Biomedical subjects

Jun Xu

Publications and source records attributed to Jun Xu.

At least 91 records · Page 5Linked to original sources

PubMed2006

[The combination of recombinant rAd-p53 and adriamycin for management of primary drug resistance in chemotherapy of lung squamous cell cancer].

OBJECTIVE: To investigate the combination of wild-type p53 (wtp53) gene substitution and adriamycin (ADM) on the lung cancer in vivo. METHODS: The effect of combination of recombinant Adeno-wtp53 (rAd-p53) and ADM on reversing primary drug resistance to ADM was studied for the non-small cell lung cancer (NSCLC) in a nude mice model developed by subcutaneously transplanting with the 16HBE lung cancer cell line. Twenty four nude mice with loaded tumors were randomly divided into 4 groups (no treatment, rAd-p53 treatment alone, ADM treatment alone, combination of rAd-p53 plus ADM chemotherapy). The effect of rAd-p53 substitution and ADM on the drug sensitivity was evaluated. RESULTS: In vivo studies on nude mice model transplanted with NSCLC showed that, rAd-p53 treatment alone suppressed tumor growth by 60.11% of the tumor weight and 85.4% by the volume (n = 6), while the combination of rAd-p53 with ADM suppressed tumor growth more significantly (82.32%, 99.5%, respectively, n = 6). The treatment with Adriamycin alone was less effective (35.4%, 73.9%, respectively, n = 6). CONCLUSION: Combination of rAd-p53 and ADM significantly increased the sensitivity of NSCLC tumor graft to ADM, suggesting that the combination of replication-deficient wild p53 adenovirus with DNA-damaging drugs may increase the efficacy of chemotherapy in NSCLC and overcome primary drug resistance.

Adenoviridae↗

PubMed2006

[Change in serum basic fibroblast growth factor level and its relationship to pulmonary arterial pressure in patients with acute exacerbation of chronic cor pulmonale on plateau].

OBJECTIVE: To assess the role of serum basic fibroblast growth factor (bFGF) in the development of hypoxic pulmonary hypertension in the patients with chronic cor pulmonale on highland (HACCP). METHODS: The levels of bFGF in serum of 38 patients with HACCP in the acute exacerbation stage, 30 patients with chronic obstructive pulmonary disease (COPD) in the remission stage and 30 normal control subjects were measured by sandwich enzyme-linked immunoadsorbent assay (ELISA). The mean pulmonary arterial pressure (MPAP) was measured by echocardiography. The partial pressure of oxygen in artery blood (PaO(2)) was measured by blood gas analyzer. RESULTS: The level of serum bFGF [(87.54+/-12.15) ng/L] and MPAP [(45.86+/-5.63)mm Hg (1 mm Hg=0.133 kPa)] in the patients with HACCP were significantly higher than those in the patients with COPD [(55.72+/-9.08) ng/L, (22.95+/-2.56)mm Hg, respectively, both P<0.01], those of the patients with COPD were both significantly higher than those of the normal control subjects [(49.83+/-8.78)ng/L, (20.34+/-2.23)mm Hg, respectively, both P<0.05]. The PaO(2) [(38.79+/-4.56)mm Hg] in the patients with HACCP was significantly lower than those in patients with COPD and normal subjects [(58.22+/-6.18) mmHg and (66.57+/-5.48)mm Hg, respectively, all P<0.01]. The level of serum bFGF in the patients with HACCP and the patients with COPD was positively correlated with MPAP (cor pulmonale group r=0.788, P<0.01; COPD group r=0.674, P<0.01)],negatively correlated with PaO(2) (cor pulmonale group r=-0.735, P<0.01; COPD group r=-0.587, P<0.01)). CONCLUSION: The level of serum bFGF in patients with HACCP is significantly increased; it may play an important role in the process of sustained hypoxic pulmonary hypertension in patients with HACCP.

Aged↗

PubMed2005

Sexually dimorphic expression of the X-linked gene Eif2s3x mRNA but not protein in mouse brain.

