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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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Inhibitory effect of silybin on pharmacokinetics of imatinib in vivo and in vitro.
Can. J. Physiol. Pharmacol.
PUBLISHED: 11-04-2014
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The objective of this work was to investigate the effect of orally administered silybin on the pharmacokinetics of imatinib in rats and the metabolism of imatinib in human liver microsome and rat liver microsomes. Eighteen healthy male SD rats were randomly divided into 3 groups: group A (control group), group B (received multiple doses of 50 mg·kg(-1) silybin for 15 consecutive days), and group C (received a single dose of 50 mg·kg(-1) silybin). A single dose of imatinib was administered orally 30 min after administration of silybin (50 mg·kg(-1)). Imatinib plasma levels were measured by UPLC-MS/MS, and pharmacokinetic parameters were calculated by DAS 3.0 software (Bontz Inc., Beijing, China). In addition, human and rat liver microsome were performed to determine the effects of silybin metabolism of imatinib in vitro. The multiple doses or single dose of 50 mg·kg(-1) silybin significantly decreased the area under the curve (0-t) of imatinib (p < 0.01). And the half-life (t1/2) of imatinib is significantly increased (p < 0.05 and p < 0.01, respectively). Also, silybin showed inhibitory effect on human and rat microsomes, the IC50 of silybin were 26.42 ?mol·L(-1) and 49.12 ?mol·L(-1) in human and rat liver microsomes, respectively. These results indicate that more attention should be paid to when imatinib is administrated combined with silybin.
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[Construction and In Vitro Study of Eukaryotic Expression Vector Carrying GITRL and IL-21 Gene].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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The aim of this study was to construct the eukaryotic expression vector carrying glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) and interleukin-21 (IL-21) gene for transfection into chronic myeloid leukemia (CML) dervied dendritic cell (DC), so as to provide an effective platform for exploring the function of target gene in CML. The recombinant eukaryotic expression vector was transfected to the purified DC by Liposome-mediated method, the interleukin-2 (IL-2) and Interferon-? (IFN-?) expression of transfected DC were analyzed by ELISA. Further, the transfected DC with purified NK were mixed and cultured to be DC-CIK, the lactate dehydrogenase release assay was performed to measure the killing activity of DC-CIK. The results indicated that the sequence of cloned target gene was same as that in GenBank. The size of endonuclease products by restriction enzyme were same as the predict one. The concentration of Interleukin-2 (IL-2) and interferon-? (IFN-?) in transfected DC all increased. The NK kill activity became stronger while induced by transfected DC. It is concluded that DC transfected by IL-21 and GITRL gene has the ability of self-activation, up-regulate cytokine secretion. Further, the results would be help to provide the theoretical evidence of advanced immunotherapy for treatment of CML patients who showed no reaction to tyrosine kinase inhibitor.
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The complete mitochondrial genome of white-tufted-ear marmoset, Callithrix jacchus (Primates: Callitrichinae).
Mitochondrial DNA
PUBLISHED: 10-21-2014
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Abstract The white-tufted-ear marmoset (Callithrix jacchus) is a New World primate that inhabits the coastal rainforests of eastern Brazil. In the present work, we report the complete mitochondrial genome sequence of white-tufted-ear marmoset for the first time. The total length of this mitogenome is 16,499?bp long, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region (D-loop region). The gene organization and arrangement is identical to typical vertebrates. The overall base composition is 32.75% of A, 26.95% of T, 26.91% C, and 13.39% G, with a slight A?+?T bias of 59.7%. All the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes. The complete mitochondrial genome sequence reported here will be useful for comparative genomics studies in primates.
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Knockout of the BK ?2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity.
J. Gen. Physiol.
PUBLISHED: 10-01-2014
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Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four ?2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 ? subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of ?2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing ?2 subunits, we generated mice in which the gene encoding ?2 was deleted (?2 knockout [KO]). Comparison of proteins from wild-type (WT) and ?2 KO mice allowed unambiguous demonstration of the presence of ?2 subunit in various tissues and its coassembly with the Slo1 ? subunit. We compared current properties and cell firing properties of WT and ?2 KO CCs in slices and found that ?2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the ?2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from ?2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of ?2 subunits may predispose to burst firing.
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Synthesis and Anticonvulsant Evaluation of some New 6-(Substituted-phenyl)thiazolo[3,2-b][1,2,4]triazole Derivatives in Mice.
Iran J Pharm Res
PUBLISHED: 09-20-2014
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Epilepsy is the most frequent nearological affiction and afflicts 1% about of the world's population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-(substituted-phenyl)thiazolo[3,2-b][1,2,4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (PTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-(4-fluorophenyl)thiazolo[3,2-b][1,2,4]triazole (3c) showed selective protection against the MES seizures with an ED50 value of 49.1 mg/Kg and a TD50 value of 94.1 mg/Kg, which provided compound 3c a protective index (PI = TD50/ED50) of 1.9 in the MES test. 6-(4-Propoxyphenyl)thiazolo[3,2-b][1,2,4]triazole (5b) was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED50 of 63.4 mg/Kg and a TD50 of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine.
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[In vitro effect of photoactivated hypericin on anti-Schistosoma japonicum adult male worms].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 09-17-2014
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To investigate the in vitro effect of photoactivated hypericin on anti-Schistosoma japonicum adult male worms.
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Gangliosides are ligands for human noroviruses.
J. Am. Chem. Soc.
PUBLISHED: 08-28-2014
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Human noroviruses (NoVs) are known to recognize histo-blood group antigens (HBGAs) as attachment factors. We report the first experimental evidence that sialic acid-containing glycosphingolipids (gangliosides) are also ligands for human NoVs. Electrospray ionization mass spectrometry-based carbohydrate binding measurements performed on assemblies (P dimer, P particle, and virus-like particle) of recombinant viral capsid proteins of two NoV strains, VA387 (GII.4) and VA115 (GI.3), identified binding to the oligosaccharides of mono-, di-, and trisialylated gangliosides. The intrinsic (per binding site) affinities measured for these ligands are similar in magnitude (10(2)-10(3) M(-1)) to those of human HBGAs. Binding of NoV VLPs, P particles, and glutathione S-transferase (GST)-P domain fusion proteins to sialic acid-containing glycoconjugates, observed in enzyme-linked immunosorbent assays, provided additional confirmation of the NoV-ganglioside interactions.
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Effect of CYP2C9 genetic polymorphism on the metabolism of flurbiprofen in vitro.
