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Find video protocols related to scientific articles indexed in Pubmed.
TGF-?-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.
J. Immunol.
PUBLISHED: 08-25-2014
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The use of TGF-?-induced CD4(+)Foxp3(+) T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-versus-host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease. We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8(+) cells and CD4(+) cells, the expression of granzyme A and B, the cytotoxic effect of donor CD8(+) cells, and the production of T cell cytokines in aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD.
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Silver-catalysed direct amination of unactivated C-H bonds of functionalized molecules.
Nat Commun
PUBLISHED: 08-20-2014
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Carbon-nitrogen bond formation from inert C-H bonds is an ideal organic transformation and a highly desirable method for the synthesis of N-containing molecules due to its high efficiency and atom economy. In this report, we develop a general reaction to achieve an unprecedented selective intramolecular amination of unactivated C-H bond in the absence of complex directing groups. Functionalized heterocyclic products are built up from readily available linear amines through simple and reliable silver catalysis, representing a new silver-based C-H functionalization. This method displays preference for primary sp(3) C-H bonds and exhibits distinct chemo- and regioselectivity compared to existing methods of direct amination (Hofmann-Löffler-Freytag reaction and nitrene insertion). The study highlights the manipulation of unfunctionalized groups in organic molecules to furnish complex structural units in the natural and bioactive molecules.
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Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis.
Biochem. Pharmacol.
PUBLISHED: 08-12-2014
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Allergic diseases, which affect up to 20-30% of the world population, are still therapeutic challenge for allergists. Tetracyclines, which belong to an antibiotic drug family that possesses a striking variety of non-antibiotic properties, have been successfully applied to a wide range of diseases. However, their roles in allergic conjunctivitis and anaphylaxis and their underlying anti-allergy mechanisms remain elusive. Here, we reported that treatment with doxycycline significantly reduced IgE release from mouse B cells and the degranulation and inflammatory cytokines production of mouse mast cells (MCs) activated by IgE-dependent way. Furthermore, doxycycline treatment significantly inhibited histamine-induced vascular hyperpermeability in vitro. Mechanistically, the doxycycline-mediated inhibition of B cells, MCs and histamine may occur via modulation of the PI3K/Akt pathway. In vivo, our results demonstrated that treatment with doxycycline significantly attenuated clinical symptoms of mouse models of experimental allergic conjunctivitis (EAC) with a significant decrease in inflammatory cell frequency, IgE production, histamine release, and a decrease in TNF-? and IL-4 production. Using mouse models of MCs-dependent passive systemic anaphylaxis (PSA), we further confirmed anti-allergy effects of doxycycline and doxycycline-mediated inhibitory effects on MCs. Furthermore, our results showed that doxycycline significantly attenuate histamine-induced systemic anaphylaxis-like reaction (HISA) with a significantly downregulation of PI3K/Akt/eNOS/VE-cadherin pathway. The doxycycline-mediated anti-allergy effects during EAC, PSA and HISA were abrogated when an Akt activator, SC79, was administered. These findings suggest that doxycycline inhibits B cell, MC and histamine function and attenuates experimental allergic conjunctivitis and systemic anaphylaxis by possible modulating the PI3K/Akt pathway.
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The association of lipopolysaccharide and inflammatory factors with hepatopulmonary syndrome and their changes after orthotopic liver transplantation.
J Thorac Dis
PUBLISHED: 08-10-2014
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The level of lipopolysaccharides (LPS) and inflammatory factors were higher in end stage liver disease patient than in normal person for the damage of intestinal mucosal barrier function. Hepatopulmonary syndrome (HPS) was a common pulmonary complication in end stage liver disease. But the association of LPS and inflammatory factors such as toll like receptor 2 (TLR2), TNF-? and ET-1 with the development of HPS was undefined.
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Graft versus host disease following liver transplantation: A case report.
Exp Ther Med
PUBLISHED: 07-17-2014
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Graft versus host disease (GVHD) is an uncommon complication following liver transplantation. In the present case report, a 53-year-old male hepatitis B virus carrier was diagnosed with primary liver cancer with post-hepatitis cirrhosis. Preoperative cytomegalovirus (CMV), Epstein-Barr virus, coxsackievirus, herpes simplex virus and autoimmune antibody series were negative. Preoperative human leukocyte antigen type was also negative. Following classic orthotropic liver transplantation, postoperative treatment included immunosuppression therapy, infection protection, anti-human immunodeficiency virus therapy and CMV infection protection therapy. Chemotherapy was initiated at day 16 following surgery. At day 26 following the transplantation, the patient developed a fever of unknown cause, and a scattered red rash was observed behind the left ear and on the neck. The patient presented with a fever of unknown cause, rash, symptoms of the digestive tract, leukocytopenia and pancytopenia. A diagnosis of GVHD was confirmed following a skin biopsy. Symptomatic therapies, including antivirals, anti-anaphylaxis drugs and steroids were administered. However, the patient succumbed to infection, acute respiratory distress syndrome and multiple organ failure at day 46 following surgery. Therefore, an effective therapeutic strategy for the treatment of GVHD following liver transplantation is yet to be established, and further research is required prior to such a regimen being developed.