Higher expression of X-linked genes in females might contribute to brain sexual differentiation. Although X-inactivation is thought to balance gene dosage between the two sexes, some X-linked genes escape X inactivation and therefore are expressed from both X chromosomes in females. Eif2s3x encodes subunit three of eukaryotic translation initiation factor 2, which regulates the rate of protein translation, and escapes X-inactivation in both humans and mice. By Northern blot analysis, we found Eif2s3x to be expressed higher in females than in males in developing and adult brains as well as adult liver. Gonadally intact XX mice had a higher level of Eif2s3x mRNA expression than XY mice regardless of whether they had testes or ovaries, suggesting that sexually dimorphic gene expression arises as a consequence of sex chromosome complement. In situ hybridization indicated that Eif2s3x mRNA was expressed preferentially in specific brain regions including the habenula, anterodorsal thalamic nucleus, hippocampus, hypothalamus, and cerebellum. Females had significantly higher levels of Eif2s3x mRNA expression than males in cortex, hippocampus and paraventricular nucleus but not in the habenula. The effect of a sex difference in Eif2s3x transcription, however, could potentially be offset by the additional expression in male brains of its Y-linked homologue Eif2s3y which was found in similar brain regions. The sex difference in Eif2s3x transcript appears not to be preserved at the protein level, since no difference in the levels of Eif2s3 protein was found between (1) males and females (2) XX and XY mice, or (3) XO and XX females.

Animals↗

PubMed2005

Integrating time-course microarray gene expression profiles with cytotoxicity for identification of biomarkers in primary rat hepatocytes exposed to cadmium.

MOTIVATION: DNA microarrays can provide information about the expression levels of thousands of genes simultaneously at the transcriptomic level, while conventional cell viability and cytotoxicity measurement methods provide information about the biological functions at the cellular level. Integrating these data at different levels provides a promising approach for evaluating or predicting how cells respond to chemical exposure. It is important to investigate the multi-scale biological system in a systematic way to better understand the gene regulation networks and signal transduction pathways involved in the cellular responses to environmental factors. RESULTS: Primary rat hepatocytes were exposed to cadmium acetate at 0, 1.25 and 2 microM. mRNA expression profiles at 0, 3, 6, 12 and 24 h were measured using the Affymetrix RatTox U34 GeneChip arrays. Simultaneously, cytotoxicity was assessed by lactase dehydrogenase leakage assay. Gene expression profiles at different time points were used to evaluate cytotoxicity at subsequent time points using partial least squares, and it was found that gene expression profiles at 0 h had the best prediction accuracy for the cytotoxicity observed at 12 h. Some biomarkers whose expression profiles showed strong relationship with cytotoxicity were identified and the underlying pathways were reconstructed to illustrate how hepatocytes respond to cadmium exposure. Permutation studies were also applied to assess the reliability of the predictive models. AVAILABILITY: Matlab source code is available upon request and DNA microarray data are available at GEO (http://www.ncbi.nlm.nih.gov/geo).

Algorithms↗

PubMed2005

Microcirculation disturbance affects rats with acute severe pancreatitis following lung injury.

AIM: To study the effects of microcirculation disturbance (MD) on rats with acute severe pancreatitis (ASP). METHODS: We developed ASP rat models, and anatomized separately after 1, 3, 5, 7, and 9 h. We took out blood and did hemorrheologic examination and erythrocyte osmotic fragility test, checked up the water content, capillary permeability, and genetic expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissues, examined the apoptosis degree of blood vessel endothelium while we tested related gene expression of Bax and Bcl-2 in lung tissues. We did the same examination in control group. RESULTS: The viscosity of total blood and plasma, the hematocrit, and the erythrocyte osmotic fragility were all increased. Fibrinogen was decreased. The water content in lung tissues and capillary permeability were increased. Apoptosis degree of blood vessel endothelium was increased too. ICAM-1 genetic expression moved up after 1 h and reached its peak value after 9 h. CONCLUSION: MD plays an important role in ASP following acute lung injury (ALI). The functional damage of blood vessel endothelium, the apoptosis of capillary vessel endothelium, WBC edging-concentration and the increasing of erythrocyte fragility are the main reasons of ALI.

Acute Disease↗

PubMed2005

Thermodynamics of DNA hybridization on gold nanoparticles.