Drug Dev Ind Pharm
PUBLISHED: 08-21-2014
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Abstract CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, and 57 cytochrome P450 2C9 alleles have been previously reported. To examine the enzymatic activity of the CYP2C9 alleles, kinetic parameters for 4'-hydroxyflurbiprofen were determined using recombinant human P450s CYP2C9 microsomes from insect cells Sf21 carrying wild-type CYP2C9*1 and other variants. The results showed that the enzyme activity of most of the variants decreased comparing with the wild type as the previous studies reported, while the enzyme activity of some of them increased, which were not in accordance with the previous researches. Of the 36 tested CYP2C9 allelic isoforms, two variants (CYP2C9*53 and CYP2C9*56) showed a higher intrinsic clearance value than the wild-type protein, especially for CYP2C9*56, exhibited much higher intrinsic clearance (197.3%) relative to wild-type CYP2C9*1, while the remaining 33 CYP2C9 allelic isoforms exhibited significantly decreased clearance values (from 0.6 to 83.8%) compared to CYP2C9*1. This study provided the most comprehensive data on the enzymatic activities of all reported CYP2C9 variants in the Chinese population with regard to the commonly used non-steroidal anti-inflammatory drug, flurbiprofen (FP). The results indicated that most of the tested rare alleles decreased the catalytic activity of CYP2C9 variants toward FP hydroxylation in vitro. This is the first report of all these rare alleles for FP metabolism providing fundamental data for further clinical studies on CYP2C9 alleles for FP metabolism in vivo.
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Effects of intermediate metabolite carboxylic acids of TCA cycle on Microcystis with overproduction of phycocyanin.
Environ Sci Pollut Res Int
PUBLISHED: 06-23-2014
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Toxic Microcystis species are the main bloom-forming cyanobacteria in freshwaters. It is imperative to develop efficient techniques to control these notorious harmful algal blooms (HABs). Here, we present a simple, efficient, and environmentally safe algicidal way to control Microcystis blooms, by using intermediate carboxylic acids from the tricarboxylic acid (TCA) cycle. The citric acid, alpha-ketoglutaric acid, succinic acid, fumaric acid, and malic acid all exhibited strong algicidal effects, and particularly succinic acid could cause the rapid lysis of Microcystis in a few hours. It is revealed that the Microcystis-lysing activity of succinic acid and other carboxylic acids was due to their strong acidic activity. Interestingly, the acid-lysed Microcystis cells released large amounts of phycocyanin, about 27-fold higher than those of the control. On the other hand, the transcription of mcyA and mcyD of the microcystin biosynthesis operon was not upregulated by addition of alpha-ketoglutaric acid and other carboxylic acids. Consider the environmental safety of intermediate carboxylic acids. We propose that administration of TCA cycle organic acids may not only provide an algicidal method with high efficiency and environmental safety but also serve as an applicable way to produce and extract phycocyanin from cyanobacterial biomass.
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Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs.
J. Virol.
PUBLISHED: 06-11-2014
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Noroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis worldwide in people of all ages. The P particle is a novel vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. This study utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies of primary infection, P particles, and virus-like particles (VLPs) against NoV infection and disease and the T cell responses to these treatments. Pigs either were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b variant and monitored for diarrhea and virus shedding for 7 days. The T cell responses in intestinal and systemic lymphoid tissues were examined. Primary NoV infection provided 83% homologous protection against diarrhea and 49% homologous protection against virus shedding, while the P particle and VLP vaccines provided cross-variant protection (47% and 60%, respectively) against diarrhea. The protection rates against diarrhea are significantly inversely correlated with T cell expansion in the duodenum and are positively correlated with T cell expansion in the ileum and spleen. The P particle vaccine primed for stronger immune responses than VLPs, including significantly higher numbers of activated CD4+ T cells in all tissues, gamma interferon-producing (IFN-?+) CD8+ T cells in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth factor ? (TGF-?)-producing CD4+ CD25- FoxP3+ Tregs in the spleen postchallenge, indicating that P particles are more immunogenic than VLPs at the same dose. In conclusion, the P particle vaccine is a promising vaccine candidate worthy of further development.
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[Roles of adenosine and cytokines in the prostate tissue of rats with acute bacterial prostatitis].
Zhonghua Nan Ke Xue
PUBLISHED: 05-31-2014
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To investigate the possible roles of adenosine and the cytokines TNF-alpha and IL-10 in the pathogenesis of acute bacterial prostatitis (ABP) in rats.
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Selection and application of agricultural wastes as solid carbon sources and biofilm carriers in MBR.
J. Hazard. Mater.
PUBLISHED: 04-29-2014
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This paper examined the feasibility of agricultural wastes used as solid carbon sources and the effect of determined agricultural wastes on improving denitrification. Eight agricultural wastes were evaluated in MBR tests to find out their carbon release capacity, denitrification potential, leaching elements and surface properties. The results showed that retinervus luffae fructus, wheat straw, corncob and rice straw had higher carbon release capacity with COD of 13.17-21.07mgg(-1)day(-1), BOD5 of 3.33-7.33mgg(-1)day(-1) and respirable carbon of 8.64-10.71mgg(-1)day(-1). Correspondingly, they displayed a good denitrification potential of 105.3-140.1mg NO3(-)-Ng(-1). Rice straw, retinervus luffae fructus and corncob were then applied in MBRs. These three agricultural wastes were found to be effective in enhancing the denitrification process, where the TN removal increased from 43.44% (control MBR) to 82.34, 68.92 and 62.97%, respectively.
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[Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms presenting for urologic care].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-24-2014
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To identify the risk factors in interstitial cystitis/painful bladder syndrome (IC/PBS) patients with lower urinary tract symptoms (LUTS) without urinary tract infection or benign prostate hyperplasia in China.
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Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor inhibit ferrous iron influx via divalent metal transporter 1 and iron regulatory protein 1 regulation in ventral mesencephalic neurons.
Biochim. Biophys. Acta
PUBLISHED: 04-19-2014
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Iron accumulation is observed in the substantia nigra of patients with Parkinson's disease. However, it is unknown whether neurotrophic factors, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) participate in the modulation of neuronal iron metabolism. Here, we investigated the effects and underlying mechanisms of BDNF and GDNF on the iron influx process in primary cultured ventral mesencephalic neurons. 6-hydroxydopamine-induced enhanced ferrous iron influx via improper up-regulation of divalent metal transporter 1 with iron responsive element (DMT1+IRE) was consistently relieved by BDNF and GDNF. Both the mRNA and protein levels of DMT1+IRE were down-regulated by BDNF or GDNF treatment alone. We further demonstrated the involvement of iron regulatory protein 1 (IRP1) in BDNF- and GDNF-induced DMT1+IRE expression. Extracellular-regulated kinase 1/2 (ERK1/2) and Akt were activated and participated in these processes. Inhibition of ERK1/2 and Akt phosphorylation abolished the down-regulation of IRP1 and DMT1+IRE induced by BDNF and GDNF. Taken together, these results show that BDNF and GDNF ameliorate iron accumulation via the ERK/Akt pathway, followed by inhibition of IRP1 and DMT1+IRE expression, which may provide new targets for the neuroprotective effects of these neurotrophic factors.
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Inhibitory effect of rhynchophylline on contraction of cerebral arterioles to endothelin 1: role of rho kinase.
J Ethnopharmacol
PUBLISHED: 04-13-2014
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Rhynchophylline (Rhy) is a major ingredient of Uncaria rhynchophylla (UR) used to reduce blood pressure and ameliorate brain ailments. This study was to examine the role of Rho kinase (ROCK) in the inhibition of Rhy on contraction of cerebral arterioles caused by endothelin 1 (ET-1).
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Effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain.
