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Find video protocols related to scientific articles indexed in Pubmed.
Fine mapping of the mutant gene varnished eye in the silkworm.
Yi Chuan
PUBLISHED: 11-20-2014
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The varnished eye (ve) mutant is one of the rare natural recessive mutants related to the abnormal phenotypes in the compound eye of silkworm (Bombyx mori). The compound eyes of the ve adults are smaller and glossier than those of the wild-type Dazao (Dz) and many tumor-like bumps are present on their surface; their small eyes are irregularly arranged and are smaller and fewer than those of the wild-type. The mutant gene ve has been located at the 32.2 locus of chromosome 6 in the classic genetic linkage map. However, it still remains unknown about the mechanism responsible for the mutant. In this study, we got a BC1 generation using male F1 (ve×Dz) with female ve for fine mapping of this mutant gene. The results showed that ve was located in a region between SNP3 and SNP6. The physical distance is approximately 1.2 Mb in the low density linkage map. By constructing a high-density map using 1563 BC1 individuals, the ve mutant gene was further mapped into a region between the SNP5 and SNP61. The physical region is about 221.8 kb and contains six potential genes but no specific mutations were found in the CDSs of these candidate genes. RT-PCR showed that the expression of BGIBMGA013642 was decreased obviously compared with that in wild type, suggesting it might be a key candidate gene for further studying the ve mutant.
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Active optical zoom system.
Appl Opt
PUBLISHED: 11-18-2014
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In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.
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Advanced Hepatic Fibrosis and Steatosis Are Associated with Persistently Alanine Aminotransferase Elevation in Chronic Hepatitis C Patients Negative for HCV RNA During Pegylated Interferon Plus Ribavirin Therapy.
J. Infect. Dis.
PUBLISHED: 11-13-2014
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?Clinical implications of persistently alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy remain unknown.
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A Juvenile Hormone-Transcription Factor Bmdimm-Fibroin H chain pathway is involved in the synthesis of silk protein in silkworm, Bombyx mori.
J. Biol. Chem.
PUBLISHED: 11-06-2014
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The genes responsible for silk biosynthesis are switched on and off at particular times in the silk glands of Bombyx mori. This switch appears to be under the control of endogenous and exogenous hormones. However, the molecular mechanisms by which silk protein synthesis is regulated by juvenile hormone (JH) are largely unknown. Here, we report a basic helix-loop-helix transcription factor (bHLH), Bmdimm, its silk gland-specific expression and its direct involvement in the regulation of fibroin H-chain (fib-H) by binding to an E-box (CAAATG) element of the fib-H gene promoter. Far-western blots, enzyme linked immunosorbent assays, and Co-Immunoprecipitation assays revealed that Bmdimm protein interacted with another bHLH transcription factor, Bmsage. Immunostaining revealed that Bmdimm and Bmsage proteins are colocalized in nuclei. Bmdimm expression was induced in larval silk glands in vivo, in silk glands cultured in vitro and in B. mori cell lines after treatment with a JH analog. The JH effect on Bmdimm was mediated by the JH-Met-Kr-h1 signaling pathway, and Bmdimm expression did not respond to JH by RNA interference with double-stranded BmKr-h1 RNA. These data suggests that the JH regulatory pathway, the transcription factor Bmdimm, and the targeted fib-H gene contribute to the synthesis of fibroin H-chain protein in B. mori.
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[Influencing factors for operational performance of a biofilm reactor with microbubble aeration using SPG membrane].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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The microbubble-aerated biofilm reactor provides a feasibility to apply microbubble aeration in aerobic wastewater treatment processes. In this study, Shirasu porous glass (SPG) membranes were used for microbubble aeration in a fixed bed biofilm reactor treating synthetic municipal wastewater. The influencing factors for operational performance of the bioreactor were investigated, including operating parameters, SPG membrane fouling and its structural changes. The results indicated that there was no significant influences of air flux, organic loading rate and packed bed on COD removal and an average COD removal efficiency of 80% -90% could be achieved under different operating conditions. On the other hand, the dissolved oxygen (DO) concentrations decreased significantly along with reducing air flux or increasing organic loading rate. As a result, the ammonia removal deteriorated gradually and the average ammonia removal efficiency decreased from 80% -90% to 20% -30% At the same time, the total nitrogen (TN) removal achieved in the simultaneous nitrification and denitrification process was also reduced from 30% -40% to about 20% , due to nitrification inhibition. Higher available porosity could be obtained when ring packing was used in the fixed bed, resulting in improvement of contaminant removal performance. An oxygen utilization efficiency of close to 100% could be achieved at low air fluxes or high organic loading rates during microbubble aeration. Both biofilm growth and organic foulant accumulation on SPC, membrane surface contributed to membrane fouling after long-term operation. The average pore size and porosity of SPG membrane increased significantly due to the chemical corrosion caused by alkali NaClO solution used for online cleaning. Then the air permeation of SPG membrane was affected by membrane fouling and destroyed pore structure.
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[Atrazine wastewater treatment in a SPG membrane-aerated genetically engineered microorganism biofilm reactor].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Membrane-aerated biofilm reactor (MABR) represent a novel membrane-biological wastewater treatment technology. In addition, bioaugmented treatment using genetically engineered microorganism (GEM) biofilm in MABR is proposed to improve refractory pollutant removal. In the present study, a SPG membrane aerated-biofilm reactor (SPG-MABR) with GEM biofilm formed on the SPG membrane surface was applied to treat atrazine wastewater. The influences of air pressure, biofilm biomass and liquid velocity on the performance of the SPG-MABR were investigated. The variation of GEM biofilm during the SPG-MABR operation was observed. The results indicated that the increased air pressure could promote atrazine and COD removal as well as re-oxygenation by increasing oxygen permeability coefficient. A higher biofilm biomass could also enhance atrazine and COD removal, but simultaneously reduce the re-oxygenation rate because biofilm thickness and oxygen transfer resistance increased. When liquid velocity in the SPG-MABR was decreased under laminar flow condition, atrazine and COD removal was improved due to the facilitated contaminant diffusion from wastewater to biofilm. The atrazine removal efficiency reached to 98.6% in the SPG-MABR after 5d treatment at air pressure of 300 kPa, biofilm biomass of 25 g x m(-2) and liquid velocity of 0.05 m x s(-1). The microbial polymorphism of GEM biofilm was observed during the SPG-MABR operation. The surface of GEM biofilm was gradually covered by other microbial cells and the distribution of GEM cells reduced, but inside the GEM biofilm, the GEM cells were still dominant.
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Influence of Three Coccidiostats on the Pharmacokinetics of Florfenicol in Rabbits.
Exp. Anim.
