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Find video protocols related to scientific articles indexed in Pubmed.
Relationship between TLR4 and NF-?B p65 protein expressions and clinical radiosensitivity of patients with esophageal squamous cell carcinoma.
Pak J Med Sci
PUBLISHED: 09-17-2014
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To study the relationship between TLR4 and NF-?B p65 protein expressions in tumor tissues after radiotherapy and clinical radiosensitivity of patients with esophageal squamous cell carcinoma.
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Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.
Urol J
PUBLISHED: 09-06-2014
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To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine.
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The association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function.
PLoS Genet.
PUBLISHED: 09-01-2014
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High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)-rs2272996-in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P=0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to rapid endoplasmic reticulum-associated degradation (ERAD) as the underlying mechanism for its reduction. Using HEK293 cells stably expressing vanin-1 variants, we showed that N131S vanin-1 was degraded significantly faster than wild type (WT) vanin-1. Consequently, there were only minimal quantities of variant vanin-1 present on the plasma membrane and greatly reduced pantetheinase activity. Application of MG-132, a proteasome inhibitor, resulted in accumulation of ubiquitinated variant protein. A further experiment demonstrated that atenolol and diltiazem, two current drugs for treating hypertension, reduce the vanin-1 protein level. Our study provides strong biological evidence for the association of the identified SNP with BP and suggests that vanin-1 misfolding and degradation are the underlying molecular mechanism.
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MiR-124 represses vasculogenic mimicry and cell motility by targeting amotL1 in cervical cancer cells.
Cancer Lett.
PUBLISHED: 08-31-2014
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miRNAs have extensive functions in differentiation, metabolism, programmed cell death, and tumor metastasis by post-transcriptional regulation. Vasculogenic mimicry is an important pathway in tumor metastasis. Many factors can regulate vasculogenic mimicry, including miRNAs. In previous studies, miR-124 was found to repress proliferation and metastasis in different types of cancers, but whether it functions in cervical cancer remained unknown. Here, we demonstrate that miR-124 can repress vasculogenic mimicry, migration and invasion in HeLa and C33A cells in vitro. Furthermore, we reveal that the effect of miR-124 on vasculogenic mimicry, migration and invasion results from its interaction with AmotL1. MiR-124 regulates AmotL1 negatively by targeting its 3'untranslated region (3'UTR). We found that miR-124 can repress the EMT process. Together, these results improve our understanding of the function of miR-124 in tumor metastasis and will help to provide new potential target sites for cervical cancer treatment.
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Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca(2+) channels and release machinery.
J. Neurochem.
PUBLISHED: 08-21-2014
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?1 -adrenoceptors (?1 -ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that ?1 -ARs stimulation enhances glutamatergic transmission via both pre- and post-synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre-synaptic mechanisms may contribute to ?1 -ARs-induced enhancement of glutamate release. In this study, we blocked the possible post-synaptic action mediated by ?1 -ARs to investigate how ?1 -ARs activation regulates pre-synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the ?1 -ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe-induced potentiation was mediated by enhancing pre-synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C-dependent pathway. The mechanisms of Phe-induced potentiation included interaction with both glutamate release machinery and N-type Ca(2+) channels, probably via a pre-synaptic Gq /phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain ?1 -ARs-mediated influence on PFC cognitive functions. Alpha1 -adrenoceptor (?1 -ARs) stimulation has been reported to enhance glutamatergic transmission in layer V/VI pyramidal neurons of the rat medial prefrontal cortex (mPFC). We found that ?1 -ARs agonist phenylephrine (Phe) increases pre-synaptic glutamate release probability and the number of released vesicles via interaction with both glutamate release machinery and N-type Ca(2+) channels. Our results may provide a cellular and molecular mechanism that helps explain ?1 -ARs-mediated influence on PFC cognitive functions. Gq, Gq protein; PLC, phospholipase C; PKC, protein kinase C; AMPA, ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; Glu, glutamate; Phe, phenylephrine.
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Trans-ethnic meta-analysis of white blood cell phenotypes.
Hum. Mol. Genet.
PUBLISHED: 08-05-2014
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White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.
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Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.
J. Nat. Prod.
PUBLISHED: 07-31-2014
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Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 ?M, and compound 15 (IC50 = 1.4 ?M) showed comparable activity to the positive control rolipram (IC50 = 0.60 ?M). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.
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Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-28-2014
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Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94?M) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40?M) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype.
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DNA Methylation-mediated repression of miR-941 enhances lysine (K)-specific demethylase 6B expression in hepatoma cells.
J. Biol. Chem.
PUBLISHED: 07-21-2014
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MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis. However, their underlying mechanisms of action in hepatocellular carcinoma (HCC) are poorly understood. Recent evidence suggests that epigenetic silencing of miRNAs through tumor suppression by CpG island hypermethylation may be a common hallmark of human tumors. Here, we demonstrated that miR-941 was significantly down-regulated in HCC tissues and cell lines and was generally hypermethylated in HCC. The overexpression of miR-941 suppressed in vitro cell proliferation, migration, and invasion and inhibited the metastasis of HCC cells in vivo. Furthermore, the histone demethylase KDM6B (lysine (K)-specific demethylase 6B) was identified as a direct target of miR-941 and was negatively regulated by miR-941. The ectopic expression of KDM6B abrogated the phenotypic changes induced by miR-941 in HCC cells. We demonstrated that miR-941 and KDM6B regulated the epithelial-mesenchymal transition process and affected cell migratory/invasive properties.
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Patients' expectations to dental implant: a systematic review of the literature.
Health Qual Life Outcomes
PUBLISHED: 07-17-2014
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To examine the current literature on the impact of patients' expectations on treatment outcomes or final patient satisfaction and to identify the theoretical frameworks, study designs and measurement instruments which have been employed to assess patients' expectations within implant dentistry.
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Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women's Health Initiative (WHI). Although GWAS of glaucoma have been conducted on several populations, this is the first to look at glaucoma in individuals of African-American and Hispanic race/ethnicity. Prevalent and incident glaucoma was determined by self-report from study questionnaires administered at baseline (1993-1998) and annually through 2005. For African Americans, there was a total of 658 prevalent cases, 1062 incident cases and 6067 individuals who never progressed to glaucoma. For our replication cohort, we used the WHI Hispanics, including 153 prevalent cases, 336 incident cases and 2685 non-cases. We found an association of African ancestry with glaucoma incidence in African Americans (hazards ratio 1.62, 95% CI 1.023-2.56, P = 0.038) and in Hispanics (hazards ratio 3.21, 95% CI 1.32-7.80, P = 0.011). Although we found that no previously identified glaucoma SNPs replicated in either the WHI African Americans or Hispanics, a risk score combining all previously reported hits was significant in African-American prevalent cases (P = 0.0046), and was in the expected direction in the incident cases, as well as in the Hispanic incident cases. Additionally, after imputing to 1000 Genomes, two less common independent SNPs were suggestive in African Americans, but had too low of an allele frequency in Hispanics to test for replication. These results suggest the possibility of a distinct genetic architecture underlying glaucoma in individuals of African ancestry.