J Palliat Med
PUBLISHED: 04-04-2014
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Systemic administration of dexmedetomidine has been shown to reduce opioid consumption and improve analgesia satisfaction. The purpose of this study was to investigate the effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain.
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Triadic motifs in the dependence networks of virtual societies.
Sci Rep
PUBLISHED: 03-31-2014
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In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.
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The Ca2+-activated K+ current of human sperm is mediated by Slo3.
Elife
PUBLISHED: 03-28-2014
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Sperm are equipped with a unique set of ion channels that orchestrate fertilization. In mouse sperm, the principal K(+) current (IKSper) is carried by the Slo3 channel, which sets the membrane potential (Vm) in a strongly pHi-dependent manner. Here, we show that IKSper in human sperm is activated weakly by pHi and more strongly by Ca(2+). Correspondingly, Vm is strongly regulated by Ca(2+) and less so by pHi. We find that inhibitors of Slo3 suppress human IKSper, and we identify the Slo3 protein in the flagellum of human sperm. Moreover, heterologously expressed human Slo3, but not mouse Slo3, is activated by Ca(2+) rather than by alkaline pHi; current-voltage relations of human Slo3 and human IKSper are similar. We conclude that Slo3 represents the principal K(+) channel in human sperm that carries the Ca(2+)-activated IKSper current. We propose that, in human sperm, the progesterone-evoked Ca(2+) influx carried by voltage-gated CatSper channels is limited by Ca(2+)-controlled hyperpolarization via Slo3. DOI: http://dx.doi.org/10.7554/eLife.01438.001.
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Branched-linear and agglomerate protein polymers as vaccine platforms.
Biomaterials
PUBLISHED: 03-20-2014
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Many viral structural proteins and their truncated domains share a common feature of homotypic interaction forming dimers, trimers, and/or oligomers with various valences. We reported previously a simple strategy for construction of linear and network polymers through the dimerization feature of viral proteins for vaccine development. In this study, technologies were developed to produce more sophisticated polyvalent complexes through both the dimerization and oligomerization natures of viral antigens. As proof of concept, branched-linear and agglomerate polymers were made via fusions of the dimeric glutathione-s-transferase (GST) with either a tetrameric hepatitis E virus (HEV) protruding protein or a 24-meric norovirus (NoV) protruding protein. Furthermore, a monomeric antigen, either the M2e epitope of influenza A virus or the VP8* antigen of rotavirus, was inserted and displayed by the polymer platform. All resulting polymers were easily produced in Escherichia coli at high yields. Immunization of mice showed that the polymer vaccines induced significantly higher specific humoral and T cell responses than those induced by the dimeric antigens. Additional evidence in supporting use of polymer vaccines included the significantly higher neutralization activity and protective immunity of the polymer vaccines against the corresponding viruses than those of the dimer vaccines. Thus, our technology for production of polymers containing different viral antigens offers a strategy for vaccine development against infectious pathogens and their associated diseases.
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Functional regulation of BK potassium channels by ?1 auxiliary subunits.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-17-2014
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Many K(+) channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) (BK) channel by associated ?1-subunits. Through expression of differing ratios of ?1:?-subunits, the results reveal an all-or-none functional regulation of BK channels by ?-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the ?1-induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The ?1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 ?-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.
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[Effects of different extracellular matrix on differentiation of human embryonic stem cells into hematopoietic progenitor cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 03-07-2014
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This study was purposed to establish a new inducing system for differentiation of human embryonic stem cells into hematopoietic progenitor cells and to explore the effect of different extracellular matrices (DEM) on production of hematopoietic cells. The 3 kinds of extracellular matrices-matrigel, fibronectin and IV type collagen (collagen IV) were chosen to package cultured plates, the direct adherent culture on extracellular matrix was used, and the hematopoietic growth factors were added into cultured plates to induce the differentiation of human embryonic stem cells into hematopoietic progenitor cells. The hematopoietic colony forming unit assay was used to determine the yielded colony forming cells, the flow cytometry and real-time quantitative PCR were used to detect the expression of markers specific to hematopoiesis and the effect of 3 extracellular matrices on production of hematopoietic progenitor cells was compared. The results showed that after being induced for 14 days, the total yield of colony forming cells, the ratio of CD34(+) cells and the expression level of SCL and CD34 on collagen IV were significantly higher than those on matrigel and fibronectin groups (P < 0.05). It is concluded that human embryonic stem cells can efficiently differentiate into hematopoietic progenitor cells by direct adherent culture on extracellular matrices, and the collagen IV can improve the hematopoietic differentiation of human embryonic stem cells.
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In vitro antimicrobial activity of hydroxypyridinone hexadentate-based dendrimeric chelators alone and in combination with norfloxacin.
FEMS Microbiol. Lett.
PUBLISHED: 03-06-2014
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The antimicrobial activity of one 3-hydroxypyridin-4-one (HPO) hexadentate (1) and three HPO hexadentate-based dendrimeric chelators (2-4) was evaluated. They were found to exhibit marked inhibitory effect on the growth of two Gram-positive bacteria and two Gram-negative bacteria. The combination treatment of dendrimeric chelator 2 with norfloxacin against Staphyloccocus aureus and Escherichia coli showed a dramatic synergistic bactericidal effect. As the dendrimeric chelator has a large molecular weight, its combination with norfloxacin may find application in the treatment of external infections.
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A comparative analysis of the statistical properties of large mobile phone calling networks.
Sci Rep
PUBLISHED: 02-25-2014
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Mobile phone calling is one of the most widely used communication methods in modern society. The records of calls among mobile phone users provide us a valuable proxy for the understanding of human communication patterns embedded in social networks. Mobile phone users call each other forming a directed calling network. If only reciprocal calls are considered, we obtain an undirected mutual calling network. The preferential communication behavior between two connected users can be statistically tested and it results in two Bonferroni networks with statistically validated edges. We perform a comparative analysis of the statistical properties of these four networks, which are constructed from the calling records of more than nine million individuals in Shanghai over a period of 110 days. We find that these networks share many common structural properties and also exhibit idiosyncratic features when compared with previously studied large mobile calling networks. The empirical findings provide us an intriguing picture of a representative large social network that might shed new lights on the modelling of large social networks.
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Design, Synthesis, and Antimicrobial Evaluation of Hexadentate Hydroxypyridinones with High Iron(III) Affinity.
Chem Biol Drug Des
PUBLISHED: 02-16-2014
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A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO-iron complexes (logK1 ) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 ?g/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.
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Effect of supersaturation on hillock of directional Growth of KDP crystals.
Sci Rep
PUBLISHED: 01-20-2014
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KDP single crystals were grown in aqueous solution by using "point seeds" with a defined crystallographic direction of 59° to the Z axis. When hillock slopes on the (100) face of KDP crystals were measured within the supersaturation (?) range of 0 < ? ? 0.06, the slope of hillocks with hollow cores depended nonlinearly on supersaturation. Below ? = 0.02, the hillock slope depended on supersaturation, but when ? was ? 0.02, the hillock slope increased more gradually and was less dependent on supersaturation. Hollow funnel-shaped growth dislocation on the (100) face of KDP crystals was observed at ? = 0.04, characterized by large holes with micro-steps and step bunching inside, the formation of which were analyzed. The result verified that the reversed growth appears to occur within hollow channels found on growth hillocks.
