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Find video protocols related to scientific articles indexed in Pubmed.
Sonic hedgehog signalling pathway regulates apoptosis through Smo protein in human umbilical vein endothelial cells.
Rheumatology (Oxford)
PUBLISHED: 11-20-2014
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The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells.
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Noise Evaluation of early images for Landsat 8 Operational Land Imager.
Opt Express
PUBLISHED: 11-18-2014
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This study performed an on-orbit evaluation of noise level for the Operational Land Imager (OLI) onboard Landsat 8 using early images over ground homogeneous sites. The signal-to-noise ratios (SNR) were higher than 160 of OLI nine bands at typical radiance level, while the noise equivalent radiance difference (NE?L) and the noise equivalent reflectance difference (NE??) were respectively lower than 0.8 W/m2/µm/sr and 0.002. Compared to pre-launch predictions, the on-orbit low noise and high SNR almost satisfied requirements for OLI bands, and can provide a prior knowledge for uncertainty analysis of OLI images in monitoring land surface, oceanic, and atmospheric status.
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Pharmacoeconomics Evaluation of Morphine, MS Contin and Oxycodone in the Treatment of Cancer Pain.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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To analyze cost-effectiveness of morphine, MS contin and oxycodone in the treatment of cancer pain, providing guidance for rational drug use in the clinic.
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Multi-responsive cellulose nanocrystal-rhodamine conjugates: an advanced structure study by solid-state dynamic nuclear polarization (DNP) NMR.
Phys Chem Chem Phys
PUBLISHED: 11-04-2014
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Multi-stimuli responsive materials based on cellulose nanocrystals (CNCs), especially using non-conventional stimuli including light, still need more explorations, to fulfill the requirements of complicated application environments. The structure determination of functional groups on the CNC surface constitutes a significant challenge, partially due to their low amounts. In this study, rhodamine spiroamide groups are immobilized onto the surface of CNCs leading to a hybrid compound being responsive to pH-values, heat and UV light. After the treatment with external stimuli, the fluorescent and correlated optical color change can be induced, which refers to a ring opening and closing process. Amine and amide groups in rhodamine spiroamide play the critical role in this switching process. Solid-state NMR spectroscopy coupled with sensitivity-enhanced dynamic nuclear polarization (DNP) was used to measure (13)C and (15)N in natural abundance, allowing the determination of structural changes during the switching process. It is shown that a temporary bond through an electrostatic interaction could be formed within the confined environment on the CNC surface during the heat treatment. The carboxyl groups on the CNC surface play a pivotal role in stabilizing the open status of rhodamine spiroamide groups.
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EPR detection of hydroxyl radical generation and oxidative perturbations in lead-exposed earthworms (Eisenia fetida) in the presence of decabromodiphenyl ether.
Ecotoxicology
PUBLISHED: 10-28-2014
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Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impacts on the oxidative perturbations and hydroxyl radical (·OH) generation in earthworms of exposure to the two chemicals remain almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the effects of Pb in earthworms Eisenia fetida in the presence of BDE209 through the use of several biomarkers in microcosms. The results have demonstrated that the addition of BDE209 (1 or 10 mg kg(-1)) decreased the enzymatic activities [superoxide dismutase, catalase (CAT), peroxidase] and total antioxidant capacity (T-AOC) compared with exposure to BDE209 alone (50, 250 or 500 mg kg(-1)). Electron paramagnetic resonance spectra indicated that ·OH radicals in earthworms were significantly induced by Pb in the presence of BDE209. The changing pattern of malondialdehyde (MDA) contents was accordant with that of ·OH intensity suggested that reactive oxygen species might lead to cellular lipid peroxidation. Furthermore, CAT exhibited more sensitive response to single Pb exposure than the other biomarkers, while T-AOC, ·OH and MDA might be three most sensitive biomarkers in earthworms after simultaneous exposure to Pb and BDE209. The results of these observations suggested that oxidative stress appeared in E. fetida, and it may play an important role in inducing the Pb and BDE209 toxicity to earthworms.
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One-Year Outcomes of Emergency Department Patients With Atrial Fibrillation: A Prospective, Multicenter Registry in China.
Angiology
PUBLISHED: 10-26-2014
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There is lack of data about patient characteristics, practice patterns, and long-term adverse outcomes in patients with atrial fibrillation (AF) attending emergency departments (EDs) in China. A total of 2016 patients from 20 representative EDs were included. During 1 year, all-cause mortality was 291 (14.6%) cases, stroke/noncentral nervous system systemic embolism rate was 159 (8.0%) cases, and major bleeding was 26 (1.3%) cases. Heart failure, the major cause of mortality, accounted for 43.0% of deaths. Of 375 (18.6%) patients who used warfarin at baseline, only 217 (57.9%) patients were still on anticoagulation therapy during 1-year follow-up. Compared with the patients who continued on warfarin, the mortality rate was higher in those who did not continue (15.9% vs 5.5%, P < .001). Patients seen in ED with AF appear to have a high incidence rate of long-term all-cause mortality and inadequate anticoagulation rate.
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[Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages].
Sheng Li Xue Bao
PUBLISHED: 10-22-2014
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The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 ?mol/L thapsigagin (TG) for 4 h. In addition, RAW264.7 cells were incubated with 0.5, 1 and 2 mg/L TM for 4 h or treated with 2 mg/L TM for 1, 2 and 4 h, respectively. The intracellular total cholesterol (TC) content was measured using a tissue/cell total cholesterol assay kit. The protein and mRNA expressions of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot and real-time PCR, respectively. Dil-ox-LDL uptake was detected using a microplate reader. The results showed that ox-LDL-induced cholesterol accumulation in macrophages was attenuated by PBA, an ERS inhibitor. Ox-LDL caused significant SR-A1 upregulation with concomitant activation of ERS as assessed by upregulation of GRP78, whereas PBA significantly inhibited the ox-LDL-induced SR-A1 upregulation (P < 0.05) and slightly decreased GRP78 expression by 39.3% (P = 0.057). TM, an ERS inducer, upregulated SR-A1 protein expression and ox-LDL uptake in dose- and time-dependent manner, but had no significant effect on SR-A1 mRNA level. However, the TM- or TG-induced SR-A1 upregulation and ox-LDL uptake were significantly mitigated by PBA. These data indicate that ERS plays a critical role in ox-LDL-induced SR-A1 upregulation, which in turn enhances the foam cell formation by uptaking more ox-LDL.
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A Missense Mutation in HK1 Leads to Autosomal Dominant Retinitis Pigmentosa.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-16-2014
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Retinitis pigmentosa (RP) is a genetically heterogeneous disease with over 60 causative genes known to date. Nevertheless, approximately 40% of RP cases remain genetically unsolved, suggesting that many novel disease-causing genes are yet to be identified. In this study, we aimed to identify the causative mutation for a large autosomal dominant RP (adRP) family with negative results from known retinal disease gene screening.
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[Analysis of SEDL gene mutation in a Chinese pedigree with X-linked spondyloepiphyseal dysplasia tarda].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 10-10-2014
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To explore the molecular mechanism for a family with hereditary X-linked spondyloepiphysealdysplasia tarda (SEDT).
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Src-dependent phosphorylation at Y406 on the thyroid hormone receptor ? confers the tumor suppressor activity.