Dynamic light scattering is used as a sensitive probe of hybridization on DNA-functionalized colloidal gold nanoparticles. When a target DNA strand possesses an 8 base "dangling end", duplex formation on the surface of the nanoparticles leads to an increase in hydrodynamic radius. Duplex melting is manifested in a drop in hydrodynamic radius with increasing temperature, and the concentration dependence of the melting temperature provides a measure of the thermodynamics of binding. The hybridization thermodynamics are found to be significantly lower at higher hybridization densities than those previously reported for initial hybridization events. The pronounced deviation from Langmuir adsorption behavior is greater for longer duplexes, and it is, therefore, consistent with electrostatic repulsion between densely packed oligonucleotides. The results have implications for sensing and DNA-directed nanoparticle assembly.

DNA↗

PubMed2005

One-step purification of epigallocatechin gallate from crude green tea extracts by isocratic hydrogen bond adsorption chromatography on beta-cyclodextrin substituted agarose gel media.

An oligomerized beta-cyclodextrin ligand coupled to brominated allyl-group substituted Sepharose HP has been used for the one-step purification of polyphenolic epigallocatechin gallate (EGCG), an important antioxidant, by isocratic hydrogen bond adsorption chromatography. With a sample load of 1.33 mg crude green tea polyphenolic extract per ml column packing and with water/ethanol/acetonitrile (57/30/13, v/v) as the optimum mobile phase, an EGCG purity of about 98% with a recovery of approximate 73% could be achieved by proper peak cutting. After about 10 sample applications, the column performance started to deteriorate but could be regenerated to its original function by cleaning with 0.35 M NaOH.

Catechin↗

PubMed2005

Adaptation is not required to explain the long-term response of axons to molecular gradients.

It has been suggested that growth cones navigating through the developing nervous system might display adaptation, so that their response to gradient signals is conserved over wide variations in ligand concentration. Recently however, a new chemotaxis assay that allows the effect of gradient parameters on axonal trajectories to be finely varied has revealed a decline in gradient sensitivity on either side of an optimal concentration. We show that this behavior can be quantitatively reproduced with a computational model of axonal chemotaxis that does not employ explicit adaptation. Two crucial components of this model required to reproduce the observed sensitivity are spatial and temporal averaging. These can be interpreted as corresponding, respectively, to the spatial spread of signaling effects downstream from receptor binding, and to the finite time over which these signaling effects decay. For spatial averaging, the model predicts that an effective range of roughly one-third of the extent of the growth cone is optimal for detecting small gradient signals. For temporal decay, a timescale of about 3 minutes is required for the model to reproduce the experimentally observed sensitivity.

Axons↗

PubMed2005

Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons.

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP(3)) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.

2-Amino-5-phosphonovalerate↗

PubMed2005

Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis.

BACKGROUND: Previous studies have shown that common human coronavirus might be neurotropic, although it was first isolated as a pathogen of the respiratory tract. We noticed that a few patients with severe acute respiratory syndrome (SARS) experienced central nervous symptoms during the course of illness. In the present study, we isolated a SARS coronavirus strain from a brain tissue specimen obtained from a patient with SARS with significant central nervous symptoms. METHODS: Using transmission electronic microscopy and nested reverse transcription-polymerase chain reaction, the causative pathogen was identified in cultures of a brain tissue specimen obtained from the patient with SARS. Histopathologic examination of the brain tissue was performed using the methods of immunohistochemistry analysis and double immunofluorescence staining. Fifteen cytokines and chemokines were detected in the blood of the patient with SARS by means of a bead-based multiassay system. RESULTS: A fragment specific for SARS human coronavirus was amplified from cultures of the brain suspension, and transmission electronic microscopy revealed the presence of an enveloped virus morphologically compatible with a coronavirus isolated in the cultures. Pathologic examination of the brain tissue revealed necrosis of neuron cells and broad hyperplasia of gliocytes. Immunostaining demonstrated that monokine induced by interferon- gamma (Mig) was expressed in gliocytes with the infiltration of CD68+ monocytes/macrophages and CD3+ T lymphocytes in the brain mesenchyme. Cytokine/chemokine assay revealed that levels of interferon- gamma -inducible protein 10 and Mig in the blood were highly elevated, although the levels of other cytokines and chemokines were close to normal. CONCLUSIONS: This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.

