expressions.
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Development of a bi-enzyme tracer competitive enzyme-linked immunosorbent assay for detection of thiacloprid and imidaclothiz in agricultural samples.
Food Chem
PUBLISHED: 04-20-2014
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A bi-enzyme tracer direct competitive enzyme-linked immunosorbent assay (dc-ELISA) was developed based on anti-imidaclothiz and anti-thiacloprid antibodies. Several affected physicochemical factors were optimised, including methanol concentration, ionic strength and pH value. Under the optimised conditions, 50% inhibiting concentration (IC50) values for thiacloprid and imidaclothiz were 182.62 and 58.17 ?g/L, with a limit of detection (LOD) of 4.25 and 2.12 ?g/L, respectively. There was no obvious cross reactivity (CR) between the two pesticides with most neonicotinoids pesticides except imidacloprid. The method analyzing the spiked samples of tomato, pear and cabbage showed satisfying recoveries (85.27-113.07%). Comparable dissipation of thiacloprid and imidaclothiz in authentic tomato samples determined with the dc-ELISA and high performance liquid chromatography (HPLC) indicated that dc-ELISA is suitable for monitoring thiacloprid and imidaclothiz residues simultaneously in agricultural samples.
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Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men.
Nat Commun
PUBLISHED: 04-11-2014
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Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. Our previous genome-wide association study (GWAS) identified three susceptibility loci for NOA in Han Chinese men. Here we test promising associations in an extended three-stage validation using 3,608 NOA cases and 5,909 controls to identify additional risk loci. We find strong evidence of three NOA susceptibility loci (P<5.0 × 10(-8)) at 6p21.32 (rs7194, P=3.76 × 10(-19)), 10q25.3 (rs7099208, P=6.41 × 10(-14)) and 6p12.2 (rs13206743, P=3.69 × 10(-8)), as well as one locus approaching genome-wide significance at 1q42.13 (rs3000811, P=7.26 × 10(-8)). In addition, we investigate the phenotypic effect of the related gene (gek, orthologous to CDC42BPA) at 1q42.13 on male fertility using a Drosophila model. These results advance our understanding of the genetic susceptibility to NOA and provide insights into its pathogenic mechanism.
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Computerized segmentation of pulmonary nodules depicted in CT examinations using freehand sketches.
Med Phys
PUBLISHED: 04-04-2014
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To aid a consistent segmentation of pulmonary nodules, the authors describe a novel computerized scheme that utilizes a freehand sketching technique and an improved break-and-repair strategy.
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A hybrid antioxidizing and antibacterial material based on Ag-La2O3 nanocomposites.
J. Inorg. Biochem.
PUBLISHED: 03-28-2014
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The Ag-La2O3 hybrid nanoparticles were prepared by loading Ag nanoparticles on the surface of the La2O3 nanorods. The synthesis was a one-step process where sodium borohydride was used as a reducing agent to convert silver ions into silver nanoparticles, which were further deposited on the La2O3 nanorods. Moreover, they were found evenly dispersed upon the surface of La2O3 supports. The as-prepared Ag-La2O3 nanocomposites showed anti-oxidizing and significant antibacterial effect in vitro. Using the results from transmission electron microscope (TEM), the plausible mechanism was also proposed to explain the inhibition of bacterial growth. The present strategy can be potentially extended to develop drug-labels and other antibacterial agents.
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A genome-wide gene-environment interaction analysis for tobacco smoke and lung cancer susceptibility.
Carcinogenesis
PUBLISHED: 03-22-2014
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Tobacco smoke is the major environmental risk factor underlying lung carcinogenesis. However, approximately one-tenth smokers develop lung cancer in their lifetime indicating there is significant individual variation in susceptibility to lung cancer. And, the reasons for this are largely unknown. In particular, the genetic variants discovered in genome-wide association studies (GWAS) account for only a small fraction of the phenotypic variations for lung cancer, and gene-environment interactions are thought to explain the missing fraction of disease heritability. The ability to identify smokers at high risk of developing cancer has substantial preventive implications. Thus, we undertook a gene-smoking interaction analysis in a GWAS of lung cancer in Han Chinese population using a two-phase designed case-control study. In the discovery phase, we evaluated all pair-wise (591 370) gene-smoking interactions in 5408 subjects (2331 cases and 3077 controls) using a logistic regression model with covariate adjustment. In the replication phase, promising interactions were validated in an independent population of 3023 subjects (1534 cases and 1489 controls). We identified interactions between two single nucleotide polymorphisms and smoking. The interaction P values are 6.73 × 10(-) (6) and 3.84 × 10(-) (6) for rs1316298 and rs4589502, respectively, in the combined dataset from the two phases. An antagonistic interaction (rs1316298-smoking) and a synergetic interaction (rs4589502-smoking) were observed. The two interactions identified in our study may help explain some of the missing heritability in lung cancer susceptibility and present strong evidence for further study of these gene-smoking interactions, which are benefit to intensive screening and smoking cessation interventions.
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A genetic variant in pseudogene E2F3P1 contributes to prognosis of hepatocellular carcinoma.
J Biomed Res
PUBLISHED: 03-16-2014
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Certain pseudogenes may regulate their protein-coding cousins by competing for miRNAs and play an active biological role in cancer. However, few studies have focused on the association of genetic variations in pseudogenes with cancer prognosis. We selected six potentially functional single nucleotide polymorphisms (SNPs) in cancer-related pseudogenes, and performed a case-only study to assess the association between those SNPs and the prognosis of hepatocellular carcinoma (HCC) in 331 HBV-positive HCC patients without surgical treatment. Log-rank test and Cox proportional hazard models were used for survival analysis. We found that the A allele of rs9909601 in E2F3P1 was significantly associated with a better prognosis compared with the G allele [adjusted hazard ratio (HR) ?=? 0.69, 95% confidence interval (CI) ?=? 0.56-0.86, P ?=? 0.001]. Additionally, this protective effect was more predominant for patients without chemotherapy and transcatheter hepatic arterial chemoembolization (TACE) treatment. Interestingly, we also detected a statistically significant multiplicative interaction between genotypes of rs9909601 and chemotherapy or TACE status on HCC survival (P for multiplicative interaction < 0.001). These findings indicate that rs9909601 in the pseudogene E2F3P1 may be a genetic marker for HCC prognosis in Chinese.
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Nurses' roles in direct nursing care delivery in China.