Oncotarget
PUBLISHED: 10-03-2014
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Association studies suggest that the thyroid hormone receptor ?1 (TR?1) could function as a tumor suppressor in cancer cells. However, the underlying molecular mechanisms remain to be elucidated. We explored how TR?1 acted as a tumor suppressor in breast cancer MDA cells. Proliferation and invasiveness were markedly inhibited in cells stably expressing TR?1 (MDA-TR?1 cells). cSrc-phosphorylated TR?1 at Y406 signaled T3-induced degradation. Mutation of Y406 to Phe (TR?1Y406F) did not affect T3 binding affinity, but blocked T3-induced degradation in cells. Importantly, cell-based studies showed that TR?1Y406F lost the inhibitory effects by TR?1 on cell proliferation and invasion. Consistently, in xenograft models, MDA-TR?1 cells exhibited significantly slower tumor growth rates than those of Neo control cells. In contrast, the tumor growth rates of MDA-TR?1Y406F cells were indistinguishable from those of Neo control cells. We further showed that markedly more TR?1Y406F than TR?1 was physically associated with cSrc in cells, leading to constitutive activation of cSrc-FAK-ERK signaling. In contrast, degradation of T3-bound TR?1 complexed with cSrc attenuated signaling to decrease cell proliferation and invasiveness, thus confirming TR?1 as a tumor suppressor. Thus, the present studies suggested that TR?1 could be tested as a novel potential therapeutic target.
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IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis.
J. Immunol.
PUBLISHED: 09-26-2014
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Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E-deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A-induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E-deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system.
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Molecular mapping of a stripe rust resistance gene in wheat line C51.
J. Genet.
PUBLISHED: 09-06-2014
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Stripe rust, a major disease in areas where cool temperatures prevail, can strongly influence grain yield. To control this disease, breeders have incorporated seedling resistance genes from a variety of sources outside the primary wheat gene pool. The wheat line C51, introduced from the International Center for Agricultural Research in the Dry Areas (ICARDA), Syria, confers resistance to all races of Puccinia striiformis f. sp. tritici (PST) in China. To map the resistant gene(s) against stripe rust in wheat line C51, 212 F8 recombinant inbred lines (RILs) derived from the cross X440 x C51 were inoculated with Chinese PST race CYR33 (Chinese yellow rust, CYR) in the greenhouse. The result showed that C51 carried a single dominant gene for resistance (designated YrC51) to CYR33. Simple sequence repeat (SSR) and resistance gene-analogue polymorphism (RGAP) markers that were polymorphic between the parents were used for genotyping the 212 F8 RILs. YrC51 was closely linked to two SSR loci on chromosome 2BS with genetic distances of 5.1 cM (Xgwm429) and 7.2 cM (Xwmc770), and to three RGAP markers C51R1 (XLRR For / NLRR For), C51R2 (CLRR Rev / Cre3LR-F) and C51R3 (Pto kin4 / NLRRINV2) with genetic distances of 5.6, 1.6 and 9.2 cM, respectively. These RGAP-linked markers were then converted into STS markers.Among them, one STS marker, C51STS-4, was located at a genetic distance of 1.4 cM to YrC51 and was closely associated with resistance when validated in several populations derived from crosses between C51 and Sichuan cultivars. The results indicated that C51STS-4 can be used for marker assisted selection (MAS) and would facilitate the pyramiding of YrC51 with other genes for stripe rust resistance.
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Endoplasmic reticulum oxidoreductin 1? mediates hepatic endoplasmic reticulum stress in homocysteine-induced atherosclerosis.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 09-03-2014
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Endoplasmic reticulum (ER) stress is emerging as an important modulator of different pathological process and as a mechanism contributing to homocysteine (Hcy)-induced hepar injury. However, the molecular event that Hcy-induced ER stress in the hepar under the atherosclerosis background is currently unknown. Endoplasmic reticulum oxidoreductin 1? (ERO1?) plays a crucial role in maintaining ER stress function. In this study, we determined the expression of ERO1? in the hepar in hyperhomocysteinemia and the effect of ERO1? in hepacytes ER stress in the presence of Hcy. HHcy model was established by feeding the methionine diet in apolipoprotein-E-deficient (ApoE-/-) mice, and the hepatocytes were incubated with folate and different concentrations of Hcy. Our results showed that Hcy triggered ER stress characterized by an increased contents of glucose-regulated protein 78 (GRP78), protein kinase RNA-like ER kinase (PERK), activating transcription factor (ATF) 6 and X-box binding protein-1 (XBP-1). The ERO1? expressions in HHcy mice and Hcy-treated hepatocytes were decreased compared with those in ApoE-/- group and control hepacytes (P < 0.05), respectively. Knocking-down the expression of ERO1? with small-interfering RNA significantly augmented Hcy-induced ER stress. Meanwhile, the expressions of ER stress-related factor including GRP78, PERK, ATF6 and XBP-1, were significantly decreased when the ERO1? gene was over-expressed in hepacytes. Our results suggested that ERO1? may be involved in Hcy-induced hepar ER stress, and the inhibition of ERO1? expression can accelerate this process.
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Testis-specific Fank1 gene in knockdown mice produces oligospermia via apoptosis.
Asian J. Androl.
PUBLISHED: 09-03-2014
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Fank1 is exclusively expressed in the testis from the meiosis phase to the haploid phase of spermatogenesis. In this study, we examined the function of Fank1 by establishing a Fank1-knockdown transgenic mouse model. The apoptotic statuses of the testes of the transgenic mice were tested using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. The FANK1 consensus DNA-binding sequence was identified using cyclic amplification of sequence target (CAST) analysis. Differentially expressed genes were examined using microarray analysis. A reduction in sperm number and an increase in apoptotic spermatocytes were observed in Fank1-knockdown mice, and the apoptotic cells were found to be primarily spermatogonia and spermatocytes. The CAST results demonstrated that the consensus DNA-binding sequence was AAAAAG, in which the percentage occurrence of each base at each position ranged from 55 to 86%. This sequence was present in the promoter regions of 10 differentially expressed genes that were examined using microarray analysis. In total, 17 genes were differentially expressed with changes in their expression levels greater than twofold. The abnormal expression of Fank1 target genes that were regulated directly or indirectly by Fank1 reduced the number of sperm in the knockdown mice. Thus, FANK1 may play a pivotal role in spermatogenesis as a transcription factor.
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Effects of iodinated contrast agents on renal oxygenation level determined by blood oxygenation level dependent magnetic resonance imaging in rabbit models of type 1 and type 2 diabetic nephropathy.
BMC Nephrol
PUBLISHED: 09-02-2014
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To evaluate the effects of contrast agents containing increasing concentrations of iodine on the renal oxygenation level determined by blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) in a rabbit model of diabetic nephropathy.
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Meteorological Parameters and the Onset of Chest Pain in Subjects with Acute ST-Elevation Myocardial Infarction: an Eight-Year, Single-Center Study in China.
Cell. Physiol. Biochem.
PUBLISHED: 09-01-2014
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Objective: The purpose of this study was to investigate the influence of weather on the occurrence of acute ST-elevation myocardial infarction in Chinese subjects. Methods: Weather and climate data, as well as the occurrence of STEMI, were monitored at 2 am, 8 am, 2 pm, and 8 pm between 2003 and 2010. Generalized additive Poisson models were utilized to plot the numbers of patients with STEMI within 6 hour intervals against climatological variations, after accounting for the effects of the hour and season. Results: The inclusion of meteorological conditions, including observed atmospheric pressure (hPa, hectopascal) variations during the previous three hours and temperature (°C, degrees Celsius), significantly affected the occurrence of STEMI, as measured every six hours. Compared with the 50th percentile of atmospheric pressure variations, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of atmospheric pressure variation over lag 0 were 1.66 (1.36?2.03), 1.47 (1.30?1.67), 1.22 (1.12?1.33), 1.16 (1.07?1.25), 1.27 (1.13?1.43), and 1.16 (0.92?1.46), respectively. Compared to the 50th percentile of temperature, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of temperature over lag 0 were 0.58 (0.40?0.83), 0.60 (0.46?0.78), 0.69 (0.57?0.83), 1.33 (1.14?1.56), 1.39 (1.13?1.71), and 1.17 (0.84?1.63), respectively. Conclusions: Based on the eight-year, single-center study, significant relationships were observed among the occurrence of STEMI and atmospheric pressure variations during the previous three hours and temperature after account for long-term time trends. © 2014 S. Karger AG, Basel.
