Biomedical subjects

Jun Chen

Publications and source records attributed to Jun Chen.

At least 127 records · Page 7Linked to original sources

PubMed2005

Enhanced inhibition of polymerization of sickle cell hemoglobin in the presence of recombinant mutants of human fetal hemoglobin with substitutions at position 43 in the gamma-chain.

Four recombinant mutants of human fetal hemoglobin [Hb F (alpha2gamma2)] with amino acid substitutions at the position 43 of the gamma-chain, rHb (gammaD43L), rHb (gammaD43E), rHb (gammaD43W), and rHb (gammaD43R), have been expressed in our Escherichia coli expression system and used to investigate their inhibitory effect on the polymerization of deoxygenated sickle cell hemoglobin (Hb S). Oxygen-binding studies show that rHb (gammaD43E), rHb (gammaD43W), and rHb (gammaD43R) exhibit higher oxygen affinity than human normal adult hemoglobin (Hb A), Hb F, or rHb (gammaD43L), and all four rHbs are cooperative in binding O2. Proton nuclear magnetic resonance (NMR) studies of these four rHbs indicate that the quaternary and tertiary structures around the heme pockets are similar to those of Hb F in both deoxy (T) and liganded (R) states. Solution light-scattering experiments indicate that these mutants remain mostly tetrameric in the liganded (R) state. In equimolar mixtures of Hb S and each of the four rHb mutants (gammaD43L, gammaD43E, gammaD43R, and gammaD43W), the solubility (Csat) of each of the pairs of Hbs is higher than that of a similar mixture of Hb S and Hb A, as measured by dextran-Csat experiments. Furthermore, the Csat values for Hb S/rHb (gammaD43L), Hb S/rHb (gammaD43E), and Hb S/rHb (gammaD43R) mixtures are substantially higher than that for Hb S/Hb F. The results suggest that these three mutants of Hb F are more effective than Hb F in inhibiting the polymerization of deoxy-Hb S in equimolar mixtures.

Dextrans↗

PubMed2005

Patterning cells in highly deformable microstructures: effect of plastic deformation of substrate on cellular phenotype and gene expression.

We describe the fabrication of deformable microstructures by low-pressure-soft-microembossing (muSEmb) that provides in vitro experimental "test-beds" to investigate the interplay of mechanical and chemical stimuli on cell behavior in a highly controlled environment. Soft microembossing exploits the softness and plasticity of parafilm to fabricate microstructures by pressing a silicon master or an elastomeric poly(dimethylsiloxane) stamp into the parafilm. We demonstrate that a protein-resistant comb polymer can be printed into the raised features of the embossed microstructures, which imparts protein, and hence cell resistance to those regions of the microstructures. These two features of our fabrication methodology-microembossing followed by spatially selective transfer of a nonfouling polymer-forms the core of our strategy to pattern cells within the parafilm microstructures, such that the cells are confined within bottoms of the microstructures. Cell culture experiments demonstrated the preferential cell attachment of NIH 3T3 fibroblasts to the fibronectin (FN) micropatterns by immunofluorescence microscopy. The actin cytoskeleton realigned along the axis of applied mechanical stress, and stretched cells showed altered gene expression of cytoskeletal and matrix proteins in response to mechanical deformation. The use of parafilm as a substrate and muSEmb as a fabrication method provides a simple and widely accessible methodology to investigate cellular behavior under well-defined conditions of plastic deformation and surface ligand density.

Animals↗

PubMed2005

TAT-mediated delivery of Bcl-xL protein is neuroprotective against neonatal hypoxic-ischemic brain injury via inhibition of caspases and AIF.

Systemic delivery of recombinant Bcl-xL fusion protein containing the TAT protein transduction domain attenuated neonatal brain damage following hypoxic ischemia (H-I). Within 30 min after intraperitoneal injection of TAT-Bcl-xL protein into 7-day-old rats, substantially enhanced levels of Bcl-xL were found in several brain regions. Administration of TAT-Bcl-xL at the conclusion of the H-I insult decreased cerebral tissue loss in a dose-dependent manner measured 1 and 8 weeks later. Neuroprotection provided by TAT-Bcl-xL was significantly greater than that of the pan-caspase inhibitor BAF, suggesting that protection is only partially attributable to caspase inhibition by TAT-Bcl-xL. TAT-Bcl-xL not only inhibited caspases-3 and -9 activities after H-I but also prevented nuclear translocation of AIF. Taken together, these results substantiate the feasibility of peripheral delivery of an anti-apoptotic factor into the brain of neonatal animals to reduce H-I-induced brain injury.

