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Lan Xu

Publications and source records attributed to Lan Xu.

At least 19 recordsLinked to original sources
PubMed2025

Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice.

Food-specific immunoglobulin E (IgE) triggers life-threatening anaphylaxis; however, for unclear reasons, some people with food-specific IgE are asymptomatic upon allergen consumption. We studied strains of mice with different sensitivities to anaphylaxis when orally challenged with allergen to identify possible causes. In resistant C57BL/6 mice, intestinal goblet cells transported less food allergen than did anaphylaxis-susceptible strains, even before allergic sensitization. In a forward genetic screen, resistance was correlated with dipeptidase 1 (Dpep1) variants. DPEP1 is expressed in intestinal epithelium and catabolizes leukotriene D4 (LTD4). Blocking DPEP1 with cilastatin, deleting Dpep1, or administering LTD4 orally enhanced allergen transport in resistant mice. Conversely, pretreatment of susceptible mice with a synthesis inhibitor, zileuton, abrogated allergen absorption and oral anaphylaxis, indicating that this could be an approach to treating food allergy.

Animals↗
PubMed2006

Regulation of Smad activities.

TGF-beta (Transforming Growth Factor-beta) cytokines employ Smad proteins as the intracellular mediator of signaling. Upon TGF-beta stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression. The cytoplasm-to-nucleus redistribution of Smads, as well as the ability of Smads to activate or repress gene transcription, is under multiple layers of regulation by factors not limited to TGF-beta. With recent advance in the knowledge of regulatory factors impinged on Smads, we are beginning to understand the complexity in cellular responses to TGF-beta.

Animals↗
PubMed2006

Role of fibrillar structure of collagenous carrier in bone sialoprotein-mediated matrix mineralization and osteoblast differentiation.

To investigate the effects of the microstructure of collagenous carriers on the in vivo function of bone sialoprotein (BSP) in mineralization and osteoblast differentiation, we examined the ultrastructure of reconstituted type I collagen (collagen) and heat-denatured collagen (gelatin) and the in vivo responses to purified bone-derived BSP that was implanted with collagen or gelatin into surgically created 8-mm rat calvarial bone defects. Scanning and transmission electron microscopies revealed that the collagen displayed a fine fibrillar structure with interconnecting spaces between the fibrils/fibers, while the gelatin completely lost this unique three-dimensional structure after denaturation. The rates of in vivo release of BSP from the collagen scaffold were significantly lower than those from the gelatin. Collagen-BSP, but not gelatin-BSP, induced early mineral deposition in the matrix of proliferating repair cells in the calvarial defects at approximately 4-7 days after implantation. Expression levels of osteoblast markers, alkaline phosphatase activity and amounts of new bone synthesized in the collagen-BSP treated defects were significantly greater than that in the gelatin-BSP treated defects (p<0.001). The data suggest that the fibrillar microstructure of reconstituted collagen is essential for retaining BSP at a higher concentration within the defects, which enhances BSP-mediated matrix mineralization and osteoblast differentiation during the repair of rat calvarial defects.

Amino Acids↗
PubMed2006

Nanoporous crystals of chicken embryo lethal orphan (CELO) adenovirus major coat protein, hexon.

CELO (chicken embryo lethal orphan) virus is an avian adenovirus that is being developed as a gene transfer vector. Its trimeric major coat protein (942 residues, 106,709 Da) has 42% sequence identity to human adenovirus type 2 (AdH2) hexon and 45% to AdH5 hexon. For structural studies, the growth of CELO virus has been optimized, and its hexon purified and crystallized. The hexon crystals, the first non-human example, diffract to 3.9 A resolution. Molecular replacement using the AdH5 model was used to identify the location of the CELO hexon within the unit cell. There is one hexon monomer in the asymmetric unit of the trigonal space group P321 (a=b=157.8 A, c=114.2 A, gamma=120 degrees) and the solvent content is 67.8%. The hexons pack in a hexagonal honeycomb so that large approximately 100 A diameter channels run through the entire crystal. This remarkable property of the crystals lends itself to their exploitation as a nanomaterial. Structural studies on CELO will elucidate the differences between avian and human adenoviruses and contribute to a better understanding of adenoviruses with non-human hosts.

Amino Acid Sequence↗
PubMed2006

Site-specific in vivo calcification and osteogenesis stimulated by bone sialoprotein.