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Genome-wide sequencing of small RNAs reveals a tissue-specific loss of conserved microRNA families in Echinococcus granulosus.
BMC Genomics
PUBLISHED: 08-29-2014
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MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown.
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Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes.
J Clin Pharmacol
PUBLISHED: 08-28-2014
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This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300??g PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3?hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity.
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Hemoglobin A1c risk score for the prediction of coronary artery disease in subjects with angiographically diagnosed coronary atherosclerosis.
Cell. Physiol. Biochem.
PUBLISHED: 08-18-2014
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To develop a risk score by incorporating Hemoglobin A1c(HbA1c) with traditional risk factors for the prediction of coronary artery disease (CAD) in Chinese subjects.
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PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer.
Cancer Res.
PUBLISHED: 08-18-2014
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Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers.
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Autophagy-like processes are involved in lipid droplet degradation in Auxenochlorella protothecoides during the heterotrophy-autotrophy transition.
Front Plant Sci
PUBLISHED: 08-14-2014
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Autophagy is a cellular degradation process that recycles cytoplasmic components in eukaryotes. Although intensively studied in yeast, plants, and mammals, autophagy in microalgae is not well understood. Auxenochlorella protothecoides is a green microalga that has the ability to grow either autotrophically when under light or heterotrophically when in media containing glucose. The two growth modes are inter-convertible and transition between them is accompanied by drastic changes in morphology and cellular composition; however, the mechanisms underlying these changes are unknown. In this study, we identified autophagy-related genes and characterized their roles in the degradation of lipid droplets during the heterotrophy-to-autotrophy (HA) transition in A. protothecoides. Most of the proteins constituting the eukaryotic "core machinery" were conserved in A. protothecoides. Two proteins, Atg4 and Atg8, were further investigated. A. protothecoides ATG4 was cloned from a cDNA library and expressed within yeast, and was able to functionally restore the autophagy pathway in atg4? yeast during nitrogen starvation. Furthermore, Atg8, which displayed high sequence identity with its yeast homolog, was able to conjugate to phosphatidylethanolamine (PE) in vitro and was recruited to the phagophore assembly site in yeast. We also identified a C-terminal glycine residue, G118, that was the cleavage site for Atg4. Finally, we used confocal and transmission electron microscopy to reveal that autophagic-like vacuoles were detectable in algal cells during the HA transition. Our data suggested that the lipid droplets in heterotrophic cells were engulfed directly by the autophagic-like vacuole instead of via autophagosomes.
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Evaluation of ghrelin level and appetite regulation in patients with acute exacerbations of chronic obstructive pulmonary disease.
Int J Chron Obstruct Pulmon Dis
PUBLISHED: 08-14-2014
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Appetite reduction is a major cause of cachexia in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study tested the correlation of appetite and circulating levels of acylated ghrelin in patients with AECOPD.
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Comparison of the clinical features and outcomes in two age-groups of elderly patients with atrial fibrillation.
Clin Interv Aging
PUBLISHED: 08-12-2014
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Atrial fibrillation (AF) disproportionately affects older adults. However, direct comparison of clinical features, medical therapy, and outcomes in AF patients aged 65-74 and ? 75 years is rare. The objective of the present study was to evaluate the differences in clinical characteristics and prognosis in these two age-groups of geriatric patients with AF.
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Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like effects and enhances adult hippocampal neurogenesis and synaptic plasticity.
Hippocampus
PUBLISHED: 08-12-2014
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The endocannabinoid ligand 2-arachidonoylglycerol (2-AG) is inactivated primarily by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments with MAGL inhibitor JZL184 produce antidepressant- and anxiolytic-like effects in a chronic unpredictable stress (CUS) model of depression in mice. However, the underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis has been implicated in animal models of anxiety and depression and behavioral effects of antidepressants. We tested whether CUS and chronic JZL184 treatments affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of mouse hippocampus. We report that CUS induced depressive-like behaviors and decreased the number of bromodeoxyuridine-labeled neural progenitor cells and doublecortin-positive immature neurons in the DG, while chronic JZL184 treatments prevented these behavioral and cellular deficits. We also investigated the effects of CUS and chronic JZL184 on a form long-term potentiation (LTP) in the DG known to be neurogenesis-dependent. CUS impaired LTP induction, whereas chronic JZL184 treatments restored LTP in CUS-exposed mice. These results suggest that enhanced adult neurogenesis and long-term synaptic plasticity in the DG of the hippocampus might contribute to antidepressant- and anxiolytic-like behavioral effects of JZL184. © 2014 Wiley Periodicals, Inc.
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RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway.
Mol. Neurobiol.
PUBLISHED: 08-10-2014
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In the present study, we investigated whether Raf-1 kinase inhibitory protein (RKIP) is important for neural cell apoptosis induced by microwave exposure and explored the role of MEK/ERK/CREB pathway regulated by RKIP in the apoptosis. Differentiated PC12 cells were exposed to continuous microwave radiation at 2.856 GHz for 5 min with average power density of 30 mW/cm(2). RKIP sense and anti-sense recombinant plasmids were constructed and transfected into PC12 cells, respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to detect cell apoptosis. The results showed that RKIP was downregulated after microwave exposure while the MEK/ERK/CREB signaling pathway was activated excessively. Moreover, the ratio of Bcl-2/Bax decreased, activity of caspase-3 increased, and thus apoptotic DNA fragmentation increased. RKIP overexpression significantly inhibited the phosphorylation of MEK, ERK, and CREB, while RKIP downregulation had the reverse effect. Furthermore, U0126 was found to antagonize the changes caused by RKIP downregulation after exposure to radiation. In conclusion, RKIP plays an important role in the neural cell apoptosis induced by microwave radiation, and the regulation of cell apoptosis by RKIP is partly through the MEK/ERK/CREB pathway. This suggests that RKIP may act as a key regulator of neuronal damage caused by microwave radiation.
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Limonoid and Steroidal Saponin from Azadirachta indica.
Nat Prod Bioprospect
PUBLISHED: 08-07-2014
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A new limonoid, 17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide (1), and a new C21 steroidal saponin, 2?,4?-dihydroxy-pregn-5-en-16-one-3?-O-D-glucopyranoside (2), together with 11 known compounds were isolated from the methanol extract of the leaves of Azadirachta indica. The structures were elucidated by means of spectroscopic analysis and putative biosynthetic origins. All the compounds were evaluated for their antibacterial activities against six bacterial strains.
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Relapse of clubfoot after treatment with the Ponseti method and the function of the foot abduction orthosis.
Clin Orthop Surg
PUBLISHED: 08-05-2014
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Ponseti clubfoot treatment has become more popular during the last decade because of its high initial correction rate. But the most common problem affecting the long-term successful outcome is relapse of the deformity. Non-compliance with Ponseti brace protocol is a major problem associated with relapse. Although more comfortable braces have been reported to improve the compliance, they all have the same design and no significant changes have been made to the protocols. After refinement in the Ponseti method and emphasizing the importance of brace to parents, the relapse rate has been markedly decreased. Nevertheless, there are patients who do not have any recurrence although they are not completely compliant with the brace treatment, whereas other patients have a recurrence even though they are strictly compliant with the brace treatment. The aim of this article is to review the relapse of clubfoot and the function of the brace and to develop an individualized brace protocol for each patient by analyzing the mechanism of the brace and the biomechanical properties of muscles, tendons, and ligaments.
