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Biomedical subjects

Wei Liu

Publications and source records attributed to Wei Liu.

At least 199 records · Page 11Linked to original sources
PubMed2005

[Human adipose derived stem cells suppress lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli].

OBJECTIVE: To study immunological properties of adipose derived stem cells (ADSC) and their in vitro immunomodulatory effects on lymphocytes. METHODS: ADSC was isolated from fat tissue by liposuction and culture expanded. Cells at passage 2 were observed for the expression of HLAI, HLAII by FACs analysis. Peripheral blood lymphocytes (PBL) were cultured with allogeneic ADSCs at dose of 1 x 10(5). A third-party ADSCs at dose of 1 x 10(2), 1 x 10(3), 1 x 10(4), 1 x 10(5) were added to the ongoing two-way mixed lymphocyte reactions (MLR) for 6 days. Value of CPM (count per minute) was calculated with luminescence counter. RESULTS: Flow cytometry showed that undifferentiated ADSCs express HLA class I but not class II. Addition of interferon gamma (IFN-gamma) for 48 hours induced greater than 90% of cells to express HLA class II. No lymphocyte response was induced by allogeneic ADSCs as stimulators. Results were similar using ADSCs pretreated with IFN-gamma. ADSCs elicited inhibit function of mixed lymphocyte cultures in a dose dependent way. Even if ADSCs were pretreated with IFN-gamma, the suppression ability was maintained. CONCLUSION: Undifferentiated ADSCs do not elicit alloreactive lymphocyte proliferative responses and could modulate immune responses in vitro.

Adipocytes↗
PubMed2005

Threshold-specific requirements for Bmp4 in mandibular development.

Mandibular development is regulated by an interplay between a specified branchial arch ectoderm and a plastic mesenchyme. Moreover, signaling from the pharyngeal endoderm has been shown to be important for mandibular morphogenesis. To gain insight into the mechanisms regulating mandibular pattern, it is important to investigate the function of the epithelial-derived signals. Bmp4 is expressed in both distal, mandibular arch ectoderm and pharyngeal endoderm. Here, we show that deletion of Bmp4 in the mandibular ectoderm and to a lesser extent in the pharyngeal endoderm, resulted in severe defects in mandibular development. Furthermore, our data uncovered different Bmp4 thresholds for expression of the Bmp-dependent Msx1 and Msx2 genes in mandibular mesenchyme. We also found that ectodermal Fgf8 expression was both activated and repressed by Bmp4 in a dosage-dependent fashion indicating a novel Bmp4 function in threshold-specific regulation of Fgf8 transcription. Lastly, we provide evidence that Prx homeobox genes repress expression of an Msx2 transgene, previously shown to be Bmp4-responsive, revealing a mechanism for differential regulation of Msx1 and Msx2 by Bmp signaling.

Animals↗
PubMed2005

Coinfection with HIV and hepatitis C virus among injection drug users in southern China.

BACKGROUND: We sought to examine coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) among injection drug users (IDUs) in Guangxi, China. METHODS: A longitudinal cohort of IDUs (547 subjects) was established to study risk factors for bloodborne infections. At each visit, participants completed questionnaires defining demographic characteristics, patterns of drug use, and sexual behaviors. Blood samples were collected and analyzed for the presence and genotype of HIV and HCV. RESULTS: Coinfection with HIV and HCV was found in 17.6% of the IDUs. HCV was present in 95.1% of HIV-positive and 70.4% of HIV-negative heroin users. The prevalence of HIV in HCV-positive and HCV-negative heroin users was 23.4% and 3.6%, respectively. Multivariate logistic regression analysis revealed that sexual activity during the past 6 months and duration of injection drug use were significantly associated with coinfection with HIV and HCV. The main circulating HCV genotypes included 6a (38%), 3b (37%), and 1a (19%), whereas genotypes 6e (4%), 3a (2%), and 1b (1%) were present in only a few IDUs. Multiple HCV genotypes were present at each study site and did not segregate by HIV status or subtype. CONCLUSIONS: HCV is highly prevalent in IDUs throughout southern China. In Guangxi, HIV infections are the result of parenteral and sexual transmission, and, therefore, all IDUs are at high risk of coinfection with HIV and HCV. Molecular tracking of HCV may be a more sensitive predictor of the future spread of the HIV-1 epidemic than is HIV subtyping. This study emphasizes that, without implementation of injection prevention and primary substance abuse programs in China, the extent and effect of coinfection with HIV and HCV will only increase.

