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Biomedical subjects

Ling Wang

Publications and source records attributed to Ling Wang.

At least 127 records · Page 7Linked to original sources
PubMed2004

Clinical observation on acupuncture treatment in 35 cases of diabetic gastroparesis.

In order to observe the therapeutic effects of acupuncture on diabetic gastroparesis, 80 cases were divided randomly into 3 groups. In addition to the routine treatment for diabetes, 35 cases in the treatment group were additionally treated with acupuncture, and 25 cases in the control group 1 with domperidone, while 20 cases in the control group 2 with nothing. The three groups were all observed for 25 days. The results turned out to be that the total effective rate in the treatment group reached 94.2%, that in the control group 1, 72%, and in the control group 2, 40%, the treatment group showing a better therapeutic effect than the other two control groups (P < 0.05, P < 0.01). It can be concluded that in addition to the routine treatment for controlling blood sugar, acupuncture can give quite good therapeutic effects on diabetic gastroparesis.

Acupuncture Therapy↗
PubMed2004

[Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM-CSF].

AIM: To investigate if GM-CSF adjuvant could enhance the inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth. METHODS: Female BALB/c mice were immunized intramuscularly with 100 microgram MUC1 gene vaccine 3 times at 3 week intervals. On 1, 3 and 5 days after intramuscular immunization, GM-CSF 100 microL(1 microg/100 microL) was given s.c. respectively. Three weeks after the last immunization, tumor challenge experiments were performed by using MUC1 expressing tumor cell line EMT6. Tumor growth inhibition was observed two weeks later. After 43 d of challenge experiments, all mice were killed and tumors were weighted. CTL-specific cytotoxicity was detected by (51)Cr release assay. RESULTS: After 43 d of challenge experiments, the size of EMT6 tumor in MUC1 DNA+GM-CSF, MUC1 DNA, pcDNA3.1(+)+GM-CSF and pcDNA3.1(+) group were (135+/-33.8) mm(3), (250+/-34.3) mm(3), (568+/-43.6) mm(3) and (596+/-48.2) mm(3), respectively. The average weight (g) of EMT6 tumors in those four groups were 0.81+/-0.42, 1.23+/-0.41, 2.30+/-0.48 and 2.28+/-0.58, respectively. EMT6 breast cancer growth in mice of MUC1 gene vaccine group was suppressed significantly(P<0.05), compared with that in pcDNA3.1(+) control group. Co-delivery of GM-CSF adjuvant and MUC1 DNA immunization enhanced the antitumour effects(P<0.05). The cytotoxicity of MUC1-specific CTLs to EMT6 target cells was different at various ratios of effector cells to target cells. At ratios of 100:1, 50:1, 25:1 and 12.5:1, the specific lysis for MUC1 DNA+GM-CSF group reached 68.5%, 53.4%, 35.9% and 28.5%, MUC1 cDNA group 54.1%, 39.8%, 26.4% and 20.1%, while for control groups 13.2%, 10%, 8.2%, 7.2% and 11.7%, 9.8%, 7.7%, 7.0%, respectively. GM-CSF enhanced the cytotoxicity of CTL induced by MUC1 DNA immunization(P<0.05). CONCLUSION: GM-CSF adjuvant significantly enhanced the inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth.

Animals↗
PubMed2004

[Applying competitive polymerase chain reaction to the detection of hepatitis B virus DNA].

OBJECTIVE: To reduce the rate of accidental false negative result in the HBV DNA PCR test on clinical serum samples. METHODS: A competitive polymerase chain reaction (C-PCR) was used to decrease the false negative ratio. In the C-PCR, a constructed inner control DNA was added for co-amplification with the HBV target DNA. RESULTS: In a 20 microl C-PCR system, about 60 to 200 copies of inner control DNA could give apparent co-amplification signal band after electrophoresis on a 2% agarose gel. Five of 120 samples of clinical serum (4.2%) could not be amplified. CONCLUSION: C-PCR has the advantage of yielding information on false negative in the HBV DNA PCR assay of clinical serum samples.

