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Biomedical subjects

Wei Li

Publications and source records attributed to Wei Li.

At least 325 records · Page 18Linked to original sources

Photocatalytic hydrogen production from water over M-doped La2Ti2O7 (M = Cr, Fe) under visible light irradiation (lambda > 420 nm).

In the search for efficient photocatalysts working under visible light, we have investigated the effect of cation substitution on a layered perovskite, La2Ti2O7. Among various metal dopants, only Cr and Fe induced intense absorption of visible light (lambda > 400 nm), and only these catalysts produced H2 photocatalytically from water in the presence of methanol under visible light irradiation (lambda > 420 nm). The polymerized complex method was found to be more efficient for fabrication of the present catalysts producing a more homogeneous structure than the solid-state reaction. The characterization by XRD, UV-vis DRS, XPS, and XANES revealed that doped Cr and Fe were present in the Cr3+ and Fe3+ states substituting for Ti sites in the La2Ti2O7 lattice. The theoretical calculation indicated that the most significant feature in the electronic band structure of the metal-doped La2Ti2O7 was the formation of a partially filled 3d band in the band gap of La2Ti2O7, while the contribution of these dopants on the valence band was negligible. Excitation of electrons from this localized interband to the conduction band of La2Ti2O7 was responsible for visible light absorption and the H2 evolution from water under visible light.

Journal Article↗

Effect of rhubarb on contractile response of gallbladder smooth muscle strips isolated from guinea pigs.

AIM: To investigate the effect of rhubarb on contractile response of isolated gallbladder muscle strips from guinea pigs and its mechanism. METHODS: Guinea pigs were killed to remove the whole gallbladder. Two or three smooth muscle strips (8 mm x 3 mm) were cut along the longitudinal direction. The mucosa on each strip was carefully removed. Each longitudinal muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees), bubbled continuously with 950 mL/L O(2) and 50 mL/L CO(2). The resting tension (g), mean contractile amplitude (mm), and contractile frequency (waves/min) were simultaneously recorded on recorders. After 2-h equilibration, rhubarb (10, 20, 70, 200, 700, 1,000 g/L) was added cumulatively to the tissue chamber in turns every 2 min to observe their effects on gallbladder. Antagonists were given 3 min before administration of rhubarb to investigate the possible mechanism. RESULTS: Rhubarb increased the resting tension (from 0 to 0.40+/-0.02, P<0.001), and decreased the mean contractile amplitude (from 5.22+/-0.71 to 2.73+/-0.41, P<0.001). It also increased the contractile frequency of the gallbladder muscle strips in guinea pigs (from 4.09+/-0.46 to 6.08+/-0.35, P<0.001). The stimulation of rhubarb on the resting tension decreased from 3.98+/-0.22 to 1.58+/-0.12 by atropine (P<0.001), from 3.98+/-0.22 to 2.09+/-0.19 by verapamil (P<0.001) and from 3.98+/-0.22 to 2.67+/-0.43 by phentolamine (P<0.005). But the effect was not inhibited by hexamethonium (P>0.05). In addition, the action of mean amplitude and frequency was not inhibited by the above antagonists. CONCLUSION: Rhubarb can stimulate the motility of isolated gallbladder muscle strips from guinea pigs. The stimulation of rhubarb might be relevant with M receptor, Ca(2+) channel and alpha receptor partly.

Adrenergic alpha-Antagonists↗

Genetic analysis of the hypothalamic corticotropin-releasing factor system.