Adult↗

PubMed2005

Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque.

Development of therapeutic agents for severe acute respiratory syndrome (SARS) viral infection using short interfering RNA (siRNA) inhibitors exemplifies a powerful new means to combat emerging infectious diseases. Potent siRNA inhibitors of SARS coronavirus (SCV) in vitro were further evaluated for efficacy and safety in a rhesus macaque (Macaca mulatta) SARS model using clinically viable delivery while comparing three dosing regimens. Observations of SARS-like symptoms, measurements of SCV RNA presence and lung histopathology and immunohistochemistry consistently showed siRNA-mediated anti-SARS efficacy by either prophylactic or therapeutic regimens. The siRNAs used provided relief from SCV infection-induced fever, diminished SCV viral levels and reduced acute diffuse alveoli damage. The 10-40 mg/kg accumulated dosages of siRNA did not show any sign of siRNA-induced toxicity. These results suggest that a clinical investigation is warranted and illustrate the prospects for siRNA to enable a massive reduction in development time for new targeted therapeutic agents.

Animals↗

PubMed2005

Age-related changes in Usp9x protein expression and DNA methylation in mouse brain.

Usp9x, a ubiquitin-specific protease implicated in synaptic development, was found to be more abundant in adult as compared to newborn mouse brain tissue. The Usp9x gene was less methylated in adults than in newborns in both the promoter and the protein coding region. Compared with newborns, the adult mouse brain also had lower levels of Dnmt1, the enzyme responsible for maintaining DNA methylation state. These age-associated changes in DNA methylation and ubiquitin system protein concentrations potentially contribute to developmental changes in brain structure and function.

Animals↗

PubMed2005

A mathematical model for regulating monomer composition of the microbially synthesized polyhydroxyalkanoate copolymers.

A mathematical model is proposed for predicting the copolymer composition of the microbially synthesized polyhydroxyalkanoate (PHA) copolymers. Based on the biochemical reactions involved in the precursor formation and polymerization pathways, the model correlates the copolymer composition with the cultivation conditions, the enzyme levels and selectivity, and the metabolic pathways. It suggests the following points: (1) in the case of a sole carbon source, the copolymer composition depends mainly on the topology of the metabolic pathways and the selectivity of both the enzymes involved in the precursor formation and the polymerization route; (2) the copolymer composition can be varied in a wide range via alteration of the flux ratio of different types of monomers channeled from two or more independent and simultaneous pathways; (3) the enzymes which should be over-expressed or inhibited to obtain the desired copolymer composition can be predicted. For example, inhibition of the beta-oxidation pathway will increase the content of the monomer units with longer chain length. To test the model, various experiments were envisaged by varying cultivation time, concentration and chain length of the sole carbon source, and molar ratio of the cosubstrates. The predictions from the model agree well with the experimental results. Therefore, the proposed model will be useful in predicting the PHA copolymer composition under different biochemical reaction conditions. In other words, it can provide a guide for the synthesis of desired PHA copolymers.

Computer Simulation↗

PubMed2005

Transporting silence: design of carriers for siRNA to angiogenic endothelium.

The recently developed siRNA oligonucleotides are an attractive alternative to antisense as a therapeutic modality because of their robust, gene selective silencing of drug target protein expression. To achieve therapeutic success, however, several hurdles must be overcome including rapid clearance, nuclease degradation, and inefficient intracellular localization. In this presentation, we discuss design strategies for development of self-assembling nanoscale carriers for neovasculature targeted delivery of siRNA inhibiting tumor or ocular angiogenesis.

Angiogenesis Inhibitors↗

PubMed2005

Luminescence 3D-ordered porous materials composed of CdSe and CdTe nanocrystals.