DNA, Viral↗
PubMed2003

Using biofunctional magnetic nanoparticles to capture vancomycin-resistant enterococci and other gram-positive bacteria at ultralow concentration.

Covalently linked to vancomycin (Van), chemically stable and highly magnetic anisotropic FePt magnetic nanoparticles (3-4 nm) become water-soluble and capture vancomycin-resistant enterococci (VRE) and other Gram-positive bacteria at concentrations approximately 10(1) cfu/mL via polyvalent ligand-receptor interactions. When a pyramidal end of a magnet "focuses" the nanoparticles into approximately 1 mm(2) area, the bacteria can be observed by an optical microscope and further identified by electron micrograph (EM). Compared to the conventional use of magnetic particles (with the sizes of 1-5 microm) in biological separation or drug delivery, magnetic nanoparticles, combined with specific receptor-ligand interactions, promise a sensitive and rapid protocol to detect pathogens.

Alloys↗
PubMed2003

Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration.

Neuropilin-1 (NRP-1) has been found to be expressed by endothelial cells and tumor cells as an isoform-specific receptor for vascular permeability factor/vascular endothelial growth factor (VEGF). Previous studies were mainly focused on the extracellular domain of NRP-1 that can bind to VEGF165 and, thus, enables NRP-1 to act as a co-receptor for VEGF165, which enhances its binding to VEGFR-2 and its bioactivity. However, the exact functional roles and related signaling mechanisms of NRP-1 in angiogenesis are not well understood. In this study we constructed a chimeric receptor, EGNP-1, by fusing the extracellular domain of epidermal growth factor receptor to the transmembrane and intracellular domains of NRP-1 and transduced it into HUVECs with a retroviral expression vector. We observed that NRP-1/EGNP-1 mediates ligand-stimulated migration of human umbilical vein endothelial cells (HUVECs) but not proliferation. Our results show that NRP-1 alone can mediate HUVEC migration through its intracellular domain, and its C-terminal three amino acids (SEA-COOH) are essential for the process. We demonstrate that phosphatidylinositol 3-kinase inhibitor Ly294002 and the p85 dominant negative mutant can block NRP-1-mediated HUVEC migration. NRP-1-mediated migration can be significantly reduced by overexpression of the dominant negative mutant of RhoA (RhoA-19N). In addition, Gq family proteins and Gbetagamma subunits are also required for NRP-1-mediated HUVEC migration. These results show for the first time that NRP-1 can independently promote cell signaling in endothelial cells and also demonstrate the importance of last three amino acids of NRP-1 for its function.

Base Sequence↗
PubMed2003

Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.

OBJECTIVE: The aim of this study is to investigate whether ambroxol inhibits inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury (ALI). METHODS: Mice (n=295) were first intratracheally instilled with lipopolysaccharide (LPS) to induce ALI and then received an intraperitoneal (i.p.) injection of either normal saline (NS), ambroxol (30 or 90 mg/kg per day) or dexamethasone (2.5 or 5 mg/kg per day) for 7 days. Metabolism (n=10, each), lung morphology (n=5, each) and wet-to-dry lung weight ratio (n=10, each) were studied. The levels of tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6) and transforming growth factor (TGF-beta1) and the protein concentration (n=5 or 7, each) in bronchoalveolar lavage (BAL) were measured. RESULTS: Mice with LPS-induced ALI that were treated with ambroxol at a dosage of 90 mg/kg per day significantly gained weight compared to the control and dexamethasone-treated groups. Ambroxol and dexamethasone significantly reduced the lung hemorrhage, edema, exudation, neutrophil infiltration and total lung injury histology score at 24 and 48 h. In addition, ambroxol and dexamethasone significantly attenuated the lung wet-to-dry weight ratio at 24 and 48 h (p<0.05). Compared to the control group, TNF-alpha, IL-6 and TGF-beta1 levels in the BAL in both ambroxol- and dexamethasone-treated groups were significantly reduced at 24 and 48 h. The protein in BAL, an index of vascular permeability, was also significantly decreased in the ambroxol- and dexamethasone-treated groups (p<0.05). CONCLUSION: Ambroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI.