PUBLISHED: 10-17-2014
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In-feed Medication has been used for a long time to prevent coccidiosis, a worldwide protozoal disease in rabbits. Florfenicol (FFC) has been widely used in veterinary clinics for bacterial diseases treatment. Therefore, the use of combinations of coccidiostats with FFC in rabbits is common. In the present study, we aimed to evaluate the effect of three coccidiostats, sulfaquinoxaline (SUL), robenidine (ROB), and toltrazuril (TOL), as feed additives on the pharmacokinetic profile of FFC in rabbits. The disposition kinetics of FFC in rabbits were investigated after a single intravenous injection (25 mg/kg) in rabbits fed anticoccidial-free diets or feeds containing SUL (250 ppm), ROB (66 ppm), or TOL (2 ppm), respectively, for 20 days. Plasma FFC concentrations were determined by the high performance liquid chromatography (HPLC) method. The pharmacokinetic parameters of FFC were analyzed using a non-compartmental analysis based on the statistical moment theory. The results demonstrated that ROB feeding resulted in an obvious decrease in plasma FFC level as compared with anticoccidial-free feeding. The terminal elimination half-life (t1/2z), area under the concentration-time curve (AUC), area under the first moment curve (AUMC), and mean residence time (MRT) significantly decreased, whereas the elimination rate constant (?z) and total body clearance (CLz) obviously increased in rabbits pretreated with ROB. However, we did not find that SUL or TOL feeding had any effect on the pharmacokinetic profile of FFC. Our findings suggested that more attention should be paid to the use of FFC in rabbits supplemented with ROB.
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Serum Biomarkers Predictive of Significant Fibrosis and Cirrhosis in Chronic Hepatitis B.
J. Clin. Gastroenterol.
PUBLISHED: 10-17-2014
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Aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 index are noninvasive biomarkers to evaluate hepatic fibrosis. However, their usefulness in chronic hepatitis B (CHB) patients remains unclear.
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Identification of Causative Pathogens in Mouse Eyes with Bacterial Keratitis by Sequence Analysis of 16S rDNA Libraries.
Exp. Anim.
PUBLISHED: 10-15-2014
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The clone library method using PCR amplification of the 16S ribosomal RNA (rRNA) gene was used to identify pathogens from corneal scrapings of C57BL/6-corneal opacity (B6-Co) mice with bacterial keratitis. All 10 samples from the eyes with bacterial keratitis showed positive PCR results. All 10 samples from the normal cornea showed negative PCR results. In all 10 PCR-positive samples, the predominant and second most predominant species accounted for 20.9% to 40.6% and 14.7% to 26.1%, respectively, of each clone library. The predominant species were Staphylococcus lentus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The microbiota analysis detected a diverse group of microbiota in the eyes of B6-Co mice with bacterial keratitis and showed that the causative pathogens could be determined based on percentages of bacterial species in the clone libraries. The bacterial species detected in this study were mostly in accordance with results of studies on clinical bacterial keratitis in human eyes. Based on the results of our previous studies and this study, the B6-Co mouse should be considered a favorable model for studying bacterial keratitis.
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Lycopene Attenuated Hepatic Tumorigenesis via Differential Mechanisms Depending on Carotenoid Cleavage Enzyme in Mice.
Cancer Prev Res (Phila)
PUBLISHED: 10-07-2014
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Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10'-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9',10'-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)-promoted liver inflammation, and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 expression is important using BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs. 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs. 20%) and multiplicity (58% vs. 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic proinflammatory signaling (phosphorylation of NK-?B p65 and STAT3; IL6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress-mediated unfolded protein response (ER(UPR)), through decreasing ER(UPR)-mediated protein kinase RNA-activated like kinase-eukaryotic initiation factor 2? activation, and inositol requiring 1?-X-box-binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals, including Met mRNA, ?-catenin protein, and mTOR complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression. Cancer Prev Res; 7(12); 1-9. ©2014 AACR.
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Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.
J Int AIDS Soc
PUBLISHED: 08-28-2014
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The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated.
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[Simultaneous nitrification and denitrification in a microbubble-aerated biofilm reactor].
Huan Jing Ke Xue
PUBLISHED: 08-28-2014
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Simultaneous nitrification and denitrification (SND) is a new wastewater treatment process for biological nitrogen removal, which shows some significant advantages compared with conventional biological nitrogen removal processes. The SND process in a fixed bed biofilm reactor with microbubble aeration was investigated in this study. The removal efficiencies of COD and nitrogen were determined under different operational conditions and the functional bacterial populations for nitrogen removal in the biofilm were detected. The results showed that efficient SND process could be achieved in the biofilm reactor with microbubble aeration. The SND could be improved at lower dissolved oxygen (DO) concentration and larger porosity of packing bed when the COD loading rate and C/N ratio were increased. The removal efficiencies of COD and total nitrogen (TN) were 97.6% and 70.2%, respectively, at a COD loading rate of 0.86 kg x (m3 x d)(-1), a TN loading rate of 0.10 kg x (m3 x d)(-1), and a packing bed porosity of 81%, indicating the simultaneous efficient removal of COD and TN. Under these conditions, the oxygen utilization efficiency reached as high as 91.8% due to the enhanced oxygen mass transfer by microbubble aeration. In addition, the biofilm activity and the abundance of nitrifiers and denitrifiers were consistent with the removal capacity of COD, ammonia and TN under different operational conditions.
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Computation of the memory functions in the generalized Langevin models for collective dynamics of macromolecules.
J Chem Phys
PUBLISHED: 08-20-2014
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We present a numerical method to approximate the memory functions in the generalized Langevin models for the collective dynamics of macromolecules. We first derive the exact expressions of the memory functions, obtained from projection to subspaces that correspond to the selection of coarse-grain variables. In particular, the memory functions are expressed in the forms of matrix functions, which will then be approximated by Krylov-subspace methods. It will also be demonstrated that the random noise can be approximated under the same framework, and the second fluctuation-dissipation theorem is automatically satisfied. The accuracy of the method is examined through several numerical examples.
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The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo.
Mol Ther Nucleic Acids
PUBLISHED: 08-19-2014
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Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) under current antiviral therapy is a major barrier to eradication of chronic hepatitis B (CHB). Curing CHB will require novel strategies for specific disruption of cccDNA. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target DNA sequence. To examine whether this system can cleave HBV genomes, we designed eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the CRISPR/Cas9 system significantly reduced the production of HBV core and surface proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight screened gRNAs, two effective ones were identified. Interestingly, one gRNA targeting the conserved HBV sequence acted against different genotypes. Using a hydrodynamics-HBV persistence mouse model, we further demonstrated that this system could cleave the intrahepatic HBV genome-containing plasmid and facilitate its clearance in vivo, resulting in reduction of serum surface antigen levels. These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing templates both in vitro and in vivo, indicating its potential in eradicating persistent HBV infection.
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Comorbidities among the HIV-infected patients aged 40 years or older in Taiwan.
PLoS ONE
PUBLISHED: 08-13-2014
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With the widespread use of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients has significantly prolonged. An increasing number of HIV-infected patients are aging and concurrent use of medications are not uncommon for management of metabolic complications and cardiovascular diseases related to aging and prolonged exposure to cART.
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Incidence and risk factors of skin rashes and hepatotoxicity in HIV-infected patients receiving nevirapine-containing combination antiretroviral therapy in Taiwan.
Int. J. Infect. Dis.