Animals↗

PubMed2005

Disposition of flavonoids via recycling: comparison of intestinal versus hepatic disposition.

The purpose of this study was to compare intestinal versus hepatic disposition of six flavonoids to fully characterize their first-pass metabolism. The perfused rat intestinal model and microsomes prepared from rat liver, duodenum, jejunum, ileum, and colon were used. The results indicated that isoflavone (12.5 microM) glucuronidation was highly variable among different microsomes prepared from liver or intestine. Comparing to liver metabolism, the intestinal metabolism had higher K(m) values (>2-fold). Likewise, the hepatic intrinsic clearance (IC, or a ratio of V(max)/K(m)) values of isoflavones were generally higher than their intestinal IC values (200-2000% higher), except for prunetin, for which the jejunal IC value was 50% higher than its hepatic IC. When comparing intestinal metabolism, the results showed that intestinal metabolism rates and V(max) values of isoflavones were less when an additional A-ring electron-donating group was absent (i.e., daidzein and formononetin). In the rat perfusion model using the whole small intestine, genistein (10 microM) was well absorbed (77% or 352 nmol/120 min). The first-pass metabolism of genistein was extensive, with 40% of absorbed genistein excreted as conjugated metabolites into the intestinal lumen. In contrast, the bile excretion of genistein conjugates was much less (6.4% of absorbed genistein). In conclusion, intestinal glucuronidation is slower in isoflavones without an additional A-ring substitution. Perfusion studies suggest that intestine is the main organ for genistein glucuronide formation and excretion in rats and may serve as its main first-pass metabolism organ.

Animals↗

PubMed2005

Template-synthesized LiCoO2, LiMn2O4, and LiNi0.8 Co0.2 O2 nanotubes as the cathode materials of lithium ion batteries.

The first point of this work is to synthesize LiCoO2, LiNi0.8 Co0.2 O2, and LiMn2O4 nanotubes with the template of porous anodic aluminum oxide by thermal decomposition of sol-gel precursors. The as-synthesized materials were open-ended nanotubes with uniform shape and size based on the analysis of scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. An "in situ reaction from nanoparticle to nanotube" mechanism was discussed for the formation process of the nanotubes. The second point of this paper is to investigate the electrochemical properties of the as-synthesized nanotubes for the cathode materials of lithium ion batteries. It was found that the nanotube electrodes exhibited better reversibility and higher discharge capacities than that of their nanocrystalline counterparts. The reason for the improved electrochemical performance of the nanotube electrodes was also interpreted.

Journal Article↗

PubMed2005

Synthesis, characterization, and electrochemical application of Ca(OH)2-, Co(OH)2-, and Y(OH)3-Coated Ni(OH)2 tubes.

We report on the synthesis, characterization, and electrochemical application of Ca(OH)2-, Co(OH)2-, and Y(OH)3-coated Ni(OH)2 tubes with mesoscale dimensions. These composite tubes were prepared via a two-step chemical precipitation within an anodic alumina membrane under ambient conditions. The morphology and structure of the as-synthesized samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM) equipped with energy dispersive spectroscopy (EDS). The results showed that the size of the tubes was of mesoscale dimension and the proportion of the tube morphology was about 95%. The as-prepared composite tubes were further investigated as the positive-electrode materials of rechargeable alkaline batteries. Electrochemical measurements revealed that the Ni(OH)2 tubes coated with Ca(OH)2, Co(OH)2, and Y(OH)3 exhibited superior electrode properties including high discharge capacity, excellent high-temperature and high-rate discharge ability, and good cycling reversibility. The mechanism analysis suggests that both the coated layers and the unique hollow-tube structures play an indispensable role in optimizing the electrochemical performance of nickel hydroxide electrodes.

Journal Article↗

PubMed2005

Cyclooxygenase-2 expression is induced in rat brain after kainate-induced seizures and promotes neuronal death in CA3 hippocampus.