The goal of this study was to use BxD recombinant inbred mice to search for genes that control the hypothalamic corticotrophin-releasing factor (CRF) system. The specific phenotype that was measured was abundance of transcripts that encode CRF, CRF receptor (Crf-R1), CRF binding protein, and arginine vasopressin (AVP) in total hypothalamic RNA. The strain distribution patterns for the transcript abundances for each target were continuously distributed, consistent with these being quantitative traits. Marker regression and interval mapping revealed associations with quantitative trait loci (QTL) for CRF transcript abundance on chromosome 1 (at 89.2 cM), chromosome 12 (between 54-58 cM), and chromosome 13 (between 26-30 cM); for Crf-R1 transcript abundance on chromosome 7 (at 1.5 cM), chromosome 12 (at 37 cM), and chromosome X (at 30 cM); for CRF binding protein transcript abundance on chromosome 7 (at 48.5 cM), chromosome 8 (at 65 cM), and chromosome 12 (at 19 cM); and for AVP transcript abundance on chromosome 7 (at 1 cM), chromosome 12 (at 13 cM), and chromosome 13 (at 45 cM). The transcript abundance QTL were not linked to their respective structural genes. Interval mapping on chromosome 7 reveals substantial overlap between QTL that control AVP and Crf-R1 transcript abundance and on chromosome 12 for QTL that control CRF and Crf-R1, which may indicate loci that coordinate regulation of the CRF system. There are QTL for all four targets on chromosome 12. There are a number of neurodevelopmental genes in very close proximity to the transcript abundance QTL that are potential candidate genes.

Animals↗

Frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not the nucleus accumbens of freely moving rats.

The mechanism of morphine-, methamphetamine-, and nicotine-induced ascorbic acid (AA) release in the striatum and nucleus accumbens (NAc) is not well understood. In the present study, the roles of the corticostriatal and corticoaccumbens pathways in drug-induced AA release were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). The results showed that morphine (20 mg/kg), methamphetamine (3.0 mg/kg), or nicotine (1.5 mg/kg) intraperitoneally (i.p.) significantly stimulated AA release in the striatum to more than 180%, 190%, and 140% compared with saline groups, respectively. These effects could be completely eliminated by frontal decortication, or antagonized by MK-801 (1.0 mg/kg). Moreover, methamphetamine or nicotine also significantly induced AA release in the NAc to more than 180% and 150% compared with saline groups, respectively. However, these effects could not be eliminated by frontal decortication. Although the effects of methamphetamine or nicotine in the NAc could be antagonized by MK-801, two-way ANOVA analysis did not show a significantly interaction between MK-801 and methamphetamine, or nicotine. The results indicates that the corticostriatal glutamatergic pathway may be a common and necessary pathway in drug-induced AA release in the striatum, but the corticoaccumbens glutamatergic pathway may not be crucial in drug-induced AA release in the NAc. The present study implies that different mechanisms might be involved in drug-induced AA release in the striatum and the NAc in rats.

Animals↗

Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display.

Autoimmune uveitis is a group of ocular inflammatory disorders with unknown causes. As in other autoimmune diseases, identification of autoantigens from uveitis patients would markedly improve our understanding of the disease mechanism. Here, we report that a candidate autoantigen was identified by phage display in an unbiased fashion. A bacteriophage T7 display cDNA library was generated from human eye and characterized. Patient-specific phages were enriched by four rounds of phage display with purified patient IgG. Enriched phages demonstrated a 20-fold increase in binding specificity to the patient IgG compared with control IgG. Two clonal phages with particularly high relative binding specificities were isolated and characterized. The encoded genes, tribbles homolog 2 (TRB2) and an unknown protein, had 170- and 42-fold increases in their binding specificities to the patient IgG, respectively. The patient-specific immunoreactivities were further confirmed by Western blotting. Anti-TRB2 antibody activities were detected in several uveitis patients but not in control subjects, suggesting that TRB2 is a uveitis-associated candidate autoantigen. These results demonstrate that autoantigens can be identified by phage display using uveitis patient serum.

Antibody Specificity↗

An oligonucleotide microarray for microRNA expression analysis based on labeling RNA with quantum dot and nanogold probe.