PUBLISHED: 08-08-2014
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To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors.
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Planar integrated metasurfaces for highly-collimated terahertz quantum cascade lasers.
Sci Rep
PUBLISHED: 07-24-2014
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We report planar integration of tapered terahertz (THz) frequency quantum cascade lasers (QCLs) with metasurface waveguides that are designed to be spoof surface plasmon (SSP) out-couplers by introducing periodically arranged SSP scatterers. The resulting surface-emitting THz beam profile is highly collimated with a divergence as narrow as ~4° × 10°, which indicates a good waveguiding property of the metasurface waveguide. In addition, the low background THz power implies a high coupling efficiency for the THz radiation from the laser cavity to the metasurface structure. Furthermore, since all the structures are in-plane, this scheme provides a promising platform where well-established surface plasmon/metasurface techniques can be employed to engineer the emitted beam of THz QCLs controllably and flexibly. More importantly, an integrated active THz photonic circuit for sensing and communication applications could be constructed by incorporating other optoelectronic devices such as Schottky diode THz mixers, and graphene modulators and photodetectors.
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Aberrant Serum Immunoglobulin G Glycosylation in Chronic Hepatitis B Is Associated With Histological Liver Damage and Reversible by Antiviral Therapy.
J. Infect. Dis.
PUBLISHED: 07-10-2014
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?Aberrant serum immunoglobulin G (IgG) glycosylation and its immunomodulatory effect are rarely addressed in chronic hepatitis B virus (HBV) infection.
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Association of serum IgG N-glycome and transforming growth factor-?1 with hepatitis B virus e antigen seroconversion during entecavir therapy.
Antiviral Res.
PUBLISHED: 06-13-2014
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Aberrant serum IgG N-glycome has been demonstrated in various autoimmune diseases and viral infections. However, the correlation between serum IgG N-glycome and cytokine is unclear. In addition, the clinical relevance of IgG glycosylation and cytokine changes in the treatment outcome of chronic hepatitis B (CHB) has never been assessed. One hundred and three treatment-naive patients with CHB and 101 healthy controls were enrolled in this retrospective cohort study. Serum samples in patients before and after 48weeks of entecavir treatment were collected. In-gel trypsinized serum IgG heavy chain was analyzed using liquid chromatography-tandem mass spectrometry. Selected ion chromatograms corresponding to 10 N-glycoforms on asparagine 297 were individually extracted to calculate the percentage of each glycoforms. Serum cytokine profiles were examined using enzyme-linked immunosorbent assay. Forty-eight weeks of entecavir treatment resulted in decreases in galactose-deficient (total G0) IgG and transforming growth factor (TGF)-?1 levels (both P<0.001) in patients with CHB. The changes in TGF-?1 (?TGF-?1) and IgG total G0 (?total G0) levels during treatment were significantly correlated (r=0.403, P<0.001). Furthermore, higher levels of ?total G0 (P<0.01) and ?TGF-?1 (P<0.001) were found in hepatitis B virus e antigen (HBeAg)-positive patients than in HBeAg-negative patients and were also found in patients with HBeAg seroconversion at week 48. The area under the receiver operating characteristic (ROC) curves for ?total G0 and ?TGF-?1 to discriminate a week-48 HBeAg seroconversion were 0.835 and 0.830, respectively. These results suggested a correlation between serum cytokine and IgG N-glycome and its effect on the outcome of entecavir treatment in patients with CHB.
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Micro-evolution of the Hepatitis B Virus Genome in Hepatitis B e-Antigen-Positive Carriers: Comparison of Genotypes B and C at Various Immune Stages.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-12-2014
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Patients with hepatitis B virus (HBV) genotype B infection experience hepatitis B e antigen (HBeAg) seroconversion at an earlier stage than do patients with genotype C infection. Therefore, this study investigated whether the differential phenotypes are related to HBV genomic evolution.
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Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-?.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-28-2014
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Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-?, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.
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Two novel lignans from Gaultheria yunnanensis.
J Asian Nat Prod Res
PUBLISHED: 03-26-2014
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Two new lignans, 9-salicyl-(+)-isolariciresinol (1) and gaultheroside G (2), together with seven known compounds, were isolated from the ethanolic extract of the whole plant of Gaultheria yunnanensis. Their structures were determined by extensive NMR and MS analyses. Gaultheroside G (2) was found to have an unusual ether linkage between the 2 and 9' positions of aryl-tetralin lignan skeleton. All nine compounds were assayed for inhibitory effects against nitric oxide and pro-inflammatory cytokines TNF-? and IL-6 release in LPS-induced RAW 246.7 macrophages, while no significant activities were observed for the evaluated compounds.
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Self-mode-locked 2 ?m Tm(3+)-doped double-clad fiber laser with a simple linear cavity.
Appl Opt
PUBLISHED: 03-26-2014
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We demonstrate the self-mode-locking operation of a thulium (Tm)-doped fiber laser (TDFL) with a simple linear cavity. Since the laser cavity does not include any specific mode-locker, we experimentally investigate and analyze the self-mode-locking mechanism. The mode-locking operation is attributed to the combination of the self-phase modulation effect and the weak saturable absorption of the high-concentration Tm-doped fiber. The mode-locked TDFL operates at a central wavelength of 1985.5 nm with the 3 dB spectral linewidth of 0.18 nm. The self-mode-locking generates a large pulse energy of 32.7 nJ with a pulsed repetition rate of 2.05 MHz and is stable with a radio-frequency signal-to-noise ratio of more than 54 dB. To the best of our knowledge, it is the first demonstration of a 2 ?m Tm-doped fiber laser mode-locked by such technique.
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Matrix metalloproteinase-1 (MMP-1) expression in rat spinal cord injury model.
Cell. Mol. Neurobiol.
PUBLISHED: 03-22-2014
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Matrix metalloproteinase-1 (MMP-1), a member of the matrix metalloproteinases family, plays an integral role in extracellular matrix degradation and has been reportedly involved in the regulation of the brain or spinal cord traumatic neurovascular remodeling. Although the critical involvement of MMP-1 in the metastasis of tumors has been extensively documented, the role of MMP-1 in the pathology of neurological diseases remains largely elusive. In the present study, we established an adult rat spinal cord injury (SCI) model and investigated a potential role of MMP-1 in the pathological process of SCI. Using Western blot analysis, we identified notable expression change of MMP-1 after SCI. Immunohistochemistry showed that MMP-1 was distributed widely in rat spinal cord. Double immunofluorescence staining revealed that MMP-1 immunoreactivity was predominantly increased in neurons and astrocytes following SCI. Moreover, after injury, colocalization of MMP-1/active caspase-3 in neurons (NeuN-positive), and colocalization of MMP-1/PCNA in astrocytes (GFAP-positive) were clearly observed. We also examined the protein expression of PCNA, active caspase-3, Bcl-2, and Bax and found that the expression of the proteins was closely correlated with that of MMP-1. Taken together, our findings indicate that MMP-1 might play an important role in the regulation of neuronal apoptosis and astrocyte proliferation after SCI.