Cyclooxygenase-2 (COX-2) is the predominant isoform of cyclooxygenase in brain. COX-2 activity produces oxidative stress and results in the production of prostaglandins that have many injurious effects. COX-2 transcription is induced by synaptic activity; therefore, COX-2 activity could contribute to epileptic neuronal injury. To address this hypothesis, COX-2 protein expression and PGE2 production were determined after kainate-induced limbic seizures in rats. The effects of a specific COX-2 inhibitor, SC58125, on neuronal survival and PGE2 concentration in the hippocampus were also determined. COX-2 protein expression was increased in CA3, dentate gyrus, and cortex at 18-24 h after seizures. Hippocampal PGE2 levels were increased at 24 h following seizures, and treatment with the selective COX-2 inhibitor SC58125, 3 mg/kg p.o., attenuated the increase in PGE2 concentration. The survival of CA3 neurons at 7 days after seizures was increased in rats treated with SC58125 compared to vehicle controls. There was no effect of drug treatment on body or brain temperature, nor on the duration or rate of Type IV EEG activity. These results suggest that COX-2 activity can contribute to epileptic neuronal injury and that selective COX-2 inhibitors are neuroprotective.

Animals↗

PubMed2005

Scattering and absorption effects in the determination of glucose in whole blood by near-infrared spectroscopy.

Optical properties of whole bovine blood are examined under conditions of different glucose loadings. A strong dependency is established between the scattering properties of the whole blood matrix and the concentration of glucose. This dependency is explained in terms of variations in the refractive index mismatch between the scattering bodies (predominately red blood cells) and the surrounding plasma. Measurements in the presence of a well-known glucose transport inhibitor indicate that variations in refractive index mismatch are related to the penetration of glucose into the red blood cells and demonstrate that increased scattering involves the uptake of glucose by red blood cells. Finally, multivariate calibration models are presented for the measurement of glucose in a whole blood matrix. These models are based on near-infrared spectral data collected from 80 different samples prepared from a single whole blood matrix. Calibration studies are performed over the combination, first-overtone, and short-wavelength spectral regions. The best calibration model is generated from combination region spectra, providing a standard error of prediction (SEP) of less than 1 mM over the concentration range of 3-30 mM. The model based on the first-overtone region is slightly degraded but still provides acceptable performance (SEP = 1.20 mM). The model based on the short-wavelength region is further degraded (SEP = 2.53 mM). To rationalize these results, an analysis of the selectivity of the calibration models is performed by computing the glucose net analyte signal. It is established that the models based on the combination and first-overtone regions are dominated by glucose absorption information, while the model computed from the short-wavelength region is based primarily on scattering information. This result provides evidence that absorption information is needed in order to obtain a glucose calibration model with acceptable performance.

Animals↗

PubMed2005

Correlations between edema and the immediate and prolonged painful consequences of inflammation: therapeutic implications?

The precise relationship between the degree of pain and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of an anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between-group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the injected paw (P< or =0.003), and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose tested (P< 0.05). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determining which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.

Animals↗

PubMed2005

BimEL up-regulation potentiates AIF translocation and cell death in response to MPTP.

This study attempted to elucidate the signaling mechanism underlying dopaminergic cell death in the MPP+ model for Parkinson's disease. In neuronal-differentiated PC12 cells, through the regulation by activated JNK and c-jun, BimEL expression was markedly increased in response to MPP+ treatment, which led to the cell degeneration. In lieu of Smac translocation as seen in other paradigms, up-regulation of BimEL effected an increase in calpain I activity that, in turn, mediated AIF release from the mitochondria. In support, we found that knocking down BimEL expression resulted in a decrease in calpain I activity, as well as AIF release from the mitochondria and cell death. Finally, inhibition of calpain activity mitigated AIF release from the mitochondria and cell death. Under cell-free conditions, activated purified calpain I could induce the release of AIF from isolated mitochondria without the participation of BimEL or activated JNK, suggesting that AIF release is a direct consequence of calpain I activity. In concert, the results suggest a novel signaling pathway for dopaminergic cell degeneration, in which MPP+ induces the up-regulation of BimEL, which in turn potentiates an elevation in calpain I activity that mediates AIF release and cell death in a caspase-independent manner.

1-Methyl-4-phenylpyridinium↗

PubMed2005

Storage and long-distance distribution of telecommunications-band polarization entanglement generated in an optical fiber.

We demonstrate storage of polarization-entangled photons for 125 micros, a record storage time to date, in a 25-km-long fiber spool, using a telecommunications-band fiber-based source of entanglement. With this source we also demonstrate distribution of polarization entanglement over 50 km by separating the two photons of an entangled pair and transmitting them individually over separate 25-km fibers. The measured two-photon fringe visibilities were 82% in the storage experiment and 86% in the distribution experiment. Preservation of polarization entanglement over such long-distance transmission demonstrates the viability of all-fiber sources for use in quantum memories and quantum logic gates.

Journal Article↗

PubMed2005

Estrogen regulates CCR gene expression and function in T lymphocytes.