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MicroRNAs Regulate the Epithelial to Mesenchymal Transition (EMT) in Cancer Progression.
Microrna
PUBLISHED: 07-09-2014
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MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by targeting mRNAs and leading to either translation repression or RNA degradation. miRNAs have fundamental effects in the regulation of intracellular processes, and their importance during malignant transformation and metastasis is becoming increasingly well understood. The epithelial-mesenchymal transition (EMT), which reprograms tumor cells transcription, has been highlighted as a powerful process in tumor invasion, metastasis and tumorigenicity. In recent years, many studies have significantly enhanced our knowledge of EMT by the characterization of miRNAs that influence the signaling pathways and downstream events that define EMT on a molecular level. In this review, we detail the miRNAs and signal transduction pathways involved in the EMT process and demonstrate their importance in the study of cancer progression. We believe this information will improve prognostication and reveal new opportunities for therapeutic intervention.
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Determination of the Absolute Configuration of Two Pairs of C-8?-?C-9' Linked Neolignan Enantiomers.
Chirality
PUBLISHED: 07-01-2014
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Two pairs of new neolignan enantiomers, (±)-torreyayunan A (/) and (±)-torreyayunan B (/), featuring a rare C-8?-?C-9' linked skeleton, were isolated from leaves and twigs of Torreya yunnanensis. Their absolute configuration involving two chiral centers was determined by combined spectral and Density Functional Theory (DFT) calculation. This is the first report of the absolute configuration of this group of neolignans. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
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Limonoids from the fruits of Cipadessa cinerascens.
J Asian Nat Prod Res
PUBLISHED: 06-11-2014
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A new limonoid, 3-de(2-methylbutanoyl)-3-propanoylcipadesin (1), along with 10 known limonoids and 1 known triterpenoid, was isolated from the fruits of Cipadessa cinerascens. Their structures were elucidated on the basis of spectroscopic analysis. All compounds were evaluated for their antimicrobial activities, and compounds 6 and 12 showed weak antimicrobial activities against MRSA 82(#) and MRSA 92(#).
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Leveraging population admixture to characterize the heritability of complex traits.
Nat. Genet.
PUBLISHED: 06-09-2014
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Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)?). We show that h(2)? = 2FSTC?(1 - ?)h(2), where FSTC measures frequency differences between populations at causal loci and ? is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).
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NF-?B-modulated miR-130a targets TNF-? in cervical cancer cells.
J Transl Med
PUBLISHED: 05-20-2014
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Nuclear factor-?B (NF-?B) induces a variety of biological processes through transcriptional gene control whose products are components in various signaling pathways. MicroRNAs are a small endogenous non-coding RNAs that regulate gene expression and are involved in tumorigenesis. Using human cervical cancer cell lines, this study aimed to investigate whether NF-?B could regulate miR-130a expression and the functions and targets of miR-130a.
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Resistance to Botrytis cinerea in Solanum lycopersicoides involves widespread transcriptional reprogramming.
BMC Genomics
PUBLISHED: 04-25-2014
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Tomato (Solanum lycopersicum), one of the world's most important vegetable crops, is highly susceptible to necrotrophic fungal pathogens such as Botrytis cinerea and Alternaria solani. Improving resistance through conventional breeding has been hampered by a shortage of resistant germplasm and difficulties in introgressing resistance into elite germplasm without linkage drag. The goal of this study was to explore natural variation among wild Solanum species to identify new sources of resistance to necrotrophic fungi and dissect mechanisms underlying resistance against B. cinerea.
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Polyhydroxy cyclohexanols from a Dendrodochium sp. fungus associated with the sea cucumber Holothuria nobilis Selenka.
J. Nat. Prod.
PUBLISHED: 04-21-2014
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Four cyclohexanol analogues, dendrodochols A-D (1-4), were isolated from a Dendrodochium sp. fungus associated with the sea cucumber Holothuria nobilis Selenka collected from the South China Sea. The structures were elucidated by means of detailed spectroscopic analysis. The absolute configurations were assigned using a solution TDDFT/ECD calculation approach and the modified Mosher's method. In an in vitro bioassay, these compounds exhibited no growth inhibition activity against the A549 and MG63 cell lines. Dendrodochols 1 and 3 exhibited modest antifungal activity against Candida strains, Cryptococcus neoformans, and Trichophyton rubrum, whereas 2 and 4 showed no activity against the tested strains.
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Downregulation of miR-101-3p by hepatitis B virus promotes proliferation and migration of hepatocellular carcinoma cells by targeting Rab5a.
Arch. Virol.
PUBLISHED: 04-08-2014
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RAB GTPase 5A (RAB5A), a member of the Rab subfamily of small GTPases, acts as an oncogene and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Recently, it has been reported that the Rab5a gene is involved in the progression of cancer. Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers, and it is usually associated with persistent hepatitis B virus (HBV) infections. Emerging evidence suggests that HBV alters microRNA (miRNA) expression profiles, but the mechanisms underlying this process have not yet been fully elucidated. Here, we examine how HBV affects the production of miR-101-1, which has been shown to be downregulated in HCC. We found that HBV could repress miR-101-3p by inhibiting its promoter activity. Downregulation of miR-101-3p promoted cancer cell growth and migration, and a specific miR-101-3p inhibitor was able to enhance proliferation and migration. Moreover, we identified Rab5a was one of the target genes of miR-101-3p in HBV-related HCC. Forced expression of miR-101-3p in liver cell lines resulted in a marked reduction of the expression of Rab5a at both the mRNA and protein level by directly targeting the 3'untranslated region of Rab5a. Overexpression of Rab5a resulted in a reversal of the suppression of proliferation and migration of SMMC-7721 cells mediated by miR-101-3p. Taken together, our data show that HBV can downregulate miR-101-3p expression by inhibiting its promoter activity and that downregulation of miR-101-3p promotes HCC cell proliferation and migration by targeting Rab5a. This provides new insights into the mechanisms of HBV-related HCC pathogenesis.