Appl Nurs Res
PUBLISHED: 03-15-2014
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To study the nurses' roles in direct nursing care delivery in the neurology ward in China.
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Association of polymorphisms at HORMAD2 and prognosis in advanced non-small-cell lung cancer patients.
Cancer Epidemiol
PUBLISHED: 03-15-2014
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Cancer-testis (CT) genes are predominantly expressed in the testis and are ectopically activated in a wide range of cancers. The expression of CT antigens has been shown to significantly affect the survival of patients with non-small-cell lung cancer (NSCLC). Recently, a genome-wide association study (GWAS) and expression analysis have identified a novel CT gene (HORMAD2) associated with lung cancer risk in Han Chinese people. Thus, the aim of this study is to evaluate the potential prognostic value of HORMAD2 polymorphisms in Han Chinese patients with advanced NSCLC and undergoing first-line platinum-based chemotherapy.
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Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population.
Cancer Sci.
PUBLISHED: 03-06-2014
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Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome-wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk-related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case-control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81-0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double-edged sword, as modulator between the carcinogenesis processes of stomach and esophagus.
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Genetic variants in Ser-Arg protein-coding genes are associated with the risk of nonobstructive azoospermia in Chinese men.
Fertil. Steril.
PUBLISHED: 02-18-2014
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To evaluate the association between genetic variants in Ser-Arg (SR) protein-coding genes and the susceptibility of nonobstructive azoospermia (NOA) in Chinese men.
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Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population.
Mol. Carcinog.
PUBLISHED: 02-11-2014
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Aminoacyl-tRNA synthetases (ARSs) are responsible for cellular protein synthesis and cell viability involving in various process of tumorigenesis. We hypothesized that genetic variants in core ARSs genes may play an important role in the development of breast cancer. Thus, we conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of 28 potentially functional polymorphisms in 12 core ARSs genes (AARS, CARS, EPRS, HARS, KARS, LARS, MARS, QARS, RARS, VARS, WARS, and YARS) with breast cancer risk. We found significant associations with the risk of breast cancer for rs34087264 in AARS [odds ratio (OR)?=?1.15, 95% confidence interval (CI)?=?1.01-1.31], rs801186 in HARS (OR?=?1.29, 95% CI?=?1.08-1.54), rs193466 in RARS (OR?=?1.17, 95% CI?=?1.02-1.35), and rs2273802 in WARS (OR?=?1.14, 95% CI?=?1.01-1.30). We further observed significant interactions between rs2273802 and age at the first live birth (P?=?0.041), and between rs801186 and age on breast cancer risk (P?=?0.018). Combined analysis of these four SNPs showed a significant allele-dosage association between the number of risk alleles and breast cancer risk (Ptrend ?=?2.00?×?10(-4) ). Compared with individuals with "0-2" risk alleles, those carrying "3," "4," or "5 or more" risk alleles had a 1.32 (95% CI?=?1.07-1.64), 1.48 (95% CI?=?1.45-1.91), or 1.60 folds (95% CI?=?1.06-2.41) risk of breast cancer, respectively. These findings indicate that genetic variants in core ARSs genes may modify the individual susceptibility to breast cancer in Chinese population. © 2014 Wiley Periodicals, Inc.
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ABCC4 copy number variation is associated with susceptibility to esophageal squamous cell carcinoma.
Carcinogenesis
PUBLISHED: 02-07-2014
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Esophageal squamous cell carcinoma (ESCC) is the eighth most common cause of cancer-related death worldwide. However, previous genome-wide single nucleotide polymorphism association analyses have not explained the high heritability associated with ESCC. In this study, we performed genome-wide copy number variation (CNV) analysis on 128 discordant sibling pairs to identify novel genes that contribute to ESCC susceptibility. A total of 57 774 individual CNVs were identified, and an interactive network of common CNV-associated genes was constructed, which showed that several ABC transporter genes contain CNVs in ESCC patients. Independent validation of a CNV at 13q32.1 in 1048 northern Chinese Han subjects demonstrated that the amplification of ABCC4 significantly correlated with ESCC risk [odds ratio: 3.36 (1.65-7.93), P = 0.0013]. Immunohistochemistry staining suggested that high copy numbers correlated with increased protein levels. High expression of ABCC4 was an independent poor prognostic factor for ESCC [relative risk: 1.73 (1.10-2.73), P = 0.0181]. The CNV region showed strong enhancer activity. Furthermore, inhibition of ABCC4 protein in ESCC cells decreased cell proliferation and motility via the inhibition of COX-2, PGE2 receptors and c-Myc expression; AKT, extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation; and ?-catenin nuclear translocation in ESCC cells. In conclusion, the CNV at 13q32.1 is associated with ESCC susceptibility, and a gene within this locus, ABCC4, activates the oncogenic pathways in ESCC and thus facilitates cancer cell development and progression. A direct genetic contribution of ESCC risk through CNV common variants was determined in this study, and ABCC4 might therefore have predictive and therapeutic potential for ESCC.
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Effect of Yangyinqingfei decoction on radiation-induced lung injury via downregulation of MMP12 and TIMP-1 expression.
Exp Ther Med
PUBLISHED: 02-03-2014
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The aim of this study was to evaluate the effect and underlying mechanism of Yangyinqingfei decoction on radiation-induced lung injury in rats. Wistar rats (n=75) were randomly divided into five experimental groups (A-E). Rats in two of the groups were administered saline solution, whereas rats in the remaining three groups were administered different doses of Yangyinqingfei decoction. After one week, the rats were irradiated with a single dose of 25 Gy to their right hemi-thoraxes by a (60)Co ?-ray, with the exception of the control group, which underwent sham irradiation. The effect of Yangyinqingfei decoction was assessed one, two and four weeks post-irradiation according to the pathological changes and the right lung index (wet weight of right lung/body weight ×100%). Expression levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of metalloproteinases-1 (TIMP-1) in lung tissue were determined using the reverse transcription-polymerase chain reaction and western blot analysis. Pretreatment with Yangyinqingfei resulted in a significant dose-dependent resistance to radiation-induced body weight loss. The expression of MMP-12 and TIMP-1 increased following irradiation. However, the levels of MMP-12 and TIMP-1 in groups receiving Yangyinqingfei were lower four weeks after irradiation compared with those in rats administered saline. Cumulatively, these results suggest that Yangyinqingfei has a protective effect on radiation-induced lung injury in rats, possibly by downregulating MMP-12 and TIMP-1 expression.