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High-refined-carbohydrate and high-fat diets induce comparable hepatic tumorigenesis in male mice.
J. Nutr.
PUBLISHED: 03-19-2014
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Previous studies demonstrated that diet-induced obese mice fed a semi-purified high-fat diet (HFD) had greater liver tumorigenesis than mice fed a non-semi-purified diet. Because ingredients present in standard unpurified diets may elicit potential chemopreventive properties that are not present in semi-purified diets, the present study evaluated hepatic tumorigenic effects of dietary fat by replacing it with refined carbohydrates [digestible saccharides; high-carbohydrate diet (HCD)] in a semi-purified diet without altering other components. Two-wk-old C57Bl/6J male mice were randomly injected i.p. with either the liver-specific carcinogen diethylnitrosamine (25 mg/kg body weight) to induce liver cancer or saline as the nontumor control. At age 6 wk, mice with or without cancer initiation were further randomly assigned to an HFD (26% and 60% energy from carbohydrates and fat, respectively) or an HCD (66% and 12% energy from carbohydrates and fat, respectively) and consumed food ad libitum for 24 wk. Results showed that HCD-fed mice had a comparable degree of hepatic tumorigenesis (tumor number and volume) as HFD-fed mice, despite having significantly reduced body weights. HCD feeding induced greater hepatic endoplasmic reticulum (ER) stress-mediated protein kinase RNA-activated-like kinase (PERK) activation and oncogenic interleukin-6/signal transducer and activator of transcription 3 signaling than HFD feeding. HCD-stimulated PERK signaling was associated with elevated expression of prosurvival markers in tumors, including induced protein kinase B activation, increased extracellular signal-regulated kinases 1/2 phosphorylation, and elevated cyclin D1 protein expression. However, HCD-mediated PERK activation in tumors was also positively associated with markers of proapoptosis, which included elevated CCAAT/enhancer-binding protein homology protein expression and increased cleaved caspase-3. HCD-fed mice had greater severity in hepatic steatosis than HFD-fed mice. HCD-induced steatosis exacerbation was associated with increased expression in hepatic de novo lipogenic markers that can promote ER stress. Together, these data indicated that chronic HCD consumption by mice can produce comparable severity of hepatic tumorigenesis as HFD consumption, potentially through upregulating PERK-mediated ER stress.
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Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection.
Clin. Infect. Dis.
PUBLISHED: 03-05-2014
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Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV.
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Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy.
Biomaterials
PUBLISHED: 03-02-2014
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Developing safe and effective carriers of small interference RNA (siRNA) is a significant demand for the systemic delivery of siRNA. In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytometry showed that LDL-coupled nanoparticles were more easily taken up than Dox-SCS-NPs. Results of confocal microscopy and reverse transcription-PCR revealed the highly efficient uptake of siRNA and the decrease in mdr1 mRNA expression. LDL-coupled nanoparticles protected siRNA from macrophage phagocytosis by dynamic observation using live cell station. In vivo tumor-targeting suggested that Cy7-labelled Dox-LDL-SCS-NPs were markedly accumulated in an analyzed in situ liver tumor model. Results indicated that LDL-SCS-NPs were effective tumor-targeting vectors and that the preparation form may provide a new strategy for co-delivering siRNA and antitumor drugs.
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An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers.
Mol Biosyst
PUBLISHED: 02-22-2014
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Heavy smoking is associated with the development of chronic obstructive pulmonary disease (COPD). However, there is no valuable biomarker for evaluating COPD development in heavy smokers because they are usually asymptomatic. This study is aimed at evaluating whether the levels of serum miRNAs can serve as biomarkers for predicting the occurrence of COPD. A rat model of emphysema was induced by enforced smoking, and the dynamic miRNAs expression profile at different stages of emphysema with varying periods of smoking were analyzed by microarray and quantitative real-time polymerase chain reaction (qRT-PCR). The differentially expressing miRNAs were analyzed using Gene Ontology and the KEGG PATHWAY database. The levels of three serum candidate miRNAs were measured by qRT-PCR in 41 healthy controls (HC), 40 asymptomatic heavy smokers, and 49 COPD patients. Following smoking for varying periods, different severities of lung emphysema were observed in different groups of rats, accompanied by altered levels of some serum miRNAs associated with regulating some pathways. Furthermore, the levels of miR-21 were significantly higher in the COPD patients and asymptomatic heavy smokers than in the HC (P < 0.001), while the levels of miR-181a were significantly lower in the COPD patients and asymptomatic heavy smokers than in the HC (P < 0.001). Accordingly, the levels of serum miR-21 and miR-181a as well as their ratios had a high sensitivity (0.854) and specificity (0.850) for evaluating the development of COPD. Our data suggest that the levels of serum miR-21 and miR-181a may be valuable for evaluating the development of COPD in heavy smokers.
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Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.
World J. Gastroenterol.
PUBLISHED: 02-12-2014
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To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
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Efficacy of entecavir in chronic hepatitis B patients with persistently normal alanine aminotransferase: randomized, double-blind, placebo-controlled study.
Antivir. Ther. (Lond.)
PUBLISHED: 01-27-2014
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It is still inconclusive whether chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT) should receive nucleos(t)ides analogues. This study is to evaluate the efficacy of entecavir in improving liver histology in CHB patients with PNALT.
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Netrin-1 controls sympathetic arterial innervation.
J. Clin. Invest.
PUBLISHED: 01-15-2014
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Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.
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Revaccination with 7-valent pneumococcal conjugate vaccine elicits better serologic response than 23-valent pneumococcal polysaccharide vaccine in HIV-infected adult patients who have undergone primary vaccination with 23-valent pneumococcal polysaccharide vaccine in th
Vaccine
PUBLISHED: 01-02-2014
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HIV-infected adults who had received 23-valent pneumococcal polysaccharide vaccine (PPV23) five years or more earlier consecutively underwent revaccination with one dose of PPV23 (127 subjects) from December 2005 through October 2007, or upon change in standard of care, non-randomly one (50) or two doses (44) of 7-valent pneumococcal conjugate vaccine (PCV7) from October 2008 through June 2010. Serologic response was defined as ? 2-fold increase in the IgG level plus a level ? 1000ng/ml 48 weeks following revaccination. At week 48, the response rate was significantly higher in the 2-dose PCV7 group compared with that in the 1-dose PCV7 or PPV23 group (63.6% vs 32.0% vs 8.7%, respectively; P<0.05). Revaccination with one dose of PCV7 (AOR, 4.57), two doses of PCV7 (AOR, 22.66), and CD4 >350 cells/?l (AOR, 3.24) and undetectable viral load (AOR, 3.87) at revaccination were statistically significantly associated with a better serologic response at week 48. Despite the limitation that study arms were neither randomized nor contemporaneous, we conclude that revaccination with PCV7 appears to elicit a better serologic response than PPV23 in the HIV-infected adults who have received PPV23 five years or more earlier (clinical trial registration number: NCT00885625).