Bone sialoprotein (BSP) is one of the major non-collagenous glycosylated phosphoproteins of the extracellular matrix in bone. In vitro studies suggest that BSP may play important roles in the initiation and/or growth of calcium-phosphate crystals. To investigate the potential role of BSP in more complex in vivo environments, we implanted purified bovine BSP with type-I collagen as a carrier into surgically created rat calvarial defects and thoracic subcutaneous pouches. The responses to the implants were assessed by histochemistry, immunohistochemistry, in situ hybridization, quantitative real-time PCR, and biochemical analyses. BSP-collagen, but not collagen alone, elicited mineral deposition in the matrix of proliferating cells near the dura at days 4-5 followed by osteoblast differentiation and synthesis of new bone in the mid-portion of the calvarial defects. In contrast, implantation of BSP-collagen into subcutaneous pouches did not induce calcification or osteogenesis over the same experimental period. We explored the underlying mechanisms for the site-specific responses to BSP-collagen implants and found that higher levels of calcium content and alkaline phosphatase activity at the cranial site at days 2-5 were associated with the BSP-mediated calcification. We also found that BSP stimulated osteoblast differentiation through up-regulation of cbfa1 and osterix, key transcription factors of osteoblast differentiation, which occurred in the calvarial defects but not in the subcutaneous tissue. These results demonstrate that BSP stimulates calcification and osteogenesis in a site-specific manner, and that local environment and the specificities of responding cells may play critical roles in the function of BSP in vivo.

Alkaline Phosphatase↗
PubMed2006

Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase.

Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors. Herein we report the discovery of a potent, nonpolyglutamatable, and selective inhibitor of GAR Tfase. Compound 12, which possesses a tetrazole in place of the gamma-carboxylic acid in the l-glutamate subunit of the potent GAR Tfase inhibitor 1, was active in cellular-based functional assays exhibiting purine-sensitive cytotoxic activity (IC(50) = 40 nM, CCRF-CEM) and was selective for inhibition of rhGAR Tfase (K(i) = 130 nM). Notably, 12 was only 2.5-fold less potent than 1 in cellular assays and 4-fold less potent against rhGAR Tfase. Like 1, this functional activity of 12 in the cell-based assay benefits from and requires transport into the cell by the reduced folate carrier but, unlike 1, is independent of folyl polyglutamate synthase (FPGS) expression levels and polyglutamation.

Aminobutyrates↗
PubMed2006

Identification of phosphatases for Smad in the BMP/DPP pathway.

Phosphorylation of the SSXS motif of Smads is critical in activating the transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) pathways. However, the phosphatase(s) involved in dephosphorylating and hence inactivating Smads remained elusive. Through RNA interference (RNAi)-based screening of serine/threonine phosphatases in Drosophila S2 cells, we identified pyruvate dehydrogenase phosphatase (PDP) to be required for dephosphorylation of Mothers against Decapentaplegic (MAD), a Drosophila Smad. Biochemical and genetic evidence suggest that PDP directly dephosphorylates MAD and inhibits signal transduction of Decapentaplegic (DPP). We show that the mammalian PDPs are important in dephosphorylation of BMP-activated Smad1 but not TGF-beta-activated Smad2 or Smad3. Thus, PDPs specifically inactivate Smads in the BMP/DPP pathway.

Animals↗
PubMed2006

Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF.

Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.

Animals↗
PubMed2006

Highly selective iodide electrode based on the copper(II)-N,N'-bis(salicylidene)-1,2-bis(p-aminophenoxy)ethane tetradentate complex.

In this paper, a new PVC-based liquid-membrane anion-selective electrode based on a copper(II) of N,N'-bis(salicylidene)-1,2-bis(p-aminophenoxy)ethane tetradentate complex (Cu(II)BBAP) is described, which displays a preferential potentiometric response to iodide ion at pH 2.0 and an anti-Hofmeister selectivity sequence: I->SCN->ClO4->NO2->H2PO4->NO3->SO4(2-)>Br->Cl-. The electrode exhibits a near-Nernstian potential linear range of 8.2x10(-7)-1.0x10(-1) M with a detection limit of 5.3x10(-7) M and a slope of -58.8 mV per decade. The A.C. impedance technique and the UV/Vis spectroscopy technique were used to analyze the response mechanism. The electrode could be applied to determine iodide in medicine analysis, and the obtained results were fairly satisfactory.

Journal Article↗
PubMed2006

[Mentality and behavior of children suffering from viral myocarditis].

OBJECTIVE: The present study was designed to investigate the influence of viral myocarditis on mental behavior of the children. METHODS: Mentality and behavior of the 178 children suffering from viral myocarditis were examined with Achenbach Child Behavior Checklist (CBCL) edited by Gong Yao-xian in 1986 and 104 sex, age, education and achievement-matched children with pneumonia or upper respiratory infection were enrolled as controls. RESULTS: The mentality and behavior of the children with viral myocarditis were distinctly abnormal. The abnormal rates of boys and girls suffering from acute and deferment viral myocarditis were evidently higher than those of control children (P < 0.01). The behavioral abnormalities of boys were hypochondria, social difficulties, unwell of body and attack. Whereas, the girls presented hypochondria, unwell of body, social flinch and disobeyed discipline, which was significantly different from the control children. The total and hypochondria cursory mark of the second check result of deferment boys were evidently higher than those of the first check (P < 0.05). The total cursory mark of the second check result of deferment girls was higher than that of the first check (P < 0.05) and evidently higher than that of the acute second check result (P < 0.01). The abnormal rates of mentality and behavior correlated positively with the age of children and they were associated with the severity of the illness. CONCLUSION: Viral myocarditis evidently affected the mentality and behavior of children, which should be paid great attention to.

