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Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

At least 181 records · Page 10Linked to original sources
PubMed2001

Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells.

The mechanisms responsible for the divergent physiological responses of endothelial cells to vascular endothelial growth factor (VEGF) are incompletely understood. We hypothesized that VEGF elicits increased endothelial permeability and cell migration via differential activation of intracellular signal transduction pathways. To test this hypothesis, we established a model of VEGF-induced endothelial barrier dysfunction and chemotaxis with bovine pulmonary endothelial cells. We compared the effects of VEGF on transendothelial electrical resistance (TER), actin cytoskeletal remodeling, and chemotaxis of lung endothelial cells and then evaluated the role of the mitogen-activated protein kinases (MAPKs) p38 and extracellular signal-regulated kinase (ERK)1/2 in VEGF-mediated endothelial responses. The dose response of pulmonary arterial and lung microvascular endothelial cells to VEGF differed when barrier regulation and chemotaxis were evaluated. Inhibition of tyrosine kinase, phosphoinositol 3-kinase, or p38 MAPK significantly attenuated VEGF-mediated TER, F-actin remodeling, and chemotaxis. VEGF-mediated decreased TER was also significantly attenuated by inhibition of ERK1/2 MAPK but not by inhibition of fetal liver kinase-1 (flk-1) or Src kinase. In contrast, VEGF-mediated endothelial migration was not attenuated by ERK1/2 inhibition but was abolished by inhibition of either flk-1 or Src kinase. These data suggest potential mechanisms by which VEGF may differentially mediate physiological responses in vivo.

Actins↗
PubMed2001

alpha(1)-Adrenergic receptors activate NHE1 and NHE3 through distinct signaling pathways in epithelial cells.

The Na+/H+ exchanger (NHE) regulates intracellular pH, cell volume, Na+ absorption and H+ secretion in epithelial cells of the renal proximal tubule (PT). alpha(1)-Adrenergic receptors (ARs) increase NHE activity in PT cells. The purpose of this study was to determine the mechanism of alpha(1)-AR activation of NHE isoforms expressed in PT cells. Northern and Western blotting demonstrate transcripts and protein expression of NHE1 and NHE3 in PT cells. An anti-NHE1 antibody predominately labels protein expressed at basal and lateral membranes. In contrast, NHE3 protein is expressed exclusively at the apical membrane. To determine NHE isoforms regulated by alpha(1)-ARs, antisense oligodeoxynucleotides (AS-ODNs) specific for NHE1 and NHE3 isoforms were introduced into cells with streptolysin O permeabilization. Cells incubated with AS-ODNs a total of three times exhibited a reduction in protein expression of ~85%. Na uptake and changes in intracellular pH (pH(i)) were used as measures of NHE activity in PT cells. alpha(1)-AR stimulation increased Na uptake from 8.5 to 13.8 nmol. min(-1). mg protein(-1). AS-ODNs to NHE3 significantly reduced alpha(1)-AR stimulated Na uptake and increases in pH(i); no effect was observed in sense-ODN-treated cells. Inhibition of NHE1 but not NHE3 expression abolishes amiloride-suppressible NHE activity. alpha(1)-AR stimulation of NHE1 is inhibited by the protein kinase C (PKC) inhibitor calphostin C whereas NHE3 activity is abolished by the mitogen-activated protein kinase (MAPK) inhibitor PD-98059. In PT cells transfected with MAPK kinase MEKK1(COOH), a truncated version of MEKK1 that activates MAPK, NHE3 but not NHE1 activity is stimulated. We conclude that alpha(1)-ARs activate distinct signaling pathways to regulate specific NHE isoforms localized on opposite membranes in polarized renal epithelial cells. alpha(1)-AR activation of NHE1 is regulated by PKC whereas NHE3 is controlled by MAPK and serves to separately regulate pH(i), Na absorption, and proton excretion in PT cells.

Animals↗
PubMed2001

Mechanism of heme oxygenase-1 gene induction by curcumin in human renal proximal tubule cells.