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MicroRNA expression profile of gastric cancer stem cells in the MKN-45 cancer cell line.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 01-02-2014
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MicroRNAs (miRNAs) play important roles in post-transcriptional gene silencing of target messenger RNAs, which are involved in virtually all biological processes. Previously, we have demonstrated that spheroid body-forming cells from the MKN-45 cancer cell line possessed gastric cancer stem cell (CSC) properties. In this study, we aimed to determine the miRNA profile of the gastric CSCs and to explore the role of miRNAs in gastric CSCs. Human miRNA microarrays, which contain probes specific for 1887 human miRNAs were used to determine the expression profiles of the gastric CSCs. A total of 182 miRNAs with a more than 2-fold change were identified to be differentially expressed between the spheroid body-forming cells and the parental cells. Of these miRNAs, 9 miRNAs were over-expressed in the spheroid body-forming cells, while the other 173 miRNAs were all under-expressed, indicating that the role of most miRNAs in human gastric CSCs may be tumor suppressors. The results of microarray analysis were validated by quantitative real-time polymerase chain reaction, and the consistence rate is 70% (7 out of 10). The target genes for the validated miRNAs were predicted by using three online software programs, miRanda, PicTar, and TargetScan. Most of the potential targets of the miRNAs were relevant to the regulation of actin cytoskeleton, focal adhesion, extracellular matrix-receptor interaction, and the pathways in cancer. Especially, several genes are associated with some pivotal signaling pathways of the 'stem cell genes'. Evaluating the characteristic miRNAs of the gastric CSCs may be a new method for studying gastric cancer and developing therapeutic strategies, which aimed at eradicating the subpopulation of CSCs in gastric cancer.
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Antiretroviral therapy (ART) management of Low-Level Viremia in Taiwan (ALLEVIATE).
J Int AIDS Soc
PUBLISHED: 01-01-2014
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This retrospective study aimed to investigate that if switch of combination antiretroviral therapy (cART) would result in viral suppression (<40 copies/mL) at 48 weeks for patients with persistent low-level viremia after having received cART for six months or more at two hospitals designated for HIV care in Taiwan.
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Seroincidence of HIV and prevalence of transmitted drug resistance of HIV-1 strains among persons seeking voluntary counselling and testing in Taiwan.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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The total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re-emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital.
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Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994-2000, 2.29 in 2001-2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006-2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital.
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Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Wide inter-patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients.
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Evolutionarily Conserved Repulsive Guidance Role of Slit in the Silkworm Bombyx mori.
PLoS ONE
PUBLISHED: 01-01-2014
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Axon guidance molecule Slit is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the function of Slit in the silkworm Bombyx mori was unknown. Here we showed that the structure of Bombyx mori Slit (BmSlit) was different from that in most other species in its C-terminal sequence. BmSlit was localized in the midline glial cell, the neuropil, the tendon cell, the muscle and the silk gland and colocalized with BmRobo1 in the neuropil, the muscle and the silk gland. Knock-down of Bmslit by RNA interference (RNAi) resulted in abnormal development of axons and muscles. Our results suggest that BmSlit has a repulsive role in axon guidance and muscle migration. Moreover, the localization of BmSlit in the silk gland argues for its important function in the development of the silk gland.
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Association of adjuvant antiviral therapy with risk of cancer progression and deaths in patients with hepatitis-B-virus-related hepatocellular carcinoma following curative treatment: a nationwide cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Limited information about tumor status and the time at which antiviral therapy was initiated may have influenced effect estimation in previous research. The aim of this study was to investigate the effect of antiviral therapies on HBV-related HCC progression and deaths in patients receiving curative treatment based on clear clinical-pathological cancer status and the association of start time of adjuvant antiviral therapy initiation and outcomes.
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Basic helix-loop-helix transcription factor Bmsage is involved in regulation of fibroin H-chain gene via interaction with SGF1 in Bombyx mori.
PLoS ONE
PUBLISHED: 01-01-2014
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Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells.
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Transcriptome analysis of integument differentially expressed genes in the pigment mutant (quail) during molting of silkworm, Bombyx mori.
PLoS ONE
PUBLISHED: 01-01-2014
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In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6% (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integument formation and pigmentation using silkworm q mutant. The results estimated the number and types of genes that drive new integument formation.
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Glycan masking of hemagglutinin for adenovirus vector and recombinant protein immunizations elicits broadly neutralizing antibodies against H5N1 avian influenza viruses.
PLoS ONE
PUBLISHED: 01-01-2014
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The highly pathogenic avian influenza (HPAI) H5N1 virus, a known trigger of diseases in poultry and humans, is perceived as a serious threat to public health. There is a clear need for a broadly protective H5N1 vaccine or vaccines for inducing neutralizing antibodies against multiple clades/subclades. We constructed single, double, and triple mutants of glycan-masked hemagglutiinin (HA) antigens at residues 83, 127 and 138 (i.e., g83, g127, g138, g83+g127, g127+g138, g83+g138 and g83+g127+g138), and then obtained their corresponding HA-expressing adenovirus vectors and recombinant HA proteins using a prime-boost immunization strategy. Our results indicate that the glycan-masked g127+g138 double mutant induced more potent HA-inhibition, virus neutralization antibodies, cross-clade protection against heterologous H5N1 clades, correlated with the enhanced bindings to the receptor binding sites and the highly conserved stem region of HA. The immune refocusing stem-specific antibodies elicited by the glycan-masked H5HA g127+g138 and g83+g127+g138 mutants overlapped with broadly neutralizing epitopes of the CR6261 monoclonal antibody that neutralizes most group 1 subtypes. These findings may provide useful information in the development of a broadly protective H5N1 influenza vaccine.
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Seroprevalence of hepatitis B virus among adults at high risk for HIV transmission two decades after implementation of nationwide hepatitis B virus vaccination program in Taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Seroprevalence of hepatitis B virus (HBV) after implementation of universal neonatal HBV vaccination and catch-up vaccination programs remains rarely investigated among the adults who were born in the vaccination era (in or after 1986) and engaged in high-risk sexual behaviors.
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Therapeutic drug monitoring and pharmacogenetic study of HIV-infected ethnic Chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.
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The posterior cricoarytenoid muscle is spared from MuRF1-mediated muscle atrophy in mice with acute lung injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Skeletal muscle wasting in acute lung injury (ALI) patients increases the morbidity and mortality associated with this critical illness. The contribution of laryngeal muscle wasting to these outcomes is unknown, though voice impairments and aspiration are common in intensive care unit (ICU) survivors. We evaluated the intrinsic laryngeal abductor (PCA, posterior cricoarytenoid), adductor (CT, cricothyroid) and limb (EDL, extensor digitorum longus) muscles in a mouse model of ALI.
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[Research on the compatibility laws in treating rheumatoid arthritis patients of cold-dampness obstruction syndrome].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 11-27-2013
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To find out Chinese herbal compounds (CHCs) with high frequency in treating rheumatoid arthritis (RA) patients of cold-dampness obstruction syndrome (CDOS) by inductively reviewing literatures concerning clinical application of CHCs, thus improving theoretical and medical practice levels of Chinese medical recipes.