Ambroxol↗
PubMed2003

Function of gamma-aminobutyric acid receptor/channel rho 1 subunits in spinal cord.

gamma-Aminobutyric acid (GABA) receptor/channel rho 1 subunits are important components in inhibitory pathways in the central nervous system. However, the precise locations and roles of these receptors in the central nervous system are unknown. We studied the expression localization of GABA receptor/channel rho 1 subunit in mouse spinal cord and dorsal root ganglia (DRG). The immunohistochemistry results indicated that GABA receptor/channel rho 1 subunits were expressed in mouse spinal cord superficial dorsal horn (lamina I and lamina II) and in DRG. To understand the functions of the GABA receptor/channel rho 1 subunit in these crucial sites of sensory transmission in vivo, we generated GABA receptor/channel rho 1 subunit mutant mice (rho 1-/-). GABA receptor/channel rho 1 subunit expression in the rho 1-/- mice was eliminated completely, whereas the gross neuroanatomical structures of the rho 1-/- mice spinal cord and DRG were unchanged. Electrophysiological recording showed that GABA-mediated spinal cord response was altered in the rho 1-/- mice. A decreased threshold for mechanical pain in the rho 1-/- mice compared with control mice was observed with the von Frey filament test. These findings indicate that the GABA receptor/channel rho 1 subunit plays an important role in modulating spinal cord pain transmission functions in vivo.

Animals↗
PubMed2003

YXXM motifs in the PDGF-beta receptor serve dual roles as phosphoinositide 3-kinase binding motifs and tyrosine-based endocytic sorting signals.

Phosphoinositide 3-kinases (PI 3-kinases) are important regulators of endocytic trafficking. Previous studies have shown that mutant human platelet-derived growth factor-beta receptors (PDGFR), which contain Phe in place of Tyr at the two p85/p110 PI 3-kinase binding sites (PDGFR-F/F), are defective for both p85 binding and ligand-stimulated degradation. This suggested that p85/p110 regulates PDGFR trafficking. However, more recent work has identified hVPS34, and not p85/p110, as the major PI 3-kinase regulating the movement of receptors through the endosomal system. To reconcile this discrepancy, we hypothesized that YXXM motifs in the PDGFR might play a second role as Tyr-based lysosomal sorting motifs (YXXPhi). To test this, we replaced both YXXM motifs with a motif from LAMP-1, YQTI. This mutant PDGFR (PDGFR-YQTI) still underwent PDGF-stimulated autophosphorylation but did not bind p85. In CHO cells, both wild-type and YQTI receptors showed PDGF-stimulated turnover, whereas F/F receptors did not. In addition, uptake and degradation of cell surface-labeled YXXM and YQTI receptors was fast relative to F/F receptors. We also constructed chimeras containing extracellular and membrane-spanning domains from CD25 (Tac) and cytoplasmic tails containing the YQTI motif, two YXXM motifs, or two mutant FXXM motifs. The YXXM and YQTI chimeras mediated lysosomal delivery of fluorescein isothiocyanate-labeled anti-CD25 antibodies, whereas the F/F chimera was defective. Thus, YQTI motifs can target PDGFR for degradation in the absence of p85/p110 binding, and the p85/p110 binding motifs from PDGFR are sufficient to target Tac chimeras to the lysosome. These data suggest that the YXXM motifs in the PDGFR serve two distinct functions: PI 3-kinase recruitment and lysosomal targeting.

Amino Acid Motifs↗
PubMed2003

[Effect of motilin on gastric smooth contraction induced by interstitial cells of Cajal].