Acute Disease↗
PubMed2005

Effects of dendritic cells from cord blood CD34+ cells on human hepatocarcinoma cell line BEL-7402 in vitro and in SCID mice.

AIM: To develop a cancer vaccine of dendritic cells derived from human cord blood CD34+ cells and to investigate its cytotoxicity on human hepatocarcinoma cells in vitro and in severe combined immunodeficiency (SCID) mice. METHODS: Lymphocytes from cord blood or peripheral blood were primed by DCs, which were derived from cord blood and pulsed with whole tumor cell lysates. Nonradiative neutral red uptake assay was adopted to detect the cytotoxicity of primed lymphocytes on human hepatocarcinoma cell line BEL-7402 in vitro. The anti-tumor effect of primed lymphocytes in vivo was detected in SCID mice, including therapeutic effect and vaccination effect. RESULTS: The cytotoxicity of DC vaccine primed lymphocytes from cord blood or peripheral blood on human hepatocarcinoma cell line BEL-7402 was significantly higher than that of unprimed lymphocytes in vitro (44.09% vs 14.69%, 47.92% vs 19.44%, P<0.01). There was no significant difference between the cytotoxicity of primed lymphocytes from cord blood and peripheral blood (P>0.05). The tumor growth rate and tumor size were smaller in SCID mice treated or vaccinated with primed lymphocytes than those with unprimed lymphocytes. SCID mice vaccinated with primed lymphocytes had a lower tumor incidence (80% vs 100%, P<0.05) and delayed tumor latent period compared with mice vaccinated with unprimed lymphocytes (11 d vs 7 d, P<0.01). CONCLUSION: Vaccine of cord blood derived-DCs has an inhibitory activity on growth of human hepatocarcinoma cells in vitro and in SCID mice. The results also implicate the potential role of cord blood derived-DC vaccine in clinical tumor immunotherapy.

Animals↗
PubMed2005

Nuclear targeting of transforming growth factor-beta-activated Smad complexes.

Upon stimulation by the transforming growth factor beta (TGF-beta), Smad2 and Smad3 are phosphorylated at their C termini and assemble into stable heteromeric complexes with Smad4. These complexes are the functional entities that translocate into the nucleus and regulate the expression of TGF-beta target genes. Here we report that the TGF-beta-activated phospho-Smad3/Smad4 complex utilizes an importin-independent mechanism for nuclear import and engages different nucleoporins for nuclear import compared with the monomeric Smad4. Within the heteromeric complex, phospho-Smad3 appears to dominate over Smad4 in the nuclear import process and guides the complex to its nuclear destination. We also demonstrate that the binding of phospho-Smad3 to Smad4 prevents Smad4 from interacting with the nuclear export receptor chromosome region maintenance 1. In this way, TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and thereby targets Smad4 into the nucleus. Indeed tumorigenic mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta.

Active Transport, Cell Nucleus↗
PubMed2005

A novel salicylate-selective electrode based on a Sn(IV) complex of salicylal-imino acid Schiff base.

A novel poly(vinyl chloride) membrane electrode with high selectivity toward salicylate (Sal-), based on the use of the salicylal-imino acid Schiff base dibenyl complex of Sn(IV) [Sn(IV)-SIADBen] as ionophore is described. The influence of lipophilic charged additives on the performance of the electrode was studied. The results suggested that Sn(IV)-SIADBen according to a positively-charged carrier mechanism. The influence of several other variables was investigated in order to optimize the potentiometric response and selectivity of the electrode. The electrode based on Sn(IV)-SIADBen, with 30.44 wt% PVC, 64.55 wt% plasticizer [dioctyl phthalate (DOP)], 3.81 wt% ionophore, and 1.2 wt% anionic additive exhibited a linear response for the Sal- ion over the concentration range 1.0x10(-1) to 2.5x10(-6) mol l-1, and displayed an anti-Hofmeister selectivity sequence as follows: salicylate>>perchlorate>thiocyanate>benzoate>iodide>nitrate>chloride>nitrite approximately acetate>citrate>sulfate. UV-Visible absorption spectra were used to examine the specific interaction of salicylate with the ionophore. The electrode was applied to clinical medical analysis, and the results obtained were consistent with those obtained by conventional methods.