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Cardiac structural and functional changes in old elderly patients with obstructive sleep apnoea-hypopnoea syndrome.
J. Int. Med. Res.
PUBLISHED: 01-20-2014
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To investigate cardiac structural changes in elderly patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and the impact on left ventricular systolic and diastolic function.
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Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.
Virology
PUBLISHED: 01-15-2014
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Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.
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Design, synthesis and evaluation of the antidepressant and anticonvulsant activities of triazole-containing quinolinones.
Eur J Med Chem
PUBLISHED: 01-14-2014
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A series of 1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-ones were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. Interestingly, compounds 5i, 5j, 5m, and 5n led to significant reductions in the immobility time in the forced swimming test at a dose of 50 mg/kg, and exhibited higher levels of efficacy than the reference standard fluoxetine. In addition, compound 5i exhibited greater efficacy than fluoxetine in the tail suspension test. The results of an open field test further confirmed that compound 5i provided a good antidepressant effect. In the maximal electroshock seizure screen, compounds 5c and 5d showed moderate levels of anticonvulsant activity and protected 100% of the animals at a dose of 100 mg/kg. None of the synthesized compounds showed any neurotoxicity in the rotarod test at a dose of 100 mg/kg.
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An artemisinin derivative of praziquantel as an orally active antischistosomal agent.
PLoS ONE
PUBLISHED: 01-01-2014
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Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma. Here, we report our systematic biological evaluation of DW-3-15, a new lead compound developed based on our conjugation design rationale as an effective anti-schistosomal agent.
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Expression and clinical significance of the programmed cell death 5 gene and protein in laryngeal squamous cell carcinoma.
J. Int. Med. Res.
PUBLISHED: 11-23-2013
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To determine the expression of the gene programmed cell death 5 (PDCD5) and its protein PDCD5 in laryngeal squamous cell carcinoma and to analyse possible correlations with clinicopathological parameters.
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Protective effects of Notoginsenoside R1 on intestinal ischemia/reperfusion injury in rats.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 11-14-2013
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Intestinal ischemia and reperfusion (I/R) is a clinical problem occurred for diverse causes with high mortality. Prophylaxis and treatment of intestinal I/R remains a challenge for clinician. The present study was to explore the role of Notoginsenoside R1 (R1), a major component form Panax. Notoginseng, in management of intestinal I/R injury. Intestinal I/R was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 90 min followed by reperfusion for 60 min or 3 days. R1 (10 mg/kg/h) was administered either 20 min before ischemia or 20 min after reperfusion. Intestinal microcirculation was evaluated by intravital microscopy over 60 min reperfusion. Sixty min or 3 days after reperfusion, rats were killed for histological examination of the jejunum tissue and immunohistochemical localization of myeloperoxidase and CD68. ATP, ADP and AMP content in jejunum tissue was assessed by ELISA. Activation of NF-?B, expression of ATP5D and tight junction proteins were determined by Western blotting. The results demonstrated that R1 is capable of attenuating intestinal I/R-induced microvascular hyperpermeability, inflammatory cytokine production, NF-?B activation and loss of tight junction proteins, as well as improving energy metabolism during I/R. The results of the present study suggest R1 as an option in protecting against intestinal I/R injury.
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Synthesis and biological evaluation of (E)-1-(substituted)-3-phenylprop-2-en-1-ones bearing rhodanines as potent anti-microbial agents.
J Enzyme Inhib Med Chem
PUBLISHED: 10-09-2013
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Abstract Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC?=?1-8?µg/mL) against multi-drug-resistant Gram-positive organisms, including methicillin resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g was found to be the most potent with minimum inhibitory concentration (MIC) value of 1?µg/mL against two methicillin-resistant S. aureus.
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Review of 10 years of clinical experience with Chinese domestic trivalent influenza vaccine Anflu(®)
Hum Vaccin Immunother
PUBLISHED: 10-08-2013
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Influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. However, the majority of the worlds total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. A safe and effective preventive vaccine for the developing countries is urgent. Anflu(®), a Chinese domestic preservative-free, split-virus trivalent influenza vaccine (TIV), was introduced by Sinovac Biotech Ltd. in 2006. Until now, 20.6 million doses worldwide of Anflu(®) were sold. Since 2003, 13 company-sponsored clinical studies investigating the immunogenicity and safety of Anflu(®) have been completed, in which 6642 subjects participated and were vaccinated by Anflu(®). Anflu(®) was generally well tolerated in all age groups, and highly immunogenic in healthy adults and elderly and exceeded the licensure criteria in Europe. This review presents and discusses the experience with Anflu(®) during the past decade. A new Chinese domestic, preservative-free, unadjuvanted, inactivated split-virus trivalent influenza vaccine (TIV), Anflu(®), was introduced into human clinical trials in 2003 and then licensed in China in 2006. The vaccine contains 15 µg /0.5 ml haemagglutinin from each of the three influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype and an influenza B virus) that are expected to be circulating in the up-coming influenza season. The clinical data pertaining to Anflu(®) will be reviewed and compared with other TIVs available at present.
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c-Met function requires N-linked glycosylation modification of pro-Met.
J. Cell. Biochem.
PUBLISHED: 09-26-2013
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c-Met, the receptor for hepatocyte growth factor (HGF), is cell surface tyrosine kinase that controls cancer cell growth, survival, invasion, and metastasis. Post-translational modification, such as glycosylation, plays an essential role in regulating the function of cell surface molecules. Whether glycosylation modification regulates the enzymatic properties of c-Met is unknown. In this study, we investigated the effect of glycosylation on the function of c-Met. We found that c-Met is an N-linked glycosylated protein. Both pro-Met and p145Met (the ? subunit of mature c-Met) have N-linked glycosylation. Glycosylation inhibitor studies revealed that the N-glycosylation modification of p145Met is from pro-Met, but not due to the further modification of pro-Met. Importantly, blocking the N-glycosylation targets pro-Met to cytoplasm and initiates its phosphorylation independent of HGF engagement. Nonglycosylated pro-Met activates c-Met downstream pathways to a certain extent to compensate for the degradation of p145Met induced by glycosylation blocking-mediated endoplasmic reticulum (ER) stress.
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Identifying human milk glycans that inhibit norovirus binding using surface plasmon resonance.