Estrogen has been implicated in the observed female bias in autoimmune diseases. However, the mechanisms behind this gender dimorphism are poorly defined. We have previously reported that in vivo T cell trafficking is gender- and estrogen-dependent. Chemokine receptors are critical determinants of T cell homing and immune response. In this study, we show that the female gender is associated with increased CD4(+) T cell CCR1-CCR5 gene and protein expression in mice. The increased CCR expression correlates with enhanced in vitro chemotaxis response to MIP-1beta (CCL4). In vivo treatment of young oophorectomized and postmenopausal female mice with 17beta-estradiol also increased CD4(+) T cell CCR expression. Finally, 17beta-estradiol enhances tyrosine phosphorylation in T cells stimulated with MIP-1alpha in a time-dependent manner. Our results indicate an important role of estrogen in determining T cell chemokine response that may help explain the increased susceptibility and severity of autoimmune diseases in females.

Animals↗

PubMed2005

Evidence for peripherally antinociceptive action of propofol in rats: behavioral and spinal neuronal responses to subcutaneous bee venom.

In the present study, behavioral and in vivo electrophysiological methods were used to examine the peripheral effects of propofol on tonic ongoing pain-related responses produced by subcutaneous bee venom-induced inflammatory pain state. Local administration of 0.5 microg propofol produced significant suppression of the well-established ongoing pain responses in both conscious rats and dorsal horn nociceptive neurons. The locally antinociceptive action of propofol is not caused by systemic effect, because contralateral administration of the same dose of drug did not produce any effect. This result indicates that besides central actions, propofol has peripherally antinociceptive action as well.

Analgesics↗

PubMed2005

Transfection of apoptosis related gene Fas ligand in human hepatocellular carcinoma cells and its significance in apoptosis.

AIM: To evaluate the expression of apoptosis related gene Fas ligand (FasL) in human hepatocellular carcinoma (HCC) cells HepG2 and its significance in apoptosis. METHODS: Levels of soluble Fas ligand (sFasL) in a group of patients with hepatitis B virus (HBV)-induced chronic hepatitis, HBV-positive liver cirrhosis and HCC were evaluated. In a further study, the recombinant eukaryotic expression plasmid pcDNA3.1hisB-FasL was transfected into HCC cells HepG2 by lipofection, and then soluble FasL was examined in the supernatant of culture cells by EIA, FasL expression in HepG2 cells was detected by immunohistochemistry. After being stained by annexin V and propidium iodine, cells were passed through a flow cytometer and examined by a fluorescence microscope and a laser scanning microscope. RESULTS: The sFasL levels were significantly lower in patients with HCC when compared to the patients with hepatitis or liver cirrhosis. In comparison with untransfected cells, the soluble FasL could be detected in the supernatant of transfected cells. FasL was expressed on the membranes and cytoplasm of transfected cells. The apoptotic cell rate was 36.30% in transfected cells, and was 11.53% in untransfected cells. Moreover, the different stage of apoptotic cells could be distinguished by annexin V and propidium iodine staining. CONCLUSION: Fas ligand is an apoptotic pathway of HCC cells.

Apoptosis↗

PubMed2005

Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress.

Endothelium-derived microparticles have recently been described as a new marker of endothelial cell dysfunction. Increased levels of circulating microparticles have been documented in inflammatory disorders, diabetes mellitus, and many cardiovascular diseases. Perturbations of angiogenesis play an important role in the pathogenesis of these disorders. We demonstrated previously that isolated endothelial microparticles (EMPs) impair endothelial function in vitro, diminishing acetylcholine-induced vasorelaxation and nitric oxide production by rat aortic rings and simultaneously increasing superoxide production. Herein, using the Matrigel assay of angiogenesis in vitro and a topological analysis of the capillary-like network by human umbilical vein endothelial cells (HUVECs), we investigated the effects of EMPs on formation of the vascular network. All parameters of angiogenesis were affected by treatment for 48 h with isolated EMPs in a concentration of 10(5) but not 10(3) or 10(4) EMPs/ml. The effects included decreases in total capillary length (24%), number of meshes (45%), and branching points (36%) and an increase in mesh area (38%). The positional and topological order indicated that EMPs affect angiogenic parameters uniformly over the capillary network. Treatment with the cell-permeable SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (Mn-TBAP) partially or completely restored all parameters of angiogenesis affected by EMPs. EMPs reduced cell proliferation rate and increased apoptosis rate in time- and dose-dependent manners, and this phenomenon was also prevented by Mn-TBAP treatment. Our data demonstrate that EMPs have considerable impact on angiogenesis in vitro and may be an important contributor to the pathogenesis of diseases that are accompanied by impaired angiogenesis.