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Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells.
FEBS Lett.
PUBLISHED: 03-24-2014
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PPP2R5E belongs to the phosphatase 2A regulatory subunit B family and acts as a tumor suppressor in human cancer. However, the role of PPP2R5E in the tumorigenesis of gastric cancer is unclear. Here, we declare that PPP2R5E is downregulated by miR-23a and induces cell growth inhibition and apoptosis in gastric cancer cells. Furthermore, ASO-miR-23a suppresses tumor growth derived from MGC803 cells in vivo. PPP2R5E is identified as a new target of miR-23a. Moreover, overexpression of PPP2R5E reversed the negative effects of miR-23a. We highlight the significance of miR-23a and PPP2R5E in the proliferation and apoptosis of gastric cancer cells.
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Reduction of glutamate release probability and the number of releasable vesicles are required for suppression of glutamatergic transmission by ?1-adrenoceptors in the medial prefrontal cortex.
Neuropharmacology
PUBLISHED: 03-23-2014
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The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of ?1-adrenoceptor (?1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that ?1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the ?1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that ?1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain ?1-AR-induced PFC dysfunction.
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Organochlorine pesticides and polychlorinated biphenyls in grass, yak muscle, liver, and milk in Ruoergai high altitude prairie, the eastern edge of Qinghai-Tibet Plateau.
Sci. Total Environ.
PUBLISHED: 03-14-2014
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In highland pastures, where no agricultural and industrial activities exist, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are believed to be mainly coming from water-soil-grass system which is subject to air-water and air-soil exchanges and atmospheric precipitation. Samples of grass and yak muscle, liver, and milk were measured for OCPs and PCBs in the summer and winter of 2011. The total concentrations of HCHs, DDTs, endosulfans, HCB, and PCBs in grass samples were in the range of 0.53-2.45, 1.6-6.0, 1.10-4.38, 0.30-1.24, 0.65-2.04 ng g(-1) dw (dry weight), with the means 1.38, 2.86, 2.06, 0.73, and 1.19 ng g(-1) dw, respectively. The mean concentrations of HCHs and DDTs in yak muscle were 1.65 and 0.55 ng g(-1) fw (fresh weight), respectively; no significant seasonal differences. The average total concentrations of HCHs, DDTs, HCB, endosulfans, and PCBs in yak milk were 4.46, 0.59, 1.00, 0.27, and 0.097 ng g(-1) fat, respectively. Among the POPs investigated, ?-HCH and HCB were dominant in yak muscle and liver, whereas ?-HCH dominated the yak milk. Consistent with the results of other studies, PCB 153, 138, and 180 were detected in yak milk that is in accordance with the case reported for farmed cow milk in China and other countries. A human health risk was conducted based on the intake of OCPs via consumptions of the yak muscle and milk. Since the daily intake of HCHs and DDTs was lower than WHO or USEPA's acceptable daily intake or minimal risk level, showing that the consumptions of the yak muscle and milk would not pose any immediate risk to local people.
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Norditerpenoids from Flickingeria fimbriata and their inhibitory activities on nitric oxide and tumor necrosis factor-? production in mouse macrophages.
Molecules
PUBLISHED: 03-10-2014
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Bioassay-guided fractionation of the ethanolic extract of the leaves of Flickingeria flimbriata led to the isolation of two new degraded diterpenoids 1 and 2, a new ent-pimarane type diterpenoid 3, and four known steroids 4-7. The structures of 1-3 were elucidated by spectroscopic analysis, and their absolute configurations were determined by chemical methods, TDDFT quantum chemical calculations of ECD spectra, and CD exiton chirality method. Compounds 1 and 2, named flickinflimilins A and B, possess a rare 15,16-dinor-ent-pimarane skeleton. Compounds 1-7 were screened for the inhibitory activity against lipopolysaccharide (LPS)-induced NO and TNF-? production in RAW264.7 cells. Compounds 1-3 exhibited potent inhibitory activities, with IC50 values of less than 10 µM.
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Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis.
Biochem. Cell Biol.
PUBLISHED: 03-10-2014
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MicroRNA-101(miR-101) has been shown to be down-regulated in hepatocellular carcinoma (HCC). The hepatitis B virus (HBV) is a major risk factor in the development and progression of HCC. However, the correlation between HBV and miR-101 has not yet been fully elucidated. In this study, we reported that HBV could repress miR-101-3p by inhibiting its promoter activity and identified the potential effects of miR-101-3p on some important biological properties of HCC cells by targeting Rap1b. Dual-luciferase reporter assays showed that HBV down-regulated miR-101-3p by inhibiting its promoter activity. Down-regulation of miR-101-3p promoted cell proliferation, migration, and reduced apoptosis, and resulted in up-regulation of Rap1b, while overexpression of miR-101-3p inhibited these processes. Moreover, overexpression of Rap1b was able to reverse the suppressed cell proliferation and migration mediated by miR-101-3p. Our data showed that HBV down-regulated miR-101-3p expression by inhibiting its promoter activity, which resulted in up-regulation of Rap1b, and down-regulation of miR-101-3p or up-regulation of Rap1b promoted proliferation and migration of HCC cells. This provides a new understanding of the mechanism of HBV-related HCC pathogenesis and the potential application of miR-101-3p in cancer therapy.
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Modeling 3D facial shape from DNA.
PLoS Genet.
PUBLISHED: 03-01-2014
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Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers.
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Reconstruction of large-size abdominal wall defect using biodegradable poly-p-dioxanone mesh: an experimental canine study.
World J Surg Oncol
PUBLISHED: 02-19-2014
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Reconstruction of large-size abdominal wall defect (AWDs) is a huge challenge faced in current surgical practice. In this study, we aimed to evaluate the effectiveness and safety of biodegradable poly-p-dioxanone (PDO) mesh for reconstructing large-size AWDs in an experimental canine model.
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Stabilization of multiple rib fractures in a canine model.
J. Surg. Res.
PUBLISHED: 02-14-2014
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Operative stabilization is frequently used in the clinical treatment of multiple rib fractures (MRF); however, no ideal material exists for use in this fixation. This study investigates a newly developed biodegradable plate system for the stabilization of MRF.
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Up-regulated MicroRNA-181a induces carcinogenesis in hepatitis B virus-related hepatocellular carcinoma by targeting E2F5.