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Wogonin Reverses Multi-Drug Resistance of Human myelogenous leukemia K562/A02 cells via Downregulation of MRP1 Expression by Inhibiting Nrf2/ARE Signaling Pathway.
Biochem. Pharmacol.
PUBLISHED: 07-28-2014
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Constitutive NF-E2-related factor 2(Nrf2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Previously, much effort has been devoted to the investigation of blocking Nrf2 function in cultured cells and cancer tissues, but few research has been undertaken to evaluate the precise mechanism of flavonoids-induced sensitivity by inhibiting Nrf2. In this study, we investaged the reversal effect of Wogonin, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, in resistant human myelogenous leukemia. Data indicated that Wogonin had strong reversal potency by inhibiting functional activity and expression of MRP1 at both protein and mRNA in adriamycin(ADR)-induced resistant human myelogenous leukemia K562/A02 cells. Consequently, the inhibition of MRP1 by Wogonin was dependent on Nrf2 through the decreased binding ability of Nrf2 to antioxidant response element(ARE). Further research revealed Wogonin modulated Nrf2 through the reduction of Nrf2mRNA at transcriptional processes rather than RNA degradation, which is regulated by the PI3K/Akt pathway. Moreover, DNA-PKcs was found to be involved in the Wogonin-induced downregulation of Nrf2 mRNA at transcriptional levels. In summary, these results clearly demonstrated the effectiveness of using Wogonin via inhibiting Nrf2 to combat chemoresistance and suggested that Wogonin can be developed into an efficient natural sensitizer for resistant human myelogenous leukemia.
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Platelet-Rich Plasma in Arthroscopic Rotator Cuff Repair: A Meta-Analysis of Randomized Controlled Trials.
Arthroscopy
PUBLISHED: 07-27-2014
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The purpose of this study was to appraise the retear rate and clinical outcomes of platelet-rich plasma use in patients undergoing arthroscopic full-thickness rotator cuff repair.
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The S28H mutation on mNeptune generates a brighter near-infrared monomeric fluorescent protein with improved quantum yield and pH-stability.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 07-25-2014
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For living deep-tissue imaging, the optical window favorable for light penetration is in near-infrared wavelengths, which requires fluorescent proteins with emission spectra in the near-infrared region. Here, we report that a single mutant Ser28His of mNeptune with a near-infrared (?650 nm) emission maxima of 652 nm is found to improve the brightness, photostability, and pH stability when compared with its parental protein mNeptune, while it remains as a monomer, demonstrating that there is still plenty of room to improve the performance of the existing near infrared fluorescence proteins by directed evolution.
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Development of a sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nine active compounds in rat plasma and its application to a pharmacokinetic study after administration of Viscum coloratu
J Sep Sci
PUBLISHED: 07-24-2014
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A simple, specific, and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous quantification of nine compounds including a new compound, rhamnazin-3-?-?-d-(6''-?-hydroxy-?-methyglutaryl)-?-d-glucoside-4'-?-?-d-glucoside, in rat plasma using baicalin as an internal standard. The plasma samples were pretreated and extracted by protein precipitation with 0.2% formic acid in acetonitrile. The analytes were separated on a Thermo Syncronis C18 column by gradient elution with a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at a flow rate of 0.25 mL·min(-1) . The detection of the analytes was performed on an electrospray ionization interface operating in positive ion and multiple reaction-monitoring acquisition modes. The calibration curves of these analytes showed good linearity (r > 0.99) within the test ranges. The lower limit of quantification ranged from 0.4 to 20.1 ng·mL(-1) for the analytes. The intra- and inter-day precision and accuracy were all within ±15%, and the recoveries were higher than 80.0%. The validated method was successfully applied to a pharmacokinetic study of the nine flavonoids after administration of the Viscum coloratum extracts by intravenous injection. This article is protected by copyright. All rights reserved.
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Effects of PLCE1 gene silencing by RNA interference on cell cycling and apoptosis in esophageal carcinoma cells.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-22-2014
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Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase C? gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigate the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.
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[Influence of particle sizes and content of effective compositions of Panax notoginseng powders crashing by superfine somminution technique].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-22-2014
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In this study, superfine comminution technique was applied to destroy the cell wall of the Panax notoginseng, and then the influence of the particle sizes and the content of effective composition of the P. notoginseng powders were learned, comparing with the common powders. Superfine comminution technique was used for 0.5, 1, 1.5, 2 h, respectively and the particle sizes, unifirmity were regarded as the evaluation index. Then, the sizes of the powders was measured that were crashed with different time by Malvern Mastersizer 2000 + Scricco 2000 and the total content of ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1 in the superfine powder of P. notoginseng were determined by HPLC-ELSD. Finally, the powder that crashed for two hours possess the more uniform in sizes that is at cell level, D50 is about 9.599 microm, the size distribution was presented as one peak, the other three samples were two peaks. The total content of the three saponins in the four samples that crashed for 0.5, 1, 1.5, 2 h by superfine comminution technique were 7.7%, 7.5%, 7.5%, 8.3%. However, the total content of the three ingredients in the common powder was 5.0%. This investigation indicated that superfine comminution technique has remarkable effect on particle size and uniformity of the common powder of P. notoginseng. By comparing the superfine powder and common powder, it was found that the method obviously improved the total content of the saponins and provided a basis for reducing dosage of notoginseng in clinical application, but the content and the crashed time were not the linear relationship. The crashed time can be chosen by combining with the demand partical sizes in the production.
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Synergistic signaling of KRAS and thyroid hormone receptor ? mutants promotes undifferentiated thyroid cancer through MYC up-regulation.
Neoplasia
PUBLISHED: 06-17-2014
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Undifferentiated thyroid carcinoma is one of the most aggressive human cancers with frequent RAS mutations. How mutations of the RAS gene contribute to undifferentiated thyroid cancer remains largely unknown. Mice harboring a potent dominant negative mutant thyroid hormone receptor ?, TR?PV (Thrb(PV/PV)), spontaneously develop well-differentiated follicular thyroid cancer similar to human cancer. We genetically targeted the Kras(G12D) mutation to thyroid epithelial cells of Thrb(PV/PV) mice to understand how Kras(G12D) mutation could induce undifferentiated thyroid cancer in Thrb(PV/PV)Kras(G12D) mice. Thrb(PV/PV)Kras(G12D) mice exhibited poorer survival due to more aggressive thyroid tumors with capsular invasion, vascular invasion, and distant metastases to the lung occurring at an earlier age and at a higher frequency than Thrb(PV/PV) mice did. Importantly, Thrb(PV/PV)Kras(G12D) mice developed frequent anaplastic foci with complete loss of normal thyroid follicular morphology. Within the anaplastic foci, the thyroid-specific transcription factor paired box gene 8 (PAX8) expression was virtually lost and the loss of PAX8 expression was inversely correlated with elevated MYC expression. Consistently, co-expression of KRAS(G12D) with TR?PV upregulated MYC levels in rat thyroid pccl3 cells, and MYC acted to enhance the TR?PV-mediated repression of the Pax8 promoter activity of a distant upstream enhancer, critical for thyroid-specific Pax8 expression. Our findings indicated that synergistic signaling of KRAS(G12D) and TR?PV led to increased MYC expression. Upregulated MYC contributes to the initiation of undifferentiated thyroid cancer, in part, through enhancing TR?PV-mediated repression of the Pax8 expression. Thus, MYC might serve as a potential target for therapeutic intervention.