Glycobiology
PUBLISHED: 09-10-2013
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Human milk glycans inhibit binding between norovirus and its host glycan receptor; such competitive inhibition by human milk glycans is associated with a reduced risk of infection. The relationship between the presence of specific structural motifs in the human milk glycan and its ability to inhibit binding by specific norovirus strains requires facile, accurate and miniaturized-binding assays. Toward this end, a high-throughput biosensor platform was developed based on surface plasmon resonance imaging (SPRi) of glycan microarrays. The SPRi was validated, and its utility was tested, by measuring binding specificities between defined human milk glycan epitopes and the capsids of two common norovirus strains, VA387 and Norwalk. Human milk oligosaccharide (HMOS)-based neoglycoconjugates, including chemically derived neoglycoproteins and oligosaccharide-glycine derivatives, were used to represent polyvalent glycoconjugates and monovalent oligosaccharides, respectively, in human milk. SPRi binding results established that the glycan motifs that bind norovirus capsids depend upon strain; VA387 capsid interacts with two neoglycoproteins, whereas Norwalk capsid binds to a different set of HMOS motifs in the form of both polyvalent neoglycoproteins and monovalent oligosaccharides. SPRi competitive binding assays further demonstrated that specific norovirus-binding glycans are able to inhibit norovirus capsid binding to their host receptors. A polyvalent neoglycoconjugate with clustered carbohydrate moieties is required for the inhibition of VA387 capsid binding to host receptor glycans, whereas both monovalent oligosaccharides and polyvalent neoglycoconjugates are able to inhibit Norwalk capsid binding to its host receptor. Binding of HMOS and HMOS-based neoglycoconjugates to norovirus capsids depends upon the specific strain characteristics, implying that HMOS and their polyvalent derivatives are potential anti-adhesive agents for norovirus prophylaxis.
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Rabeprazole 10 mg versus 20 mg in preventing relapse of gastroesophageal reflux disease: a meta-analysis.
Chin. Med. J.
PUBLISHED: 08-29-2013
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Several randomized controlled trials (RCTs) have compared endoscopic and symptomatic relapses in patients with erosive gastroesophageal reflux disease (GERD). We have summarized current evidence for rabeprazole 10 or 20 mg once daily for GERD maintenance treatment over 1 or 5 years.
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Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa.
J. Gen. Physiol.
PUBLISHED: 08-28-2013
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During passage through the female reproductive tract, mammalian sperm undergo a maturation process termed capacitation that renders sperm competent to produce fertilization. Capacitation involves a sequence of changes in biochemical and electrical properties, the onset of a hyperactivated swimming behavior, and development of the ability to undergo successful fusion and penetration with an egg. In mouse sperm, the development of hyperactivated motility is dependent on cytosolic alkalization that then results in an increase in cytosolic Ca(2+). The elevation of Ca(2+) is thought to be primarily driven by the concerted interplay of two alkalization-activated currents, a K(+) current (KSPER) composed of pore-forming subunits encoded by the Kcnu1 gene (also termed Slo3) and a Ca(2+) current arising from a family of CATSPER subunits. After deletion of any of four CATSPER subunit genes (CATSPER1-4), the major remaining current in mouse sperm is alkalization-activated KSPER current. After genetic deletion of the Slo3 gene, KSPER current is abolished, but there remains a small voltage-activated K(+) current hypothesized to reflect monovalent flux through CATSPER. Here, we address two questions. First, does the residual outward K(+) current present in the Slo3 (-/-) sperm arise from CATSPER? Second, can any additional membrane K(+) currents be detected in mouse sperm by patch-clamp methods other than CATSPER and KSPER? Here, using mice bred to lack both SLO3 and CATSPER1 subunits, we show conclusively that the voltage-activated outward current present in Slo3 (-/-) sperm is abolished when CATSPER is also deleted. Any leak currents that may play a role in setting the resting membrane potential in noncapacitated sperm are likely smaller than the pipette leak current and thus cannot be resolved within the limitation of the patch-clamp technique. Together, KSPER and CATSPER appear to be the sole ion channels present in mouse sperm that regulate membrane potential and Ca(2+) influx in response to alkalization.
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Synthesis and negative inotropic effects evaluation of 7-substituted-4,5-dihydro-[1,2,4]oxadiazolo[4,3-a]quinolin-1-ones.
Arch. Pharm. Res.
PUBLISHED: 06-28-2013
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A series of 7-alkoxy-4,5-dihydro-[1,2,4]oxadiazolo[4,3-a]quinolin-1-ones was synthesized and their negative inotropic effects were evaluated by measuring the left atrium stroke volume in isolated rabbit heart preparations. All compounds moderated the cardiac workload by decreasing heart rate and contractility (inotropic effects). Among them, compound 6 was found to be best potent with a -28.89 ± 1.91 % decrease in the stroke volume at a concentration of 3 × 10(-5) M in our in vitro study.
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[Influence of yeast extract on the fermentation of glucose by the demulsifying strain Alcaligenes sp. S-XJ-1].
Huan Jing Ke Xue
PUBLISHED: 06-27-2013
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The demulsifying strain Alcaligenes sp. S-XJ-1, isolated from oil contaminated soil, was cultivated with glucose as the carbon source. The influences of yeast extract on the growth, demulsifying ability and the element composition of the strain were investigated. The results showed that the yeast extract could increase the biomass and enhance the glucose utilization of Alcaligenes sp. S-XJ-1. When the concentration of the yeast extract was 5 g x L(-1), the biomass was increased up to 3.0 g x L(-1), and the glucose utilization achieved 58%. The demulsifying ability of the strain was improved with increasing yeast extract concentration. When the concentration of the yeast extract was 10 g x L(-1), the demulsification ratio of the obtained cell was 76%. While the C/N ratio of the cells decreased with the increasing concentration of yeast extract. The proteins of cells were extracted and measured. The results showed that the proteins of the obtained cell increased with the increasing concentration of yeast extract, in accordance with the increased concentrations of proteins on the surface of the cells as measured by FTIR. It is estimated that the increase of the proteins leads to the improvement of the demulsifying ability of the demulsifying strain and theses proteins play essential roles in the demulsifying process.
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The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats.
Biomed Res Int
PUBLISHED: 06-26-2013
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The purpose of this study was to determine the effect of apigenin on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Healthy male SD rats were randomly divided into four groups: A group (the control group), B group (the long-term administration of 165?mg/kg apigenin for 15 days), C group (a single dose of 165?mg/kg apigenin), and D group (a single dose of 252?mg/kg apigenin). The serum concentrations of imatinib and N-desmethyl imatinib were measured by HPLC, and pharmacokinetic parameters were calculated using DAS 3.0 software. The parameters of AUC(0-t), AUC(0-?), T max, V z /F, and CL z /F for imatinib in group B were different from those in group A (P < 0.05). Besides, MRT(0-t) and MRT(0-?) in groups C and D differed distinctly from those in group A as well. The parameters of AUC(0-t) and C max for N-desmethyl imatinib in group C were significantly lower than those in group A (P < 0.05); however, compared with groups B and D, the magnitude of effect was modest. Those results indicated that apigenin in the short-term study inhibited the metabolism of imatinib and its metabolite N-desmethyl imatinib, while in the long-term study the metabolism could be accelerated.
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Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age.