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Parkinson?s disease-related modulation of functional connectivity associated with the striatum in the resting state in a nonhuman primate model.
Brain Res.
PUBLISHED: 01-26-2014
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The goal of this study was to describe Parkinson?s disease (PD)-related modulation of functional connectivity (FC) associated with the striatum in the resting state in a nonhuman primate model of early-stage PD. Weekly intravenous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (0.5 mg/kg body weight) were performed until parkinsonian motor symptoms developed in four macaques. After 13 weeks of MPTP treatment, all monkeys displayed parkinsonian symptoms. During the course of the experiment, each animal underwent four magnetic resonance imaging scans and four positron emission tomography (PET) scans with the vesicular monoamine transporter 2 (VMAT2)-selective ligand 9-[(18)F] fluoropropyl-(+)-dihydrotetrabenazine, performed prior to the beginning of MPTP administration as well as after 4, 9, and 13 MPTP injections. The FC profile of the striatum was evaluated using a seed voxel correlation approach and post hoc region of interest analysis on resting-state functional magnetic resonance imaging data. The PET images were subjected to region of interest analysis to examine brain regional reductions in VMAT2 density in the PD model. Significant reductions in the connectivity pattern of the striatal regions were observed: limbic striatum and left hippocampus; caudate nucleus/associative and brain regions, including the right pre-supplementary motor area and bilateral dorsolateral prefrontal cortex; putamen/associative region and left inferior temporal gyrus or right orbital and medial prefrontal cortex; and putamen/motor and cortical structures, including the right superior temporal gyrus and bilateral postcentral gyrus. Subsequent PET studies showed the progressive loss of striatal VMAT2 in the striatum with the presentation of parkinsonism. Significant differences between the specific uptake ratio reductions in each striatal subdivision were not found. By using a long-term, low-dose MPTP-lesioned nonhuman primate model, this study demonstrated PD-related decreased corticostriatal FC in a resting state; moreover, altered sensorimotor integration was also found in early-stage PD.
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A rapid and precise method for quantification of fatty acids in human serum cholesteryl esters by liquid chromatography and tandem mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 01-18-2014
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We described a rapid and precise method for simultaneous quantification of eleven fatty acids in human serum cholesteryl esters (CEFAs) by liquid chromatography and tandem mass spectrometry (LC-MS/MS). After extraction of serum lipids with isopropanol, CEFAs were separated on reversed phase liquid chromatography and detected by mass spectrometry in positive ion mode with multiple reaction monitor. Individual CEFA was quantified by peak area normalization method and expressed as molar percent of total CEFAs. The run time was less than 5 min and detection limits were from 0.31 to 14.50 × 10(-5)mmol/L. Recoveries of the CEFAs ranged from 91.85% to 104.83% with a mean of 99.12%. The intra and total CVs for the measurement of CEFAs were 0.87-7.70% and 1.02-7.65%, respectively. This LC-MS/MS method required no internal standards, eliminated natural isotope interferences, and provided reproducible and reliable results for 11 major CEFAs in human serum. This method can be used in monitoring and evaluating dietary fatty acid intake. Additional studies are needed to evaluate the associations between serum CEFAs and cardiovascular disease risk factors.
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Bidirectional elastic image registration using B-spline affine transformation.
Comput Med Imaging Graph
PUBLISHED: 01-14-2014
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A registration scheme termed as B-spline affine transformation (BSAT) is presented in this study to elastically align two images. We define an affine transformation instead of the traditional translation at each control point. Mathematically, BSAT is a generalized form of the affine transformation and the traditional B-spline transformation (BST). In order to improve the performance of the iterative closest point (ICP) method in registering two homologous shapes but with large deformation, a bidirectional instead of the traditional unidirectional objective/cost function is proposed. In implementation, the objective function is formulated as a sparse linear equation problem, and a sub-division strategy is used to achieve a reasonable efficiency in registration. The performance of the developed scheme was assessed using both two-dimensional (2D) synthesized dataset and three-dimensional (3D) volumetric computed tomography (CT) data. Our experiments showed that the proposed B-spline affine model could obtain reasonable registration accuracy.
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Methylation-associated silencing of microRNA-34b in hepatocellular carcinoma cancer.
Gene
PUBLISHED: 01-11-2014
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MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human cancers including HCC. Previous studies have identified miR-34 family as an important component of the tumor suppressor network during carcinogenesis. In this study, we investigated the methylation status of miR-34 family in HCC tumor and adjacent non-tumor tissues using methylation-specific PCR (MSP). The methylation frequencies of miR-34a and miR-34b/c were 72.1% (31/43) and 79.1% (34/43) in HCC tissues, which were significantly higher than that in the adjacent non-tumor tissues (P < 0.05), respectively. The results were validated by bisulfite sequencing PCR (BSP). Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that the expression of miR-34a and miR-34b was significantly down-regulated in HCC tissues compared with adjacent non-tumor tissues (P < 0.05). Moreover, the expression of miR-34b was inversely correlated to CpG island methylation in tumor tissues, but not for miR-34a. In summary, our results suggest that DNA methylation may be involved in the inactivation of miR-34b in HCC.
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Mediation of dopamine D2 receptors activation in post-conditioning-attenuated cardiomyocyte apoptosis.
Exp. Cell Res.
PUBLISHED: 01-09-2014
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The physiological and pathological roles of dopamine D2 receptors (DR2) in the regulation of cardiovacular functions have been recognized. DR2 activation protects hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and apoptosis, and ischemic post-conditioning (PC) plays a critical role in cardioprotection as well; however the involvement of the DR2 activation in the PC-induced cardioprotection is unknown. In the present study, we found that the H/R increased the expressions of DR2 mRNA and protein in cardiomyocytes, which were significantly enhanced by PC. Bromocriptine (Bro, a DR2 agonist) further increased DR2 expression, but Haloperidol (Hal, a DR2 antagonist) reversed the Bro-induced DR2 expressions. PC protected against H/R-induced apoptosis, the rise of [Ca(2+)]i, the expressions of cleaved caspase-3 and -9, release of cytochrome c, and mPTP opening. In addition, PC counteracted the reduction of cell viability caused by H/R, increased the phosphorylation of ERK1/2, PI3K, Akt, GSK-3? and mitochondrial membrane potential. PC further increased Bcl-2 expression, promoted PKC-? translocation to cell membrane, and activated the mitochondrial ATP-sensitive K channels (mKATP). Bro further enhanced the cardioprotective roles of PC, but Hal reversed these effects of Bro. Meanwhile, we found that DR2 was expressed in cell membrane and interacted with PKC-? in PC. In conclusion, these results suggest that PC attenuates cardiomyocyte apoptosis via inhibition of mPTP opening by DR2-mediated activation of ERK1/2, PI3K-Akt-GSK-3? and PKC-?-mKATP. These findings provide a novel target for the treatment of ischemic cardiomyopathy.