Adult↗
PubMed2005

Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823.

AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA. METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR. RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells was exposed to GA for 24, 48 and 72 h, the IC(50) value were 1.02+/-0.05, 1.41+/-0.20 and 1.14+/-0.19 micromol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by Annexin-V/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 micromol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR. CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo.

Animals↗
PubMed2005

Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema.

Th1/Tc1 inflammation and remodeling responses characterized by tissue atrophy and destruction frequently coexist in human diseases and disorders. However, the mechanisms that are used by Th1/Tc1 cytokines, like IFN-gamma, to induce these responses have not been defined. To elucidate the mechanism(s) of IFN-gamma-induced tissue remodeling and destruction, we characterized the pathway that lung-targeted, transgenic IFN-gamma uses to induce alveolar remodeling in a murine pulmonary emphysema modeling system. In these mice, transgenic IFN-gamma caused epithelial cell DNA injury and apoptosis detectable with TUNEL (Roche) and dual annexin V and propidium iodide staining. These responses were associated with death receptor and mitochondrial apoptosis pathway activation. Importantly, apoptosis inhibition with a caspase inhibitor (N-benzylcarboxy-Val-Ala-Asp-fluoromethyl-ketone) or a null mutation of caspase-3 blocked this DNA injury and apoptosis response and significantly ameliorated IFN-gamma-induced emphysema. These interventions also ameliorated IFN-gamma-induced inflammation and decreased pulmonary protease burden. Selective cathepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury, apoptosis, emphysema, inflammation, and protease accumulation. These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a critical event in the pathogenesis of IFN-gamma-induced alveolar remodeling and emphysema. They also link inflammation, protease/antiprotease alterations, and protease-dependent apoptosis in the pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive responses.

Animals↗
PubMed2005

Differential proteomic analysis of bronchoalveolar lavage fluid in asthmatics following segmental antigen challenge.

Allergic asthma is characterized by persistent airway inflammation and remodeling. Bronchoalveolar lavage conducted with fiberoptic bronchoscopy has been widely used for investigating the pathogenesis of asthma and other lung disorders. Identification of proteins in the bronchoalveolar lavage fluid (BALF) and their expression changes at different stages of asthma could provide further insights into the complex molecular mechanisms involved in this disease. In this report, we describe the first comprehensive differential proteomic analysis of BALF from both asthmatic patients and healthy subjects before and 24 h after segmental allergen challenge. Our proteomic analysis involves affinity depletion of six abundant BALF proteins, SDS-PAGE fractionation, protein in-gel digestion, and subsequent nano-LC-MS/MS analysis in conjunction with database searching for protein identification and semiquantitation. More than 1,500 distinct proteins were identified of which about 10% displayed significant up-regulation specific to the asthmatic patients after segmental allergen challenge. The differentially expressed proteins represent a wide spectrum of functional classes such as chemokines, cytokines, proteases, complement factors, acute phase proteins, monocyte-specific granule proteins, and local matrix proteins, etc. The majority of these protein expression changes are closely associated with many aspects of the pathophysiology of asthma, including inflammation, eosinophilia, airway remodeling, tissue damage and repair, mucus production, and plasma infiltration. Importantly a large portion of these proteins and their expression changes were identified for the first time from BALF, thus providing new insights for finding novel pathological mediators and biomarkers of asthma.

Adult↗
PubMed2005

One-dimensional Ising model built on small-world networks: competing dynamics.