Apoptosis↗

PubMed2005

Determination of WR-1065 in human blood by high-performance liquid chromatography following fluorescent derivatization by a maleimide reagent ThioGlo3.

In order to improve the sensitivity and stability of human blood samples containing WR-1065 (i.e., active metabolite of the cytoprotective agent amifostine), a high-performance liquid chromatographic method was developed and validated using fluorescent derivatization with ThioGlo3. Using a sample volume of only 100 microl, the method was specific, sensitive (limit of quantitation=10 nM in deproteinized blood or 20 nM in whole blood), accurate (error < or = 3.2%) and reproducible (CV < or = 8.7%). In addition, the stability of WR-1065 in deproteinized and derivatized blood samples was assured for at least four weeks at -20 degrees C. This method should be particularly valuable in translating the kinetic-dynamic relationship of WR-1065 in preclinical models to that in cancer patients.

Amifostine↗

PubMed2005

Neural mechanisms of attentional modulation of perceptual grouping by collinearity.

Psychophysical research showed that detection of an oriented visual target is facilitated when the target is grouped with collinear visual flankers. However, this collinear grouping effect is evident only when the flankers are attended. This study examined neural mechanisms underlying the interaction between attention and grouping by collinearity. Event-related potentials were recorded from study participants who judged whether oriented Gabor patches (i.e. visual elements consisting of a sinusoidal contrast modulation convolved with a Gaussian function) along the cued orientation were collinear or orthogonal. Event-related potentials showed an enhanced negativity over the posterior occipital cortex at 48-72 ms when collinear patches were congruent rather than incongruent with the cued orientation. A negative shift between 260 and 380 ms was observed over the occipital-parietal areas in the congruent rather than incongruent conditions. The long-latency effect, however, was evident only when the collinear patches were allocated along 45 degrees . The event-related potential results suggest that the interaction between attention and collinear grouping may take place as early as in the primary visual cortex and is independent of global orientations of perceptual groups.

Adolescent↗

PubMed2005

[Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases].

OBJECTIVE: To analyze the clinical characteristics of Chinese patients suffering from chronic fatigue syndrome (CFS) and provide clinical and laboratory evidence for the study of its etiology and treatment. METHODS: 82 patients with CFS diagnosed based on the CDC criteria 1994 were recruited. History was collected, and physical examination was made. SCL-90 and memory test were used, and Hamilton Anxiety Rating Scale was used to those showing depression and/or anxiety. Laboratory examination, including examination of electrolytes, blood sugar, creatinine, bilirubin, alkaline phosphatase, alanine trasaminase, etc, was conducted. Western blotting was used to detect the protein-24 of Borna disease virus (BDV) in the plasma of 61 patients and 73 healthy controls. High-pressure chromatography was conducted to detect n-6 fatty acids on the membrane of erythrocytes of 42 patients and 37 healthy controls. Plasma L-carnitine in 61 patients and 73 healthy controls was detected by zymological analysis. In different examinations sex and age-matched controls were used. RESULTS: Most of the patients were 21 approximately 50 years old (74/82, 90.24%). No gender difference was found. The patients usually had 4 approximately 6 symptoms besides distinctive fatigue. Descent of remembrance and/or attention was the most conspicuous accompanying symptoms (69/82, 84.15%). Abnormalities in SCL-90 scores were present in 57 patients (69.51%), e.g, somatization existed most commonly (32/82, 39.02%), and anxiety and depression were 20.73% (17/82) and 18.29% (15/82) respectively. The prevalence of anti-BDV-p24 antibody was 20.73% (17/82), significantly higher than that of the controls (0%, chi(2) = 6.673, P = 0.010). The arachidonic acid level was significantly lower in the CFS group than in the controls (P > 0.05) and there were no differences in linoleic acid and ETA (both P > 0.05). The level of L-carnitine was 6.4336 +/- 3.4225, significantly lower than that of the control group (7.6666 +/- 3.5819, t = 2.025, P = 0.045) and the L-carnitine level was increased 2 weeks after supplementary treatment, together with improvement of symptoms. CONCLUSION: Most of the CFS patients are young and middle-aged. Descent of reorganization is common in these patients. Psychological abnormalities exist in most patients. Some patients are infected with BDV, some with deficiency of nutrition and/or abnormality of energy metabolism.

Adult↗