Biomedical subjects

Aiguo Wu

Publications and source records attributed to Aiguo Wu.

At least 19 recordsLinked to original sources

PubMed2004

Prevention of lethal respiratory vaccinia infections in mice with interferon-alpha and interferon-gamma.

The antiviral efficacy of interferons (IFNs) was evaluated using a vaccinia intranasal infection model in mice in this study. We provide evidence that intranasal administration of IFN-alpha and IFN-gamma (days -1 to +3) resulted in 100 and 90% survival against a lethal respiratory vaccinia infection (8 LD50) in mice, respectively; whereas no animals in the placebo group survived through the study period (21 days). The IFN treatment consisted of a single daily dose of 5x10(3) U per mouse for 5 consecutive days. The efficacy of IFN-gamma was evident even when the IFN-gamma treatments started 1-2 days after infection and when a lower dose (2x10(3) U per mouse) was used. The treatment of IFN-alpha and IFN-gamma reduced the virus titers in the lungs of infected mice by 1000-10,000-fold, when the administration started 1 day after infection. Our data suggest that IFN-alpha and IFN-gamma are effective in protecting vaccinia-infected mice from viral replication in lungs and mortality, and may be beneficial in other human orthopoxvirus infections.

Animals↗

PubMed2004

Atomic force microscope investigation of large-circle DNA molecules.

A circular bacterial artificial chromosome of 148.9kbp on human chromosome 3 has been extended and fixed on bare mica substrates using a developed fluid capillary flow method in evaporating liquid drops. Extended circular DNA molecules were imaged with an atomic force microscope (AFM) under ambient conditions. The measured total lengths of the whole DNA molecules were in agreement with sequencing analysis data with an error range of +/-3.6%. This work is important groundwork for probing single nucleotide polymorphisms in the human genome, mapping genomic DNA, manipulating biomolecular nanotechnology, and studying the interaction of DNA-protein complexes investigated by AFM.

Aluminum Silicates↗

PubMed2004

IL-15 induces IFN-beta and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells.

The effects of interleukine-15 (IL-15) on macrophage activation and antiviral activity have been investigated in this study. We have provided evidence that IL-15 stimulates murine macrophage RAW 264.7 cells to release nitric oxide (NO) and inhibit vaccinia virus (VV) replication in bystander human 293 cells in a dose-dependent manner. The IL-15-induced antiviral activity was partially mediated by NO, as blocking NO production by NO synthase (iNOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMA) partially restored the virus replication. Interferon-gamma (IFN-gamma) was not detectable by ELISA in the cell supernatant of IL-15-activated macrophages or in the co-cultures of macrophages and infected bystander cells. Neutralizing anti-IFN-gamma, anti-IFN-gamma receptor R2, anti-TNF-alpha, or anti-IL-12 antibodies had no effect on NO production or antiviral activity. In contrast, neutralizing anti-IFN-alpha/beta antibody completely restored the VV replication and reduced the NO level to one third of that in the control. Elevated mRNA levels of IFN-beta and iNOS genes were detected in IL-15-activated RAW 264.7 cells by RT-PCR. Our data suggest that IL-15 is capable of inducing IFN-beta, which could participate in NO-mediated antiviral effect.

Animals↗

PubMed2004

Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.

Omega-3 fatty acids (i.e., docosahexaenoic acid; DHA) regulate signal transduction and gene expression, and protect neurons from death. In this study we examined the capacity of dietary omega3 fatty acids supplementation to help the brain to cope with the effects of traumatic injury. Rats were fed a regular diet or an experimental diet supplemented with omega-3 fatty acids, for 4 weeks before a mild fluid percussion injury (FPI) was performed. FPI increased oxidative stress, and impaired learning ability in the Morris water maze. This type of lesion also reduced levels of brain-derived neurotrophic factor (BDNF), synapsin I, and cAMP responsive element-binding protein (CREB). It is known that BDNF facilitates synaptic transmission and learning ability by modulating synapsin I and CREB. Supplementation of omega-3 fatty acids in the diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning disability. The reduction of oxidative stress indicates a benevolent effect of this diet on mechanisms that maintain neuronal function and plasticity. These results imply that omega-3 enriched dietary supplements can provide protection against reduced plasticity and impaired learning ability after traumatic brain injury.

Animals↗

PubMed2004

The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition.