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Limb salvage surgery following resection of a melanoma: Foot and ankle reconstruction using cutaneous flaps.
Oncol Lett
PUBLISHED: 06-12-2014
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Melanomas affect the foot and ankle region and are associated with a poor prognosis. The aim of the current study was to evaluate the functional and oncological outcomes of salvage surgery using cutaneous flaps for soft tissue reconstruction of the foot and ankle following the extended resection of a melanoma. A retrospective review was conducted to evaluate patients who presented with foot melanoma and underwent salvage surgery and defect reconstruction using three types of cutaneous flap (group S) or amputation (group A) between January 1999 and December 2010 at the First Hospital of Jilin University (Changchun, China). The postoperative mortality, surgical complications, functional outcomes and oncological outcomes were evaluated. Of the 21 patients, 11 were enrolled into group S and 10 were enrolled into group A. The median follow-up time of the patients was 58 months (range, 6-92 months). In group S, a reverse sural neurocutaneous island flap was used in six patients to perform the foot reconstruction, medial plantar flaps were used in four patients and lateral malleolus flaps were used in one patient. All 11 cutaneous flaps survived and provided satisfactory coverage. Only one cutaneous flap showed partial necrosis and required treatment comprising of debridement and regular changes to the wound dressing. The overall survival rate of patients was 65.0% and patients in the two groups experienced similar oncological outcomes. Salvage surgery with cutaneous flap reconstruction was found to be a reliable option for patients presenting with malignant melanoma of the foot and ankle.
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Synthesis, structure and spectroscopic properties of the trinuclear cobalt(II) and nickel(II) complexes based on 2-hydroxynaphthaldehyde and bis(aminooxy)alkane.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 06-08-2014
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A new Salen-type bisoxime ligand, 2,2'-[ethylenedioxybis(nitrilomethylidyne)]dinaphthol (H2L) and its corresponding cobalt(II) and nickel(II) complexes, [{CoL(DMF)}2(OAC)2Co] and [{NiL(H2O)}2(OAc)2Ni]?2C2H5OH have been synthesized, and characterized by elemental analyses, IR spectra, UV-vis spectra, TG-DTA and molar conductance measurements, etc. The X-ray crystal structure studies reveal that the cobalt(II) and nickel(II) complexes are symmetric trinuclear structures. All of the M(II) (Co(II) or Ni(II)) ions for the cobalt(II) or nickel(II) complexes are six-coordinated and have slightly distorted octahedral coordination geometries.
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Toxic effects of the joint exposure of decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) on soil microorganism and enzyme activity.
Environ. Toxicol. Pharmacol.
PUBLISHED: 05-29-2014
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Decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) are the main contaminants at e-waste recycling sites, and their potential toxicological effects have received extensive attention. However, the impact on soil culturable microbial population and enzyme activity of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the eco-toxicological response in the joint presence of BDE209 and TBBPA for the first time. The results have demonstrated some notable toxic effects due to long-term exposure to either or both contaminants. The inhibition ratios of microbial populations increased with incubation time and increasing concentrations of BDE209 or TBBPA following certain dose-response relationships and time-effect trends. The response sensitivity sequence was fungi>bacteria>actinomycete. The influence of the two chemicals on soil enzymes reached peak values on day 7, and highly significant differences (P<0.01) were observed compared to the controls. Urease was more susceptive to the two chemicals than catalase and saccharase activities. Generally, the joint toxicity of both contaminants on soil microbes, catalase or saccharase activities indicated antagonistic effects, while, as for urease activity, addition role was dominant. Such observations have provided the useful information of potential ecological effects of brominated flame retardants contamination in the environment.
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UBTD1 induces cellular senescence through an UBTD1-Mdm2/p53 positive feedback loop.
J. Pathol.
PUBLISHED: 05-25-2014
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The tumor suppressor p53 plays an important role in tumorigenesis. Besides inducing apoptosis, it regulates cellular senescence, which constitutes an important barrier to tumorigenesis. The mechanism of regulation of cellular senescence by p53 and its downstream pathway are poorly understood. Here, we report that the ubiquitin domain-containing 1 gene (UBTD1), a new downstream target of p53, induces cellular senescence and acts as a novel tumor suppressor by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular senescence induced by serial passaging of culture, as well as by exposure to DNA-damaging drugs that induce premature senescence. Overexpression of UBTD1 induces senescence in human fibroblasts and cancer cells, and attenuation of the transformed phenotype in cancer cells. UBTD1 is downregulated in gastric and colorectal cancer tissues, and its lower expression correlates with a more aggressive phenotype and worse prognosis. Multivariate analysis revealed that UBTD1 expression was an independent prognostic factor for gastric cancer patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein. Importantly,UBTD1 and p53 function mutually depend on each other in regulating cellular senescence and proliferation. Thus, our data suggests that upon DNA damage, p53 induction by UBTD1 creates a positive feedback mechanism to further increase p53 expression. Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumorigenesis.
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Percutaneous First Annular Pulley Release for Trigger Digits: A Systematic Review and Meta-Analysis of Current Evidence.
J Hand Surg Am
PUBLISHED: 05-09-2014
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To determine the overall success rate and potential influencing factors within the current evidence for percutaneous first annular pulley release.
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Optimal therapeutic dose and time window of picroside II in cerebral ischemic injury.
Neural Regen Res
PUBLISHED: 05-06-2014
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A preliminary study from our research group showed that picroside II inhibited neuronal apoptosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside II inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows: (1) 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; (2) 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; (3) 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and (4) 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.
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1,10-Phenanthroline-5,6-dione ethanol monosolvate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 05-01-2014
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In the title compound, C12H6N2O2·C2H5OH, the mol-ecule of the 1,10-phenanthroline-5,6-dione is approximately planar, with a maximum deviation of 0.051?(1)?Å. In the crystal, mol-ecules are linked by O-H?N and weak C-H?O hydrogen bonds, forming supra-molecular chains propagating along [110]. ?-? stacking inter-actions are observed between the pyridine rings of neighbouring chains, the centroid-centroid separations being 3.6226?(11) and 3.7543?(11)?Å.
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Asymmetric multibranched conjugated molecules: synthesis, structure and photophysical properties.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 04-29-2014
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The symmetric multibranched ?-conjugated compounds with C3 or C6 configuration have been intensively studied. The reports on asymmetric multibranched compounds are very limited. In this work, we designed and synthesized two asymmetric multibranched ?-conjugated molecules using truxene as the central core, diphenylamino and thiophenyl (or thiophenylethynyl) groups as the different branches respectively: 2,7-di(N,N-diphenylamino)-12-(2-thiophenyl)-5,5',10,10',15,15'-hexaethyltruxene and 2,7-di(N,N-diphenylamino)-12-(2-thiophenylethynyl)-5,5',10,10',15,15'-hexaethyltruxene. Their photophysical properties have been explored combining with their theoretical calculation and X-ray single-crystal structure of a key intermediate. Though their different ?-conjugation length of branches, the two title compounds exhibit almost same absorption maxima. However, their emission peaks behave a gradual red-shift with the increase of the conjugation length. The theoretical calculation results indicate that the two asymmetric compounds behave a main transition from the HOMO-1 to the LUMO or from the HOMO to the LUMO+1 upon excited.
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Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.
Mol. Neurobiol.
PUBLISHED: 04-27-2014
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Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.
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AP-2? downregulation by cigarette smoke condensate is counteracted by p53 in human lung cancer cells.
Int. J. Mol. Med.