BMC Cancer
PUBLISHED: 02-11-2014
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Accumulating evidence showed that microRNAs are involved in development and progression of multiple tumors. Recent studies have found that miR-181a were dysregulated in several types of cancers, however, the function of miR-181a in hepatocellular carcinoma (HCC) remains unclear. In this study we assessed the potential association between miR-181a, HBV and HCC.
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Activation of ??-adrenoceptors enhances excitatory synaptic transmission via a pre- and postsynaptic protein kinase C-dependent mechanism in the medial prefrontal cortex of rats.
Eur. J. Neurosci.
PUBLISHED: 02-04-2014
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The physiological effects of ??-adrenoceptors (??-ARs) have been examined in many brain regions. However, little is known about the mechanism of modulation on synaptic transmission by ??-ARs in the medial prefrontal cortex (mPFC). The present study investigated how ??-AR activation regulates glutamatergic synaptic transmission in layer V/VI pyramidal cells of the rat mPFC. We found that the ??-AR agonist phenylephrine (Phe) induced a significant enhancement of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). The facilitation effect of Phe on the frequency of mEPSCs involved a presynaptic protein kinase C-dependent pathway. Phe produced a significant enhancement on the amplitude of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R)- and N-methyl-D-aspartic acid receptor (NMDA-R)-mediated evoked excitatory postsynaptic currents (eEPSCs). Phe enhanced inward currents evoked by puff application of glutamate or NMDA. The Phe-induced facilitation of AMPA-R- and NMDA-R-mediated eEPSCs required, in part, postsynaptic Gq , phospholipase C and PKC. These findings suggest that ??-AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells via both pre- and post-synaptic PKC-dependent mechanisms.
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A variational Bayes discrete mixture test for rare variant association.
Genet. Epidemiol.
PUBLISHED: 02-01-2014
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Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that "aggregate" tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.
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Analysis of 7 synthetic musks in cream by supported liquid extraction and solid phase extraction followed by GC-MS/MS.
Talanta
PUBLISHED: 01-29-2014
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A new method for the simultaneous determination of 7 synthetic musks (musk amberette, musk tibetene, musk moskene, musk ketone, musk xylene, phantolide, and tonalide) in cream by means of supporting liquid extraction (SLE) coupled with LC-Alumina-N SPE, then followed by GC-MS/MS has been established. In this study, 7 synthetic musks are extracted and pre-purified by a mixture solution of water and isopropanol from cream, and separated and purified by tandem columns containing SLE column and LC-Alumina-N SPE column, which were seldom reported before. Ultrasonic and mechanical shaking were applied to improve the extraction efficiency. Different experiment conditions, such as the type of extraction solution, extraction time of ultrasonic and mechanical shaking, the type of SLE and SPE column, and matrix effects were optimized and the recoveries of 7 synthetic musks for each part were above 86.61%. In addition, the use of isotope internal standards was systemically discussed. The method showed satisfactory linearity over the range assayed (5-1000 ng g(-1)), and the limits of detections (LODs) ranged from 0.15 to 4.86 ng g(-1), and the limits of quantifications (LOQs) were ranging from 0.49 to 16.21 ng g(-1). The recoveries using this method at three spiked concentration levels (10, 100, and 1000 ng g(-1)) range from 85.6% to 109%. The relative standard deviation was lower than 9.8% in all case. The proposed analytical method has been successfully applied for the analysis of 7 synthetic musks in commercial cream.
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A new surgical procedure for palmar hyperhidrosis: is it possible to perform endoscopic sympathectomy under deep sedation without intubation?
Eur J Cardiothorac Surg
PUBLISHED: 01-19-2014
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Palmar hyperhidrosis (PH) is a common dysfunctional disorder, with endoscopic thoracic sympathectomy (ETS) being the most popular treatment method. However, until now, there is little improvement to this technique. In this paper, we present a new alternative to the conventional surgical method.
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Complex interactions between microRNAs and hepatitis B/C viruses.
World J. Gastroenterol.
PUBLISHED: 01-15-2014
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MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate the expression of many target genes via mRNA degradation or translation inhibition. Many studies have shown that miRNAs are involved in the modulation of gene expression and replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) and play a pivotal role in host-virus interactions. Increasing evidence also demonstrates that viral infection leads to alteration of the miRNA expression profile in hepatic tissues or circulation. The deregulated miRNAs participate in hepatocellular carcinoma (HCC) initiation and progression by functioning as oncogenes or tumor suppressor genes by targeting various genes involved in cancer-related signaling pathways. The distinct expression pattern of miRNAs may be a useful marker for the diagnosis and prognosis of virus-related diseases considering the limitation of currently used biomarkers. Moreover, the role of deregulated miRNA in host-virus interactions and HCC development suggested that miRNAs may serve as therapeutic targets or as tools. In this review, we summarize the recent findings about the deregulation and the role of miRNAs during HBV/HCV infection and HCC development, and we discuss the possible mechanism of action of miRNAs in the pathogenesis of virus-related diseases. Furthermore, we discuss the potential of using miRNAs as markers for diagnosis and prognosis as well as therapeutic targets and drugs.
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Briarane diterpenes from the South China Sea gorgonian coral, Junceella gemmacea.
Mar Drugs
PUBLISHED: 01-13-2014
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Four new briarane diterpenoids, junceellolides M-P (1-4), were isolated together with seven known analogs (5-11) from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1-3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.
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Protein kinase D is increased and activated in lung epithelial cells and macrophages in idiopathic pulmonary fibrosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. Hence, there is a profound need for the identification of novel drugable targets to develop more specific and efficacious therapeutic intervention in IPF. In this study, we performed immunohistochemical analyses to assess the cell type-specific expression and activation of protein kinase D (PKD) family kinases in normal and IPF lung tissue sections. We also analyzed PKD activation and function in human lung epithelial cells. We found that PKD family kinases (PKD1, PKD2 and PKD3) were increased and activated in the hyperplastic and regenerative alveolar epithelial cells lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs compared with normal controls. We also found that PKD family kinases were increased and activated in alveolar macrophages, bronchiolar epithelium, and honeycomb cysts in IPF lungs. Interestingly, PKD1 was highly expressed and activated in the cilia of IPF bronchiolar epithelial cells, while PKD2 and PKD3 were expressed in the cell cytoplasm and nuclei. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts. We lastly found that PKD was predominantly activated by poly-L-arginine, lysophosphatidic acid and thrombin in human lung epithelial cells and that PKD promoted epithelial barrier dysfunction. These findings suggest that PKD may participate in the pathogenesis of IPF and may be a novel target for therapeutic intervention in this disease.