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Is the Excessive Use of Microblogs an Internet Addiction? Developing a Scale for Assessing the Excessive Use of Microblogs in Chinese College Students.
PLoS ONE
PUBLISHED: 01-01-2014
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More and more college students are using microblogs, with some excessive users demonstrating addiction-like symptoms. However, there is currently no published scale available for use in assessing excessive use of these microblogs, a significant impediment to advancing this area of research. We collected data from 3,047 college students in China and developed a Microblog Excessive Use Scale (MEUS) for Chinese college students, comparing it with criteria used for assessing Internet addiction. Our diagnostic scale featured three factors, two of which-"withdrawal and health problem" and "time management and performance"-are already included in Internet addiction assessment scales. The third factor, "social comfort," does not appear in Internet addiction assessment scales. Our study found that females have significantly higher MEUS scores than males, and that total MEUS scores positively correlated with scores from "self-disclosure" and "real social interaction" scales. These findings differ from results obtained in previous investigations into Internet addiction. Our results indicate that some characteristics of the excessive use of microblogs are different to those of Internet addiction, suggesting that microblog overuse may not correspond exactly to the state of Internet addiction.
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Astragalus mongholicus regulate the toll-like-receptor 4 meditated signal transduction of dendritic cells to restrain stomach cancer cells.
Afr J Tradit Complement Altern Med
PUBLISHED: 01-01-2014
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According to the traditional view, we depend on three methods to treat tumors; surgery, chemotherapy and radiotherapy. However, these methods have its own limitations in application. Traditional Chinese Medicine (TCM) is one of the oldest healing systems. Astragalus mongholicus (AMs) that is the common herbal medicine, the biggest part of TCM, have been proved to be effective in treating cancers from lots of clinical cases. However, we have not fully understood the anti-tumor mechanism of AMs, and this has lead to some doubt for some Western-Medicine scholars and restricts its wide use. The main objective of this research is to discuss the effect and mechanism of AMs to human stomach cancer.
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Replication of the 4p16 susceptibility locus in congenital heart disease in Han Chinese populations.
PLoS ONE
PUBLISHED: 01-01-2014
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Congenital heart disease (CHD) is the most common form of congenital human birth anomalies and a leading cause of perinatal and infant mortality. Some studies including our published genome-wide association study (GWAS) of CHD have indicated that genetic variants may contribute to the risk of CHD. Recently, Cordell et al. published a GWAS of multiple CHD phenotypes in European Caucasians and identified 3 susceptibility loci (rs870142, rs16835979 and rs6824295) for ostium secundum atrial septal defect (ASD) at chromosome 4p16. However, whether these loci at 4p16 confer the predisposition to CHD in Chinese population is unclear. In the current study, we first analyzed the associations between these 3 single nucleotide polymorphisms (SNPs) at 4p16 and CHD risk by using our existing genome-wide scan data and found all of the 3 SNPs showed significant associations with ASD in the same direction as that observed in Cordell's study, but not with other subtypes- ventricular septal defect (VSD) and ASD combined VSD. As these 3 SNPs were in high linkage disequilibrium (LD) in Chinese population, we selected one SNP with the lowest P value in our GWAS scan (rs16835979) to perform a replication study with additional 1,709 CHD cases with multiple phenotypes and 1,962 controls. The significant association was also observed only within the ASD subgroup, which was heterogeneous from other disease groups. In combined GWAS and replication samples, the minor allele of rs16835979 remained significant association with the risk of ASD (OR = 1.22, 95% CI = 1.08-1.38, P = 0.001). Our findings suggest that susceptibility loci of ASD identified from Cordell's European GWAS are generalizable to Chinese population, and such investigation may provide new insights into the roles of genetic variants in the etiology of different CHD phenotypes.
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Analysis of cross-reactive neutralizing antibodies in human HFMD serum with an EV71 pseudovirus-based assay.
PLoS ONE
PUBLISHED: 01-01-2014
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Hand, foot and mouth disease, associated with enterovirus 71 (EV71) infections, has recently become an important public health issue throughout the world. Serum neutralizing antibodies are major indicators of EV71 infection and protective immunity. However, the potential for cross-reactivity of neutralizing antibodies for different EV71 genotypes and subgenotypes is unclear. Here we measured the cross-reactive neutralizing antibody titers against EV71 of different genotypes or subgenotypes in sera collected from EV71-infected children and vaccine-inoculated children in a phase III clinical trial (ClinicalTrials.gov Identifier: NCT01636245) using a new pseudovirus-based neutralization assay. Antibodies induced by EV71-C4a were cross-reactive for different EV71 genotypes, demonstrating that C4a is a good candidate strain for an EV71 vaccine. Our study also demonstrated that this new assay is practical for analyses of clinical samples from epidemiological and vaccine studies.
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Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent studies have determined that branched-chain (BCAAs) and aromatic (AAAs) amino acids are strongly correlated with obesity and atherogenic dyslipidemia and are strong predictors of diabetes. However, it is not clear if these amino acids are capable of identifying subjects with coronary artery disease (CAD), particularly with subclinical atherosclerosis who are at risk of developing CAD.
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A genetic variant in primary miR-378 is associated with risk and prognosis of hepatocellular carcinoma in a Chinese population.
PLoS ONE
PUBLISHED: 01-01-2014
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MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis.
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Epidemiological and etiological characteristics of fever, thrombocytopenia and leukopenia syndrome in Henan Province, China, 2011-2012.
PLoS ONE
PUBLISHED: 01-01-2014
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The Fever, Thrombocytopenia and Leukopenia Syndrome (FTLS) is caused by a bunyavirus known as the FTLS virus (FTLSV), which was recently discovered in China. We examined the epidemiological and etiological features of 637 laboratory-confirmed cases of FTLS with onset from January 2011 to December 2012 in Henan Province, China. The highest incidence of FTLS occurred between May and August: 76.5% of all laboratory-confirmed cases occurred during those four months. Of the laboratory-confirmed cases, 60.9% were in the 46-69 years old age groups; 96.1% (612/637) occurred in farmers; 98.1% (625/637) were reported from Xinyang Prefecture. During the same time period, 2047 cases were reported in China. The nucleotide and amino acid sequences of FTLSV strains identified during 2011-2012 in Henan Province were ? 96% identical. This findings provides insight for developing public-health interventions for the control and prevention of FTLS in epidemic area.