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an adaptive and protective response to several inflammatory stimuli. The transcription factor activator protein-1 (AP-1) has been implicated in the activation of the HO-1 gene. To elucidate the molecular mechanism of HO-1 induction, we examined the effects of diferuloylmethane (curcumin), an inhibitor of the transcription factor AP-1. Surprisingly, curcumin by itself was a very potent inducer of HO-1. Curcumin has anti-inflammatory, antioxidant, and renoprotective effects. To evaluate the mechanism of curcumin-mediated induction of HO-1, confluent human renal proximal tubule cells were exposed to curcumin (1-8 microM). We observed a time- and dose-dependent induction of HO-1 mRNA that was associated with increased HO-1 protein. Coincubation of curcumin with actinomycin D completely blocked the upregulation of HO-1 mRNA. Blockade of nuclear factor-kappaB (NF-kappaB) with an IkappaBalpha phosphorylation inhibitor attenuated curcumin-mediated induction of HO-1 mRNA and protein. These data demonstrate that curcumin induces HO-1 mRNA and protein in renal proximal tubule cells. HO-1 induction by curcumin is mediated, at least in part, via transcriptional mechanisms and involves the NF-kappaB pathway.

Antioxidants↗
PubMed2001

Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial cell chemotaxis. Involvement of G(ialpha2)-linked Rho kinase activity.

We compared stimulus-coupling pathways involved in bovine pulmonary artery (PA) and lung microvascular endothelial cell migration evoked by sphingosine-1-phosphate (S1P), a potent bioactive lipid released from activated platelets, and by vascular endothelial growth factor (VEGF), a well-recognized angiogenic factor. S1P-induced endothelial cell migration was maximum at 1 microM (approximately 8-fold increase with PA endothelium) and surpassed the maximal response evoked by either VEGF (10 ng/ml) (approximately 2.5-fold increase) or hepatocyte growth factor (HGF) (approximately 2.5-fold increase). Migration induced by S1P, but not by VEGF, was significantly inhibited by treatment with antisense oligonucleotides directed to Edg-1 and Edg-3 (endothelial differentiation gene) S1P receptors and by G protein modification. These strategies included pretreatment with pertussis toxin, or transfection with mini-genes encoding a betagamma subunit inhibitory peptide of the beta-adrenergic receptor kinase, or an 11-amino-acid peptide that inhibits G(1alpha2) signaling. Various strategies to interrupt Rho family signaling, including C(3) exotoxin, dominant/negative Rho, or the addition of Y27632, a cell-permeable Rho kinase inhibitor, significantly attenuated S1P- but not VEGF-induced migration. Conversely, pharmacologic inhibition of either myosin light chain kinase, src family tyrosine kinases, or phosphatidylinositol-3' kinase reduced basal endothelial cell migration and abolished VEGF-induced endothelial cell migration but did not inhibit the increase in S1P-induced migration. Whereas VEGF and S1P increased both p42/p44 extracellular regulated kinase and p38 mitogen-activated protein (MAP) kinase activities, only p38 MAP kinase inhibition significantly reduced VEGF- and S1P-stimulated migration. These data confirm S1P as a potent endothelial cell chemoattractant through G(1alpha2)-coupled Edg receptors linked to Rho-associated kinase and p38 MAP kinase activation. The divergence in signaling pathways evoked by S1P and VEGF suggests complex and agonist-specific regulation of endothelial cell angiogenic responses.

Animals↗
PubMed2001

Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement.

Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular endothelial cells. This substance also reversed barrier dysfunction elicited by the edemagenic agent thrombin. Sph-1-P-mediated barrier enhancement was dependent upon G(ialpha)-receptor coupling to specific members of the endothelial differentiation gene (Edg) family of receptors (Edg-1 and Edg-3), Rho kinase and tyrosine kinase-dependent activation, and actin filament rearrangement. Sph-1-P-enhanced TER occurred in conjunction with Rac GTPase- and p21-associated kinase-dependent endothelial cortical actin assembly with recruitment of the actin filament regulatory protein, cofilin. Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability.

Actin Depolymerizing Factors↗
PubMed2001

The HMG I proteins: dynamic roles in gene activation, development, and tumorigenesis.