J. Gen. Virol.
PUBLISHED: 06-26-2013
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Human noroviruses (NoVs), a major cause of viral gastroenteritis, are difficult to study due to the lack of a cell-culture and a small-animal model. Pigs share with humans the types A and H histo-blood group antigens on the intestinal epithelium and have been suggested as a potential model for studies of NoV pathogenesis, immunity and vaccines. In this study, the effects of age and a cholesterol-lowering drug, simvastatin, on the susceptibility of pigs to NoV infection were evaluated. The median infectious dose (ID50) of a genogroup II, genotype 4 (GII.4) 2006b variant was determined. The ID50 in neonatal (4-5 days of age) pigs was ?2.74×10(3) viral RNA copies. In older pigs (33-34 days of age), the ID50 was 6.43×10(4) but decreased to <2.74×10(3) in simvastatin-fed older pigs. Evidence of NoV infection was obtained by increased virus load in the intestinal contents, cytopathological changes in the small intestine, including irregular microvilli, necrosis and apoptosis, and detection of viral antigen in the tip of villi in duodenum. This GII.4 variant was isolated in 2008 from a patient from whom a large volume of stool was collected. GII.4 NoVs are continuously subjected to selective pressure by human immunity, and antigenically different GII.4 NoV variants emerge every 1-2 years. The determination of the ID50 of this challenge virus is valuable for evaluation of protection against different GII.4 variants conferred by NoV vaccines in concurrence with other GII.4 variants in the gnotobiotic pig model.
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Investigations on the clinical significance of FOXP3 protein expression in cervical oesophageal cancer and the number of FOXP3+ tumour-infiltrating lymphocytes.
J. Int. Med. Res.
PUBLISHED: 06-12-2013
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Investigations of FOXP3 protein expression in cervical oesophageal cancer cells and the number of FOXP3 + lymphocytes infiltrating tumour tissue were undertaken.
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First prospective, population-based inflammatory bowel disease incidence study in mainland of China: the emergence of "western" disease.
Inflamm. Bowel Dis.
PUBLISHED: 05-15-2013
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Previously a disease of the West and rarely seen in China, inflammatory bowel disease (IBD) is now increasing in incidence in China. However, its true incidence is unknown. The incidence of IBD in Wuhan, a major city in central China, was investigated using population-based methods.
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Novel arylhydrazone derivatives bearing a rhodanine moiety: synthesis and evaluation of their antibacterial activities.
Arch. Pharm. Res.
PUBLISHED: 05-14-2013
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A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of 2-4 ?g/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 ?g/mL.
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Computed tomography urography for diagnosis of calyceal diverticulum complicated by urolithiasis: the accuracy and the effect of abdominal compression and prolongation of acquisition delay.
Urology
PUBLISHED: 05-12-2013
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To evaluate the accuracy of computed tomography urography (CTU) in the detection of caliceal diverticulum (CD) complicated with urolithiasis and the effect of compression and prolongation of acquisition delay.
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Inhibitory effect of sulfated lentinan and lentinan against tobacco mosaic virus (TMV) in tobacco seedlings.
Int. J. Biol. Macromol.
PUBLISHED: 05-12-2013
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The antiviral activities of sulfated lentinan (sLNT) and lentinan (LNT) against tobacco mosaic virus (TMV) in tobacco seedlings and the underlying mechanism were investigated. Compared with LNT, sLNT showed significantly higher inhibitory effects on viral infection and TMV multiplication in a dose-dependent way, which might be due to its binding with TMV coat protein. In addition, both sLNT and LNT induced the transient production of H2O2 and expression of some defense-related genes (stilbene synthase, glucanase, acidic chitinase class IV, phenylalanine ammonia-lyase and 5-epi-aristolochene synthase) both locally and systemically. These results suggested that sLNT and LNT could control TMV incidence and the action mechanism might be associated with the affinity towards TMV coat protein and activation of some defense genes.
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Inhibition of Tulane virus replication in vitro with RNA interference.
J. Med. Virol.
PUBLISHED: 04-18-2013
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RNA interference (RNAi), a conserved mechanism triggered by small interfering RNA (siRNA), has been used for suppressing gene expression through RNA degradation. The replication of caliciviruses (CVs) with RNAi was studied using the Tulane virus (TV) as a model. Five siRNAs targeting the non-structural, the major (VP1) and minor (VP2) structural genes of the TV were developed and the viruses were quantified using quantitative real time PCR (qPCR) and tissue culture infective dose (TCID(50) ) assay. Treatment of the cells with siRNA 4 hr before viral inoculation significantly reduced viral titer by up to 2.6 logs and dramatically decreased viral RNA copy numbers and viral titers 48 hr post infection in four of the five siRNAs studied. The results were confirmed by Western blot, in which the major structural protein VP1 was markedly reduced in both the cells and the culture medium. Two small protein bands of the shell (S) and protruding (P) domains of the viral capsid protein were also detected in the cell lysates, although their role in viral replication remains unknown. Since the TV shares many biological properties with human noroviruses (NoVs), the successful demonstration of RNAi in TV replication would provide valuable information in control of acute gastroenteritis caused by human NoVs.
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[Liver disease spectrum in hospitalized type 2 diabetes and related risk factors analysis of non-alcoholic fatty liver disease].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-13-2013
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To explore the liver disease spectrum in patients with type 2 diabetes (T2DM) and the risk factors of non-alcoholic fatty liver disease (NAFLD).
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Emodin improves lipopolysaccharide-induced microcirculatory disturbance in rat mesentery.
Microcirculation
PUBLISHED: 03-27-2013
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Sepsis is a systemic inflammatory response syndrome. Emodin is a major ingredient of Rheum Palmatum, a Chinese herb that is widely used in China for treatment of endotoxemia-related diseases. This study intended to examine the effect of Emodin on LPS-induced rat mesenteric microcirculatory disturbance and the underlying mechanisms.
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Synthesis and biological evaluation of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties as positive inotropic agents.
Chem Biol Drug Des
PUBLISHED: 03-26-2013
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Two series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)tetrazolo[5,1-a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5)  m. The chronotropic effects of the compounds that exhibited good potency were also evaluated.
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Synthesis and evaluation of the anticonvulsant activity of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives.
J Enzyme Inhib Med Chem
PUBLISHED: 03-12-2013
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Abstract Two series of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives (6a-q and 7a-q) were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. All of the compounds prepared were effective in the MES screens. Among which, compound 7j was considered as the most promising one with an ED50 value of 26.3?mg/kg and a superior protective index value of 12.6. The potency of compound 7j against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid and bicuculline suggested that two different mechanisms of action might potentially be involved in its anticonvulsant activity, including the inhibition of voltage-gated ion channels and the modulation of GABAergic activity. A computational study was also conducted to predict the pharmacokinetic properties of the compounds prepared, with the results supporting the use of these compounds as a group of promising antiepileptic agents.
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Synthesis and biological evaluation of rhodanine derivatives bearing a quinoline moiety as potent antimicrobial agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-05-2013
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Three series of rhodanine derivatives bearing a quinoline moiety (6a-h, 7a-g, and 8a-e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, 6g and 8c were identified as the most effective with minimum inhibitory concentration (MIC) values of 1 ?g/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA, respectively). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 ?g/mL. The cytotoxic activity assay showed that compounds 6g, 7g and 8e exhibited in vitro antibacterial activity at non-cytotoxic concentrations. Thus, these studies suggest that rhodanine derivatives bearing a quinoline moiety are interesting scaffolds for the development of novel Gram-positive antibacterial agents.
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[Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1?, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 02-23-2013
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To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1? (HIF-1?), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH).
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Polyvalent complexes for vaccine development.