PUBLISHED: 03-29-2014
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Cumulative findings have demonstrated that the dysregulation of tumor suppressor genes may be implicated in cigarette smoke-induced carcinogenesis. Activating enhancer-binding protein 2 (AP-2) is a eukaryotic transcriptional factor that plays a significant role in embryonic development and tumorigenesis. The vertebrate AP-2 family consists of AP-2?, AP-2?, AP-2?, AP-2? and AP-2?. Previous studies have suggested that cigarette smoking disrupts AP-2 regulation. In the present study, we investigated the effects of cigarette smoke condensate (CSC) on AP-2? expression in human lung cancer cell lines (NCI-H1299, NCI-H446 and A549), as well as the potential mechanisms involved. Using RT-qPCR, we found that CSC decreased AP-2? expression by suppressing its transcription in human lung cancer cell lines, particularly in p53-deficient NCI-H1299 cells. Western blotting and luciferase assays were implemented and we found that the restoration of p53 expression rescued the NCI-H1299 cells from CSC-induced AP-2? loss, while the silencing of p53 resulted in increased AP-2? loss induced by CSC, suggesting an antagonizing role of p53 in the regulation of AP-2? by CSC. Our results indicate that AP-2? downregulation may be involved in smoke-induced lung carcinogenesis.
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Angiotensin II protects cortical neurons against oxygen-glucose deprivation-induced injury in vitro.
Biomed Rep
PUBLISHED: 03-21-2014
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Ischemic cerebrovascular disease is a common type of cerebrovascular disease and the leading cause of disability and mortality worldwide. Therefore, it is crucial to elucidate its pathogenesis and develop novel therapeutic strategies. This study was performed to investigate whether angiotensin (Ang) II exerts a protective effect against cerebral ischemia/reperfusion (I/R) injury in vitro. The primary cultured neurons were prepared and an I/R model was established by incubation of cortical neurons with Na2S2O4, followed by culture in fresh medium. The protective effect of Ang II and its underlying mechanisms were investigated by morphology observation, MTT assay, flow cytometry analysis and reverse transcription-polymerase chain reaction (RT-PCR). The data demonstrated that Ang II significantly ameliorated the neuronal injury caused by oxygen-glucose deprivation. Furthermore, Ang II increased cell viability through inhibiting cell apoptosis. The RT-PCR results revealed that Ang II was able to reverse the increased bax mRNA and the decreased bcl2 mRNA expression. Of note, the protective activity of Ang II may be attenuated by co-treatment with Ang II type 2 (AT2) receptor blockade (PD123319), but not Ang II type 1 (AT1) receptor blockade (valsartan). These findings suggested that Ang II exerted a protective effect against neuronal injury induced by oxygen-glucose deprivation through decreasing cell apoptosis. Therefore, Ang II may be used as a potential therapeutic target in the future.
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Association between the ABO blood group and risk of common cancers.
J Evid Based Med
PUBLISHED: 03-20-2014
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To investigate the association between five common cancers in western China population and ABO blood group.
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Relationship of renin-angiotensin-aldosterone system polymorphisms and phenotypes to mortality in Chinese coronary atherosclerosis patients.
Sci Rep
PUBLISHED: 03-12-2014
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We performed a large, long-term cohort study to evaluate the association of renin-angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all-cause mortality among patients with angiographically confirmed coronary atherosclerosis. The study included 1075 subjects who underwent coronary angiography. Patients were genotyped for eight polymorphisms (rs4343, rs5186, rs5182, rs5049, rs5051, rs699, rs4762, and rs1799998), and their baseline plasma angiotensin II and aldosterone levels were measured. The interval between baseline and follow-up time-points ranged from 6.39 to 9.59 years. The results of multivariate regression analysis further indicated that high baseline angiotensin II levels (1.226 (1.024-1.468), p = 0.027) were independently associated with all-cause death. Therefore, we found that an increased baseline plasma angiotensin II level was associated with higher long-term all-cause mortality, even after correcting for established cardiovascular risk factors.
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Non-association of IL-16 rs4778889 T/C polymorphism with cancer risk in Asians: a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 02-27-2014
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The IL-16 rs4778889 T/C polymorphism is associated with cancer risk. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using PubMed, Embase and Web of Science databases. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. A total of 6 studies including 1,603 cases and 2,342 controls were identified. With all studies involved, results showed no statistically significant association between IL-16 rs4778889 T/C polymorphism and cancer risk (CC vs. CT+TT: OR=0.74, 95%CI: 0.55-1.02, Ph=0.15; CC+CT vs. TT: OR=0.89, 95%CI: 0.72-1.10, Ph =0.03; CC vs. TT: OR=0.73, 95%CI: 0.53- 1.00, Ph =0.08; CT vs. TT: OR=0.91, 95%CI: 0.79-1.05, Ph =0.08; C vs. T: OR=0.89, 95%CI: 0.74-1.07, Ph =0.02). In addition, the results were not changed when studies were stratified by cancer type. However, to verify our findings, it is essential to perform more well-designed studies with larger sample sizes in the future.
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Reversible posterior leukoencephalopathy syndrome induced by bevacizumab plus chemotherapy in colorectal cancer.
World J. Gastroenterol.
PUBLISHED: 02-20-2014
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Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare brain-capillary leak syndrome, characterized by clinical symptoms of headache, visual loss, seizures and altered mental functioning. This syndrome is usually reversible and is associated with hypertension, nephropathy, and use of immunosuppressive medication and cytotoxic agents. We describe two rare cases of RPLS occurring in colorectal cancer, both of which presented with coma, that we believe can be directly attributed to bevacizumab, a monoclonal antibody that inhibits the angiogenesis of tumours by specifically blocking vascular endothelial growth factor. We analysed the clinical features, risk factors and outcomes of RPLS in these two patients, and although no typical finding was identified on imaging examination, we found that inadequate blood pressure control was one of the risk factors leading to RPLS and that supportive treatment including intensive blood pressure control improved outcomes. Due to the increasing use of bevacizumab in colorectal cancer, clinicians should be aware of this potential complication.
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Resveratrol attenuates intermittent hypoxia?induced insulin resistance in rats: Involvement of Sirtuin 1 and the phosphatidylinositol?4,5?bisphosphate 3?kinase/AKT pathway.
Mol Med Rep
PUBLISHED: 02-09-2014
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Obstructive sleep apnea can induce chronic intermittent hypoxia (CIH) during sleep and is associated with obesity and diabetes. Resveratrol (RSV), a polyphenolic phytoalexin, can regulate glucose metabolism, thereby reducing insulin resistance. The present study aimed to assess whether RSV attenuates CIH?induced insulin resistance in rats and the underlying mechanisms. A total of 40 rats were randomly assigned into five groups: i) Control; ii) subjected to CIH only; iii) subjected to CIH and treated with 3 mg/kg/day of RSV; iv) subjected to CIH and treated with 30 mg/kg/day of RSV; v) subjected to CIH and treated with 60 mg/kg/day of RSV. All animals were sacrificed following 28 days of treatment. Subsequently, the blood and livers were harvested and blood insulin and glucose levels were measured. Levels of sirtuin (Sirt) 1, insulin receptor (InsR) and glucose transporter 2 (Glut2) in the liver were measured. RSV treatment was demonstrated to suppress weight gain and improve hepatic morphology. RSV treatment also significantly reduced the homeostasis model assessment estimate of insulin resistance of the rats exposed to CIH. This effect occurred in a dose?dependent manner. RSV significantly upregulated liver Sirt1 levels and inhibited InsR and Glut2 expression in the liver. Additionally, RSV activated the phosphorylation of phosphatidylinositol?4,5?bisphosphate 3?kinase (PI3K) and AKT. The present study demonstrates that RSV prevents CIH?induced insulin resistance in rats. Upregulation of Sirt1 and activation of PI3K/AKT signaling may be involved in this process.