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Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1.
Stem Cells Dev.
PUBLISHED: 05-27-2014
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The mechanisms responsible for the inhibitory effects of mesenchymal stem cells (MSCs) on dendritic cells (DCs) are still poorly understood. Our investigation of the potential signaling pathways revealed for the first time that human umbilical-cord-derived MSCs (UC-MSCs) instruct DCs to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1. This subset of MSC-DCs exhibited a tolerogenic pattern, with a clear decrease in the expression of co-stimulatory molecules and the capacity to stimulate CD3(+) T cell proliferation and inflammatory factor secretion, and a significant increase in the production of inhibitory cytokine IL-10 and the ability to induce Treg cells and Th2 responses. Adoption of this tolerogenic pattern required the activation of SOCS1, which blocked DC maturation by impairing TLR4 signaling. The effects of UC-MSCs on SOCS1 activation were essentially mediated by the JAK-STAT pathway via IL-6 secretion. In summary, our data identify a new mechanism, involving the IL-6-mediated upregulation of SOCS1, by which UC-MSCs instruct DCs to acquire tolerogenic phenotypes.
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MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-18-2014
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Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI.
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A hydrothermal synthesis of Pr3+ doped mesoporous TiO2 for UV light photocatalysis.
J Nanosci Nanotechnol
PUBLISHED: 04-25-2014
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Pr3+ doped mesoporous TiO2 photocatalysts with a different molar ratio of Pr to Ti were prepared by a hydrothermal method using triblock copolymer as the template. The as-prepared samples were systematically characterized by X-ray diffraction, N2 adsorption-desorption, X-ray photoelectron spectra, transmission electron microscopy and UV-visible diffuse reflectance spectroscopy. The characterizations indicated all the samples had mesoporous structure and narrow pore size distribution. Pr3+ doping enlarged the surface area and decreased the crystallite size. The surface area of the samples varied from 136 to 170 m2/g, and the average crystallite size ranged between 5.04 and 7.60 nm. The effect of Pr3+ doping amount on the photocatalytic activity of mesoporous TiO2 was evaluated by the degradation of methyl orange under UV light irradiation. The results showed that the suitable amount of Pr3+ doped samples exhibited the higher photocatalytic activity than mesoporous TiO2. Among the samples, 1 at.% Pr3+ doped mesoporous TiO2 showed the highest photocatalytic activity.
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Conservation in China of a novel group of HCV variants dating to six centuries ago.
Virology
PUBLISHED: 04-14-2014
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We characterized a novel group of HCV variants that are genetically related but distinct from each other belonging to genotype 6 (HCV-6). From 26 infected Austronesian-descended aborigines on Hainan Island, China, HCV sequences were determined followed by genetic analyses. Six nearly full-length genomes and 20 E1 sequences of HCV were obtained, which differ from each other and from all known HCV lineages by nucleotides above the intra-subtype level of 13%. Together with subtypes 6g and 6w, they constitute a phylogenetic group sharing a common ancestor dating from the end of the 12th century.
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Rhodium-catalyzed asymmetric arylation of ?,?-unsaturated ?-ketoamides for the construction of nonracemic ?,?-diarylcarbonyl compounds.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-14-2014
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A highly regio- and enantioselective rhodium-catalyzed 1,4-addition of arylboronic acids to ?,?-unsaturated ?-ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic ?,?-diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline-2-carboxylamide.
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Different effects of local anesthetics on extracellular signal-regulated kinase phosphorylation in rat dorsal horn neurons.
Eur. J. Pharmacol.
PUBLISHED: 03-14-2014
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Local anesthetics, which are widely known to be neuronal voltage-gated Na(+) channel blockers, also affect a variety of other ion channels, N-methyl-d-asparate (NMDA) receptors and ?-amino-3-hydroxy-5-methyl-4-izoxazolepropionic acid (AMPA) receptors. Glutamate, which is released from presynaptic fibers, activates extracellular signal-regulated kinase (ERK) through NMDA and AMPA receptors in spinal dorsal horn neurons. ERK plays a key role in central sensitization, which contributes to the chronicity of pain. We investigated the effects of four representative local anesthetics, lidocaine, tetracaine, levobupivacaine, and ropivacaine on ERK phosphorylation induced by capsaicin, which releases glutamate from presynaptic neurons, NMDA, AMPA, or ionomycin, a calcium ionophore, in dorsal neurons. We observed capsaicin-induced phosphorylation of ERK, which was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. NMDA-induced phosphorylation of ERK was suppressed by lidocaine, tetracaine, or levobupivacaine, but not by ropivacaine. AMPA-induced phosphorylation of ERK was suppressed by lidocaine or tetracaine, but not by levobupivacaine or ropivacaine. Finally, ionomycin-induced ERK phosphorylation was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. Our results suggest that local anesthetics contribute to the prevention of the incidence of persistent postsurgical pain with varying intensities and through different mechanisms of action.