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Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Genetic variants in human microRNA (miRNA) genes may alter mature miRNA processing and/or target selection, and likely contribute to cancer susceptibility and disease progression. Previous studies have suggested that miR-101 may play important roles in the development of cancer by regulating key tumor-associated genes. However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in breast cancer susceptibility remains unclear. In this study, we genotyped 11 SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study of 1064 breast cancer cases and 1073 cancer-free controls. The results revealed that rs462480 and rs1053872 in the flank regions of pre-miR-101-2 were significantly associated with increased risk of breast cancer (rs462480 AC/CC vs AA: adjusted OR = 1.182, 95% CI: 1.030-1.357, P = 0.017; rs1053872 CG/GG vs CC: adjusted OR = 1.179, 95% CI: 1.040-1.337, P = 0.010). However, the remaining 9 SNPs were not significantly associated with risk of breast cancer. Additionally, combined analysis of the two high-risk SNPs revealed that subjects carrying the variant genotypes of rs462480 and rs1053872 had increased risk of breast cancer in a dose-response manner (P(trend) = 0.002). Compared with individuals with "0-1" risk allele, those carrying "2-4" risk alleles had 1.29-fold risk of breast cancer. In conclusion, these findings suggested that the SNPs rs462480 and rs1053872 residing in miR-101-2 gene may have a solid impact on genetic susceptibility to breast cancer, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.
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A genetic variant in the promoter region of miR-106b-25 cluster predict clinical outcome of HBV-related hepatocellular carcinoma in Chinese.
PLoS ONE
PUBLISHED: 01-01-2014
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MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.
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Hepcidin is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Stz-Induced Diabetic Rats.
Diabetes
PUBLISHED: 12-30-2013
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Iron overload is frequently observed in type 2 diabetes mellitus (DM2) but the underlying mechanisms remains unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2.We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption and liver hepcidin expression in rats treated with streptozotocin (STZ) which was given alone or after a high-fat diet induced insulin resistance. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells.STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption, serum iron and hepatic iron content. Insulin obviously up-regulated hepcidin expression in HepG2 cells and enhanced STAT3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when STAT3 pathway was blocked, and could be partially inhibited by U0126.In conclusion, the present study suggests that hepcidin can be directly regulated by insulin and the suppressed liver hepcidin synthesis may be an important reason of the iron overload in DM2.
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A genome-wide gene-gene interaction analysis identifies an epistatic gene pair for lung cancer susceptibility in Han Chinese.
Carcinogenesis
PUBLISHED: 12-09-2013
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Lung cancer is the leading cause of cancer-related deaths worldwide. By now, genome-wide association studies (GWAS) have identified numerous loci associated with the risk of developing lung cancer. However, these loci account for only a small fraction of the familial lung cancer risk. We hypothesized that epistasis may contribute to the missing heritability. To test this hypothesis, we systematically evaluated the association of epistasis of genetic variants with risk of lung cancer in Han Chinese cohorts. We conducted a pair-wise genetic interaction analysis of 591,370 variants, using BOolean Operation-based Screening and Testing (BOOST), in an ongoing GWAS of lung cancer that includes 2,331 cases and 3,077 controls. Pairs of epistatic loci with PBOOST ? 1.00 × 10(-6) were further evaluated by a logistic regression model (LRM) with covariate adjustment. Four promising epistatic pairs identified at the screening stage (PLRM ? 2.86 × 10(-13)) were validated in two replication cohorts: the first from Beijing (1,534 cases and 1,489 controls), and the second from Shenyang and Guangzhou (2,512 cases and 2,449 controls). Using this combined analysis, we identified an interaction between rs2562796 and rs16832404 at 2p32.2 that was significantly associated with the risk of developing lung cancer (PLRM = 1.03 × 10(-13) in total 13,392 subjects). This study is the first investigation of epistasis for lung cancer on a genome-wide scale in Han Chinese. It addresses part of the missing heritability in lung cancer risk and provides novel insight into the multifactorial etiology of lung cancer.
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[Predictive equations of lung function for adults in north China urban areas].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 11-26-2013
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To establish predictive equations of lung function for adults in urban areas in north China.
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T-Box20 Suppresses Oxidized Low-Density Lipoprotein-induced Human Vascular Endothelial Cell Injury by Upregulation of PPAR-?.
Cell. Physiol. Biochem.
PUBLISHED: 09-13-2013
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Background: Atherosclerosis is a chronic inflammation disease which is initiated by endothelial cell injury Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. Many transcription factors take part in the initiation and progression of atherosclerosis. As a transcription factor mainly expressed in cardiovascular system, T-box20 (Tbx20) plays an important role in embryonic cardiovascular system development and homeostasis. However, the role of Tbx20 in endothelial cell injury and atherosclerosis is still not clear. We showed that Tbx20 might affect ox-LDL-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). Methods and Results: First, Tbx20 expression was down regulated in the C57BL/6 mice with high-fat diet-induced artery injury, which was accompanied by elevated reactive oxygen species (ROS) generation and cell adhesion molecule expression. Second, ox-LDL led to concurrent decreased Tbx20 expression and increased levels of ROS and adhesion molecules in the HUVECs. Third, over-expression of Tbx20 by adenovirus reduced ox-LDL-induced HUVEC injury via attenuation of ROS generation and cell adhesion molecule expression. Fourth, knock down of Tbx20 by siRNA significantly increased adhesion molecule expression and decreased cell viability. Moreover, Tbx20 could directly regulate PPAR-? expression, as shown by Tbx20 knock down and PPAR-? inhibition, which significantly reversed Tbx20s HUVEC protection effect. Conclusions: These results indicate that misregulation of Tbx20 could reduce HUVEC tolerance of ox-LDL-induced cell injury, suggesting that Tbx20 might be a crucial regulator and potential therapeutic target for atherosclerosis. © 2013 S. Karger AG, Basel.
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Analysis of drugs of abuse in wastewater from two Canadian cities.
Sci. Total Environ.