The luminescence porous materials of CdTe or CdSe nanocrystals (NCs) were prepared by filling the corresponding NCs into the voids of colloidal crystal by co-deposition of polymer beads and NCs. After removing the beads with tetrahydrofuran (THF), the 3D-ordered porous materials of CdTe (or CdSe) NCs were obtained. The wavelength of maximum photoluminescence of the NCs porous material shows obvious red shift compared with their aqueous dispersion. Under the excitation of high-energy electron the porous materials of CdTe and CdSe NCs will emit photons that can be collected to form a cathode luminescence (CL) image.

Journal Article↗

PubMed2005

Codoping Na+ to modulate the spectroscopy and photoluminescence properties of Yb3+ in CaF2 laser crystal.

Three kinds of Yb3+ - and Na+-codoped CaF2 laser crystal with different Na:Yb ratios of 0, 1.5, and 10 are grown by the temperature gradient technique. Room-temperature absorption, photoluminescence spectra, and fluorescence lifetimes belonging to the transitions between ground state 2F7/2 and excited state 2F5/2 of Yb3+ ions in the three crystals are measured to study the effect of Na+. Experimental results show that codoping Na+ ions in different Na:Yb ratios can modulate the spectroscopy and photoluminescence properties of Yb3+ ions in a CaF2 lattice in a large scope.

Journal Article↗

PubMed2005

Spatially and temporally specific expression in mouse hippocampus of Usp9x, a ubiquitin-specific protease involved in synaptic development.

We studied the distribution of the ubiquitin-specific protease Usp9x in mouse brain as it relates to the potential role of ubiquitin proteasome system in synaptic plasticity. Usp9x is the mouse homolog of faf, known for its function in synaptic development in Drosophila. In adults, high levels of expression of Usp9x protein were found in layer V of neocortex, Purkinje cells in cerebellum, and specific hippocampal subfields. In hippocampal pyramidal cells, Usp9x expression was higher in CA3 than in CA1. This regional specificity was detected at postnatal day 22 but not at postnatal day 15. In adult mice, the CA1-CA3 difference was partially accounted for by a difference in the level of Usp9x mRNA, suggesting that transcription of Usp9x was differentially regulated between hippocampal subfields. Two synaptic marker proteins, synaptotagmin and spinophilin, were both more abundant in the striatum oriens of CA3 than in the similar region of CA1, correlating with the distribution of Usp9x, a result compatible with a role for Usp9x in synaptic development in mouse hippocampus. Ube1x, the enzyme responsible for the initial step in ubiquitin conjugation, was preferentially concentrated in the dendrites of the CA1 neurons instead of the CA3 neurons, suggesting a reciprocal relationship between ubiquitin conjugation and deubiquitination in CA3 and CA1. This spatial and temporal specificity in expression of Usp9x and Ube1x protein raises interesting questions about the roles of these ubiquitin enzymes in the differential functions of CA1 and CA3.

Animals↗

PubMed2005

Evaluation by indirect immunofluorescent assay and enzyme linked immunosorbent assay of the dynamic changes of serum antibody responses against severe acute respiratory syndrome coronavirus.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emerging virus that gives rise to SARS patients with high rates of infectivity and fatality. To study the humoral immune responses to SARS-CoV, the authors evaluated IgG and IgM specific antibodies in patients' sera. METHODS: Two methods, enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent assay (IFA), were used to detect specific serum IgG and IgM against SARS-CoV in 98 SARS patients and 250 controls consisting of patients with pneumonia, health-care professionals and healthy subjects. The serum antibody profiles were investigated at different times over one and a half years in 18 of the SARS patients. RESULTS: The sensitivity and specificity of ELISA for detecting IgG against SARS-CoV were 100.0% and 97.2% and for IgM 89.8% and 97.6% respectively; the figures using IFA for IgG were 100.0% and 100.0% and for IgM 81.8% and 100.0% respectively. During the first seven days of the antibodies trace test, no IgG and IgM were detected, but on day 15, IgG response increased dramatically, reaching a peak on day 60, remaining high up to day 180 and decreasing gradually until day 540. On day 15, IgM was detected, rapidly reached a peak, then declined gradually until day 180 when IgM was undetectable. CONCLUSION: The detection of antibodies against SARS virus is helpful in the clinical diagnosis of SARS.

Adult↗