The high mobility group I, Y, and I-C proteins are low-molecular-weight, nonhistone chromosomal proteins that play a general role modulating gene expression during development and the immune response. Consistent with their role in early development, all three proteins are expressed at high levels during embryogenesis, and their expression is markedly diminished in differentiated cells. Exceptions to the general repression of these genes in adult tissues involve (1) A burst of synthesis of the HMG I protein during the immune response (during lymphocyte activation and preceding cytokine/adhesion molecule gene expression), (2) A constitutive expression of the HMG I and Y proteins in photoreceptor cells, and (3) Derepression of HMG I, Y, and often I-C expression in neoplastic cells. Work from several laboratories has now uncovered how these proteins participate in gene activation: (1) By altering the chromatin structure around an inducible gene-and thus influencing accessibility of the locus to regulatory proteins-(2) By facilitating the loading of transcription factors onto the promoters, and (3) By bridging adjacent transcription factors on a promoter via protein/protein interactions. Despite the similar structures and biochemical properties of the three proteins, the work has also provided clues to a division of labor between these proteins. HMG I and Y have demonstrable roles in enhanceosome formation, whereas HMG I-C has a specific role in adipogenesis. C-terminal truncations of HMG I-C and wild-type HMG Y appear to function in a manner analogous to oncogenes, as assessed by cellular transforation assays and transgenic mice. Future work should clearly define the similarities and differences in the biological roles of the three proteins, and should evolve to include attempts at pharmaceutical intervention in disease, based upon structural information concerning HMG I interactions with DNA and with regulatory proteins.

Adipocytes↗
PubMed2001

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.

Biomarkers, Tumor↗
PubMed2001

Absorption spectra of the 4f electron transitions of the praseodymium complex with 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(4-ethyl-1-piperazinyl) -4-oxo-3-quinoline carboxylic acid hydrochloride and its analytical application.

The absorption spectra of the praseodymium complex with 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(4-ethyl-1-piperazinyl)-4-oxo-3- quinoline carboxylic acid hydrochloride (NNFX) has been studied by normal and derivative spectrophotometry. The complex showed maximum absorption at 350 nm at pH 6.0. The stoichiometry of the Pr-NNFX complex was calculated by the molar ratio and continuous variation methods. The ratio of Pr to NNFX was 1:3. The absorption bands of the 4f electron transitions of the praseodymium complex with NNFX are enhanced markedly, especially the wavelength at 481 nm. Using the third-derivative spectrum, the calibration graph is linear over the range 2.5 x 10(-5)-3.5 x 10(-4) mol dm-3 for praseodymium. The detection limits (signal-to-noise ratio of 2) is 1.4 x 10(-6) mol dm-3. The relative standard deviation is 1.2% for 7.0 x 10(-5) mol dm-3 of praseodymium. A method for the direct determination of praseodymium in rare earth mixtures with good accuracy and selectivity is described.

Journal Article↗
PubMed2001

A new molecular target of insulin action: regulating the pivotal PDK1.

Over the last several years, a great level of interest has rallied behind understanding how the pivotal kinase, 3'-phosphoinositide dependent kinase 1 (PDK1) is regulated. PDK1 phosphorylates and activates members of the AGC kinase family shown to be activated downstream of phosphoinositide 3-kinase (P13K); however, the functional dependency of PDK1 on P13K for activation of its targets is less clear. The P13K signaling pathway mediates numerous cellular responses upon growth factor and hormone stimulation. Specifically, P13K signaling influences many of the metabolic and mitogenic functions of the anabolic hormone, insulin. Thus, the regulation of P13K and its downstream targets by insulin has become an important topic for investigation. Given its central role as the kinase upstream of those signaling pathways linked to P13K, the regulation of PDK1 by insulin and other factors is at the height of many of these investigations. Current theories on PDK1 regulation propose substrate conformation and subcellular localization as the primary mediators of PDK1 function. The array of PDK1 substrates suggests, however, that in cells PDK1 may be more tightly regulated. Recent data support phosphorylation as a potential regulatory mechanism that may play an additional role in directing the specificity of PDK1 towards its physiological substrates. The combination of these regulatory mechanisms along with the potential for multiple PDK1 isoforms with select tissue distribution may contribute to the diversified actions of insulin signaling. The targeting of these various aspects of PDK1 regulation may provide for novel therapeutic treatments for diseases such as diabetes and cancer.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2001

[Effect of a complex tea on reducing blood lipid in rabbits].