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Increased survival in hepatocellular carcinoma with iodine-125 implantation plus radiofrequency ablation: A prospective randomized controlled trial.
J. Hepatol.
PUBLISHED: 02-21-2014
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The purpose of this study was to evaluate whether use of combined radiofrequency ablation (RFA) and percutaneous iodine-125 ((125)I) seed implantation results in better progression-free survival compared with the use of RFA alone in patients with hepatocellular carcinoma.
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Distal bile duct cancers complicated with cholangiobronchopleural fistula after ERCP: A case report.
Oncol Lett
PUBLISHED: 01-23-2014
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Distal (lower) bile duct cancers arise in the lower half of the biliary tree closer to the small intestine. Biliary disease complicated with cholangiobronchopleural fistula, which may occur in cases of multiple hepatobiliary stones or biliary ascariasis-associated severe infection, has rarely been reported in the literature, particularly following endoscopic retrograde cholangiopancreatography (ERCP). The present study describes the case of a 60-year-old female with distal cholangiocarcinoma complicated with cholangiobronchopleural fistula after ERCP for this rare disease. This complication was likely due to the inability to control retrograde infection following ERCP and, thus, the infection was disseminated. This resulted in mixed infection involving the diaphragm and pleura, and further penetrating the bronchus. The patient was managed with pancreatoduodenectomy and has since remained in good health.
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Direct borylation of primary C-H bonds in functionalized molecules by palladium catalysis.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-21-2014
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Organoborane compounds are among the most commonly employed intermediates in organic synthesis and serve as crucial precursors to alcohols, amines, and various functionalized molecules. A simple palladium-based system catalyzes the conversion of primary C(sp(3) )?H bonds in functionalized complex organic molecules into alkyl boronate esters. Amino acids, amino alcohols, alkyl amines, and a series of bioactive molecules can be functionalized with the use of readily available and removable directing groups in the presence of commercially available additives, simple ligands, and oxygen (O2 ) as the terminal oxidant. This approach represents an economic and environmentally friendly method that could find broad applications.
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Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.
Exp Ther Med
PUBLISHED: 01-15-2014
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The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.
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Selection of nectar plants for use in ecological engineering to promote biological control of rice pests by the predatory bug, Cyrtorhinus lividipennis, (Heteroptera: Miridae).
PLoS ONE
PUBLISHED: 01-01-2014
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Ecological engineering for pest management involves the identification of optimal forms of botanical diversity to incorporate into a farming system to suppress pests, by promoting their natural enemies. Whilst this approach has been extensively researched in many temperate crop systems, much less has been done for rice. This paper reports the influence of various plant species on the performance of a key natural enemy of rice planthopper pests, the predatory mirid bug, Cyrtorhinus lividipennis. Survival of adult males and females was increased by the presence of flowering Tagetes erecta, Trida procumbens, Emilia sonchifolia (Compositae), and Sesamum indicum (Pedaliaceae) compared with water or nil controls. All flower treatments resulted in increased consumption of brown plant hopper, Nilaparvata lugens, and for female C. lividipennis, S. indicum was the most favorable. A separate study with a wider range of plant species and varying densities of prey eggs showed that S. indicum most strongly promoted predation by C. lividipennis. Reflecting this, S. indicum gave a relatively high rate of prey search and low prey handling time. On this basis, S. indicum was selected for more detailed studies to check if its potential incorporation into the farming system would not inadvertently benefit Cnaphalocrocis medinalis and Marasmia patnalis, serious Lepidoptera pests of rice. Adult longevity and fecundity of both pests was comparable for S. indicum and water treatments and significantly lower than the honey solution treatment. Findings indicate that S. indicumis well suited for use as an ecological engineering plant in the margins of rice crops. Sesame indicum can be a valuable crop as well as providing benefits to C. lividipennis whilst denying benefit to key pests.
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Restoration of intrahepatic regulatory T cells through MMP-9/13-dependent activation of TGF-? is critical for immune homeostasis following acute liver injury.
J Mol Cell Biol
PUBLISHED: 11-28-2013
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During the acute liver injury, immune responses are provoked into eliciting inflammation in the acute phase. In the healing phase, the inflammation is terminated for wound healing and restoration of immune homeostasis. In this study, we sought to address how regulatory T cells (Tregs) are involved in the progression of liver injury and repair. In the acute phase, intrahepatic Tregs (CD4(+)FoxP3(+)Helios(+)) diminished promptly through apoptosis, which was followed by inflammation and tissue injury. In the healing phase, a new subset of Tregs (CD4(+)Foxp3(+)Helios(-)) was generated in correlation with the matrix metalloproteinase (MMP) cascade and transforming growth factor-beta (TGF-?) activation that were manifested mainly by hepatic stellate cells. Moreover, the induction of induced Tregs and wound healing were both impaired in mice lacking TGF-? signaling or MMPs. The depletion of induced Tregs also impeded wound healing for tissue repair. Together, this study demonstrates the mechanism that the loss of nTregs through apoptosis in the acute phase may facilitate inflammation, while regenerated Tregs through MMP9/13-dependent activation of TGF-? in the healing phase are critical to terminate inflammation and allow for wound healing.