MicroRNAs (miRNAs) play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. They have diverse expression patterns and might regulate various developmental and physiological processes. Profiling miRNA expression is very helpful for studying biological functions of miRNAs. We report a novel miRNA profiling microarray, in which miRNAs were directly labeled at the 3' terminus with biotin and hybridized with complementary oligo-DNA probes immobilized on glass slides, and subsequently detected by measuring fluorescence of quantum dots labeled with streptavidin bound to miRNAs through streptavidin-biotin interaction. The detection limit of this microarray for miRNA was approximately 0.4 fmol, and the detection dynamic range spanned about 2 orders of magnitude. We made a model microarray to profile 11 miRNAs from leaf and root of rice (Oryza sativa L. ssp. indica) seedlings. The analysis results of the miRNAs had a good reproducibility and were consistent with the northern blot result. To avoid using high-cost detection equipment, colorimetric detection, a method based on nanogold probe coupled with silver enhancement, was also successfully introduced into miRNA profiling microarray detection.

Biotinylation↗

New GlcNAc/GalNAc-specific lectin from the ascidian Didemnum ternatanum.

Previously we isolated GlcNAc-specific lectin (DTL) from the ascidian Didemnum ternatanum by affinity chromatography on cross-linked ovalbumin. Here we report the purification and characterization of new D-GlcNAc/D-GalNAc-specific lectin DTL-A from the same ascidian. This lectin was isolated from non-bound cross-linked ovalbumin fraction and further was purified by gel filtration on Sepharose CL-4B, affinity chromatography on GlcNAc-agarose and gel filtration on Superdex 200. SDS-polyacrylamide gel electrophoresis and gel filtration of purified lectin on Sepharose CL-4B indicates that it exists as large aggregates in the native state. Investigations of the carbohydrate specificity of DTL-A by enzyme-linked lectin assay suggest the multi-specificity of this lectin. DTL-A binds BSM, asialo-BSM as well as heparin and dextran sulfate. The binding of DTL-A to BSM was inhibited by monosaccharides D-GlcNAc and D-GalNAc, their alpha- but not beta-anomers. Among polysaccharides and glycoconjugates, DTL-A binding to BSM was effectively inhibited by BSM, asialo-BSM, pronase-treated BSM and synthetic alpha-D-GalNAc-PAA. Fetuin and asialofetuin showed a much lower inhibitory potency, heparin and dextran sulfate were noninhibitory. On the other hand, DTL-A binding to heparin was effectively inhibited by dextran sulfate, fucoidan, whereas BSM showed insignificantly inhibitory effect. DTL-A binding to heparin was not inhibited by D-GlcNAc and D-GalNAc.

Acetylgalactosamine↗

Gelsolin mediates calcium-dependent disassembly of Listeria actin tails.

The role of intracellular Ca2+ in the regulation of actin filament assembly and disassembly has not been clearly defined. We show that reduction of intracellular free Ca2+ concentration ([Ca2+]i) to <40 nM in Listeria monocytogenes-infected, EGFP-actin-transfected Madin-Darby canine kidney cells results in a 3-fold lengthening of actin filament tails. This increase in tail length is the consequence of marked slowing of the actin filament disassembly rate, without a significant change in assembly rate. The Ca2+-sensitive actin-severing protein gelsolin concentrates in the Listeria rocket tails at normal resting [Ca2+]i and disassociates from the tails when [Ca2+]i is lowered. Reduction in [Ca2+]i also blocks the severing activity of gelsolin, but not actin-depolymerizing factor (ADF)/cofilin microinjected into Listeria-infected cells. In Xenopus extracts, Listeria tail lengths are also calcium-sensitive, markedly shortening on addition of calcium. Immunodepletion of gelsolin, but not Xenopus ADF/cofilin, eliminates calcium-sensitive actin-filament shortening. Listeria tail length is also calcium-insensitive in gelsolin-null mouse embryo fibroblasts. We conclude that gelsolin is the primary Ca2+-sensitive actin filament recycling protein in the cell and is capable of enhancing Listeria actin tail disassembly at normal resting [Ca2+]i (145 nM). These experiments illustrate the unique and complementary functions of gelsolin and ADF/cofilin in the recycling of actin filaments.