Biomaterials
PUBLISHED: 01-30-2013
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Homotypic interaction is a common phenomenon of many proteins, through which they form dimers. We developed a simple approach to turn small dimeric proteins into large polyvalent complexes for increased immunogenicity and functionality. This was achieved via a fusion of two or more dimeric proteins together to induce polyvalent complex formation through intermolecular dimerizations. Two types of polyvalent complexes, linear and network, assembled spontaneously when a dimeric glutathione S-transferase (GST) was fused with one or two protruding (P) domains of norovirus (NoV). Additionally, a monomeric antigen, the peptide epitope M2e of the influenza virus (IV) or the VP8* antigen of rotavirus (RV), can be inserted to the polyvalent complexes. Mouse immunization demonstrated that the polyvalent complexes induced significantly higher antibody and CD4(+) T cell responses to the complex components than those induced by the free epitope and antigens. Further evaluations indicated that the polyvalent complex vaccines exhibited significantly higher neutralization activity against NoV and RV and stronger protection against IV challenges in a mouse model than those of the monomeric or dimeric vaccines. The binding of NoV P proteins to their HBGA ligands was also significantly increased through the polyvalent complex formation. Therefore, our polyvalent complex system provides a new strategy for novel vaccine development and may find various applications throughout biomedicine.
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High-dose chlorogenic acid induces inflammation reactions and oxidative stress injury in rats without implication of mast cell degranulation.
J Ethnopharmacol
PUBLISHED: 01-28-2013
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Chlorogenic acid (CA) exits widely in those Chinese herbal injections that have antibacterial and antiphlogistic effects and belongs to the ethnopharmacological family of medicines. Chinese herbal injections containing high levels of CA have been reported to increase the adverse drug reactions, but the mechanism for which is still unclear. In this study, we investigated the mechanism of the CA derived adverse drug reactions.
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Development of a novel class of pyrrolo-[1,2,5]benzothiadiazepine derivatives as potential anti-schistosomal agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-16-2013
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Analogues of pyrrolo-[1,2,5]benzothiadiazepine were prepared and evaluated against Schistosoma japonica. The biological data revealed that most benzothiazepine derivatives show anti-schistosomal activity to some extent, while ?-chloronation of the title compound and another bioisosteric derivative pyrrolo-[1,2,5]benzodiazepine displayed the most distinct worm killing activity. This study proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents.
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Calling patterns in human communication dynamics.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-14-2013
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Modern technologies not only provide a variety of communication modes (e.g., texting, cell phone conversation, and online instant messaging), but also detailed electronic traces of these communications between individuals. These electronic traces indicate that the interactions occur in temporal bursts. Here, we study intercall duration of communications of the 100,000 most active cell phone users of a Chinese mobile phone operator. We confirm that the intercall durations follow a power-law distribution with an exponential cutoff at the population level but find differences when focusing on individual users. We apply statistical tests at the individual level and find that the intercall durations follow a power-law distribution for only 3,460 individuals (3.46%). The intercall durations for the majority (73.34%) follow a Weibull distribution. We quantify individual users using three measures: out-degree, percentage of outgoing calls, and communication diversity. We find that the cell phone users with a power-law duration distribution fall into three anomalous clusters: robot-based callers, telecom fraud, and telephone sales. This information is of interest to both academics and practitioners, mobile telecom operators in particular. In contrast, the individual users with a Weibull duration distribution form the fourth cluster of ordinary cell phone users. We also discover more information about the calling patterns of these four clusters (e.g., the probability that a user will call the c(r)-th most contact and the probability distribution of burst sizes). Our findings may enable a more detailed analysis of the huge body of data contained in the logs of massive users.
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Development-Specific Differences in the Proteomics of Angiostrongylus cantonensis.
PLoS ONE
PUBLISHED: 01-01-2013
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Angiostrongyliasis is an emerging communicable disease. Several different hosts are required to complete the life cycle of Angiostrongylus cantonensis. However, we lack a complete understanding of variability of proteins across different developmental stages and their contribution to parasite survival and progression. In this study, we extracted soluble proteins from various stages of the A. cantonensis life cycle [female adults, male adults, the fifth-stage female larvae (FL5), the fifth-stage male larvae (ML5) and third-stage larvae (L3)], separated those proteins using two-dimensional difference gel electrophoresis (2D-DIGE) at pH 4-7, and analyzed the gel images using DeCyder 7.0 software. This proteomic analysis produced a total of 183 different dominant protein spots. Thirty-seven protein spots were found to have high confidence scores (>95%) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Comparative proteomic analyses revealed that 29 spots represented cytoskeleton-associated proteins and functional proteins. Eight spots were unnamed proteins. Twelve protein spots that were matched to the EST of different-stage larvae of A. cantonensis were identified. Two genes and the internal control 18s were chosen for quantitative real-time PCR (qPCR) and the qPCR results were consistent with those of the DIGE studies. These findings will provide a new basis for understanding the characteristics of growth and development of A. cantonensis and the host-parasite relationship. They may also assist searches for candidate proteins suitable for use in diagnostic assays and as drug targets for the control of eosinophilic meningitis caused by A. cantonensis.
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Norovirus P particle efficiently elicits innate, humoral and cellular immunity.
PLoS ONE
PUBLISHED: 01-01-2013
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Norovirus (NoV) P domain complexes, the 24 mer P particles and the P dimers, induced effective humoral immunity, but their role in the cellular immune responses remained unclear. We reported here a study on cellular immune responses of the two P domain complexes in comparison with the virus-like particle (VLP) of a GII.4 NoV (VA387) in mice. The P domain complexes induced significant central memory CD4(+) T cell phenotypes (CD4(+) CD44(+) CD62L(+) CCR7(+)) and activated polyclonal CD4(+) T cells as shown by production of Interleukin (IL)-2, Interferon (IFN)-?, and Tumor Necrosis Factor (TNF)-?. Most importantly, VA387-specific CD4(+) T cell epitope induced a production of IFN-?, indicating an antigen-specific CD4(+) T cell response in P domain complex-immunized mice. Furthermore, P domain complexes efficiently induced bone marrow-derived dendritic cell (BMDC) maturation, evidenced by up-regulation of co-stimulatory and MHC class II molecules, as well as production of IL-12 and IL-1?. Finally, P domain complex-induced mature dendritic cells (DCs) elicited proliferation of specific CD4(+) T cells targeting VA387 P domain. Overall, we conclude that the NoV P domain complexes are efficiently presented by DCs to elicit not only humoral but also cellular immune responses against NoVs. Since the P particle is highly effective for both humoral and cellular immune responses and easily produced in Escherichia coli (E. coli), it is a good choice of vaccine against NoVs and a vaccine platform against other diseases.
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[Advances in research on antischistosomal drugs].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 12-15-2011
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The article summarizes the newest researches of antischistosomal drugs and discusses the possible alternatives to praziquantel from three aspects, so as to provide the evidence for the development of antischistosomal drugs.
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[Causes, location and management of BPH surgery-related urethral stricture].
Zhonghua Nan Ke Xue
PUBLISHED: 11-24-2011
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To analyze the possible causes of BPH surgery-related urethral stricture and summarize the experience in its clinical management.