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Effect of tomato extract supplementation against high-fat diet-induced hepatic lesions.
Hepatobiliary Surg Nutr
PUBLISHED: 11-26-2013
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Higher intake of tomatoes or tomato-based products has been associated with lower risk for liver cancer. In this study, we investigated the effects of supplementing tomato extract (TE), which contains mainly lycopene (LY) and less amounts of its precursors, phytoene (PT) and phytofluene (PTF) against high-fat-diet related hepatic inflammation and lipid profiles, and carcinogenesis. Four groups of rats were injected with a hepatic carcinogen, diethylnitrosamine (DEN) and then fed either Lieber-DeCarli control diet (35% fat, CD) or high fat diet (71% fat, HFD) with or without TE supplementation for 6 weeks. Results showed that the supplementation of TE significantly decreased the multiplicity of both inflammatory foci and altered hepatic foci (AHF) expressing placental form glutathione-S transferase (p-GST) in the liver of HFD-fed rats. High-performance liquid chromatography (HPLC) analysis showed that TE supplementation results in a significantly higher accumulation of both PT and PTF than LY in livers of rats. In addition, the TE supplementation led to a decrease of plasma cholesterol levels but an overall increase in hepatic lipids which is associated with changes in the genes on lipid metabolism, including the peroxisome proliferator-activated receptor gamma (PPAR?) and the sterol-regulatory element binding protein (SREBP-1). These data suggest that TE supplementation decreases hepatic inflammation and plasma total cholesterol associated with high dietary fat intake. Moreover, TE supplementation results in an accumulation of hepatic PT and PTF as well as increased lipogenesis suggesting further investigation into their biological function(s).
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Intense splenic 99mTc-MDP uptake in a patient with myelofibrosis.
Clin Nucl Med
PUBLISHED: 10-25-2013
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99mTc-MDP bone scan was performed in a 49-year-old woman with breast cancer. Whole-body bone scan showed multiple foci of increased MDP activity in the bone and intense splenic 99mTc-MDP uptake. Initial bone marrow aspiration in multiple locations yielded no blood cells. A subsequent bone marrow biopsy in the left anterior superior iliac spine showed myelofibrosis in addition to the known bone metastasis.
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Lycopene metabolite, apo-10-lycopenoic Acid, inhibits diethylnitrosamine-initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice.
Cancer Prev Res (Phila)
PUBLISHED: 10-01-2013
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Obesity is associated with increased risk in hepatocellular carcinoma (HCC) development and mortality. An important disease control strategy is the prevention of obesity-related hepatic inflammation and tumorigenesis by dietary means. Here, we report that apo-10-lycopenoic acid (APO10LA), a cleavage metabolite of lycopene at its 9,10-double bond by carotene-9,10-oxygenase, functions as an effective chemopreventative agent against hepatic tumorigenesis and inflammation. APO10LA treatment on human liver THLE-2 and HuH7 cells dose dependently inhibited cell growth and upregulated sirtuin 1 (SIRT1), a NAD(+)-dependent protein deacetylase that may suppress hepatic carcinogenesis. This observed SIRT1 induction was associated with decreased cyclin D1 protein, increased cyclin-dependent kinase inhibitor p21 protein expression, and induced apoptosis. APO10LA supplementation (10 mg/kg diet) for 24 weeks significantly reduced diethylnitrosamine-initiated, high fat diet (HFD)-promoted hepatic tumorigenesis (50% reduction in tumor multiplicity; 65% in volume) and lung tumor incidence (85% reduction) in C57Bl/6J mice. The chemopreventative effects of APO10LA were associated with increased hepatic SIRT1 protein and deacetylation of SIRT1 targets, as well as with decreased caspase-1 activation and SIRT1 protein cleavage. APO10LA supplementation in diet improved glucose intolerance and reduced hepatic inflammation [decreased inflammatory foci, TNF?, interleukin (IL)-6, NF-?B p65 protein expression, and STAT3 activation] in HFD-fed mice. Furthermore, APO10LA suppressed Akt activation, cyclin D1 gene, and protein expression and promoted PARP protein cleavage in transformed cells within liver tumors. Taken together, these data indicate that APO10LA can effectively inhibit HFD-promoted hepatic tumorigenesis by stimulating SIRT1 signaling while reducing hepatic inflammation. Cancer Prev Res; 6(12); 1304-16. ©2013 AACR.
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Effect of thermal-alkaline pretreatment on the anaerobic digestion of streptomycin bacterial residues for methane production.
Bioresour. Technol.
PUBLISHED: 09-01-2013
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The anaerobic digestion of streptomycin bacterial residues, solutions with hazardous waste treatments and bioenergy recovery, was tested in laboratory-scale digesters at 35°C at various organic loading rates (OLRs). The methane production and biomass digestion were efficient at OLRs below 2.33gVSL(-1)d(-1) but were deteriorated as OLR increased because of the increased total ammonia nitrogen (TAN) concentration from cell protein decay. The thermal-alkaline pretreatment with 0.10 NaOH/TS at 70°C for 2h significantly improved the digestion performance. With the thermal-alkaline pretreatment, the volumetric reactor productivity and specific methane yield of the pretreated streptomycin bacterial residue increased by 22.08-27.08% compared with those of the unpretreated streptomycin bacterial residue at an OLR of 2.33gVSL(-1)d(-1). The volatile solid removal was 64.09%, with less accumulation of TAN and total volatile fatty acid.
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Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds.
Science
PUBLISHED: 07-18-2013
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Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous "master genes" are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.
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[Clinical situation and analysis on the detection result of HIV antibody in Shandong province from 2003 to 2011].
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi
PUBLISHED: 07-17-2013
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To provide the basis for clinical acquired immunodeficiency syndrome (AIDS) surveillance and to avoid cross infection in hospital, we study the infection status of AIDS in Shandong province.
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Size-dependent melting and coalescence of tungsten nanoclusters via molecular dynamics simulation.
Phys Chem Chem Phys
PUBLISHED: 07-15-2013
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We obtained the melting temperatures of the W nanoclusters with diameters in the range of 2.5-5.0 nm which manifest the good linear fitting to the size of nanoclusters (N(-1/3)). Four different initial configurations at each size produce nearly the same melting points, with the maximum discrepancies less than 40 K. The extrapolated bulk melting point 4210 K is lower than the simulated bulk value 4520 K. Surface premelting is detected by density profiles, deformation parameters and bond orientational order parameters. Moreover, by dividing particles into surface and subsurface layers, we analyzed the different behaviors of the inner and outer shell atoms during melting in detail. During coalescence of W nanoclusters (W(N) + W(N)? W(2N)), the shape change is along the path of peanut ? rod-like ? spherical ? liquid structure. The obtained melting points from W(2N) are in good agreement with those from W(N) + W(N), indicating that melting temperatures are mainly relevant to the number of atoms, and nearly not affected by the different surface areas in nanoclusters.
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Co-expression of CD44 and ABCG2 in spheroid body-forming cells of gastric cancer cell line MKN45.