PUBLISHED: 09-10-2013
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Several drugs of abuse, including amphetamines, cocaine and its metabolite, benzoylecgonine and several opioid prescription drugs were detected in wastewater from two Canadian cities, a small community (75,000 population) and a large urban center (1.6million population). The objective of this study was to evaluate community use of these drugs in two cities with large differences in population size and demographics. In addition, we evaluated the use of the Polar Organic Chemical Integrative Sampler (POCIS) as a monitoring tool for drugs of abuse. Heroin was not detected at either location, probably because this illicit drug is metabolized to morphine prior to excretion. Acetylcodeine and acetylmorphine were also not detected. Estimates of community consumption from wastewater analysis indicated that the most widely used drug was cocaine at a median level of consumption in the larger city of approximately 38 doses per day per 1000 people. Consumption of the substituted amphetamine, ephedrine, as well as methamphetamine was also higher in the larger city, at 21 and 1.8 doses per day per 1000 people, respectively. Use of amphetamine, MDMA and tramadol were similar in both centers, but use of oxycodone was greater in the smaller city. Use of MDMA (ecstasy) peaked on weekends. Ketamine was detected in wastewater from the larger city; the first report of abuse of this veterinary anesthetic in a North American city. POCIS sampling rates were determined for the first time for 7 of the target compounds. Comparing the time weighted average concentrations estimated from POCIS data to the concentrations obtained from 24-h composite samples, the data were generally comparable, except for some compounds which were not detected in POCIS deployed in the untreated wastewater, probably because of biofouling or accumulation of debris on the cages containing the POCIS. This study indicates that the size and demographics of population centers can influence the patterns of abuse of drugs.
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Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations.
Carcinogenesis
PUBLISHED: 07-29-2013
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Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent case-control study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] = 0.69, 95% confidence interval [95% CI] = 0.55-0.87) and replication stage (OR = 0.80, 95% CI = 0.68-0.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream of TERT) was significantly associated with a decreased risk of gastric cancer (OR = 0.76, 95% CI = 0.67-0.87, P = 5.35 × 10(-5)). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P = 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.
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A potentially functional polymorphism in the promoter region of let-7 family is associated with survival of hepatocellular carcinoma.
Cancer Epidemiol
PUBLISHED: 07-27-2013
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Background: The let-7 family plays a vital role in the normal cellular activity of liver cells and the carcinogenesis of hepatocellular carcinoma (HCC). In the previous study, we have detected the association between single nucleotide polymorphisms (SNPs) in the promoter region of let-7 and susceptibility to HCC. However, it is still unknown whether these polymorphisms are associated with HCC prognosis. Methods: We investigated the effect of two potentially functional SNPs in the promoter region of let-7 family, rs10877887 (T>C) and rs13293512 (T>C), on the overall survival of 331 HCC patients. Log-rank test and Cox proportional hazard models were used for the survival analyses. Results: We found that HCC patients carrying the C allele of rs10877887 had a significantly increased death risk (adjusted HR=1.22, 95%CI=1.02-1.47, P=0.03 in the additive model), compared to those with T allele. In the stratified analysis, the risk effect was evident in HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B (adjusted HR=1.24, 95%CI=1.02-1.51, P=0.03) and in those who received chemotherapy or intervention (adjusted HR=1.25, 95%CI=1.02-1.53, P=0.04). Conclusions: Our results suggest that rs10877887 in the promoter region of let-7 may be a prognostic biomarker for HCC patients, which need the validation from other larger studies in different populations.
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The synergistic therapeutic effect of hepatocyte growth factor and granulocyte colony-stimulating factor on pulmonary hypertension in rats.
Heart Vessels
PUBLISHED: 07-12-2013
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Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary arterial pressure and vascular resistance. Despite advances in therapy for PAH, its treatment and prognosis remain poor. We aimed to investigate whether the transplantation of bone marrow mesenchymal stem cells (MSCs) overexpressing hepatocyte growth factor (HGF), alone or in combination with granulocyte colony-stimulating factor (G-CSF), attenuates the development of experimental monocrotaline (MCT)-induced PAH. Three weeks after MCT administration, rats were divided into the following groups: (1) untreated (PAH); (2) HGF treated; (3) MSCs administered; (4) HGF-MSCs treated; and (5) HGF-MSCs plus G-CSF treated. After 3 weeks, hemodynamic changes, histomorphology, and angiogenesis were evaluated. To elucidate the molecular mechanisms of vascular remodeling and angiogenesis, serum levels of transforming growth factor (TGF)-? and endothelin-1 (ET-1) were measured, and the gene and protein expression levels of vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) were determined. Compared with the PAH, MSC, and G-CSF groups, the HGF and HGF+G-CSF groups exhibited significantly reduced right ventricular hypertrophy and mean pulmonary arterial pressure (P < 0.05). Histologically, vessel muscularization or thickening and collagen deposition were also significantly decreased (P < 0.05). The number of vessels in the HGF+G-CSF group was higher than that in the other groups (P < 0.05). The TGF-? and ET-1 concentrations in the plasma of pulmonary hypertensive rats were markedly lower in the HGF and HGF+G-CSF groups (P < 0.05). Furthermore, HGF induced the expression of VCAM-1, and HGF treatment together with G-CSF synergistically stimulated MMP-9 expression. Transplanted HGF-MSCs combined with G-CSF potentially offer synergistic therapeutic benefit for the treatment of PAH.
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Genetic polymorphisms of xeroderma pigmentosum group D and prostate cancer risk: a meta-analysis.
J Cancer Res Ther
PUBLISHED: 06-18-2013
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The Xeroderma pigmentosum group D (XPD, also referred to as excision repair cross complementing gene 2, ERCC2) is one of key genes involved in nucleotide excision repair and two potentially functional polymorphisms of XPD (Asp312Asn and Lys751Gln) have been widely investigated in various cancers including prostate cancer. However, the results were conflicting rather than conclusive. Aims: Thus, we conducted a meta-analysis to evaluate the associations between these two polymorphisms of XPD and the risk of prostate cancer.
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Increasing glucagon secretion could antagonize the action of exogenous insulin for glycemic control in streptozocin-induced diabetic rhesus monkeys.