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The current hepatitis C virus prevalence in China may have resulted mainly from an officially encouraged plasma campaign in the 1990s: a coalescence inference with genetic sequences.
J. Virol.
PUBLISHED: 08-28-2013
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In this study, we investigated hepatitis C virus (HCV) molecular epidemiology and evolutionary dynamics. Both E1 and NS5B sequences were characterized in 379 of 433 patients in southern China and classified into five major subtypes: 1b in 256 patients, 6a in 67 patients, 2a in 29 patients, 3a in 14 patients, and 3b in 13 patients. Using the E1 sequences obtained, along with those from other studies using samples from China, we inferred the HCV epidemic history by means of coalescence strategies. Five Bayesian skyline plots (BSPs) were estimated for the five subtypes. They concurrently highlighted the rapid growth in the HCV-infected population size from 1993 to 2000, followed by an abrupt slowing. Although flanked on both sides by variable population sizes, the plots showed distinct patterns of rapid HCV growth. Coincidently, 1993 to 2000 was a period when contaminated blood transfusions were common in China due to a procedural error in an officially encouraged plasma campaign. The abrupt slowing in 1998 to 2000 corresponded to the central government outlawing paid blood donations in 1998. Using a parametric model, the HCV population growth rates were estimated during 1993 to 2000. It was revealed that the 6a rate was the highest, followed by those of 1b, 2a, 3b, and 3a. Because these rates differed significantly (P < 1e-9) from each other, they may help explain why 6a is increasingly prevalent in southern China and 1b is predominant nationwide. These rates are approximately 10-fold higher than those reported elsewhere. These findings suggested that during the plasma campaign, certain barriers to efficient viral transmission were removed, allowing wide HCV dissemination.
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Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity.
Med. Oncol.
PUBLISHED: 06-17-2013
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Substantial evidence indicates that cancer-associated fibroblasts (CAFs) are critical components in the process of cancer progression. However, the role of CAFs in the immunopathogenesis of human cancer remains elusive. In this study, we demonstrate that purified colorectal carcinoma-derived fibroblasts exhibit activated phenotypes characterized by substantial ?-smooth muscle actin expression. These CAFs sharply suppress natural killer (NK) cell functions in co-culture experiments. In contrast, normal skin fibroblasts had only a minimal effect on NK cell phenotype and function. Moreover, we demonstrated that prostaglandin E2 (PGE2) was released by fibroblasts in co-culture experiments. Thus, the functional modulation of NK cells by CAFs may represent a novel mechanism linking the pro-inflammatory response to immune tolerance within the tumor milieu.
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Advances in nano-scaled biosensors for biomedical applications.
Analyst
PUBLISHED: 06-10-2013
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Recently, a growing amount of attention has been focused on the utility of biosensors for biomedical applications. Combined with nanomaterials and nanostructures, nano-scaled biosensors are installed for biomedical applications, such as pathogenic bacteria monitoring, virus recognition, disease biomarker detection, among others. These nano-biosensors offer a number of advantages and in many respects are ideally suited to biomedical applications, which could be made as extremely flexible devices, allowing biomedical analysis with speediness, excellent selectivity and high sensitivity. This minireview discusses the literature published in the latest years on the advances in biomedical applications of nano-scaled biosensors for disease bio-marking and detection, especially in bio-imaging and the diagnosis of pathological cells and viruses, monitoring pathogenic bacteria, thus providing insight into the future prospects of biosensors in relevant clinical applications.
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Use of a pooled clone method to isolate a novel Bacillus thuringiensis Cry2A toxin with activity against Ostrinia furnacalis.
J. Invertebr. Pathol.
PUBLISHED: 03-18-2013
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A pooled clone method was developed to screen for cry2A genes. This metagenomic method avoids the need to analyse isolated Bacillus thuringiensis strains by performing gene specific PCR on plasmid-enriched DNA prepared from a pooled soil sample. Using this approach the novel holotype gene cry2Ah1 was cloned and characterized. The toxin gene was over-expressed in Escherichia coli Rosetta (DE3) and the expressed toxin accumulated in both the soluble and insoluble fractions. The soluble Cry2Ah1 was found to have a weight loss activity against Ostrinia furnacalis, and a growth inhibitory activity to both Cry1Ac-susceptible and resistant Helicoverpa armigera populations.
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Liver transplant may improve erectile function in patients with benign end-stage liver disease: single-center Chinese experience.
Exp Clin Transplant
PUBLISHED: 02-20-2013
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No investigation in mainland China concerning erectile function in men with liver transplant for benign end-stage liver disease has been performed.