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Post-esophagectomy tube feeding: a retrospective comparison of jejunostomy and a novel gastrostomy feeding approach.
PLoS ONE
PUBLISHED: 01-01-2014
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McKeown-type esophagectomy combined with retrosternal reconstruction is a common surgical treatment for esophageal cancer. Various enteral feeding options are available post-esophagectomy, but no definitive preference exists.
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Organochlorine pesticides and polychlorinated biphenyls in surface soils from Ruoergai high altitude prairie, east edge of Qinghai-Tibet Plateau.
Sci. Total Environ.
PUBLISHED: 01-01-2014
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Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in surface soils along a transect from source areas (a petro-chemical industrial city, Lanzhou and its adjacent agricultural areas) to Ruoergai highland prairie (3,552 m above sea level (a.s.l.)), where livestock farming was the only human economic activity, were studied. OCPs in Ruoergai soils were dominated by HCHs. The land types, organic carbon contents and pH affected the POP preservation in soil. OCPs and PCBs in surface soils in Ruoergai wetland and grassland showed different contamination patterns; OCP levels in wetland soils were higher than those in grassland. Significant correlations were observed between total organic carbon (TOC) contents and PCB concentrations in the soils. The land type determines TOC content in soils, which in turn was a major factor on soil concentrations of POPs. The transect was divided into two sections: The first section (Gradient I) is from Lanzhou (1,740 ma.s.l.) to Luqu (2,400 ma.s.l.) with decreasing agricultural activities, and the second section (Gradient II) is from Luqu to Ruoergai (3,500 ma.s.l.) with grassland as the main land type. Soils of Ruoergai area were dominated by ?-HCH, ?-HCH, HCB, and PCB28, suggesting that the behaviors of POPs in the high plateau region were different from high mountain cold-trapping effect, and that the POPs' behaviors in high plateau region were similar to Polar Regions.
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Selaginpulvilins A-D, New Phosphodiesterase-4 Inhibitors with an Unprecedented Skeleton from Selaginella pulvinata.
Org. Lett.
PUBLISHED: 12-12-2013
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Selaginpulvilins A-D (1-4), four new phenols with an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins (5-8) were isolated from Selaginella pulvinata. Their structures were elucidated by spectroscopic analysis and chemical correlation. The structure of 1 was confirmed by single-crystal X-ray diffraction. Compounds 1-8 exhibited remarkable inhibitory activities (IC50 values in the range of 0.11-5.13 ?M) against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease.
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Protein Kinase D Promotes Airway Epithelial Barrier Dysfunction and Permeability through Down-regulation of Claudin-1.
J. Biol. Chem.
PUBLISHED: 11-21-2013
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At the interface between host and external environment, the airway epithelium serves as a major protective barrier. In the present study we show that protein kinase D (PKD) plays an important role in the formation and integrity of the airway epithelial barrier. Either inhibition of PKD activity or silencing of PKD increased transepithelial electrical resistance (TEER), resulting in a tighter epithelial barrier. Among the three PKD isoforms, PKD3 knockdown was the most efficient one to increase TEER in polarized airway epithelial monolayers. In contrast, overexpression of PKD3 wild type, but not PKD3 kinase-inactive mutant, disrupted the formation of apical intercellular junctions and their reassembly, impaired the development of TEER, and increased paracellular permeability to sodium fluorescein in airway epithelial monolayers. We further found that overexpression of PKD, in particular PKD3, markedly suppressed the mRNA and protein levels of claudin-1 but had only minor effects on the expression of other tight junctional proteins (claudin-3, claudin-4, claudin-5, occludin, and ZO-1) and adherent junctional proteins (E-cadherin and ?-catenin). Immunofluorescence study revealed that claudin-1 level was markedly reduced and almost disappeared from intercellular contacts in PKD3-overexpressed epithelial monolayers and that claudin-4 was also restricted from intercellular contacts and tended to accumulate in the cell cytosolic compartments. Last, we found that claudin-1 knockdown prevented TEER elevation by PKD inhibition or silencing in airway epithelial monolayers. These novel findings indicate that PKD negatively regulates human airway epithelial barrier formation and integrity through down-regulation of claudin-1, which is a key component of tight junctions.
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miR-181b promotes cell proliferation and reduces apoptosis by repressing the expression of adenylyl cyclase 9 (AC9) in cervical cancer cells.
FEBS Lett.
PUBLISHED: 11-02-2013
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MicroRNAs are a class of small, endogenous, non-coding RNAs that function as post-transcriptional regulators. In this study, we found that miR-181b promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells. And we validated a new miR-181b target gene, adenylyl cyclase 9 (AC9). miR-181b restricted cAMP production by post-transcriptionally downregulating AC9 expression. Phenotypic experiments indicated that miR-181b and AC9 exerted opposite effects on cell proliferation and apoptosis.
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Downregulation of miR-7 upregulates Cullin 5 (CUL5) to facilitate G1/S transition in human hepatocellular carcinoma cells.
IUBMB Life
PUBLISHED: 10-23-2013
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MicroRNAs (miRNAs) are small, non-coding RNAs that participate in the regulation of gene expression. In this study, we demonstrate that miR-7 was downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent non-tumor tissue. Over-expression of miR-7 in QGY-7703 and HepG2 cell lines inhibited colony formation and induced G1/S phase arrest, whereas knockdown of miR-7 produced the opposite phenotype. A tumor suppressor gene, CUL5, was identified as a direct target of miR-7, and CUL-5 is upregulated upon the binding of miR-7 to its 3UTR. Furthermore, suppression of CUL5 also suppressed cell colony formation and induced cell cycle arrest. Ectopic expression of CUL5 abrogated the effects of miR-7 inhibition on QGY-7703 and HepG2 cell lines. These results indicate that miR-7 suppresses colony formation and causes cell cycle arrest via upregulation of CUL5, and it may function as a tumor suppressor in HCC. © 2013 IUBMB Life, 65(12):1026-1034, 2013.
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[Evaluation of synthetic peptide vaccines against foot-and-mouth disease type A].
Wei Sheng Wu Xue Bao
PUBLISHED: 09-14-2013
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We developed a synthetic vaccine against foot-and-mouth disease type A.
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A Comparison of the Performances of an Artificial Neural Network and a Regression Model for GFR Estimation.
Am. J. Kidney Dis.