Exp. Biol. Med. (Maywood)
PUBLISHED: 06-14-2013
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Although intraislet insulin signaling is known to play a critical role in regulating glucagon secretion, it is unknown whether abnormal glucagon secretion influences the hypoglycemic effect of exogenous insulin with intraislet insulin deletion. We performed a longitudinal study using 16 streptozocin (STZ)-induced diabetic rhesus monkeys to explore ?-cell function under the absence ?-cells and to assess whether increasing glucagon secretion antagonizes the action of exogenous insulin for glycemic control. We found that although the ?-cells were impaired and the basal secretion levels of glucagon decreased rapidly after STZ (80-90 mg/kg) administration, as based on long-term observation post-STZ injection, glucagon secretion and the number of ?-cells were increased. Glycemic control was increasingly difficult, the insulin resistance (HOMA-IR) index was significantly higher, and the triglycerides (TG) levels were gradually decreased. Moreover, a significant correlation between the levels of glucagon and HOMA-IR was found. Under the long-term absence of ?-cells, the inhibitory effect on ?-cell activity is profoundly attenuated, leading to an increase in glucagon secretion and the amount of ?-cells and even ?-cell dysfunction. Increased glucagon levels have a serious impact on the insulin sensitivity in vivo and result in an antagonization of the hypoglycemic effect of exogenous insulin.
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IL-17 plays a central role in initiating experimental Candida albicans infection in mouse corneas.
Eur. J. Immunol.
PUBLISHED: 06-05-2013
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The pathogenesis of fungal infection in the cornea remains largely unclear. To understand how the immune system influences the progression of fungal infection in corneas, we inoculated immunocompetent BALB/c mice, neutrophil- or CD4? T-cell-depleted BALB/c mice, and nude mice with Candida albicans. We found that only immunocompetent BALB/c mice developed typical Candida keratitis (CaK), while the other mouse strains lacked obvious clinical manifestations. Furthermore, CaK development was blocked in immunocompetent mice treated with anti-IL-17A or anti-IL-23p19 to neutralize IL-17 activity. However, no significant effects were observed when Treg cells, ?? T cells, or IFN-? were immunodepleted. Upon infection, the corneas of BALB/c mice were infiltrated with IL-17-producing leukocytes, including neutrophils and, to a lesser degree, CD4? T cells. In contrast, leukocyte recruitment to corneas was significantly diminished in nude mice. Indeed, nude mice produced much less chemokines (e.g. CXCL1, CXCL2, CXCL10, CXCL12, CCL2, and IL-6) in response to inoculation. Remarkably, addition of CXCL2 during inoculation restored CaK induction in nude mice. In contrast to its therapeutic effect on CaK, neutralization of IL-17 exacerbated Candida-induced dermatitis in skin. We conclude that IL-17, mainly produced by neutrophils and CD4? T cells in the corneas, is essential in the pathogenesis of CaK.
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Molecular cloning, characterization and expression analysis of multiple leptin genes in Jian carp (Cyprinus carpio var. Jian).
Comp. Biochem. Physiol. B, Biochem. Mol. Biol.
PUBLISHED: 06-04-2013
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Three leptin genes (jlLEP-A1, jlLEP-A2 and jlLEP-B) were cloned and characterized in Jian carp (Cyprinus carpio var. Jian), with a highly conserved organization encoded by two exons and one intron. jlLEP-A1 and jlLEP-A2 contained 93 and 102bp introns, respectively, encoding a 171-amino acid protein. jlLEP-B contained a 687bp intron encoding a 168-aa protein. jlLEP-A1 and jlLEP-A2 shared 82.5% identity, but only 29.2% and 28.6% with jlLEP-B, respectively. jlLEP-A1, jlLEP-A2, and jlLEP-B were expressed in a wide range of tissues, but the expression pattern differed between juveniles and adults (and females and males). In juveniles, the expression of jlLEP-A1 and jlLEP-B was higher than jlLEP-A2, and was the highest in the liver and gonad. In females, jlLEP-A1 and jlLEP-A2 expression was the highest in the hypothalamus and liver, whereas jlLEP-B mRNA was detected at low levels in all tissues. In males, jlLEP-A1 mRNA was expressed primarily in the hypothalamus, with only very low levels in the peripheral tissues. jlLEP-A2 and jlLEP-B mRNA were primarily expressed in the muscle, hypothalamus, and liver. The expression of jlLEP-A1 and jlLEP-B mRNA was high in the ovary and testis, respectively. Our results suggest that leptins play an important physiological role in reproduction.
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Flavipin in Chaetomium globosum CDW7, an endophytic fungus from Ginkgo biloba, contributes to antioxidant activity.
Appl. Microbiol. Biotechnol.
PUBLISHED: 05-21-2013
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1,2-Benzenedicarboxaldehyde-3,4,5-trihydroxy-6-methyl (flavipin) was found to be antagonistic against nematodes and fungi. Here we demonstrated that flavipin is a potent antioxidant in vitro and in vivo, which has great potential in the therapy for free radical-associated diseases. Therefore, flavipin-producing bio-source was screened from 80 endophytes in Ginkgo biloba. Seven endophytic fungi were able to synthesize antioxidant substances and identified by ITS rDNA sequences. Among them, Chaetomium globosum CDW7 was a remarkable producer of flavipin. The fermentation parameters of CDW7 were then optimized for high flavipin production. Cultured under the optimal condition (25 °C, 100/250 mL flask, 12 discs/flask, 150 rpm, pH 6.5) for 14 days, CDW7 was able to synthesize flavipin at a production of 315.5 mg/L. In addition, flavipin output was positively correlated to antioxidant activities of crude extracts with a correlation coefficient of 0.8235, indicating that flavipin was the major antioxidant component of CDW7s metabolites. These data demonstrated that CDW7 was a highly yielded bio-source of antioxidant flavipin.
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Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population.
Gene
PUBLISHED: 05-07-2013
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Autophagy is a cellular process directed at recycling of cellular proteins and removal of intracellular microorganisms, which is important for balancing sources of energy at critical times in development and in response to nutrient stress. It has been reported to be a critical process in cancer initiation and progression. We hypothesized that genetic variants in critical genes of autophagy may be involve in the development of breast cancer. Thus, we systematically screened 14 potentially functional polymorphisms in six autophagy-related genes (ATG3, ATG5, ATG7, ATG10, and ATG12 and LC3) that are core components in autophagosome formation. We conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of these variants with breast cancer risk. We found that rs1864182 and rs10514231 in ATG10 were significantly associated with a decreased risk of breast cancer [odds ratios (OR)=0.77, 95% confidence interval (CI): 0.61-0.96, P=0.023; and OR=0.75, 95% CI: 0.59-0.93, P=0.010, respectively]. Similar protective effects for both loci were observed between subgroups stratified by ages at diagnosis/recruitment, menarche and first live birth, and status of menopause, estrogen receptor (ER) and progesterone receptor (PR). These results suggest that genetic variants in ATG10 may implicate with breast cancer susceptibility in Chinese population. Further large and functional studies are needed to confirm our findings.