Hepatogastroenterology
PUBLISHED: 06-28-2013
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The cancer stem cell (CSC) theory hypothesizes that CSCs are regarded as the cause of tumor formation, recurrence and metastasis. This study aimed to investigate whether spheroid body-forming cells in human gastric cancer cell were enriched for CSC properties, and to assess the expression of candidate CSC markers, cluster of differentiation 44 (CD44) and adenosine triphosphate binding cassette transporter G 2 (ABCG2) in the MKN45 spheroid body cells.
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[Clinical value of radial endorectal ultrasound in the assessment of preoperative staging of rectal carcinoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 05-30-2013
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To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma.
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Probing water micro-solvation in proteins by water catalysed proton-transfer tautomerism.
Nat Commun
PUBLISHED: 05-23-2013
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Scientists have made tremendous efforts to gain understanding of the water molecules in proteins via indirect measurements such as molecular dynamic simulation and/or probing the polarity of the local environment. Here we present a tryptophan analogue that exhibits remarkable water catalysed proton-transfer properties. The resulting multiple emissions provide unique fingerprints that can be exploited for direct sensing of a site-specific water environment in a protein without disrupting its native structure. Replacing tryptophan with the newly developed tryptophan analogue we sense different water environments surrounding the five tryptophans in human thromboxane A? synthase. This development may lead to future research to probe how water molecules affect the folding, structures and activities of proteins.
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Mitofusin2 decreases intracellular cholesterol of oxidized LDL-induced foam cells from rat vascular smooth muscle cells.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 04-17-2013
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Mitofusin2 (Mfn2) plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the effects of Mfn2 on the trafficking of intracellular cholesterol in the foam cells derived from rat VSMCs (rVSMCs) and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 (ABCA1), adenosine triphosphate-binding cassette subfamily G member 1 (ABCG1) and peroxisome proliferator-activated receptor gamma (PPAR?). The rVSMCs were co-cultured with oxidized low density lipoprotein (LDL, 80 ?g/mL) to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers (20, 40 and 60 pfu/cell) of recombinant adenovirus containing Mfn2 gene (Adv-Mfn2) were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group (P<0.05), and the expression levels significantly increased when the titer of Adv-Mfn2 increased (P<0.05). At 24 or 48 h after oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased (P<0.05), but it was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05), and it also significantly decreased when the titer of Adv-Mfn2 increased (P<0.05). The mRNA and protein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05). Though the mRNA and protein expression levels of PPAR? was not significantly increased (P>0.05), the phosporylation levels of PPAR? were significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05). These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR? phosporylation and then increasing protein expression levels of ABCA1 and ABCG1, which may be helpful to suppress the formation of foam cells.
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A case of pyodermatitis-pyostomatitis vegetans.
Am. J. Med. Sci.
PUBLISHED: 03-23-2013
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Pyodermatitis-pyostomatitis vegetans (PD-PSV) is a rare disorder characterized by mucocutaneous involvement and associated with inflammatory bowel disease. A 42-year-old woman with ulcerative colitis who manifested verrucous and pyogenic lesions on her scalp, neck, axillae, inguinal areas, umbilicus, trunk and oral cavity for about 11 months is described. She also experienced general fatigue and swelling in her lower extremities. Histology revealed eosinophilic inflammation with microabscesses and pseudoepitheliomatous hyperplasia, but she was negative on direct immunofluorescence for IgA, IgG and C3. She was diagnosed with PD-PSV and treated with infusions of 20% human albumin (100 mL) for 5 days, followed by methylprednisolone (40 mg/d), with remission of lesions observed after 1 month. The differential diagnosis of PD-PSV and pemphigus vegetans is discussed.
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[Influence of microbubble and its generation process on mixed liquor properties of activated sludge].
Huan Jing Ke Xue
PUBLISHED: 03-16-2013
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Microbubble aeration is supposed to be able to provide potential advantage for aerobic biological wastewater treatment due to enhancement of oxygen mass transfer. On the other hand, microbubble and its generation methods might affect mixed liquor properties of activated sludge. Then SPG membrane microbubble generation system was used to investigate mixed liquor properties of activated sludge in microbubble aeration. The results indicated that sludge floatation happened in microbubble aeration due to attachment of microbubbles to sludge flocs, resulting in a decrease in mixed liquor suspended solid (MLSS) concentration in the bioreactor and poor sludge settleability. The strong shear stress caused by liquid recycling pump (centrifugal type) during microbubble generation led to sludge broken. As a result, sludge floc size decreased significantly and sludge EPS released. The release of sludge EPS was considered to be responsible for increased turbidity and organic carbon (especially colloidal organic carbon) concentration in the supernatant. The re-flocculation ability of sludge flocs also almost lost due to sludge EPS release. In addition, the mixed liquor viscosity increased along with sludge broken and sludge EPS release, but the surface tension of mixed liquor remained constant.
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Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus-infected and -uninfected men who have sex with men.
Hepatology
PUBLISHED: 03-14-2013
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The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV-uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV-infected MSM received either two doses of HAV vaccine (1,440 enzyme-linked immunosorbent assay units) (n = 140) with the second dose given at week 24 or three doses (n = 225) with the second and third dose given at weeks 4 and 24, respectively, while HIV-uninfected MSM (n = 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti-HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention-to-treat analysis for two-dose HIV-infected, three-dose HIV-infected, and two-dose HIV-uninfected MSM, respectively. The GMC of anti-HAV antibody at week 48 for three-dose HIV-infected MSM (2.29 ± 0.73 log10 mIU/mL) was significantly higher than that for two-dose HIV-infected MSM (1.94 ± 0.66; P < 0.01), but was lower than HIV-uninfected MSM (2.49 ± 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/?L increase, 1.13; 95% confidence interval [CI], 1.05-1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10-3.28) before HAV vaccination were predictive of seroconversion in HIV-infected patients. Conclusion: Serologic response rate to three and two doses of HAV vaccine was similar in HIV-infected MSM, which was lower than that in HIV-uninfected MSM receiving two doses. HAV vaccination in HIV-infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate.
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Heterologous prime-boost immunization regimens using adenovirus vector and virus-like particles induce broadly neutralizing antibodies against H5N1 avian influenza viruses.
Biotechnol J
PUBLISHED: 03-05-2013
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Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to trigger severe diseases in poultry and humans, prompting efforts to develop an effective vaccine. Toward that goal, we constructed a recombinant adenovirus vector encoding influenza hemagglutin (rAd-HA) and a flagellin-containing virus-like particle (FliC-VLP). Using a murine model, we investigated a heterologous prime-boost vaccination regimen combining these two vectors. Our results indicate that priming with the rAd-HA vector followed by a FliC-VLP booster induced the highest HA-specific total IgG, IgG1and IgG2a. Maximum neutralizing antibody titers against homologous and heterologous clades of H5N1 virus strains and hemagglutination inhibition resulted from the heterologous vaccination strategy. Our results are likely to contribute to the development of more effective H5N1 vaccines.
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High-energy passively Q-switched 2 ?m Tm(3+)-doped double-clad fiber laser using graphene-oxide-deposited fiber taper.