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?Klotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3?/cyclin D1 signaling pathway.
PLoS ONE
PUBLISHED: 01-03-2013
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?Klotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of ?Klotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of ?Klotho compared with normal hepatocyte cells. Reintroduction of ?Klotho into hepatoma cells inhibited their proliferation. The anti-proliferative effect of ?Klotho might be linked with G1 to S phase arrest, which was mediated by Akt/GSK-3?/cyclin D1 signaling, since forced expression ?Klotho reduced the phosphorylation level of Akt and GSK-3? and induced down-regulation of cyclin D1. Furthermore, ?Klotho overexpression could inhibit tumorgenesis, while constitutively activated Akt could override the suppressive effects of ?Klotho in vivo. These data suggest ?Klotho suppresses tumor growth in hepatocellular carcinoma.
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Symptom Experienced Three Years after Liver Transplantation under Immunosuppression in Adults.
PLoS ONE
PUBLISHED: 01-01-2013
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Immunosuppression-related symptom experience has not been covered thoroughly in long-term liver transplant recipients. The aim of this study was to assess the symptom experience of immunosuppressive therapy three years after liver transplantation and to correlate it with adherence to medications and sociodemographic or disease-related characteristics.
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Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO.
Cancer Lett.
PUBLISHED: 09-16-2011
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Defects in natural killer (NK) cell function are necessary for tumor immune escape, but the underlying regulatory mechanisms in human cancers remain largely unknown. Here we show that fibroblasts derived from hepatocellular carcinoma (HCC) were significantly superior to foreskin-derived fibroblasts at inducing NK cell dysfunction, which is characterized by low expression of cytotoxic molecules and surface markers for cell activation, impaired production of cytokines, and decreased cytotoxicity against K562 cells in vitro. Our results also indicate that PGE2 and IDO, derived from activated fibroblasts, suppress the activation of NK cells and thereby create favorable conditions for tumor progression.
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[Effect of exercise on the quality of life and pulmonary function in patients with chronic obstructive pulmonary disease].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 08-30-2011
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To investigate the effect of exercise therapy on activity of daily living (ADL) and lung function in patients with chronic obstructive pulmonary disease (COPD).
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Enhanced antitumor efficacy of a novel fiber chimeric oncolytic adenovirus expressing p53 on hepatocellular carcinoma.
Cancer Lett.
PUBLISHED: 03-15-2011
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Oncolytic adenoviruses may offer a new treatment option and improve the prognosis for patients with hepatocellular carcinoma (HCC). However, the antitumor efficacy of oncolytic adenoviruses on HCC cells is compromised due to low expression of the adenovirus serotype 5 (Ad5) receptor on the target cells. In this study we showed that all HCC cell lines and clinical samples expressed high level of CD46, the receptor for Adenovirus 35 (Ad35) and constructed new fiber chimeric oncolytic adenoviruses with or without a p53 gene expression cassette, SG635-p53 and SG635, respectively. These variants were derived from the previously described Ad5 vectors SG600-p53 and SG600 by replacing the Ad5 fiber with a chimeric Ad5/35 fiber. It was found that the 5/35 fiber chimeric adenovirus vector (Ad5/35-EGFP) demonstrated significantly improved transduction in all tested HCC cell lines compared with the Ad5 vector (Ad5-EGFP). The new fiber chimeric oncolytic adenoviruses produced more progeny viruses in HCC cells than did the Ad5-based viruses but replicated weakly in normal fibroblast BJ cells. In addition, SG635-p53 mediated a higher level of transgenic expression than SG600-p53 in Hep3B and Huh7 cells and showed a markedly enhanced antitumor effect on HCC cells in vitro compared with SG635 or SG600-p53 without causing significant cytotoxicity to normal cells. Antitumor activity of SG635-p53 was shown in Hep3B subcutaneous xenograft tumor models following intratumoral injection, resulting in significant inhibition of tumor growth and prolonged survival of animals. Our data suggest that SG635-p53, as a fiber chimeric oncolytic adenovirus in combination with p53 expression, may serve as a novel, promising and safe anticancer agent for the treatment of HCC.
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Hepatocyte-targeted psiRNA delivery mediated by galactosylated poly(ethylene glycol)-graft-polyethylenimine in vitro.