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LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-14-2011
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KSper, a pH-dependent K(+) current in mouse spermatozoa that is critical for fertility, is activated by alkalization in the range of pH 6.4-7.2 at membrane potentials between -50 and 0 mV. Although the KSper pore-forming subunit is encoded by the Slo3 gene, heterologously expressed Slo3 channels are largely closed at potentials negative to 0 mV at physiological pH. Here we identify a Slo3-associating protein, LRRC52 (leucine-rich repeat-containing 52), that shifts Slo3 gating into a range of voltages and pH values similar to that producing KSper current activation. Message for LRRC52, a homolog of the Slo1-modifying LRRC26 protein, is enriched in testis relative to other homologous LRRC subunits and is developmentally regulated in concert with that for Slo3. LRRC52 protein is detected only in testis. It is markedly diminished from Slo3(-/-) testis and completely absent from Slo3(-/-) sperm, indicating that LRRC52 expression is critically dependent on the presence of Slo3. We also examined the ability of other LRRC subunits homologous to LRRC26 and LRRC52 to modify Slo3 currents. Although both LRRC26 and LRRC52 are able to modify Slo3 function, LRRC52 is the stronger modifier of Slo3 function. Effects of other related subunits were weaker or absent. We propose that LRRC52 is a testis-enriched Slo3 auxiliary subunit that helps define the specific alkalization dependence of KSper activation. Together, LRRC52 and LRRC26 define a new family of auxiliary subunits capable of critically modifying the gating behavior of Slo family channels.
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Standardized ultrasound hepatic/renal ratio and hepatic attenuation rate to quantify liver fat content: an improvement method.
Obesity (Silver Spring)
PUBLISHED: 10-20-2011
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Accurate measures of liver fat content are essential for investigating the role of hepatic steatosis in the pathophysiology of multiple metabolic disorders. No traditional imaging methods can accurately quantify liver fat content. [(1)H]-magnetic resonance spectroscopy (MRS) is restricted in large-scale studies because of the practical and technological issues. Previous attempts on computer-aided ultrasound quantification of liver fat content varied in method, and the ultrasound quantitative parameters measured from different ultrasound machines were hardly comparable. We aimed to establish and validate a simple and propagable method for quantitative assessment of liver fat content based on the combination of standardized ultrasound quantitative parameters, using [(1)H]-MRS as gold standard. Totally 127 participants were examined with both ultrasonography (US) and [(1)H]-MRS. Ultrasound hepatic/renal echo-intensity ratio (H/R) and ultrasound hepatic echo-intensity attenuation rate (HA) were obtained from ordinary ultrasound images using computer program. Both parameters were standardized using a tissue-mimicking phantom before analysis. Standardized ultrasound H/R and HA were positively correlated with the liver fat content by [(1)H]-MRS (r = 0.884, P < 0.001 and r = 0.711, P < 0.001, respectively). Linear regression analysis showed ultrasound H/R could modestly predict the amount of liver fat (adjusted explained variance 78.0%, P < 0.001). The addition of ultrasound HA slightly improved the adjusted explained variance to 79.8%. Difference of estimated liver fat contents between different ultrasound machines and operators was reasonably well. Thus, computer-aided US is a valid method to estimate liver fat content and can be applied extensively after standardization of ultrasound quantitative parameters.
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[Expressions and significance of COX-2 and P-gp in human hepatocellular carcinoma tissues].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 10-13-2011
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To investigate the effect of the COX-2 gene on the oncogenesis and development of the hepatocellular carcinoma and the influence of COX-2 gene on the expression of P-gp protein.
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Surface modification of magnetite nanoparticles using gluconic acid and their application in immobilized lipase.
Colloids Surf B Biointerfaces
PUBLISHED: 10-08-2011
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Superparamagnetic magnetite nanoparticles (SMN) were surface-modified with gluconic acid (GLA) to improve their hydrophilicity and bio-affinity. Gluconic acid was successfully coated on the surface of magnetite nanoparticles and characterized using Fourier transform infrared spectroscopy (FT-IR). With water-soluble carbodiimide (EDC) as the coupling reagent, lipase was successfully immobilized onto the hydroxyl-functionalized magnetic nanoparticles. The immobilized lipase had better resistance to temperature and pH inactivation in comparison to the free form and hence widened the reaction pH and temperature range. Thermostability and storage stability of the enzyme improved upon covalent immobilization. Immobilized lipase showed higher activity after recycling when compared to the free one and could be recovered by magnetic separation.
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[Bioactivity and action modes of bisdemethoxycurcumin against Tetranychus cinnabarinus Bois. (Acari:Tetranychidae)].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 09-28-2011
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This paper determined the contact-killing and fumigant activities of natural plant product bisdemethoxycurcumin (BDMC) on the important phytophagous mite Tetranychus cinnabarinus (Acari:Tetranychidae) at its different life stages, and studied the repellency effects of BDMC on the mite larvae, nymphs, and adults, and the inhibition efficiency of BDMC on the female mite oviposition under the conditions of 26 degrees C +/- 1 degree C, 60%-80% RH, and light cycle 14L : 10D h. The median lethal concentration (LC50) of BDMC at 48 h against female adults determined by slide-dip method was 0.433 mg x mL(-1). At concentration 0.883 mg x mL(-1) (LC70), the contact-killing activity of BDMC against different life stage T. cinnabarinus was in the order of larva > nymph > adult > egg, and the corrected mortality of larvae at 24 h and 48 h was 60.0% and 83.3%, respectively. BDMC had no obvious fumigant activity against different life stage T. cinnabarinus, and the corrected mortality was all less than 3% after treatment 24 h and 48 h. BDMC had stronger repellency activity against the mite, with the repellency rate against larvae at different treatment times all above 85%, followed by against nymphs, and that against adults after 72 h being only 47.8%. BDMC had obvious oviposition inhibition activity against female adults, with the inhibition rate after 120 h reached 89.3%. All the results suggested that the main action modes of BDMC against T. cinnabarinus were contact-killing, repellency, and oviposition inhibition.
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CXCR4 antagonist AMD3100 modulates claudin expression and intestinal barrier function in experimental colitis.
PLoS ONE
PUBLISHED: 08-30-2011
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Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of colonic claudin-1, claudin-3, claudin-5, claudin-7 and claudin-8 were markedly decreased after DSS administration, whereas colonic claudin-2 expression was significantly decreased. Treatment with AMD3100 prevented all these changes. However, AMD3100 had no influence on claudin-3, claudin-5, claudin-7 and claudin-8 expression in HT-29/B6 cells. Cytokines as TNF-?, IL-6, and IFN-? increased apoptosis and monolayer permeability, inhibited the wound-healing and the claudin-3, claudin-7 and claudin-8 expression in HT-29/B6 cells. We suggest that AMD3100 acted on colonic claudin expression and intestinal barrier function, at least partly, in a cytokine-dependent pathway.
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[Clinical features of feeding intolerance in preterm infants].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 08-19-2011
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To study the clinical features of feeding intolerance in preterm infants in order to provide clinical evidence for preventing feeding intolerance.
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