OBJECTIVE: To investigate the role of interstitial cells of Cajal (ICC) in contraction of gastric smooth muscle and the effect of motilin on this role. METHODS: Two kinds of smooth muscle segments with ICC were isolated from the pacemaker area at the upper 1/3 of stomach body and from the gastric antrum of 90 rats and immersed into Krebs solution and linked with tonotransducer to record their contraction. Both kinds of smooth muscle segments were divided into 5 groups equally: group A (control group), group B (methylene blue and intense illumination were used to destroy the ICC therein), group C (motilin was added into the Krebs solution), group D (both motilin and anti-motilin serum were added), and group E (motilin and atropin or hexahydroxy-quaternary ammonium were added). RESULTS: stable contractile activity was recorded in these 2 kinds of smooth muscle segments with higher frequency and amplitude of contraction in those from the gastric antrum than those from the stomach body. The frequency and amplitude of contraction in the smooth muscle segments with the ICC destroyed by methylene blue and intense illumination were decreased by 80% approximately 90%. Motilin increased the frequency and amplitude of contraction in the smooth muscle segments from the gastric antrum and stomach body dose-dependently. Anti-motilin serum and atropin, but not hexahydroxy-quaternary ammonium blocked the effect of motilin. The smooth muscle segments with destroyed ICC showed no significant differences in the frequency and amplitude of contraction in comparison with the smooth muscle segments with destroyed ICC plus motilin. CONCLUSION: The pacemaker cells of the contractile activity of gastric smooth muscle cells are ICC, Motilin regulates the gastric smooth muscle contraction initiated by ICC.

Animals↗
PubMed2003

Disruption of the estrogen receptor beta gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis.

Proliferation of pluripotent, bone marrow stem cells, which develop to lymphoid and myeloid progenitors, is negatively regulated by estrogen. Although in estrogen deficiency and in estrogen receptor knockout mice there is significant alteration in bone marrow hematopoiesis, the effects of aging on estrogen receptor deficiencies in mice have not been investigated yet. In this study we show that by 1.5 years of age, estrogen receptor beta knockout (ERbeta-/-) mice develop pronounced splenomegaly that is much more severe in females than in males. Further characterization of these mice revealed myelogenous hyperplasia in bone marrow, an increase in the number of granulocytes and B lymphocytes in blood, lymphadenopathy, and infiltration of leukocytes in the liver and lung. Analysis by flow cytometry of the bone marrow cells revealed that the percentage and total number of Gr-1hi/Mac-1hi-positive granulocytes were increased by 15-30% and 100%, respectively. The numbers of B cells in the bone marrow and spleen were significantly higher in ERbeta-/- mice than in WT littermates. Some of the ERbeta-/- mice also had a severe lymphoproliferative phenotype. Thus the absence of ERbeta results in a myeloproliferative disease resembling human chronic myeloid leukemia with lymphoid blast crisis. Our results indicate a previously unknown role for ERbeta in regulating the differentiation of pluripotent hematopoietic progenitor cells and suggest that the ERbeta-/- mouse is a potential model for myeloid and lymphoid leukemia. Furthermore, we suggest that ERbeta agonists might have clinical value in the treatment of leukemia.

Animals↗
PubMed2003

Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation.