Actin Depolymerizing Factors↗

A push-pull mechanism for regulating integrin function.

Homomeric and heteromeric interactions between the alphaIIb and beta3 transmembrane domains are involved in the regulation of integrin alphaIIbbeta3 function. These domains appear to interact in the inactivated state but separate upon integrin activation. Moreover, homomeric interactions may increase the level of alphaIIbbeta3 activity by competing for the heteromeric interaction that specifies the resting state. To test this model, a series of mutants were examined that had been shown previously to either enhance or disrupt the homomeric association of the alphaIIb transmembrane domain. One mutation that enhanced the dimerization of the alphaIIb transmembrane domain indeed induced constitutive alphaIIbbeta3 activation. However, a series of mutations that disrupted homodimerization also led to alphaIIbbeta3 activation. These results suggest that the homo- and heterodimerization motifs overlap in the alphaIIb transmembrane domain, and that mutations that disrupt the alphaIIb/beta3 transmembrane domain heterodimer are sufficient to activate the integrin. The data also imply a mechanism for alphaIIbbeta3 regulation in which the integrin can be shifted from its inactive to its active state by destabilizing an alphaIIb/beta3 transmembrane domain heterodimer and by stabilizing the resulting alphaIIb and beta3 transmembrane domain homodimers.

Animals↗

Rosuvastatin attenuates monocyte-endothelial cell interactions and vascular free radical production in hypercholesterolemic mice.

One of the earliest observable events in atherogenesis is enhanced monocyte adhesion to the endothelium. In addition to reducing circulating levels of cholesterol, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are thought to have direct salutary effects upon vascular cells. We hypothesized that the new statin, rosuvastatin, would have anti-inflammatory effects on the vessel wall. Eight-week-old apolipoprotein E-deficient mice were fed a normal chow diet for a period of 12 weeks. During this time mice were administered vehicle or rosuvastatin at a dose of 0, 1, 5, or 20 mg/kg by subcutaneous injection at the same time daily for a period of 2 or 6 weeks prior to sacrifice. At the end of the study, rosuvastatin-treated animals displayed lower plasma total cholesterol levels, whereas showing little change in high-density lipoprotein cholesterol or triglycerides. Using a functional binding assay, we also demonstrated that endothelial adhesiveness for monocytes was significantly attenuated after 2 weeks of treatment with rosuvastatin. Quantitative real-time polymerase chain reaction determined that rosuvastatin reduced the expression of vascular cell adhesion molecule-1, monocyte chemotactic protein-1, and metalloproteinase-9 in the vessel wall. In addition, rosuvastatin inhibited vascular expression of p22(phox) and superoxide production, as well as diminishing plasma 8-isoprostanes concentrations. Thus, treatment with rosuvastatin has acute anti-inflammatory actions that likely participate in its beneficial actions during atherogenesis.

Animals↗

Resolving overlapped spectra with curve fitting.

A novel method of curve fitting based on Gaussian function, which is used to resolve the overlapped peaks, is presented in this paper. The resolution of several kinds of overlapped peaks with noise simulated by computer has been performed and discussed in details. This method has been used for resolving of the UV-vis overlapped spectrum. The results indicate that the proposed algorithm can been used to resolve overlapped spectra effectively and satisfactorily.

Algorithms↗

Phosphoinositide 3-kinase is required for intracellular Listeria monocytogenes actin-based motility and filopod formation.