A diet high in saturated fat (HF) decreases levels of brain-derived neurotrophic factor (BDNF), to the extent that compromises neuroplasticity and cognitive function, and aggravates the outcome of brain insult. By using the antioxidant power of vitamin E, we performed studies to determine the role of oxidative stress as a mediator for the effects of BDNF on synaptic plasticity and cognition caused by consumption of the HF diet. Male adult rats were maintained on a HF diet for 2 months with or without 500 IU/kg of vitamin E. Supplementation of the HF diet with vitamin E dramatically reduced oxidative damage, normalized levels of BDNF, synapsin I and cyclic AMP-response element-binding protein (CREB), caused by the consumption of the HF diet. In addition, vitamin E supplementation preserved the process of activation of synapsin I and CREB, and reversed the HF-impaired cognitive function. It is known that BDNF facilitates the synapse by modulating synapsin I and CREB, which have been implicated in synaptic plasticity associated to learning and memory. These results show that oxidative stress can interact with the BDNF system to modulate synaptic plasticity and cognitive function. Therefore, studies appear to reveal a mechanism by which events classically related to the maintenance of energy balance of the cell, such as oxidative stress, can interact with molecular events that modulate neuronal and behavioural plasticity.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

DNA network structures on various solid substrates investigated by atomic force microscopy.

We have fabricated DNA network structures on glass and sapphire substrates. As a comparison, we also formed the network structure on mica substrate. For titanate strontium substrate, however, DNA network can not be obtained even if it is wet-treated by Na2HPO4 solution to make it hydrophilic. We also discuss the factors that affect the DNA networks formed on various substrates.

Aluminum Oxide↗

PubMed2003

AFM studies of DNA structures on mica in the presence of alkaline earth metal ions.

As counterions of DNA on mica, Mg(2+), Ca(2+), Sr(2+) and Ba(2+) were used for clarifying whether DNA molecules equilibrate or are trapped on mica surface. End to end distance and contour lengths were determined from statistical analysis of AFM data. It was revealed that DNA molecules can equilibrate on mica when Mg(2+), Ca(2+) and Sr(2+) are counterions. When Ba(2+) is present, significantly crossovered DNA molecules indicate that it is most difficult for DNA to equilibrate on mica and the trapping degree is different under different preparation conditions. In the presence of ethanol, using AFM we have also observed the dependence of B-A conformational transition on counterion identities. The four alkaline earth metal ions cause the B-A transition in different degrees, in which Sr(2+) induces the greatest structural transition.

Adsorption↗

PubMed2003

Anaerobic induction of Bacillus anthracis hemolytic activity.

A number of genes in Bacillus anthracis encode for proteins homologous to the membrane-damaging factors known as pathogenic determinants in different bacteria. B. anthracis, however, has been traditionally considered non-hemolytic, and the recently identified hemolytic genes have been suggested to be transcriptionally silent. We found that the hemolytic genes of B. anthracis, collectively designated as anthralysins (Anls), could be induced in strict anaerobic conditions. We also demonstrate that Anl genes are expressed at the early stages of infection within macrophages by vegetating bacilli after spore germination. Cooperative and synergistic enhancement of the pore-forming and phospholipase C (PLC) activities of the Anls was found in hemolytic tests on human, but not sheep, red blood cells (RBC). These findings imply Anls as B. anthracis pathogenic determinants and highlight oxygen limitation as environmental factor controlling their expression at both early and late stages of infection.

Anaerobiosis↗

PubMed2003

Effects of caloric restriction on cognition and behavior in developing mice.

The effects of caloric restriction (CR) on cognition and behavior in developing mice were investigated in this study. Male and female Kunmin mice were fed a standard rodent diet ad libitum (Control); 80% of control (20% CR) or 65% of control (35% CR) for 6 months. Body weight gain was significant reduced in CR mice relative to control. Learning and memory retention test in a Y maze demonstrated that CR increased learning but not retention in male mice, whereas CR did not affect learning or retention in females. Open field test revealed no difference in exploratory activity between CR and control mice. These findings suggest that CR produce sex-dependent effect on cognition, but not exploratory activity, in developing animals.

Aging↗

PubMed2003

Deltamethrin induces apoptotic cell death in cultured cerebral cortical neurons.

In this study we investigated the induction of apoptotic cell death and its potential mechanisms in cultured cortical neurons in response to deltamethrin exposure. The cultured cortical neurons were treated at 7 days with deltamethrin at concentrations of 10, 100, and 1000 nM, respectively. MTT assay showed that higher concentrations of deltamethrin (100 and 1000 nM) decreased neuronal viability in a time- and dose-dependent way. TUNEL staining revealed that numerous apoptotic cells appeared in the treated cultures compared to controls at 24, 48, and 72 h after treatment of 100 nM deltamethrin. Western blot analysis demonstrated that p53 and Bax expression were dramatically increased at the same time points, whereas Bcl-2 expression was significantly reduced at all time points after deltamethrin treatment. Further, we found that nitric oxide synthase inhibitor N(G)-nitro-L-arginine prevented deltamethrin-induced neuronal apoptosis and altered expression of p53, Bax, and Bcl-2. These results suggest that nitric oxide synthase might mediate deltamethrin-elicited neuronal apoptosis through modulating the expression of apoptosis-related genes.