J Biomater Appl
PUBLISHED: 05-28-2010
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Gene silencing in liver disease could be achieved by delivering siRNA with nonviral vectors. However, the transfection efficiency of plasmid siRNA (psiRNA) applied through this approach in hepatocytes is generally low. Based on the fact that the asialoglycoprotein receptors present on hepatocytes can recognize galactose, we synthesized galactosylated poly(ethylene glycol)-graft-polyethylenimine (Gal-PEG-PEI) as a nonviral psiRNA carrier for hepatocyte targeting. Our results indicate that 0.2% (molar percentage) of amine groups of PEI was conjugated with PEG having galactose on its distal end. Increasing the molar ratios of Gal-PEG-PEI to psiRNA in complexation led to a decrease in particle size but an increase in zeta potential of complexes. The transfection efficiency of nanocomplexes, that is, Gal-PEG-PEI/psiRNA, in HepG2 cell line depends on the N/P value, which reflects the molar ratio of Gal-PEG-PEI to psiRNA in the complex. The highest transfection efficiency was 37.34%, which was obtained at N/P 8. At the same N/P value, the transfection efficiency with the nontargeting PEG-PEI/psiRNA or Lipofectamine 2000/psiRNA was much lower. The transfection efficiency of Gal-PEG-PEI/psiRNA dropped to 3.60% from 37.34% after an excessive amount of free galactose was added into the medium for HepG2 cell incubation. By contrast, the similar phenomenon was observed neither when using PEG-PEI or Lipofectamine 2000 as a delivery vector nor in human embryonic kidney 293 cell line lacking ASGR. Real-time PCR analysis and western blot assay demonstrate that the knockdown of HLA-E gene expression by psiRNA/Gal-PEG-PEI (N/P 8) can reach about 60% in HepG2 cells after a 48-h transfection.
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Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome?
BMC Cancer
PUBLISHED: 03-08-2010
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Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with "multiple tumors more than 5 cm", "major vascular invasion", "invasion of adjacent organs", and "perforation of visceral peritoneum". The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC.
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[Interactive effects of temperature and nitrogen fertilizer on the survival, development, and reproduction of brown planthopper Nilaparvata lugens].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 10-07-2009
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A laboratory study was made on the interactive effects of temperature (20 degrees C, 23 degrees C, 26 degrees C, 29 degrees C, and 32 degrees C) and nitrogen fertilization level (0 and 250 kg x hm(-2)) on the survival, development, and reproduction of brown planthopper (BPH) Nilaparvata lugens. With increasing temperature from 20 degrees C to 29 degrees C, the egg hatchability, nymphal survival, and adult fecundity of BPH increased and the developmental duration of all stages shortened; while at 32 degrees C, it was in adverse. At all test temperatures, the BPH on rice plants treated with 250 kg N x hm(-2) had higher egg hatchability, nymphal survival and adult fecundity, and shorter developmental duration of eggs and nymphs, compared with no nitrogen fertilization, which suggested that high level nitrogen fertilization enhanced the ecological adaptability of BPH to stress conditions. There were significant interactive effects of temperature and nitrogen fertilizer on the egg hatchability, nymphal duration, and adult fecundity of BPH, implying that global warming and long-term high level application of nitrogen fertilizer could be responsible for the outbreaks of BPH in recent years.
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Downregulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats.
Cell Res.
PUBLISHED: 08-11-2009
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Portal hypertension (PHT) gastropathy is a frequent complication of liver cirrhosis and one of the leading causes of death from cirrhosis. Apoptosis is widely considered to be an active energy-dependent mode of cell death and a distinct entity from necrotic cell death. It is unclear whether gastric mucosal apoptosis is involved in PHT gastropathy. Prostaglandins (PGs) produced through cyclooxygenase (COX) are thought to play a key role in protection of the gastrointestinal mucosa from injury and apoptosis. However, the role of COX in PHT gastropathy is still not clearly understood. The aims of this study were to investigate whether (1) gastric mucosal apoptosis is involved in PHT gastropathy and (2) downregulation of COX contributes to this apoptosis. In this study, we show that gastric mucosal apoptosis was remarkably increased while mucosal proliferation was inhibited in PHT rats. Gastric mucosal COX-1 was significantly suppressed at both the mRNA and protein levels, and PGE(2) was reduced in PHT rats. Further, PGE(2) treatment suppressed gastric mucosal apoptosis in PHT rats. However, gastric mucosal COX-2 levels did not differ between sham-operated rats and PHT rats. Gastric mucosal levels of tumor necrosis factor-alpha (TNF-alpha) and Fas ligand, but not TNF-related apoptosis-inducing ligand, were increased, and activated caspase-8 and caspase-3 levels were upregulated in PHT rats. The release of cytochrome c from the mitochondria to the cytosol was not observed in PHT rats. Our data indicate that downregulation of COX-1 is involved in gastric mucosal apoptosis via death signaling-mediated type-I cell death in PHT rats.
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Anode distance effect on field electron emission from carbon nanotubes: a molecular/quantum mechanical simulation.
J Phys Chem A
PUBLISHED: 06-19-2009
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Field electron emission from single-walled (5,5) carbon nanotubes was simulated with a quantum chemistry method, emphasizing the effect of distance between the anode and apex. The emission probability and the field enhancement factor were obtained for different anode-apex separations with two representative applied macroscopic fields. The quantum chemistry simulation was compared to the classical finite element calculation. It was found that the field enhancement factor was overestimated by about a factor 2 in the classical calculation (for the capped carbon nanotube). The effective work function lowering due to the field penetration into the apex has important contribution to the emission probability. A peculiar decrease of the effective work function with the anode-apex separation was found for the capped carbon nanotube, and its quantum mechanical origin is discussed.