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Bis-(thio-cyanato-?N)[tris(pyridin-2-yl-meth-yl)amine-?(4) N]-iron(II).
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 02-01-2014
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In the title complex, [Fe(NCS)2(C18H18N4)], the Fe(II) cation is chelated by a tris-(2-pyridyl-meth-yl)amine ligand and coordin-ated by two thio-cyanate anions in a distorted N6 octa-hedral geometry. In the crystal, weak C-H?S hydrogen bonds and ?-? stacking inter-actions between parallel pyridine rings of adjacent mol-ecules [centroid-centroid distance = 3.653?(3)?Å] link the mol-ecules into a two-dimensional supra-molecular architecture. The structure contains voids of 124?(9)?Å(3), which are free of solvent molecules.
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Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.
Int. J. Mol. Med.
PUBLISHED: 01-31-2014
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Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose?induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose?induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose?induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures.
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The operating performance of a biotrickling filter with Lysinibacillus fusiformis for the removal of high-loading gaseous chlorobenzene.
Biotechnol. Lett.
PUBLISHED: 01-20-2014
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Removal of gaseous chlorobenzene (CB) by a biotrickling filter (BTF) filled with modified ceramics and multi-surface hollow balls during gas-liquid mass transfer at the steady state was by microbial degradation rather than dissolution in the spray liquid or emission into the atmosphere. The BTF was flexible and resistant to the acid environment of the spray liquid, with the caveat that the spray liquid should be replaced once every 6-7 days. The BTF, loaded with Lysinibacillus fusiformis, performed well for purification of high-loading CB gas. The maximum CB gas inlet loading rate, 103 g m(-3) h(-1), CB elimination capacity, 97 g m(-3) h(-1), and CB removal efficiency, 97.7 %, were reached at a spray liquid flow rate of 27.6 ml min(-1), an initial CB concentration of up to 1,300 mg m(-3), and an empty bed retention time of more than 45 s.
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Chemical and toxicological investigations of a previously unknown poisonous European mushroom Tricholoma terreum.
Chemistry
PUBLISHED: 01-20-2014
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The established tradition of consuming and marketing wild mushrooms has focused attention on mycotoxicity, which has become a global issue. In the present study, we describe the toxins found in a previously unknown poisonous European mushroom Tricholoma terreum. Fifteen new triterpenoids terreolides?A-F (1-6) and saponaceolides?H-P (8-16) were isolated from the fruiting bodies of the toxic mushroom T. terreum. Terreolides?A-C (1-3) possessed a unique 5/6/7 trioxaspiroketal system, whereas terreolides D-F (4-6) possessed an unprecedented carbon skeleton. Two abundant compounds in the mushroom, saponaceolide?B (7) and saponaceolide?M (13), displayed acute toxicity, with LD50 values of 88.3 and 63.7?mg?kg(-1) when administered orally in mice. Both compounds were found to increase serum creatine kinase levels in mice, indicating that T. terreum may be the cause of mushroom poisoning ultimately leading to rhabdomyolysis.
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Omentin-1 promotes the growth of neural stem cells via activation of Akt signaling.
Mol Med Rep
PUBLISHED: 01-13-2014
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Omentin is a novel adipokine, which is expressed in and released from omental adipose tissue. In the present study, the effect of omentin on neural stem cells (NSCs) was investigated. NSCs are a subtype of stem cell in the nervous system, which are able to self?renew and generate neurons and glia for repairing neural lesions. Mouse NSCs were isolated and cultured in vitro. Treatment with recombinant omentin for 3 and 5 days significantly increased the size of NSC neurospheres (P<0.01) and enhanced NSC cell viability in normal conditions. In addition, omentin protected against the decrease in cell viability induced by the pro?inflammatory cytokine tumor necrosis factor??. In the NSCs, incubation of omentin for 2, 4, 6, 8 and 16 h enhanced the phosphorylation of Akt at the Thr308 site and of AS160 at the Ser318 site, peaking 6 h after treatment. Additionally, treatment with LY294002 (10 µM), a specific inhibitor of phosphatidylinositol 3?kinase/Akt signaling, eliminated the omentin?induced increase in neurosphere size and cell viability. Overall, the present study provided the first evidence, to the best of our knowledge, that omentin promotes the growth and survival of NSCs in vitro through activation of the Akt signaling pathway. These results may contribute to the understanding of the role of omentin in the nervous system.
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MiR-21 inhibits c-Ski signaling to promote the proliferation of rat vascular smooth muscle cells.
Cell. Signal.
PUBLISHED: 01-07-2014
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Previously, we reported that the decrease of endogenous c-Ski expression is implicated in the progression of vascular smooth muscle cell (VSMC) proliferation after arterial injury. However, the molecular mechanism of the down-regulation of c-Ski is not clear. In this study, a potential miR-21 recognition element was identified in the 3'-untranslated region (UTR) of rat c-Ski mRNA. A reporter assay revealed that miR-21 could recognize the miR-21 recognition element of c-Ski mRNA. In A10 rat aortic smooth muscle cells, overexpression of miR-21 significantly inhibited the expression of c-Ski protein and promoted cell proliferation, which could be blocked by inhibition of miR-21 or overexpression of c-Ski. Further investigation demonstrated that the effect of miR-21 on VSMC proliferation resulted from negative regulation of c-Ski to suppress p38-p21/p27 signaling, the downstream pathway of c-Ski in VSMCs. These results indicate that c-Ski is a target gene of miR-21. miR-21 specifically binds to the 3'-untranslated region of c-Ski and negatively regulates c-Ski expression to diminish the protective effects of c-Ski and stimulate VSMC proliferation in the progression of arterial injury.
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Effects of vegetation on runoff generation, sediment yield and soil shear strength on road-side slopes under a simulation rainfall test in the Three Gorges Reservoir Area, China.
Sci. Total Environ.
PUBLISHED: 01-02-2014
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Vegetation recolonization has often been used to control roadside slope erosion, and in this paper, four restoration models - Natural Restoration, Grass, Grass & Shrub, Sodded Strip - were chosen to recolonize the plants on a newly built unpaved roadside slope in the Three Gorges Reservoir Area. After eight months growth, eight rainfall simulations (intensity of 90 mm h(-1) for 60 min) and in-situ soil shear strength test were then carried out to identify the impacts of vegetation on roadside slope erosion and soil shear strength. The erosion on cutslopes was higher than that on fillslopes. The runoff coefficient and soil detachment rate were significantly lower on the Grass & Shrub model (4.3% and 1.99 g m(-2) min(-1), respectively) compared with the other three, which had the highest surface cover (91.4%), aboveground biomass (1.44 kg m(-2)) and root weight density (3.94 kg m(-3)). The runoff coefficient and soil detachment rate on roadside slopes showed a logarithmic decrease with the root weight density, root length density and aboveground biomass. The soil shear strength measured before and after the rainfall was higher on Grass & Shrub (59.29 and 53.73 kPa) and decreased on Grass (46.93 and 40.48 kPa), Sodded Strip (31.20 and 18.87 kPa) and Natural Restoration (25.31 and 9.36 kPa). Negative linear correlations were found between the soil shear strength reduction and aboveground biomass, root weight density and root length density. The variation of soil shear strength reduction was closely related to the roadside slope erosion, a positive linear correlation was found between runoff coefficient and soil shear strength reduction, and a power function was shown between soil detachment rate and soil shear strength reduction. This study demonstrated that Grass and Grass & Shrub were more suitable and highly cost-effective in controlling initial period erosion of newly built low-volume unpaved road.