In this paper, we offer a competing dynamic analysis of the one-dimensional Ising model built on the small-world network (SWN). Adding-type SWNs are investigated in detail using a simplified Hamiltonian of mean-field nature, and the result of rewiring-type is given because of the similarities of these two typical networks. We study the dynamical processes with competing Glauber mechanism and Kawasaki mechanism. The Glauber-type single-spin transition mechanism with probability p simulates the contact of the system with a heat bath and the Kawasaki-type dynamics with probability 1-p simulates an external energy flux. By studying the phase diagram obtained in the present work, we can realize some dynamical properties influenced by the small-world effect.

Journal Article↗
PubMed2005

Hepatic venoconstriction is involved in anaphylactic hypotension in rats.

We determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats and the effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused rat livers. In anesthetized rats sensitized with ovalbumin (1 mg), an intravenous injection of 0.6 mg ovalbumin caused not only a decrease in systemic arterial pressure from 120 +/- 9 to 43 +/- 10 mmHg but also an increase in portal venous pressure that persisted for 20 min after the antigen injection (the portal hypertension phase). The elimination of the splanchnic vascular beds, by the occlusions of the celiac and mesenteric arteries, combined with total hepatectomy attenuated anaphylactic hypotension during the portal hypertension phase. For the isolated perfused rat liver experiment, the livers derived from sensitized rats were hemoperfused via the portal vein at a constant flow. Using the double-occlusion technique to estimate the hepatic sinusoidal pressure, presinusoidal (R(pre)) and postsinusoidal (R(post)) resistances were calculated. An injection of antigen (0.015 mg) caused venoconstriction characterized by an almost selective increase in R(pre) rather than R(post) and liver weight loss. Taken together, these results suggest that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably because of anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension.

Anaphylaxis↗
PubMed2005

Interactions of lysozyme in guanidinium chloride solutions from static and dynamic light-scattering measurements.

The interactions of partially unfolded proteins provide insight into protein folding and protein aggregation. In this work, we studied partially unfolded hen egg lysozyme interactions in solutions containing up to 7 M guanidinium chloride (GdnHCl). The osmotic second virial coefficient (B(22)) of lysozyme was measured using static light scattering in GdnHCl aqueous solutions at 20 degrees C and pH 4.5. B(22) is positive in all solutions, indicating repulsive protein-protein interactions. At low GdnHCl concentrations, B(22) decreases with rising ionic strength: in the absence of GdnHCl, B(22) is 1.1 x 10(-3) mLmol/g(2), decreasing to 3.0 x 10(-5) mLmol/g(2) in the presence of 1 M GdnHCl. Lysozyme unfolds in solutions at GdnHCl concentrations higher than 3 M. Under such conditions, B(22) increases with ionic strength, reaching 8.0 x 10(-4) mLmol/g(2) at 6.5 M GdnHCl. Protein-protein hydrodynamic interactions were evaluated from concentration-dependent diffusivity measurements, obtained from dynamic light scattering. At moderate GdnHCl concentrations, lysozyme interparticle interactions are least repulsive and hydrodynamic interactions are least attractive. The lysozyme hydrodynamic radius was calculated from infinite-dilution diffusivity and did not change significantly during protein unfolding. Our results contribute toward better understanding of protein interactions of partially unfolded states in the presence of a denaturant; they may be helpful for the design of protein refolding processes that avoid protein aggregation.

Animals↗
PubMed2005

Helix packing and orientation in the transmembrane dimer of gp55-P of the spleen focus forming virus.

gp55-P is a dimeric membrane protein with a single transmembrane helix that is coded by the env gene of the polycythemic strain of the spleen focus forming virus. gp55-P activates the erythropoietin (Epo) receptor through specific transmembrane helix interactions, leading to Epo-independent growth of erythroid progenitors and eventually promoting erythroleukemia. We describe the use of magic angle spinning deuterium NMR to establish the structure of the transmembrane dimer of gp55-P in model membranes. Comparison of the deuterium lineshapes of leucines in the center (Leu(396-399)) and at the ends (Leu(385), Leu(407)) of the transmembrane sequence shows that gp55-P has a right-handed crossing angle with Leu(399) packed in the dimer interface. We discuss the implications of the structure of the gp55-P transmembrane dimer for activation of the Epo receptor.