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Epidemiological analysis of respiratory viral etiology for influenza-like illness during 2010 in Zhuhai, China.
Virol. J.
PUBLISHED: 04-30-2013
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Influenza-like illnesses (ILI), a subset of acute respiratory infections (ARI), are a significant source of morbidity and mortality worldwide. ILI can be caused by numerous pathogens, however; there is limited information on the etiology and epidemiology of ILI in China.
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Analysis of the complete genome sequences of one swine and two human hepatitis E virus genotype 4 strains isolated in Beijing, China.
Infect. Genet. Evol.
PUBLISHED: 04-26-2013
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Full-length sequences were determined and analyzed for two human (MO and W3) and one swine (W2-5) hepatitis E virus (HEV) isolates from Beijing, China. The genomes of the three strains were composed of 7242, 7239, 7239 nucleotides, respectively, excluding the poly (A) tails, and were 84% identical to each other. All were classified into genotype 4. Sequence analysis shows that the 2 human isolates have up to 91-94% nucleotide identity in full length genome with swine strains isolated in China, while the swine isolate share 92% identity with the human strain T1 from Beijing. At the amino acid level, the three strains share 94%, 97% and 89-92% identity in the ORF1, ORF2 and ORF3, proteins respectively. The human strains MO and W3 have the highest identity, 97%, 98-99% and 96-98% in ORFs 1-3, respectively, to swine strains CHN-XJ-SW13 and CHN-XJ-SW33 from Xinjiang, China, while swine strain W2-5 has highest identity with the human strain HE-JA2, 96%, 99% and 91% in ORFs 1-3, respectively. Genotype specific amino acid substitutions were found at a single site in all three ORFs by sequences alignment, and genotype specific short sequences (5-10aa in length) were found in ORF1 and the C-terminus of ORF3. However, no difference was found at any amino acid position that discriminates between human and swine HEVs within genotype 4 for any of the three ORFs. These results indicated that the genotype 4 HEV strains from humans and pigs in China may evolve from the common ancestor.
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Detection of a novel bunyavirus associated with fever, thrombocytopenia and leukopenia syndrome in Henan Province, China, using real-time reverse transcription PCR.
J. Med. Microbiol.
PUBLISHED: 04-25-2013
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A novel bunyavirus associated with fever, thrombocytopenia and leukopenia syndrome (FTLS) was discovered in Henan Province, China. Here, we report the development of an assay for this novel bunyavirus based on real-time reverse transcription PCR (RT-PCR). The assay exhibited high sensitivity and specificity without cross-reactivity towards 13 other viruses that cause similar symptoms. To evaluate the performance of this assay in detecting clinical samples, we analysed 261 serum samples from patients in Henan Province between 2007 and 2010. Of these samples, 91.95?% were bunyavirus positive. Compared with serological assays, the real-time PCR assay was much more sensitive in identifying infected patients 1 to 7 days after the onset of symptoms.
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Evaluation of genetic variants in microRNA biosynthesis genes and risk of breast cancer in Chinese women.
Int. J. Cancer
PUBLISHED: 04-15-2013
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MicroRNAs (miRNA) are a class of small, noncoding RNA molecules involved in a diversity of cellular functions. Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes may affect the biogenesis of miRNAs and consequently affect the miRNAs regulation. In this study, we systematically selected 24 functional SNPs located in eight key biosynthesis genes of miRNA (DROSHA, DGCR8, RAN, DICER, AGO2, GEMIN3, GEMIN4 and HIWI) and investigated the association between these SNPs and the risk of breast cancer in a Chinese population. All 24 SNPs were firstly genotyped in stage 1 (878 cases and 900 controls) and three promising SNPs (DROSHA rs2291109, RAN rs7301722 and DGCR8 rs417309) were selected for further validation in stage 2 (914 cases and 967 controls). We found that only one SNP (rs417309) located in the 3-UTR of DGCR8 was consistently associated with an increased breast cancer risk in two stages with a combined odds ratio (OR) of 1.50 [95% confidence interval (CI) = 1.16-1.93]. Based on the bioinformatics prediction, rs417309 is located at the binding sites of miR-106b and miR-579 in the 3-UTR of DGCR8. To evaluate whether rs417309 variant affects the binding capacity of miRNAs, we cotransfected luciferase reporter plasmids of DGCR8 3-UTR and miR-106b/miR-579 in three cell lines. Luciferase activity assay showed a higher expression level with rs417309 A allele compared with G allele in MCF-7 cell lines (p = 3.31 × 10(-7) , 9.29 × 10(-7) for miR-106b and miR-579, respectively). Our findings suggested that DGCR8 rs417309 G > A might affect breast cancer risk through the interruption of miRNA binding.
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A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations.
Nat. Genet.
PUBLISHED: 04-12-2013
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Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10??) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10?¹?) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10?¹²). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.
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Histopathological and ultrastructural examinations of rabbit coronary artery vasculitis caused by bovine serum albumin: an animal model of Kawasaki disease.
Ultrastruct Pathol
PUBLISHED: 04-12-2013
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To observe the histopathological and ultrastructural features of coronary artery vasculitis in rabbits caused by repeated intravenous injections of bovine serum albumin (BSA), mimicking Kawasaki disease.
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Evaluation of the efficacy and safety of hyaluronic acid vaginal gel to ease vaginal dryness: a multicenter, randomized, controlled, open-label, parallel-group, clinical trial.
J Sex Med
PUBLISHED: 04-09-2013
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Atrophic vaginitis is a common occurrence, particularly among postmenopausal women; however, few seek or receive treatment. One therapeutic solution is topically applied products. Estrogen-based treatments have been shown to be effective; however, many patients are reluctant to use such formulations due to health concerns, hence the need to assess the efficacy of acceptable alternatives.
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Expression of neuropeptide Y and pro-opiomelanocortin in hypothalamic arcuate nucleus in 17?-ethinyl estradiol-induced intrahepatic cholestasis pregnant rat offspring.
J. Obstet. Gynaecol. Res.
PUBLISHED: 04-02-2013
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The purpose of this study was to investigate the expression of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the hypothalamic arcuate nucleus of intrahepatic cholestasis pregnant (ICP) offspring.
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