In order to observe the effect of a complex tea composed of tea, ginkgo leaf, red koji and fructus lycii on reducing blood lipids in experimental rabbits, 40 rabbits weighted from 1.5 to 2.0 kg were divided randomly into 5 group: (I) normal control group, (II) hyperlipidemia model(positive control), (III) green tea control group, (IV) low dose complex tea group, and (V) high dose complex tea group. Blood triglyceride(TG), cholesterol(TC), lower density lipoprotein(LDL) and high density lipoprotein(HDL) were measured before experiment and 6.12 weeks later. Then the pathological changes of heart, aorta and liver were observed. After 12 weeks of experiment, the results showed that, (1) hyperlipidemia characterized by high TC has been induced by high-fat feeds in group II, (2) the complex tea can reduce body weight and eliminate the lipids deposition in aorta and liver. (3) the complex tea can decrease serum TG, TC,LDL and increase serum HDL in the high complex tea group. The results indicate that the complex tea is more effective than green tea on reducing blood lipids in experimental rabbits.

Animals↗
PubMed2001

[Study on abstracting method of high frequency components of ECG].

This paper presents a method to abstract high frequency components from ECG. A new signal averaging method based on vectorcardiographic loop matched alignment is proposed. It improves the crucial estimation of signal averaging and ensures that every one of the cardiographic signals participating in signal averaging comes from the same heart beat, so that each of three leads at least has uniform low pass filter effect. These conclusions have been confirmed by the analysis of ECG in clinical test.

Humans↗
PubMed2001

The role of factor XI in a dilute thromboplastin assay of extrinsic coagulation pathway.

Blood coagulation has been thought to be composed of both intrinsic and extrinsic pathways. Recent evidence strongly supports the critical role of the extrinsic pathway in the initiation of blood coagulation. This investigation established an assay that examines the role of FXI in the thromboplastin-initiated (extrinsic) coagulation based on this new concept. Plasma clotting times were measured at different concentrations of thromboplastin with activated FXII inhibited (FXIIa-inhibited Diluted Thromboplastin Time, FXIIaiDTT). Only at low concentrations of thromboplastin was FXIIaiDTT of FXI-deficient plasma significantly prolonged than that of normal plasma. Depletion of FXI from normal plasma prolonged its FXIIaiDTT and replenishment of FXI shortened it. FXIIaiDTTs of both FVIII-deficient and FIX-deficient plasma were remarkably prolonged, and addition of normal plasma dose-dependently shortened it. Furthermore, earlier alpha-thrombin inhibition was directly correlated with decreasing FXa generation. The amount of FXa production was: platelet-rich plasma > platelet-poor plasma > FXI-deficient plasma. Therefore, our findings from the FXIIaiDTT assays not only support the critical role of extrinsic pathway in blood coagulation initiation, but also demonstrate the importance of FXI as an amplifier of thrombin generation in thromboplastin-initiated coagulation.

Blood Coagulation↗
PubMed2001

[Effects of tumor necrosis factor alpha on the expression of connective tissue growth factor in hepatic stellate cells].

OBJECTIVE: To investigate the effect of tumor necrosis factor alpha (TNF-alpha) on the expression of connective tissue growth factor (CTGF) in rat hepatic stellate cells (HSC) in vitro. METHODS: HSCs were prepared from SD rats by in situ perfusion and single-step Nycodenz gradient, and were treated with TNF-alpha and TGF-beta 1. The expression of CTGF in HSC was assessed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Both TNF-alpha and TGF-beta 1 could stimulate the expression of CTGF mRNA in HSC. The expression of CTGF was not found in HSC after treatment with TNF-alpha(10microgram/L) for 6 hours, but was observed after TNF-alpha treatment for 24 and 48 hours. TGF-beta1 could induce the mRNA expression for CTGF just after 6 hours of treatment at 1microgram/L concentration. CONCLUSIONS: TNF-alpha is able to induce the expression of CTGF in HSC, and this may be one of the mechanisms for TNF-alpha involving in the liver fibrosis.