PUBLISHED: 07-03-2013
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Accurate estimation of glomerular filtration rate (GFR) is important in clinical practice. Current models derived from regression are limited by the imprecision of GFR estimates. We hypothesized that an artificial neural network (ANN) might improve the precision of GFR estimates.
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Notch-associated microRNAs in cancer.
Curr Drug Targets
PUBLISHED: 06-28-2013
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The Notch signaling plays a key role in cell differentiation, survival, and proliferation through diverse mechanisms. Thus, alterations of the Notch signaling can lead to a variety of disorders including human malignancies. Of considerable interest, recent evidence indicates that there is a significant cross-talk between Notch and microRNAs. As a key component of the Notch-mediated transcription complex, Notch can regulate expression of a number of microRNAs; at the same time, Notch ligands, Notch receptor or Notch effectors are also subject to regulation by microRNAs. Thus, a better understanding of how Notch signaling interacts with microRNAs in the context of cancer will help identify novel biomarkers and therapeutic targets. In this review, we update on recent findings on microRNAs interacting with Notch signaling at various levels, leading to tumorigenesis or chemoresistance. We also highlight the therapeutic potential of targeting Notch signaling and related microRNAs.
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Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis.
J Transl Med
PUBLISHED: 06-18-2013
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Ultraviolet-inactivated, replication-defective Sendai virus particles (Z strain) have displayed antitumor effect through enhancing the immune responses or inducing apoptosis in a variety of carcinomas. Sendai virus strain Tianjin was isolated from the lungs of marmoset and proved to be a novel genotype of Sendai virus. In this study, we explored the antitumor effect and its mechanism of ultraviolet-inactivated, replication-defective Sendai virus strain Tianjin (UV-Tianjin) in mice bearing CT26 colon carcinoma.
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Anti-HIV active daphnane diterpenoids from Trigonostemon thyrsoideum.
Phytochemistry
PUBLISHED: 05-28-2013
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Sixteen daphnane diterpenoids, trigothysoids A-P, along with 15 known ones, were isolated from the methanol extract of the twigs and leaves of Trigonostemon thyrsoideum. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The anti-HIV-1 activity of the compounds was also evaluated in vitro, and five compounds demonstrated potent anti-HIV-1 activity, with EC50 values of 0.015-0.001nM and TI values of 1618-17,619.
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Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(?-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery.
Acta Biomater
PUBLISHED: 05-26-2013
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Nanoparticles (NPs) assembled from amphiphilic polycations have been certified as potential carriers for gene delivery. Structural modification of polycation moieties may be an efficient route to further enhance gene delivery efficiency. In this study two electroneutral monomers with different hydrophobicities, 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA), were incorporated into the cationic poly(dimethylamino ethyl methacrylate) (PDMAEMA) side-chains of amphiphilic poly(?-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) (PCD) by random co-polymerization, to obtain poly(?-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl methacrylate) (PCD-HEMA) and poly(?-caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl acrylate) (PCD-HEA). Minimal HEA or HEMA moieties in PDMAEMA do not lead to statistically significant changes in particle size, zeta potential, DNA condensation properties and buffering capacity of the naked NPs. However, the incorporation of HEMA and HEA lead to reductions and increases, respectively, in the surface hydrophilicity of the naked NPs and NPs/DNA complexes, which was confirmed by water contact angle assay. These simple modifications of PDMAEMA with HEA and HEMA moieties significantly affect the gene transfection efficiency on HeLa cells in vitro: PCD-HEMA NP/DNA complexes show a much higher transfection efficiency than PCD NPs/DNA complexes, while PCD-HEA NPs/DNA complexes show a lower transfection efficiency than PCD NP/DNA complexes. Fluorescence activated cell sorter and confocal laser scanning microscope results indicate that the incorporation of hydrophobic HEMA moieties facilitates an enhancement in both cellular uptake and endosomal/lysosomal escape, leading to a higher transfection efficiency. Moreover, the process of endosomal/lysosomal escape confirmed in our research that PCD and its derivatives do not just rely on the proton sponge mechanism, but also on membrane damage due to the polycation chains, especially hydrophobic modified ones. Hence, it is proved that hydrophobic modification of cationic side-chains is a crucial route to improve gene transfection mediated by polycation NPs.
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New steroids and sesquiterpene from Turraea pubescens.
Fitoterapia
PUBLISHED: 05-20-2013
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Four new compounds, including three new steroids (1-3) and one new sesquiterpene (6), and two new natural products (4-5), as well as three known steroids (7-9) were isolated from the twigs of Turraea pubescens. Compounds 3-5 are C?? steroids isolated from the Meliaceae family for the first time. Their structures were elucidated by extensive NMR and MS analyses. Compound 1 exhibited inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cells with an IC?? value of 11.5 ?M.
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Tumor cell growth inhibitory activity and structure-activity relationship of polyoxygenated steroids from the gorgonian Menella kanisa.
Steroids
PUBLISHED: 05-17-2013
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Fourteen new polyoxygenated steroids (6, 9, 14-18, 20-23, 25-27) having carbon skeletons of cholestane, ergostane, and 24-norcholestane, were isolated together with thirteen known analogues (1-5, 7, 8, 10-13, 19, 24) from the South China Sea gorgonian Menella kanisa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data and comparisons with reported data. This is the first report of chemical investigation on the title gorgonian. Compounds 12 and 13 were reported for the first time from natural sources. These compounds exhibited different levels of growth inhibition activity against A549 and MG-63 cell lines in bioassay in vitro. Preliminary structure-activity analysis revealed an important role of side chain in the activity. A substitution of a 5?-hydroxy or an oxidation of 6?-hydroxy to a ketone carbonyl group may decrease the activity whereas the contribution of the 1-ketone group remains uncertain.
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A specific groove design for individualized healing in a canine partial sternal defect model by a polycaprolactone/hydroxyapatite scaffold coated with bone marrow stromal cells.