Journal Article↗
PubMed2005

Study on the immobilization of anti-IgG on Au-colloid modified gold electrode via potentiometric immunosensor, cyclic voltammetry, and electrochemical impedance techniques.

The immobilization of anti-IgG on Au-colloid modified gold electrodes has been investigated. A cleaned gold electrode was first immersed in a mercaptoethylamine (AET) solution, and then gold nanoparticles were chemisorbed onto the thiol groups of the mercaptoethylamine. Finally, anti-IgG was adsorbed onto the surface of the gold nanoparticles. Potentiometric immunosensor, cyclic voltammetry, and electrochemical impedance techniques were used to investigate the immobilization of anti-IgG on Au colloids. In the impedance spectroscopic study, an obvious difference of the electron transfer resistance between the Au-colloid modified electrode and the bare gold electrode was observed. The cyclic voltammogram tends to be more irreversible with increased anti-IgG concentration. Using the potentiometric immunosensor, the proposed technique is based on that the specific agglutination of antibody-coated gold nanoparticles, averaging 16 nm in diameter, in the presence of the corresponding antigen causes a potential change that is monitored by a potentiometry. It is found that the developed immunoagglutination assay system is sensitive to the concentration of IgG antigen as low as 12 ng mL(-1). Experimental results showed that the developed technique is in satisfactory agreement with the ELISA method, and that gold nanoparticles can be used as a biocompatible matrix for antibody or antigen immobilization.

Biocompatible Materials↗
PubMed2005

MyD88-dependent induction of allergic Th2 responses to intranasal antigen.

MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal antigen; thus we demonstrate what we believe to be a novel role for MyD88 in pulmonary Th2 immunity. Induction of the MyD88-independent type I IFN response to LPS is defective in the pulmonary environment. Moreover, in the absence of MyD88, LPS-induced upregulation of costimulatory molecule expression on pulmonary DCs is defective, in contrast to what has been observed with bone marrow-derived DCs (BMDCs). Reconstitution of Th2 responses occurs upon adoptive pulmonary transfer of activated BMDCs to MyD88-deficient recipients. Furthermore, the dependence of Th2 responses on MyD88 is governed by the initial route of antigen exposure; this demonstrates what we believe are novel site-specific innate mechanisms for control of adaptive Th2 immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Potentiometric membrane electrode for salicylate based on an organotin complex with a salicylal Schiff base of amino acid.

A novel salicylate-selective electrode based on an organotin complex with a salicylal Schiff base of amino acid salicylaldehydeaminoacid-di-n-butyl-Sn(IV) [Sn(IV)-SAADB] as ionophore is described, which exhibits high selectivity for salicylate over many other common anions with an anti-Hofmeister selectivity sequence: Sal- >> PhCOO- > SCN- > Cl04- > I- > NO3- > NO2- > Br- > Cl- > CH3COO-. The electrode, based on Sn(IV)-SAADB, with a 30.44 wt% PVC, a 65.45 wt% plasticizer (dioctyl phthalate, DOP), a 3.81 wt% ionophore and a 0.3 wt% anionic additive is linear in 6.0 x 10(-6) - 1.0 x 10(-1) mol l(-1) with a detection limit of 2.0 x 10(-6) mol l(-1) and a slope of 62.0 +/- 1.2 mV/decade of salicylate concentration in a phosphate buffer solution of pH 5.5 at 25 degrees C. The influence on the electrode performances by lipophilic charged additives was studied, and the possible response mechanism was investigated by UV spectra. The electrode was applied to medicine analysis and the result obtained has been satisfactory.

Amino Acids↗
PubMed2005

Evaluation of the ES-2re Dummy in Biofidelity, Component, and Full Vehicle Crash Tests.

This technical paper presents the results from tests conducted with the ES-2re, a version of the ES-2 side impact dummy that was modified by the National Highway Traffic Safety Administration (NHTSA) to improve its performance in crash tests. Through the series of biofidelity tests conducted on the ES-2re, described in International Standards Organization (ISO) Technical Report (TR)9790 (1999), the OSRP observed a final overall biofidelity ranking of 4.1 for the ES-2re, which corresponds to an ISO classification of "marginal." The biofidelity of the ES-2re is compared to that of the ES-2 and the WorldSID. Repeatability was also evaluated on the ES-2re based on the biofidelity test data. Additional pendulum tests were performed to assess the response of the dummy in oblique loading conditions, and results indicate that oblique loading from the front leads to significantly reduced rib deflections. To evaluate inconsistencies observed in the response of the ES-2, the OSRP analyzed the shoulder biofidelity via additional sled and drop tests. Due to the shoulder design of the ES-2 and ES-2re, the dummies appear to have significant sensitivity to initial conditions, potentially increasing variability in full vehicle tests. Finally, the responses of the ES-2re in full vehicle tests are compared to those of the ES-2 and the WorldSID.

Journal Article↗