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Biogeography and virulence of Staphylococcus aureus.
PLoS ONE
PUBLISHED: 03-19-2009
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Staphylococcus aureus is commonly carried asymptomatically in the human anterior nares and occasionally enters the bloodstream to cause invasive disease. Much of the global diversity of S. aureus remains uncharacterised, and is not clear how disease propensity varies between strains, and between host populations.
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MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery to T cells for immunosuppression.
Biomaterials
PUBLISHED: 01-21-2009
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Gene therapy mediated by nonviral vectors provides great advantages over conventional drug therapy in inducing immunosuppression after organ transplantation, yet it was rarely reported because T cells are normally difficult to transfect. In this paper, a nonviral vector that effectively transports genes into T cells is developed by attaching a T cell specific ligand, the CD3 single chain antibody (scAb(CD3)), to the distal ends of poly(ethylene glycol)-grafted polyethylenimine (scAb(CD3)-PEG-g-PEI). This polymer was first complexed with superparamagnetic iron oxide nanoparticles (SPIONs) and was then used to condense plasmid DNA into nanoparticles with an ideally small size and low cytotoxicity. Based on a reporter gene assay, targeting ligand functionalization of the delivery agent leads to 16 fold of enhancement in the gene transfection level in HB8521 cells, a rat T lymphocyte line. This targeting event in cell culture was successfully imaged by MRI scan. Inspiringly, delivery of a therapeutic gene DGKalpha with our MRI-visible delivery agent was likewise efficient, resulting in a 43% inhibition in the stimulated proliferation of HB8521 cells as well as a 38% inhibition in the expression of a major functional cytokine interleukin-2 (IL-2), indicating the effective T cell anergy induced by gene therapy.
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Palladium-catalyzed trifluoromethylation of aromatic C-H bond directed by an acetamino group.
Org. Lett.
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The first palladium-catalyzed ortho-trifluoromethylation of the aromatic C-H bond directed by an acetamino group is reported. This method provides an efficient and green approach to synthesize the highly biological potential key structure of ortho-CF(3) acetanilides and anilines.
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Simultaneous diagnosis and gene therapy of immuno-rejection in rat allogeneic heart transplantation model using a T-cell-targeted theranostic nanosystem.
ACS Nano
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As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T(2)*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGK? gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.
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Intrathecal endothelin-1 has antinociceptive effects in rat model of postoperative pain.
Eur. J. Pharmacol.
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Endothelin-1 is known to be a potent vasoconstrictor. Administration of endothelin-1 to the central nervous system (CNS) induces antinociceptive effects. Nociceptive stimuli affect dorsal root ganglion (DRG) neurons and neurons/astrocytes/microglia in the dorsal horn of the spinal cord. Surgical incision in the plantar aspect of the rat hindpaw is a model for postoperative pain, and withdrawal thresholds reportedly decrease around the incision. We hypothesized that intrathecal endothelin-1 would have antinociceptive effects in this model, and affect DRG neurons and microglia/neurons in the dorsal horn. Intrathecal endothelin-1 partially restored the withdrawal threshold (which was decreased by plantar incision). BQ-123, and BQ-788 (specific endothelin ET(A)- and ET(B)-receptor antagonists, respectively) attenuated the increase in withdrawal threshold induced by endothelin-1. Phosphorylation of extracellular signal-regulated kinase (ERK) in DRG neurons and microglial activation/ERK phosphorylation in the dorsal horn were observed following the incision. Endothelin-1 decreased the incision-induced increase in the numbers of phosphorylated ERK-positive neurons in DRG and activated microglia in the dorsal horn, without affecting the numbers of phosphorylated ERK-positive neurons in the dorsal horn. BQ-123 or BQ-788 partially suppressed these endothelin-1-induced alterations. Our results show that the pain threshold, which is decreased by surgical stimuli, is partially restored by intrathecal endothelin-1 through both endothelin ET(A)- and ET(B)- receptors in DRG neurons and microglia in the spinal cord. Endothelin-1 administration to the CNS may be worth considering as a new candidate for the treatment of postoperative pain and to mitigate prolonged periods of pain.
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A novel in vivo siRNA delivery system specifically targeting liver cells for protection of ConA-induced fulminant hepatitis.
PLoS ONE
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Fulminant hepatitis progresses to acute liver failure (ALF) when the extent of hepatocyte death exceeds the livers regenerative capacity. Although small interfering RNA (siRNA) appears promising in animal models of hepatitis, the approach is limited by drawbacks associated with systemic administration of siRNA. The aim of this study is to develop a hepatocyte-specific delivery system of siRNA for treatment of fulminant hepatitis.
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Photoelectrocatalytic oxidation of glutathione based on porous TiO2-Pt nanowhiskers.