Sphingosine 1-phosphate (S1P) is a pleiotropic lysosphingophospholipid stored and secreted by platelets. Using reverse transcription-polymerase chain reaction and flow cytometric analyses, we determined the expression of S1P receptors (S1P1, S1P3, S1P4, and S1P5) in peripheral blood T cells. T cells were induced to proliferate in the presence of phorbol 12-myristate 13-acetate (PMA) plus ionomycin, anti-CD3 plus anti-CD28, and allogeneic immature or mature dendritic cells. This activity was inhibited by the addition of S1P. Enhanced T-cell proliferation was observed when these cells were stimulated with the same stimuli, but were incubated in serum-free media (SFM). Addition of S1P to SFM inhibited the stimulation of T cells induced by T-cell stimuli, suggesting that S1P is an important inhibitory molecule present in the serum. T-cell proliferation was also inhibited by the addition of dihydrosphingosine 1-phosphate (DHS1P), sphingosine, and ceramide; however, the latter 2 sphingolipids required higher concentrations than S1P. Pretreatment of T cells with pertussis toxin (PTX) blocked the inhibitory effect of S1P on activation with PMA plus ionomycin, but not on activation with anti-CD3 plus anti-CD28. This is corroborated with the down-regulation of S1P1 in T cells stimulated with anti-CD3 plus anti-CD28. Similarly, PTX did not affect the inhibitory effect of S1P on T-cell proliferation when dendritic cells were used as stimuli. Further, S1P or DHS1P but not ceramide or sphingosine enhanced rather than decreased secretion of interleukin 2 and interferon gamma by T cells stimulated with anti-CD3 plus anti-CD28. These results show differential effects of S1P on polyclonal T-cell proliferation and cytokine secretion.

Antibodies↗
PubMed2003

Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion.

Omega-6 (omega-6) polyunsaturated fatty acids (PUFA), abundant in the Western diet, are precursors for a number of key mediators of inflammation including the 2-series of prostaglandins (PG). PGE(2), a cyclooxygenase (COX) metabolite of arachidonic acid, a omega-6 PUFA, is a potent mediator of inflammation and cell proliferation. Dietary supplements rich in omega-3 PUFA reduce the concentrations of 2-series PG and increase the synthesis of 3-series PG (e.g., PGE(3)), which are believed to be less inflammatory. However, studies on cellular consequences of increases in 3-series PG in comparison to 2-series PG have not been reported. In this study, we compared the effects of PGE(2) and PGE(3) on (i) cell proliferation in NIH 3T3 fibroblasts, (ii) expression and transcriptional regulation of the COX-2 gene in NIH 3T3 fibroblasts, and (iii) the production of an inflammatory cytokine, IL-6, in RAW 264.7 macrophages. PGE(3), unlike PGE(2), is not mitogenic to NIH 3T3 fibroblasts. PGE(2) and PGE(3) both induce COX-2 mRNA via similar signaling mechanisms; however, compared with PGE(2), PGE(3) is significantly less efficient in inducing COX-2 gene expression. Furthermore, although both PGE(2) and PGE(3) induce IL-6 synthesis in RAW 264.7 macrophages, PGE(3) is substantially less efficient compared with PGE(2). We further show that increasing the omega-3 content of membrane phospholipid results in a decrease in mitogen-induced PGE(2) synthesis. Taken together, our data suggest that successful replacement of omega-6 PUFA with omega-3 PUFA in cell membranes can result in a decreased cellular response to mitogenic and inflammatory stimuli.

3T3 Cells↗
PubMed2003

Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney.

Mice lacking exon 3 of perlecan (Hspg2) gene were generated by gene targeting. Exon deletion does not alter the expression or the reading frame but causes loss of attachment sites for three heparan sulfate (HS) side chains. Hspg2(Delta 3 / Delta 3) mice are viable and fertile but have small eyes. Apoptosis and leakage of cellular material through the lens capsule are observed in neonatal lenses, and lenses degenerate within 3 weeks of birth. Electron microscopy revealed altered structure of the lens capsule through which cells had formed extensions. No kidney malfunction, such as protein uria, was detected in Hspg2(Delta 3 / Delta 3) mutant mice, nor were ultrastructural changes observed in the glomerular basement membranes (BMs). To achieve further depletion in the HS content of the BMs, Hspg2(Delta 3 / Delta 3) mice were bred with collagen XVIII null mice. Lens defects were more severe in the newborn Col18a1(-/-) x Hspg2(Delta 3 / Delta 3) mice and degeneration proceeded faster than in Hspg2(Delta 3 / Delta 3) mice. The results suggest that in the lens capsule, HS chains have a structural function and are essential in the insulation of the lens from its environment and in regulation of incoming signals.

Animals↗
PubMed2003

Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing brain.