Animals↗

PubMed2003

Prolonged expression of c-Fos and c-Jun in the cerebral cortex of rats after deltamethrin treatment.

In this study we investigated the effects of deltamethrin on the expression of c-Fos and c-Jun in the cerebral cortex of rats. Immunohistochemical analysis demonstrated that the immunoreactivity for c-Fos was markedly increased in the cerebral cortex 5 h after deltamethrin treatment, and maintained at an increased level at 24 h, even though little immunoreactivity for c-Fos was seen in the same brain region of control rats. The immunostaining for c-Jun was also dramatically elevated in the same brain region, showing the same time course of c-Fos expression after deltamethrin treatment. Further, both MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, and NBQX, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (KA) receptor antagonist, attenuated deltamethrin-elicited prolonged expression of c-Fos and c-Jun. Since the persistent expression of c-Fos and c-Jun is unusual, and has been reported before in conditions involving neurodegeneration, our results are consistent with a model that deltamethrin induces neurodegeneration through a glutamate-dependent pathway.

Animals↗

PubMed2002

The structural transition of DNA-Tris(1,10-phenanthroline) cobalt(III) complexes in ethanol-water solution.

The interaction of DNA with Tris(1,10-phenanthroline) cobalt(III) was studied by means of atomic force microscopy. Changes in the morphologies of DNA complex in the presence of ethanol may well indicate the crucial role of electrostatic force in causing DNA condensation. With the increase of the concentration of ethanol, electrostatic interaction is enhanced corresponding to a lower dielectric constant. Counterions condense along the sugar phosphate backbone of DNA when epsilon is lowered and the phosphate charge density can thus be neutralized to the level of DNA condensation. Electroanalytical measurement of DNA condensed with Co(phen)(3)(3+) in ethanol solution indicated that intercalating reaction remains existing. According to both the microscopic and spectroscopic results, it can be found that no secondary structure transition occurs upon DNA condensing. B-A conformation transition takes place at more than 60% ethanol solution.

Circular Dichroism↗

PubMed2002

Modulations by dietary restriction on antioxidant enzymes and lipid peroxidation in developing mice.

The effects of dietary restriction (DR) on the activities of liver superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX) and the level of lipid peroxidation (LP) in developing mice were investigated in this study. Male and female Kunmin mice were fed a standard rodent diet ad libitum (AL), 80% of AL food intake (20% DR), or 65% of AL food intake (35% DR) for 12 or 24 wk. Both 12 and 24 wk of DR resulted in retarded body weight gain in male and female mice. The activities of SOD, Cat, and GPX and the content of LP in DR male and female mice were not different (P > 0.05) from those in controls after 12 wk of DR. However, the SOD activity was increased at 24 wk in 20% DR (P < 0.05) and 35% DR (P < 0.01) male, but not in DR female, mice. The Cat activity was elevated at 24 wk in both DR male (P < 0.05 for 20% DR, P < 0.01 for 35% DR) and female (P < 0.01) mice with a greater increase in DR female (P < 0.05) than in DR male animals. GPX activity was also increased at 24 wk in DR male (P < 0.01) and female (P < 0.01) mice with a greater elevation in DR females (P < 0.05) than in DR males. Furthermore, LP was decreased at 24 wk in both DR male (P < 0.01) and female (P < 0.01) animals with a greater reduction in DR females (P < 0.01) compared with DR males. These findings indicated that 24 wk, but not 12 wk, of DR led to differential effects on liver SOD, Cat, and GPX activities and LP content in male and female mice during development, suggesting sex-associated modulations of DR on antioxidant systems in developing animals.

Animals↗

PubMed2002

Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells.