Langmuir
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The performance of TiO(2) nanoparticles is extremely attractive in various areas of chemical and biochemical engineering as they can effectively work by combining the photocatalytic property with various superior properties of the related nanostructure. The relevant photoelectrochemical detection has attracted considerable interest and shown potential applications in a wide range of areas. In this study, we have prepared new nanowhiskers of platinum-doped titanium dioxide (TiO(2)-Pt), which could be further used to fabricate a novel nanointerface for the sensitive detection of biomolecules including glutathione (GSH). Our observations demonstrate that the sensitive TiO(2)-Pt nanowhiskers biointerface could be readily fabricated by casting the TiO(2)-Pt nanowhiskers suspension on a glassy carbon electrode (GCE), which could readily combine the photocatalytic and eletrocatalytic properties of TiO(2) nanocomposites to introduce a novel photoelectrocatalytic biosensor for GSH detection in real samples. Compared to other analysis strategies, the TiO(2)-Pt nanowhiskers-modified GCE showed a considerably high sensitivity for the detection of GSH due to the excellent photoelectrocatalytic ability of the porous TiO(2)-Pt nanowhiskers. Scanning electron microscopy (SEM), Raman spectroscopy, and electrochemical impedance spectroscopy have shown that Pt can readily blend with porous TiO(2) nanowhiskers and facilitate the relevant catalysis property of TiO(2), resulting in the enhanced photoelectrocatalytic effect. Thus, through the new strategy of the utilization of the excellent photoelectrocatalytic property of TiO(2)-Pt nanocomposites, it is possible to realize the rapid electrochemical detection of glutathione with high sensitivity, low cost, and good reproducibility.
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Preparation and characterization of visible-light-driven TiO2 photocatalyst Co-doped with nitrogen and erbium.
J Nanosci Nanotechnol
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A series of nitrogen and erbium co-doped TiO2 photocatalyst was prepared by sol-hydrothermal method. The structure and properties of the photocatalyst were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, X-ray photoelectron spectroscopy (XPS), and UV-vis diffuse reflectance spectra (DRS). The XRD and BET results showed that co-doping inhibited the increase of crystallite size and enlarged specific surface areas. XPS spectroscopy indicated nitrogen atoms were incorporated into TiO2 lattice, and erbium atoms mostly existed in the forms of Er2O3. A shift of the absorption edge to the lower energy and four absorption bands located at 654, 544, 524 and 489 nm attributed to the 4f transitions of 4I15/2 --> 4F2/9, 4I15/2 --> 4S3/2, 4I15/2 --> 2H11/2, 4I15/2 --> 4F7/2 of Er3+ were observed using DRS spectroscopy. The catalytic efficency was evaluated by the photocatalytic degradation of methyl orange (MO) under visible light irradiation. The results showed that the photocatalytic performance of the co-doped TiO2 was related with the hydrothermal temperature and the molar ratio of N/Ti, and they showed higher acitivites than pure TiO2. Results determined by fluorescence technique revealed that irradiation (lambda > 400 nm) of TiO2 photocatalyst dispersed in MO solution induces the generation of the highly active hydroxyl radicals (OH). It indicated the photocatalytic activities of TiO2 photocatalyst were correlation with the formation rate of hydroxyl radicals (OH) and other active oxygen species.
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CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma.
J. Clin. Invest.
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Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies resistant to current chemotherapies or radiotherapies, which makes it urgent to identify new therapeutic targets for HCC. In this study, we found that checkpoint kinase 1 (CHK1) was frequently overexpressed and correlated with poor clinical outcome in patients with HCC. We further showed that the CHK1 inhibitor GÖ6976 was capable of sensitizing HCC cells to cisplatin, indicating that CHK1 may have oncogenic function in HCC. We found that CHK1 phosphorylated the tumor suppressor spleen tyrosine kinase (L) (SYK[L]) and identified the phosphorylation site at Ser295. Furthermore, CHK1 phosphorylation of SYK(L) promoted its subsequent proteasomal degradation. Expression of a nonphosphorylated mutant of SYK(L) was more efficient at suppressing proliferation, colony formation, mobility, and tumor growth in HCC lines. Importantly, a strong inverse correlation between the expression levels of CHK1 and SYK(L) was observed in patients with HCC. Collectively, our data demonstrate that SYK(L) is a substrate of CHK1 in tumor cells and suggest that targeting the CHK1/SYK(L) pathway may be a promising strategy for treating HCC.
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Expression and prognostic significance of CIP2A mRNA in hepatocellular carcinoma and nontumoral liver tissues.
Biomarkers
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This study was undertaken to determine the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in predicting prognosis of hepatocellular carcinoma (HCC).
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HCV 6a prevalence in Guangdong province had the origin from Vietnam and recent dissemination to other regions of China: phylogeographic analyses.
PLoS ONE
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Recently in China, HCV 6a infection has shown a fast increase among patients and blood donors, possibly due to IDU linked transmission.
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