Cell Membrane↗
PubMed2005

1alpha,25-Dihydroxyvitamin D3 targets PTEN-dependent fibronectin expression to restore thyroid cancer cell adhesiveness.

We have previously reported that the hormonal form of 1alpha,25-dihydroxyvitamin D3 (1,25-VD3), and its noncalciomimetic analog EB1089, arrest the growth of human thyroid cancer cells by increasing the cell cycle inhibitor p27. In the present study, we investigated whether the tumor-suppressive effects of vitamin D (VD) compounds may also be mediated by mechanisms that govern cell adhesiveness. Both 1,25-VD3 and EB1089 increased cell adhesiveness, an effect that was accompanied by consistent increases in fibronectin (FN) expression. Introduction of small interfering RNA against FN resulted in down-regulation of FN expression and diminished cell adhesiveness to a collagen-type I matrix. To determine whether this action of 1,25-VD3 was mediated through the PTEN/phosphoinositol 3-kinase pathway, we examined whether this tumor suppressor protein/dual phosphatase can influence FN expression and consequently cell adhesiveness Overexpression of wild-type PTEN induced FN expression as well as cell adhesiveness. In contrast, introduction of mutant forms of PTEN failed to induce FN and led to diminished cell adhesiveness. Conversely, small interfering RNA-mediated PTEN down-regulation attenuated FN expression as well as cell adhesiveness. The attenuated FN expression was also associated with relative insensitivity to 1,25-VD3 growth-suppressive action. Cells down-regulated for FN demonstrated a more aggressive growth pattern in xenografted mice and were also relatively insensitive to 1,25-VD3 treatment. Taken together, our findings highlight the significance of FN in modulating thyroid cancer cell adhesiveness and, at least in part, in mediating VD actions on neoplastic cell growth.

Animals↗
PubMed2005

Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors.

A novel class of furo[2,3-d]pyrimidines has been discovered as potent dual inhibitors of Tie-2 and VEGFR2 receptor tyrosine kinases (TK) and a diarylurea moiety at 5-position shows remarkably enhanced activity against both enzymes. One of the most active compounds, 4-amino-3-(4-((2-fluoro-5-(trifluoromethyl)phenyl)amino-carbonylamino)phenyl)-2-(4-methoxyphenyl)furo[2,3-d]pyrimidine (7k) is <3 nM on both TK receptors and the activity is rationalized based on the X-ray crystal structure.

3T3 Cells↗
PubMed2005

[Expressions of aquaporin-1 on peritonea in hepatic cirrhotic rats with ascites].

OBJECTIVE: To investigate the changes of aquaporin (AQP-1) expressions on peritonea in liver cirrhotic rats with ascites, and to study the correlation between AQP-1 expressions and ascites form. METHODS: 32 healthy Sprague-Dawley (SD) rats were divided into two groups randomly, 20 rats were used to produce liver cirrhotic models induced with phenobarbitol sodium and CCl(4). The distribution and protein expressions of AQP-1 on the rats' peritonea were measured with immunohistochemistry assay, and the expressions of APQ-1 mRNA were tested with relative GAPDH quantitative RT-PCR. RESULTS: (1) The expressions of AQP-1 were mainly on the endothelial cells of capillary vessels and venules on the rats' peritonea, and also on mesothelial cells. (2) There was no statistically significant difference between the expressions of AQP-1 protein and mRNA in the two groups on the early stage of liver cirrhosis. (3) Downregulations of the expressions of AQP-1 protein and mRNA were observed in B group on the advanced cirrhotic stage. CONCLUSION: Expressions of AQP-1 were downregulated on the peritonea of rats with decompensated liver cirrhosis, which may play a role in the formation of ascites. The changes of AQP-1 Expressions on peritoneal mesothelial cells which were fewer than those on the endothelial cells may be few relations to ascites form.

Animals↗
PubMed2005

ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells.