Lethal toxin (LeTx) plays a central role in anthrax pathogenesis, however a cytotoxicity of LeTx has been difficult to demonstrate in vitro. No cytolytic effect has been reported for human cells, in contrast to murine cell lines, indicating that cell lysis can not be considered as a marker of LeTx activity. We have recently shown that murine macrophage-like RAW 264.7 cells treated with LeTx or infected with anthrax spores underwent changes typical of apoptotic death. Here we demonstrate that cells from human peripheral blood display a proapoptotic behavior similar to murine cells. TUNEL assay detected a nucleosomal degradation typical of apoptosis in peripheral blood mononuclear cells (PBMC) treated with LeTx. Membrane staining with apoptotic dyes was detected in macrophages derived from monocytes in presence of LeTx. The toxin inhibited production of proinflammatory cytokines in PBMC stimulated with a preparation of Bacillus anthracis cell wall. Infection of PBMC with anthrax spores led to the appearance of a large population of cells stained positively for apoptosis, with a reduced capacity to eliminate spores and vegetative bacteria. The aminopeptidase inhibitor, bestatin, capable of protecting cells from LeTx, restored a bactericidal activity of infected cells. These findings may be explained by LeTx expression within phagocytes and support an important role of LeTx as an early intracellular virulence factor contributing to bacterial dissemination and disease progression.

Anthrax↗

PubMed2002

Effects of AMPA-receptor and voltage-sensitive sodium channel blockade on high potassium-induced glutamate release and neuronal death in vivo.

High extracellular potassium induces spreading depression-like depolarizations and elevations of extracellular glutamate. Both occur in the penumbra of a focal ischemic infarct, and may be responsible for the spread of cell death from the infarct core to the penumbra. We have modeled this situation with microdialysis of an isotonic high-potassium solution into the normal rat amygdala for 70 min. This elevates extracellular glutamate up to 8-fold or more and produces irreversibly damaged, acidophilic neurons. NMDA-receptor blockade protects neurons and reduces the elevation of extracellular glutamate. Here we investigated the effects of sodium channel blockade with the voltage-sensitive sodium channel blocker tetrodotoxin and the AMPA receptor antagonist 2,3-dihydroxy-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide disodium (NBQX disodium) on high potassium-induced neuronal death and extracellular glutamate elevations. The acidophilic neurons produced are necrotic by ultrastructural examination. Tetrodotoxin, at dialysate concentrations of 33, 330 and 3300 microM (only a small fraction is extracted by tissue), markedly reduced the elevations of glutamate in rat amygdala at nearly all time points during high-potassium perfusion, but it reduced tissue edema only at the highest concentration, and it was neuroprotective only if dialyzed prior to high-potassium microdialysis (at 330 microM concentration). Although both 250 microM (6.2% is extracted by tissue) and 500 microM NBQX reduced elevations of glutamate, neither was neuroprotective, and neuropil edema was not reduced by either concentration. Our results suggest that in vivo, sodium influx through voltage-sensitive sodium channels but not through ligand-gated AMPA receptor channels contributes to high potassium-induced neuronal necrosis.

Amygdala↗

PubMed2002

A method to construct a third-generation horseradish peroxidase biosensor: self-assembling gold nanoparticles to three-dimensional sol-gel network.

A novel method for fabrication of horseradish peroxidase biosensor has been developed by self-assembling gold nanoparticles to a thiol-containing sol-gel network. A cleaned gold electrode was first immersed in a hydrolyzed (3-mercaptopropyl)-trimethoxysilane (MPS) sol-gel solution to assemble three-dimensional silica gel, and then gold nanoparticles were chemisorbed onto the thiol groups of the sol-gel network. Finally, horseradish peroxidase (HRP) was adsorbed onto the surface of the gold nanoparticles. The distribution of gold nanoparticles and HRP was examined by atomic force microscopy (AFM). The immobilized horseradish peroxidase exhibited direct electrochemical behavior toward the reduction of hydrogen peroxide. The performance and factors influencing the performance of the resulting biosensor were studied in detail. The resulting biosensor exhibited fast amperometric response (2.5 s) to H2O2. The detection limit of the biosensor was 2.0 micromol L(-1), and the linear range was from 5.0 micromol L(-1) to 10.0 mmol L(-1). Moreover, the studied biosensor exhibited high sensitivity, good reproducibility, and long-term stability.

Biosensing Techniques↗

PubMed2002

Lethal toxin of Bacillus anthracis causes apoptosis of macrophages.

Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity.

Animals↗

PubMed2002

A relocated technique of atomic force microscopy (AFM) samples and its application in molecular biology.

A kind of simple atomic force microscopy (AFM) relocated technique, which takes advantage of homemade sample locator system, is used for investigating repeatedly imaging of some specific species on the whole substrate (over 1 x 1 cm2) with resolution about 400 nm. As applications of this sample locator system, single extended DNA molecules and plasmid DNA network are shown in different AFM operational modes: tapping mode and contact mode with different tips after the substrates have been moved.

Aluminum Silicates↗