J Biomed Mater Res A
PUBLISHED: 05-14-2013
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Objective: The reconstruction of sternal defects remains clinically challenging for thoracic surgeons. Here we aimed to explore the individualized reconstruction of partial sternal defects with new biodegradable material in a large animal model. Method: We used the fused deposition modeling (FDM) technique to manufacture polycaprolactone/hydroxyapatite (PCL/HA) tissue scaffolds with individualized grooves to repair the sternal defect. The defects were surgically created in a sternocostal joint of eighteen Beagle dogs. The animals were separated into three groups (n=6): Blank group, PCL/HA group and PCL/HA/BMSCs group. Radiographic examination, histological and histomorphometric analyses were performed to evaluate the result. Result: In the blank group, the defect site couldnt maintain its original integrity due to no bone union. In the PCL/HA group and PCL/HA/BMSCs group, it was observed that the scaffolds retained their shapes without significant degradation at 12 weeks. Both groups could observe new bone-union by radiographic and histological examination. And PCL/HA/BMSCs would be more mineralized tissue area at implant sites (p<0.05). Conclusion: These results reveal that using the FDM technique to manufacture the PCL/HA scaffolds with specific grooves could repair the sternal defect satisfactorily. Furthermore the scaffolds with BMSCs-seeded could enhance the amount of bone ingrowth and seemed to be more promising.
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Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model.
J Cardiothorac Surg
PUBLISHED: 05-13-2013
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The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects.
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MicroRNA-7 downregulates XIAP expression to suppress cell growth and promote apoptosis in cervical cancer cells.
FEBS Lett.
PUBLISHED: 05-12-2013
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Our study demonstrated the functions of microRNA-7 (miR-7) in cervical cancer. The overexpression of miR-7 in the cervical cancer cell lines HeLa and C-33A suppressed cell viability and promoted cell apoptosis, whereas the inhibition of miR-7 had opposite effects. Furthermore, an oncogene, X-linked inhibitor of apoptosis protein (XIAP), was identified as a new target of miR-7, and the ectopic expression of XIAP rescued the effects induced by miR-7 in HeLa and C-33A cells. These results indicate that miR-7 targeted and downregulated the oncogene XIAP to regulate the effect of miR-7 on apoptosis and malignant behaviors of HeLa and C-33A cells.
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Hepatitis B Virus X Protein Up-Regulates AKR1C1 Expression Through Nuclear Factor-Y in Human Hepatocarcinoma Cells.
Hepat Mon
PUBLISHED: 05-01-2013
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The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells.
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Evaluation of post-mortem heart blood culture in a Chinese population.
Forensic Sci. Int.
PUBLISHED: 04-26-2013
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Post-mortem blood cultures have been used in a wide variety of research studies. However, their significance is still a matter of dispute among medico-legal experts. This study was aimed to determine the factors which influenced post-mortem blood culture results and to assess their value in determining the cause of death.
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Variation and genetic control of protein abundance in humans.
Nature
PUBLISHED: 04-26-2013
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Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.
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Assessment of glomerular filtration rate in elderly patients with chronic kidney disease.
Int Urol Nephrol
PUBLISHED: 03-26-2013
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We sought to evaluate various glomerular filtration rate (GFR) estimating equations in elderly patients with chronic kidney disease (CKD).
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Graphene-spindle shaped TiO? mesocrystal composites: facile synthesis and enhanced visible light photocatalytic performance.
J. Hazard. Mater.
PUBLISHED: 03-13-2013
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Graphene (GR)-TiO2 mesocrystal composites were prepared by a facile template-free process based on the combination of sol-gel and solvothermal methods, and were characterized using field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Raman spectroscopy, UV-vis diffuse reflectance spectroscopy (UV-vis DRS), nitrogen absorption and electron spin resonance (ESR). Visible light photocatalytic performance of GR-TiO2 composites was evaluated for photocatalytic degradation of organic dye Rhodamine B. It was found that the amount of graphene oxide (GO) added obviously affects morphologies of TiO2 mesocrystals and photocatalytic activities of as-prepared nanocomposites. Composites prepared in the presence of different amounts of GO all exhibit higher photocatalytic activity than pure TiO2 mesocrystals and P25, the composite obtained by using 20mg GO presents the most uniform TiO2 mesocrystals in the composite and shows the highest photocatalytic efficiency. The mechanism for the generation of TiO2 mesocrystals in the GR-TiO2 composite is proposed and possible reasons for the enhancement in visible light photocatalytic efficiency are also discussed.
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Steroids glycosylated with both D- and L-arabinoses from the South China Sea gorgonian Dichotella gemmacea.
J. Nat. Prod.
PUBLISHED: 03-11-2013
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Three new 19-hydroxy steroidal glycosides, namely, junceellosides E-G (2-4), were isolated together with the known analogue junceelloside C (1) from the South China Sea gorgonian Dichotella gemmacea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. These glycosides are found to have sugar moieties of both ?-l- and ?-d-arabinopyranoses by HPLC analysis of their thiocarbamoyl-thiazolidine derivatives and those of authentic d- and l-arabinoses, leading to the structure revision of junceelloside C (1). This is the first report of steroidal glycosides from the gorgonian D. gemmacea and the first report of glycosides with ?-l-arabinopyranose from marine sources.
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Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.
Nora Franceschini, Ervin Fox, Zhaogong Zhang, Todd L Edwards, Michael A Nalls, Yun Ju Sung, Bamidele O Tayo, Yan V Sun, Omri Gottesman, Adebawole Adeyemo, Andrew D Johnson, J Hunter Young, Ken Rice, Qing Duan, Fang Chen, Yun Li, Hua Tang, Myriam Fornage, Keith L Keene, Jeanette S Andrews, Jennifer A Smith, Jessica D Faul, Zhang Guangfa, Wei Guo, Yu Liu, Sarah S Murray, Solomon K Musani, Sathanur Srinivasan, Digna R Velez Edwards, Heming Wang, Lewis C Becker, Pascal Bovet, Murielle Bochud, Ulrich Broeckel, Michel Burnier, Cara Carty, Daniel I Chasman, Georg Ehret, Wei-Min Chen, Guanjie Chen, Wei Chen, Jingzhong Ding, Albert W Dreisbach, Michele K Evans, Xiuqing Guo, Melissa E Garcia, Rich Jensen, Margaux F Keller, Guillaume Lettre, Vaneet Lotay, Lisa W Martin, Jason H Moore, Alanna C Morrison, Thomas H Mosley, Adesola Ogunniyi, Walter Palmas, George Papanicolaou, Alan Penman, Joseph F Polak, Paul M Ridker, Babatunde Salako, Andrew B Singleton, Daniel Shriner, Kent D Taylor, Ramachandran Vasan, Kerri Wiggins, Scott M Williams, Lisa R Yanek, Wei Zhao, Alan B Zonderman, Diane M Becker, Gerald Berenson, Eric Boerwinkle, Erwin Bottinger, Mary Cushman, Charles Eaton, Fredrik Nyberg, Gerardo Heiss, Joel N Hirschhron, Virginia J Howard, Konrad J Karczewsk, Matthew B Lanktree, Kiang Liu, Yongmei Liu, Ruth Loos, Karen Margolis, Michael Snyder, , Bruce M Psaty, Nicholas J Schork, David R Weir, Charles N Rotimi, Michèle M Sale, Tamara Harris, Sharon L R Kardia, Steven C Hunt, Donna Arnett, Susan Redline, Richard S Cooper, Neil J Risch, D C Rao, Jerome I Rotter, Aravinda Chakravarti, Alex P Reiner, Daniel Levy, Brendan J Keating, Xiaofeng Zhu.