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A physiologic role for serotonergic transmission in adult rat taste buds.
PLoS ONE
PUBLISHED: 01-01-2014
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Of the multiple neurotransmitters and neuropeptides expressed in the mammalian taste bud, serotonin remains both the most studied and least understood. Serotonin is expressed in a subset of taste receptor cells that form synapses with afferent nerve fibers (type III cells) and was once thought to be essential to neurotransmission (now understood as purinergic). However, the discovery of the 5-HT1A serotonin receptor in a subset of taste receptor cells paracrine to type III cell suggested a role in cell-to-cell communication during the processing of taste information. Functional data describing this role are lacking. Using anatomical and neurophysiological techniques, this study proposes a modulatory role for serotonin during the processing of taste information. Double labeling immunocytochemical and single cell RT-PCR technique experiments documented that 5-HT1A-expressing cells co-expressed markers for type II cells, cells which express T1R or T2R receptors and release ATP. These cells did not co-express type III cells markers. Neurophysiological recordings from the chorda tympani nerve, which innervates anterior taste buds, were performed prior to and during intravenous injection of a 5-HT1A receptor antagonist. These experiments revealed that serotonin facilitates processing of taste information for tastants representing sweet, sour, salty, and bitter taste qualities. On the other hand, injection of ondansetron, a 5-HT3 receptor antagonist, was without effect. Collectively, these data support the hypothesis that serotonin is a crucial element in a finely-tuned feedback loop involving the 5-HT1A receptor, ATP, and purinoceptors. It is hypothesized that serotonin facilitates gustatory signals by regulating the release of ATP through ATP-release channels possibly through phosphatidylinositol 4,5-bisphosphate resynthesis. By doing so, 5-HT1A activation prevents desensitization of post-synaptic purinergic receptors expressed on afferent nerve fibers and enhances the afferent signal. Serotonin may thus play a major modulatory role within peripheral taste in shaping the afferent taste signals prior to their transmission across gustatory nerves.
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Combined Effects of Admission Serum Creatinine Concentration with Age and Gender on the Prognostic Significance of Subjects with Acute ST-Elevation Myocardial Infarction in China.
PLoS ONE
PUBLISHED: 01-01-2014
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to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China.
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Efficiency of individual dosage of digoxin with calculated concentration.
Clin Interv Aging
PUBLISHED: 01-01-2014
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Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4-1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8-2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC.
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The compound Chinese medicine "Kang Fu Ling" protects against high power microwave-induced myocardial injury.
PLoS ONE
PUBLISHED: 01-01-2014
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The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine "Kang Fu Ling" (KFL) against high power microwave (HPM)-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP) opening in KFL protection.
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Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.
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Combining automatic tube current modulation with adaptive statistical iterative reconstruction for low-dose chest CT screening.
PLoS ONE
PUBLISHED: 01-01-2014
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To reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT) by combining adaptive statistical iterative reconstruction (ASIR) and automatic tube current modulation (ATCM).
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Candesartan inhibits LPS-induced expression increase of toll-like receptor 4 and downstream inflammatory factors likely via angiotensin II type 1 receptor independent pathway in human renal tubular epithelial cells.
Sheng Li Xue Bao
PUBLISHED: 12-18-2013
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The present study was to determine whether candesartan, an angiotensin II type 1 receptor blocker (ARB), exerts anti-inflammatory effects through inhibiting the toll-like receptor 4 (TLR4) pathway in human renal tubular epithelial cells (HKCs). The experiments were carried on cultured HKCs. By means of flow cytometry, Western blot, RT-PCR and ELISA techniques, the TLR4 protein, angiotensin II type 1 receptor (AT1R) and phosphorylated nuclear factor-kappa B (NF-?B) p65 protein level, mRNA levels of macrophage chemoattractant protein-1 (MCP-1) and regulated upon expression normal T cell expressed and secreted (RANTES), as well as MCP-1 and RANTES protein concentrations in conditioned media were measured. The results showed that lipopolysaccharide (LPS) upregulated the TLR4 protein level in cultured HKCs. Application of LPS increased NF-?B activation and induced release of its downstream inflammatory factors including MCP-1 and RANTES. Candesartan reversed LPS-induced upregulation of TLR4 expression, inhibited NF-?B activation, and reduced MCP-1 and RANTES release. However, knockdown on AT1R by siRNA did not change those previous effects of candesartan. These results suggest that candesartan-induced anti-inflammatory effect may be through a novel pathway, independent of AT1R.
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Comparative serum proteomic analysis of serum diagnosis proteins of colorectal cancer based on magnetic bead separation and maldi-tof mass spectrometry.
Asian Pac. J. Cancer Prev.
PUBLISHED: 12-03-2013
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Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P < 0. 05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.
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Effects of jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion in diabetic rats.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 11-30-2013
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Objective To study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy. Methods Sixty male SD rats were randomly divided into normal group and model groups. The diabetic rat models were established using Streptozotocin (STZ) method (60 mg/kg of intraperitoneal injection), and then randomly divided Jinmaitong low, middle, and high-dose groups and vitamin C group. All the experimental rats were sacrificed at 16-week and then the DRG was isolated. The morphological changes of DRG were observed using the Nissls staining, and the NADPH oxidase subunit p22-phox, Cyt C, Bcl-2, and Caspase-3 of DRG in rats were detected by immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR). Cell apoptosis was detected by TUNEL. Results Compared with the model group, the expressions of NADPH oxidase subunit p22-phox protein, Cyt expression of C protein, Caspase-3 protein, and mRNA cell apoptosis rate in each treatment group significantly decreased whereas the expressions of Bcl-2 mRNA and protein significantly increased (P<0.05 or P<0.01). The Jinmaitong high-dose group had the best effect and was significantly different from that of the vitamin C group (P<0.01). Conclusions Jinmaitong capsule can prevent the nerve injury in rats with diabetic peripheral neuropathy by inhibiting oxidative stress and decreasing the apoptosis. The high-dose Jinmaitong capsule has the best effect and is superior to vitamin C.
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Melosuavines A-H, Cytotoxic Bisindole Alkaloid Derivatives from Melodinus suaveolens.
J. Nat. Prod.
PUBLISHED: 11-25-2013
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Eight new bisindole alkaloids, melosuavines A-C (1-3), having an aspidosperma-scandine linkage, melosuavines D-F (4-6), possessing an aspidosperma-aspidosperma skeleton, and melosuavines G and H (7 and 8) of the aspidosperma-venalatonine type, tenuicausine (9), and melodinine J (10) were isolated from the twigs and leaves of Melodinus suaveolens. The structures of 1-8 were elucidated by extensive spectroscopic methods, and compounds 9 and 10 were identified by comparison with data in the literature. The relative configuration 9 was determined from the ROESY spectrum, and some NMR signals were reassigned. Compounds 1, 2, 4-6, 8, and 10 exhibited low micromolar cytotoxicity against one or more of five human cancer cell lines.
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Genome of Drosophila suzukii, the Spotted Wing Drosophila.
G3 (Bethesda)
PUBLISHED: 10-22-2013
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Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access.
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Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells.
J. Biol. Chem.
PUBLISHED: 10-18-2013
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Pyruvate kinase M2 (PKM2) is a key player in the Warburg effect of cancer cells. However, the mechanisms of regulating PKM2 are not fully elucidated. Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis, co-activating HIF-1? and ?-catenin, and cell proliferation, while enhancing mitochondrial respiration of cancer cells. These findings demonstrate that PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer, highlighting PIM2 as a potential therapeutic target.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.