Secretory protein trafficking relies on the COPI coat, which by assembling into a lattice on Golgi membranes concentrates cargo at specific sites and deforms the membranes at these sites into coated buds and carriers. The GTPase-activating protein (GAP) responsible for catalyzing Arf1 GTP hydrolysis is an important part of this system, but the mechanism whereby ArfGAP is recruited to the coat, its stability within the coat, and its role in maintenance of the coat are unclear. Here, we use FRAP to monitor the membrane turnover of GFP-tagged versions of ArfGAP1, Arf1, and coatomer in living cells. ArfGAP1 underwent fast cytosol/Golgi exchange with approximately 40% of the exchange dependent on engagement of ArfGAP1 with coatomer and Arf1, and affected by secretory cargo load. Permanent activation of Arf1 resulted in ArfGAP1 being trapped on the Golgi in a coatomer-dependent manner. These data suggest that ArfGAP1, coatomer and Arf1 play interdependent roles in the assembly-disassembly cycle of the COPI coat in vivo.

ADP-Ribosylation Factor 1↗
PubMed2005

A kinetic model and its parameter estimation for the process of binding copper to human serum albumin by a voltammetric method.

Linear sweep anodic stripping voltammetry was applied to determine the concentration of free copper ions in the process of binding copper to human serum albumin (HSA) on the mercaptoethane sulfonate modified gold electrode surface. A kinetic model of two consecutive steps for the process of binding copper to HSA was first proposed on the basis of the electrochemical results and compared with a parallel kinetic response model by using residual analysis. The experimental data of the stripping peak currents with time was fitted according to the model and the kinetic parameters, binding rate constants, k1 and k2, were estimated to be 0.411 and 0.055 min(-1), respectively.

Copper↗
PubMed2005

Structural role of glycine in amyloid fibrils formed from transmembrane alpha-helices.

Amyloid fibrils associated with diseases such as Alzheimer's are often derived from the transmembrane helices of membrane proteins. It is known that the fibrils have a cross-beta-sheet structure where main chain hydrogen bonding occurs between beta-strands in the direction of the fibril axis. However, the structural basis for how the membrane-spanning helix is converted into a beta-sheet or how protofibrils associate into fibrils is not known. Here, we use a model peptide corresponding to a portion of the single transmembrane helix of glycophorin A to investigate the structural role of glycine in amyloid-like fibrils formed from transmembrane helices. Glycophorin A contains a GxxxG motif that is found in many transmembrane sequences including that of the amyloid precursor protein and prion protein. We propose that glycine, which mediates helix interactions in membrane proteins, also provides key packing motifs when it occurs in beta-sheets. We show that glycines in the glycophorin A transmembrane helix promote extended beta-strand formation when the helix partitions into aqueous environments and stabilize the packing of beta-sheets in the formation of amyloid-like fibrils. We demonstrate that fibrillization can be disrupted with a new class of inhibitors that target the molecular grooves created by glycine.

Amino Acid Sequence↗
PubMed2005

Rotational orientation of monomers within a designed homo-oligomer transmembrane helical bundle.

A peptide designed to form a homo-oligomeric transmembrane helical bundle was reconstituted into lipid bilayers and studied by using (2)H NMR (nuclear magnetic resonance) with magic angle spinning to confirm that the helical interface corresponds to the interface intended in the design. The peptide belongs to a family of model peptides derived from a membrane-solubilized version of the water-soluble coiled-coil GCN4-P1. The variant studied here contains two asparagines thought to engage in interhelical hydrogen bonding critical to the formation of a stable trimer. For the NMR studies, three different peptides were synthesized, each with one of three consecutive leucines in the transmembrane region deuterium labeled. Prior to NMR data collection, polarized infrared spectroscopy was used to establish that the peptides were reconstituted in lipid bilayers in a transmembrane helical conformation. The (2)H NMR line shapes of the three different peptides are consistent with a trimer structure formed by the designed peptide that is stabilized by inter-helical hydrogen bonding of asparagines at positions 7 and 14.

Amino Acid Sequence↗