Motile nonmuscle cells concentrate phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in areas of new actin filament assembly. There is great interest in assessing the in vivo functional significance of these phosphoinositides, and we have used Listeria monocytogenes to explore the contribution of PtdIns(3,4,5)P3 and PtdIns(4,5)P2 to its actin-based motility. In Listeria-infected PtK2 cells Akt-pleckstrin homology (PH)-green fluorescent protein (GFP) and phospholipase C delta (PLC delta)-PH-GFP both first concentrate at the front of motile Listeria, subsequently surrounding the bacterium and then concentrating in the actin filament tail. Surprisingly, Listeria ActA mutant strains lacking the putative phosphoinositide binding site are also able to concentrate these probes. Reduction of available PtdIns(3,4,5)P3 by expression of Akt-PH-GFP and available PtdIns(4,5)P2 by expression of PLC delta-PH-GFP both significantly slow Listeria actin-based movement. Treatment of cells with the PI 3-kinase inhibitor, LY294002, dissociates Akt-PH but not PLC delta-PH, from the bacterial surface and cell membranes, and results in near complete inhibition of Listeria actin-based motility and filopod formation. Removal of LY294002 results in rapid and full recovery of Akt-PH localization, Listeria actin-based motility, and filopod formation. These findings suggest that PtdIns(4,5)P2 is concentrated at the surface of Listeria and serves as the substrate for PtdIns(3,4,5)P3 production, indicating a central role for PI 3-kinases in Listeria intracellular actin-based motility and filopod formation.

Actins↗

Two-dimensional electrophoresis protein profiling as an analytical tool for human acute leukemia classification.

Two-dimensional electrophoresis (2-DE) was used to profile the proteins of leukemic cells from 61 cases of akute leukemia (AL) characterized by the French-American-British (FAB) classification. The differentially expressed protein spots were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). The distinct protein profiles (DPPs) of AL FAB subtypes were explored successfully, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5), and acute lymphoid leukemia (ALL), which were homogeneous within different samples of the same subgroup but clearly differed from all other subgroups. We also found a group of proteins differentially expressed between AL cells and normal white blood cells. Among the DPPs of AL subtypes, some proteins have been reported, but most of them were first reported here to mark AML differentiation and to discriminate AML from ALL. These data show that 2-DE protein profiling could be used as an analytical tool for facilitating molecular definition of human AL classification and understanding the mechanism of leukemogensis, and the extension of the present analysis to the currently less well-defined AL will identify additional subgroups and may promote the identification of new targets for specific treatment approaches.

Acute Disease↗

Outcome of treatment for advanced cervical metastatic squamous cell carcinoma.

BACKGROUND: Patients with advanced cervical metastases from mucosal squamous cell carcinoma have a poor prognosis because of their high risk of regional and distal failure. This study aims to evaluate the outcomes of patients with clinical N2 or N3 disease managed with surgery and postoperative radiotherapy. METHODS: From a comprehensive computerized database, 181 entered patients who had neck dissection for N2 or N3 disease between 1988 and 1999 were evaluated. The mean age was 62 years, and minimum follow-up was 3 years. RESULTS: A total of 233 neck dissections were performed in 181 patients, including 163 comprehensive and 70 selective dissections. Postoperative radiotherapy was given in 82% of cases. The local control rate was 75% at 5 years, and control of disease in the treated neck was achieved in 86%. Macroscopic extracapsular spread (ECS) significantly increased regional recurrence (p = .001). Adjuvant radiotherapy significantly improved neck control (p = .004) but did not alter survival. Patients with ECS (both microscopic and macroscopic) who received radiotherapy had a significantly better survival than did patients with ECS who did not receive radiotherapy. Disease-specific survival for the entire group was 39% at 5 years. By use of multivariate analysis, macroscopic ECS and N2c neck disease were independent adverse prognostic factors for survival (p = .001). CONCLUSIONS: Despite a high rate of control in the treated neck, the poor survival (39%) in this patient group indicates that adjuvant therapeutic strategies need to be considered.

Adult↗

Towards automated 3D finite element modeling of direct fiber reinforced composite dental bridge.

An automated 3D finite element (FE) modeling procedure for direct fiber reinforced dental bridge is established on the basis of computer tomography (CT) scan data. The model presented herein represents a two-unit anterior cantilever bridge that includes a maxillary right incisor as an abutment and a maxillary left incisor as a cantilever pontic bonded by adhesive and reinforced fibers. The study aims at gathering fundamental knowledge for design optimization of this type of innovative composite dental bridges. To promote the automatic level of numerical analysis and computational design of new dental biomaterials, this report pays particular attention to the mathematical modeling, mesh generation, and validation of numerical models. To assess the numerical accuracy and to validate the model established, a convergence test and experimental verification are also presented.