Animals↗
PubMed2001

[Research development of polylactide and its composites in bone-tissue engineering].

Polylactide has good biocompatibility and biodegradability in the body and is one of the biomaterials approved by FDA. The research development in the application of polylactide(PLA), hydroxylapatite(HA)/ PLA composites and bioactive organic materials/ PLA composites in bone-tissue engineering are reviewed in this paper.

Bone Substitutes↗
PubMed2001

[The establishment of three-dimensional soft tissue facial reconstruction and morphometry].

OBJECTIVE: To establish a digital three-dimensional facial soft tissue morphometry and reconstruction system for orthodontic diagnosis and analysis of the facial soft tissue. METHODS: Three-dimensonal characteristics of facial soft tissue were captured by 4 digital cameras of high resolution. The developed hardware and software system and stereophotogrammetry were used for three-dimensional facial soft tissue reconstruction and morphometry at the same time. RESULTS: The three-dimensional facial soft tissue were successfully reconstructed with high reality and the three dimensional facial image can be rotated, moved and zoomed on the purpose. The system has the following advantages: (1) rapid capture of the facial image within 1 second or so, (2) accurate identification of facial landmark within 0.5 mm of resolution, (3) easy manipulation, (4) no exposure to radiation. CONCLUSIONS: The established system has proved to be effective for three-dimensional facial soft tissue diagnosis and analysis with the advantages of high resolution, high speed and, no exposure to radiation.

Face↗
PubMed2001

Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines transfected with costimulatory B7 gene.

OBJECTIVE: To investigate the effect of U14 vaccine transfected with the B7 gene in inducing antitumor immune response to murine cervical carcinoma in Chinese 615-strain mice. METHODS: A recombinant retroviral plasmid vector expressing mouse B7-1 gene (pLNSX-mB7) was transfected into 615-strain mouse cervical carcinoma cell line No. 14 (U14) by electroporation to set up a highly-expressed mB7-1 U14 cell clonal strain (B7+ U14). In vivo experiments: (1) B7+ U14 vaccine was primed to protect the 615-strain mice against U14 re-challenge. (2) B7+ U14 vaccine was injected into tumor-bearing mice with different tumor sizes. Lifetimes and tumor sizes were recorded. In vitro cytotoxicity assay: Mice were immunized with B7+ U14 or U14 vaccine and 2 weeks later, spleen cells of those mice were cultured for 2 days. The cytotoxicity of these cells against U14 was detected by 5-diphenyl tetrazolium bromide assay. RESULTS: We obtained several B7-1 high expression clonal U14 lines. In vivo experiment, we did not find tumor growing in 3 of the 6 mice primed by B7+ U14 vaccine during their entire life after re-challenge with U14. The other 3 mice developed tumors and their average survival time was longer than that of the control group (P < 0.01). All 6 mice grew tumors in the control group. When the transplanted tumors became palpable, the mice were randomly divided into 3 groups to be injected with B7+ U14 vaccine. It was effective for tumor-bearing mice only when the tumor diameters were < 3 mm. When the diameters were > or = 3 mm, it was not efficacious to inject B7+ U14 vaccine (P < 0.05). In vitro cytotoxicity assay, cytotoxic T lymphocytes induced by B7+ U14 vaccine had a higher cytotoxicity against U14 than that induced by U14 vaccine (F = 310.8, P < 0.001). CONCLUSIONS: Vaccines of cervical cancer cells transfected with the costimulatory molecule B7 gene can induce antitumor immune protection in host mice against U14 re-challenge. This treatment may cure part of the tumor-bearing mice but be restricted by tumor size. The results suggest that transfecting the B7 gene into cervical cancer as a cell vaccine may be an efficient supplementary method to treat cervical cancer after operation.

Animals↗