The present study stems from our previous observations that the brains of adult estrogen receptor beta knockout (ERbeta-/-) mice show regional neuronal hypocellularity especially in the cerebral cortex. We now show that ERbeta is necessary for late embryonic development of the brain and is involved in both neuronal migration and apoptosis. At embryonic day (E)18.5, ERbeta-/- mouse brains were smaller than those of the wild-type (WT) littermates, and there were fewer neurons in the cortex. There were no differences in size or cellularity at E14.5. When proliferating cells were labeled with 5'-bromodeoxyuridine (BrdUrd) on E12.5, a time when cortical neurogenesis in mice begins, and examined on E14.5, there was no difference between WT and ERbeta-/- mice in the number of labeled cells in the cortex. However, when BrdUrd was administered between E14.5 and E16.5, a time when postmitotic neurons migrate to layers of the cortex, there were fewer BrdUrd-labeled cells in the superficial cortical layers by E18.5 and postnatal day 14 in mice lacking ERbeta. At E18.5, there were more apoptotic cells in the ventricular zone of mice lacking ERbeta. In addition, the processes of the cortical radial glia, which are essential for guiding the migrating neurons, were fragmented. These findings suggest that by influencing migration and neuronal survival, ERbeta has an important role in brain development.

Animals↗
PubMed2003

Lysophosphatidic acid induces human natural killer cell chemotaxis and intracellular calcium mobilization.

We have investigated the effects of the bioactive lipid lysophosphatidic acid (LPA) on several functions of activated human natural killer (NK) cells. Flow cytometric and immunoblot analyses show that these cells express LPA(1, )LPA(2) and LPA(3). LPA but not its precursor phosphatidic acid (PA) induces the chemotaxis of NK cells, an activity that is inhibited by prior treatment of the cells with pertussis toxin (PTX). In addition, LPA induces the mobilization of intracellular calcium, an effect that is markedly inhibited by PTX, but is not inhibited by the addition of EGTA. PA also induces calcium flux in NK cells, but with much lower efficacy than LPA. Cross-desensitization experiments demonstrate that LPA and PA utilize different receptors. Moreover, LPA or PA but not sphingosine 1-phosphate, enhances IFN-gamma secretion by activated NK cells. Our results may shed some light on the findings that activated NK cells are found at the sites of tumor growth.

Calcium Signaling↗
PubMed2003

Design of physostigmine-loaded polymeric microparticles for pretreatment against exposure to organophosphate agents.

Physostigmine is an anti-cholinesterase used for the pretreatment of a poisoning caused by highly toxic organophosphorus neurotoxins. The aim of this study is to design a polymeric microparticle system for sustained release of physostigmine. In this paper, we have attempted to encapsulate physostigmine in microparticles made from poly(D,L-lactide-co-glycolide) (PLGA) with various contents of glycolide and poly(D,L-lactide) (PLA) using spray-drying and single emulsion techniques. It was found that during the single emulsion process, most of the physostigmine molecules were lost in the external aqueous phase. However, more than 90% encapsulation efficiency of physostigmine was obtained using the spray-drying technique. SEM micrographs revealed that spherical microparticles containing physostigmine with a smooth surface were yielded with PLA, PLGA 50:50, RG 502 (PLGA 50:50 with a lower molecular weight) and PLGA 65:35 but PLGA 85:15, PLGA 75:25 and PLGA 50:50 with a high concentration produced microparticles with irregular shapes. An increased inlet temperature yielded a higher physostigmine release rate from the PLA microparticles. Physostigmine release from the microparticles showed a biphasic pattern, characterized by an initial burst release followed by a sustained release for PLGA 65:35, PLGA 50:50 and RG 502 or a non-detectable release for PLGA 85:15, PLGA 75:25 and PLA. A sustained-release of physostigmine with a low initial burst over 1 week was achieved from RG 502 microparticles, which would be used as an injectable dosage form in our further animal studies.

Biopolymers↗