Biocompatible Materials↗

Ribozymes against TGFbeta1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats.

BACKGROUND/AIMS: Transforming growth factor beta (TGFbeta1) is considered the key mediator in the process of liver fibrosis. The purpose of this investigation was to evaluate the activity of ribozymes against TGFbeta1 in a cell-free system and activated hepatic stellate cells (HSCs), and antifibrotic effect in activated HSCs in vitro and in rats. METHODS: Three ribozymes targeting against TGFbeta1 mRNA were designed, and then cloned into the U1 snRNA expression cassette. The chimeric ribozymes were selected for the analysis of their performances in activated HSCs through the detection of their cleavage activities in a cell-free system. After ribozyme-encoding plasmids had been transfected into HSC-T6 cells, the effects of ribozymes on activated HSCs were evaluated through the analysis of proliferation, activation and collagen deposition of HSC-T6. The adenoviral vector expressing the ribozymes was constructed, and then delivered into rat models of hepatic fibrosis induced by carbon tetrachloride. RESULTS: TGFbeta1 expression was efficiently down-regulated in activated HSCs by U1 snRNA chimeric ribozymes which possessed perfect cleavage activity in a cell-free system. Further studies demonstrated that U1 snRNA chimeric ribozymes inhibited the synthesis of collagen I, reduced deposition of collagen I, suppressed BrdU incorporation, but had no effect on desmin and alpha-SMA expression in transfected HSC-T6 cells. Histological analysis demonstrated that the adenoviral vector expressing ribozyme (Rz803) could alleviate fibrotic pathology in rats treated with carbon tetrachloride. CONCLUSIONS: The anti-TGFbeta1 ribozymes could reverse the character of activated HSCs in vitro and improve fibrotic pathology in vivo. It indicated that TGFbeta1 could be considered as a novel candidate for a therapeutic agent against hepatic fibrosis.

Animals↗

First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent.

PURPOSE: To evaluate the feasibility of first-pass contrast-enhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. MATERIALS AND METHODS: First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy volunteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The examined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 micromol Fe/kg (n = 9), or 35.8 micromol Fe/kg (n = 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 micromol Fe/mL was diluted by either four-fold (134.3 micromol Fe/mL) or eight-fold (67.1 micromol Fe/mL) for first-pass MRA. RESULTS: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhancement, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be obtained by subtraction of arterial phase images from equilibrium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. CONCLUSION: Our preliminary experience supports the feasibility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with injection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam.

Adult↗

Effect of free radical scavenger (tempol) on intrarenal oxygenation in hypertensive rats as evaluated by BOLD MRI.

PURPOSE: To demonstrate a differential response following administration of a free radical scavenger, tempol, in kidneys of hypertensive compared to normotensive rats. MATERIAL AND METHODS: Data were obtained in spontaneously hypertensive rats (SHR, N = 5). Wistar-Kyoto rats (WKY, N = 6) were used as normotensive controls. RESULTS: Consistent with prior reports, SHRs show a significant response to tempol (R(2)*decreased from 40.56 +/- 0.66 second(-1) to 28.58 +/- 0.6 second(-1) in medulla, P < 0.05), while WKY rats exhibit a minimal change (R(2)* measuring 22.36 +/- 4.38 second(-1) pre-tempol and 21.57 +/- 4.78 second(-1) post-tempol, in medulla). The post-tempol R(2)* in SHR was found to be comparable to pre-tempol values in WKY rats, suggesting an improved medullary oxygenation in SHRs. CONCLUSION: Based on both baseline R(2)* values and the differential effect of the free radical scavenger on renal medullary oxygenation, BOLD MRI can distinguish hypertensive from normal kidney in rats.

Animals↗