Am. J. Hum. Genet.
PUBLISHED: 03-01-2013
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High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.
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Chemistry and tumor cell growth inhibitory activity of 11,20-epoxy-3Z,5(6)E-diene briaranes from the South China Sea gorgonian Dichotella gemmacea.
Mar Drugs
PUBLISHED: 03-01-2013
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Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA-AR (1-18), were isolated together with three known analogs, dichotellides F (19) and I (20), and juncenolide C (21), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1-3, 5, 6, 8-12, and 14-19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.
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Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
Hum. Mol. Genet.
PUBLISHED: 02-26-2013
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Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
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A sensitive electrochemical DNA biosensor for specific detection of Enterobacteriaceae bacteria by Exonuclease III-assisted signal amplification.
Biosens Bioelectron
PUBLISHED: 02-24-2013
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A specific and sensitive methodology was developed successfully for quantitative detection of Enterobacteriaceae bacteria by integrating Exonuclease III-assisted target recycling amplification with a simple electrochemical DNA biosensor. After target DNA hybridizes with capture DNA, Exonuclease III can selectively digest the capture DNA, which releases the target to undergo a new hybridization and cleavage cycle on sensor surface, leading to a successful target recycling. Finally, the left capture DNA is recognized by detection probe to produce the detectable signal, which decreases with the increasing target DNA concentration. Under the optimal conditions, the proposed strategy could detect target DNA down to 8.7 fM with a linear range from 0.01 pM to 1 nM, showing high sensitivity. Meanwhile, the sensing strategy was successfully used for detection of Enterobacteriaceae bacteria down to 40 CFU mL?¹ in milk samples. This strategy presented a simple, rapid and sensitive platform for Enterobacteriaceae bacteria detection and would become a versatile and powerful tool for food safety, biothreat detection and environmental monitoring.
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Association of DXA-derived bone mineral density and fat mass with African ancestry.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-22-2013
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Both genes and environment have been implicated in determining the complex body composition phenotypes in individuals of European ancestry; however, few studies have been conducted in other race/ethnic groups.
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miR-371-5p down-regulates pre mRNA processing factor 4 homolog B (PRPF4B) and facilitates the G1/S transition in human hepatocellular carcinoma cells.
Cancer Lett.
PUBLISHED: 02-17-2013
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Increasing evidence has lent support to the notion that miRNAs regulate hepatocellular carcinoma (HCC) cell proliferation by directly targeting cell cycle-related genes. Among these genes, we identified PRPF4B, a CDK-like kinase, as a new target of miR-371-5p. Over-expression of miR-371-5p and knockdown of PRPF4B promotes cell growth by accelerating the G1/S transition in HCC cell lines. Moreover, miR-371-5p promotes tumor growth of QGY-7703 cells in vivo. Conversely, inhibition of miR-371-5p yields an opposing effect. Ectopic expression of PFPF4B abolishes the malignant phenotypes caused by miR-371-5p. Furthermore, contrary to PRPF4B, miR-371 was up-regulated in HCC tissues. Collectively, we highlight the significance of miR-371-5p and PRPF4B in cell cycle progression and hepatocarcinogenesis.
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Protein kinases D2 and D3 are novel growth regulators in HCC1806 triple-negative breast cancer cells.
Anticancer Res.
PUBLISHED: 02-09-2013
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The role of protein kinase D (PKD) in the context of breast cancer cell biology is not clear.
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African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Womens Health Initiative.
Am. Heart J.
PUBLISHED: 02-05-2013
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Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.
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HBx and HBs regulate RhoC expression by upregulating transcription factor Ets-1.
Arch. Virol.
PUBLISHED: 02-01-2013
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The available evidence suggests that HBV proteins play an important role in the development of hepatocellular carcinoma (HCC). RhoC, a member of the Rho subfamily of the Ras superfamily of homologous genes, had been implicated in tumorigenesis and tumor progression. In a previous study, we demonstrated that HBx and HBs could up-regulate RhoC expression by enhancing its promoter activity. However, the specific mechanisms remain unclear. Here, we demonstrate that overexpression of Ets-1 results in upregulation of RhoC promoter activity and mRNA and protein levels. Expression of transcription factor Ets-1 was significantly higher in HepG2.2.15 cells than that in HepG2 cells. Meanwhile, infection of HepG2 cells with an HBV-adenovirus recombinant virus led to up-regulation of Ets-1. Of the four HBV proteins, HBx and HBs, could increase expression of Ets-1, which consequently contributed to the upregulation of RhoC. These findings might provide a novel insight into HBV-induced HCC metastasis.
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Bioactive polyoxygenated steroids from the South China sea soft coral, Sarcophyton sp.
Mar Drugs
PUBLISHED: 01-23-2013
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Seven new polyoxygenated steroids (1-7) were isolated together with seven known analogues (8-14) from the South China Sea soft coral, Sarcophyton sp. The structures of the new compounds were identified on the basis of extensive spectroscopic analysis and comparison with reported data. All the steroids are characterized with 3?,5?,6?-hydroxy moiety, displaying carbon skeletons of cholestane, ergostane, gorgostane and 23,24-dimethyl cholestane. In the in vitro bioassay, metabolites exhibited different levels of antimicrobial activity against bacterial species Escherichia coli and Bacillus megaterium, and fungal species Microbotryum violaceum and Septoria tritici. No inhibition was detected towards microalga Chlorella fusca. Preliminary structure-activity analysis suggests that the 11?-acetoxy group may increase both antibacterial and antifungal activities. The terminal-double bond and the cyclopropane moiety at the side chain may also contribute to the bioactivity.
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Genetic architecture of skin and eye color in an African-European admixed population.
PLoS Genet.
PUBLISHED: 01-22-2013
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Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62), SLC24A5 P = 9.6 × 10(-9)) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27), TYR P = 1.1 × 10(-9), APBA2[OCA2] P = 1.5 × 10(-8), SLC45A2 P = 6 × 10(-9)) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.