Opt Express
PUBLISHED: 02-08-2013
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We have demonstrated a high-energy Q-switched double-clad thulium-doped fiber laser (TDFL) using a graphene-oxide-deposited tapered fiber (GODTF) device as a saturable absorber operating at a wavelength of 2 ?m for the first time. Because of the side-interaction of the graphene-oxide with the evanescent field on the taper waist, the GODTF devices have potential for offering high laser damage threshold. Using a 788 nm laser diode as the pump source, the TDFL generated stable single transverse mode Q-switched pulses with a single pulse energy of 6.71 ?J (corresponding to an average power of 302 mW) at a wavelength of 2032 nm. This is significantly higher than the highest pulse energy/average power from any rare-earth-doped fiber lasers employing a graphene or graphene-oxide based Q-switch so far. The demonstrated TDFL in this paper represents an encouraging step towards the practical applications of graphene or graphene-oxide based Q-switched 2 ?m TDFLs.
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Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin.
J. Appl. Physiol.
PUBLISHED: 02-07-2013
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Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po(2) = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure.
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A hybrid procedure for MSW generation forecasting at multiple time scales in Xiamen City, China.
Waste Manag
PUBLISHED: 02-05-2013
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Accurate forecasting of municipal solid waste (MSW) generation is crucial and fundamental for the planning, operation and optimization of any MSW management system. Comprehensive information on waste generation for month-scale, medium-term and long-term time scales is especially needed, considering the necessity of MSW management upgrade facing many developing countries. Several existing models are available but of little use in forecasting MSW generation at multiple time scales. The goal of this study is to propose a hybrid model that combines the seasonal autoregressive integrated moving average (SARIMA) model and grey system theory to forecast MSW generation at multiple time scales without needing to consider other variables such as demographics and socioeconomic factors. To demonstrate its applicability, a case study of Xiamen City, China was performed. Results show that the model is robust enough to fit and forecast seasonal and annual dynamics of MSW generation at month-scale, medium- and long-term time scales with the desired accuracy. In the month-scale, MSW generation in Xiamen City will peak at 132.2 thousand tonnes in July 2015 - 1.5 times the volume in July 2010. In the medium term, annual MSW generation will increase to 1518.1 thousand tonnes by 2015 at an average growth rate of 10%. In the long term, a large volume of MSW will be output annually and will increase to 2486.3 thousand tonnes by 2020 - 2.5 times the value for 2010. The hybrid model proposed in this paper can enable decision makers to develop integrated policies and measures for waste management over the long term.
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Significantly increased expression of OCT4 and ABCG2 in spheroid body-forming cells of the human gastric cancer MKN-45 cell line.
Oncol Lett
PUBLISHED: 01-29-2013
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The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor formation, recurrence and metastasis. Key to the study of CSCs is their isolation and identification. The present study investigated whether spheroid body-forming cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC properties, and also assessed the expression of the candidate CSC markers, octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding cassette transporter G2 (ABCG2) in the MKN-45 spheroid body cells. The MKN-45 cells were plated in a stem cell-conditioned culture system to allow for spheroid body formation. The expression levels of OCT4 and ABCG2 in the spheroid body cells were assessed by qPCR, western blot analysis and immunofluorescence staining, while the tumorigenicity of the spheroid body-forming cells was assessed by in vivo xenograft studies in nude mice. The MKN-45 cells were able to form spheroid bodies when cultured in stem cell-conditioned medium. The spheroid body-forming cells showed a significantly higher (P<0.01) expression of OCT4 and ABCG2 compared with the parental cells. These data suggest that the spheroid body cells from the MKN-45 GC cell line cultured in stem cell-conditioned medium possessed gastric CSC properties. The co-expression of OCT4 and ABCG2 by these cells may represent the presence of a subpopulation of gastric CSCs.
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Numerical modeling of mid-infrared fiber optical parametric oscillator based on the degenerated FWM of tellurite photonic crystal fiber.
Appl Opt
PUBLISHED: 01-23-2013
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Mid-infrared fiber optical parametric oscillators (MIR FOPOs) based on the degenerate four-wave mixing (DFWM) of tellurite photonic crystal fibers (PCFs) are proposed and modeled for the first time. Using the DFWM coupled-wave equations, numerical simulations are performed to analyze the effects of tellurite PCFs, single-resonant cavity, and pump source on the MIR FOPO performances. The numerical results show that: (1) although a longer tellurite PCF can decrease the pump threshold of MIR FOPOs to a few watts only, the high conversion-efficiency of MIR idler usually requires a short-length optimum PCF with low loss; (2) compared with the single-pass DFWM configurations of the MIR fiber sources published previously, the stable oscillation of signal light in single-resonant cavity can significantly promote the MIR idler output efficiency. With a suggested tellurite PCF as parametric gain medium, the theoretical prediction indicates that such a MIR FOPO could obtain a wide MIR-tunable range and a high conversion efficiency of more than 10%.
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The role of the IL-23/IL-17 axis in the pathogenesis of Graves disease.
Endocr. J.
PUBLISHED: 01-17-2013
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This study is to explore the role of IL-23/IL-17 axis in subjects with Graves disease, while IL-23/IL-17 axis plays an important role in a number of autoimmune diseases, but its not clear in Graves disease. Thirty-three patients with Graves disease as a GD group, 15 patients with euthyroid GD as eGD group and 22 healthy volunteers as a control group whose age- and sex-matched. Peripheral blood was collected and peripheral blood mononuclear cells (PBMCs) were isolated in the both groups, then PBMCs were cultured in the presence or absence of IL-23 in vitro. The expression of retinoid-related orphan receptor gamma t (ROR?t) and IL-17 mRNA were examined by Semi-quantitative RT-PCR, and the levels of IL-17 protein were measured by enzyme-linked immunosorbent assay. The expression of ROR?t, IL-17 mRNA and IL-17 protein levels were markedly higher in GD and euthyroid GD group as compared with the control group. IL-17 levels were still higher in euthyroid GD patients. When PBMCs derived from the three groups were cultured in vitro with or without IL-23, the expression of ROR?t in GD group with IL-23 dramatically increased as compared with that in GD group without IL-23 and in control group with IL-23. ROR?t expression of PBMCs from eGD group cultured with IL-23 was increased compared with that cultured without IL-23. The levels of IL-17 mRNA and the protein were also significantly higher than that of GD and eGD cultured without IL-23 and control group. There was no difference of the expression of ROR?t mRNA and IL-17 protein levels between GD and eGD group cultured with or without IL-23. Our studies demonstrated that IL-23/IL-17 axis is associated with the pathogenesis of Graves disease in it activated term. This effect is not dependent on thyroid function, but may be associated to the immunity.
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Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy.
Hum Vaccin Immunother
PUBLISHED: 01-08-2013
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Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART). : Methods: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes. : Results: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23-4.78] and 3.58 [95% CI. 1.76-7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60-3.64] and 3.62 [95% CI, 1.11-11.81], respectively). : Conclusions: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses.
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