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Biomedical subjects

Jun Liu

Publications and source records attributed to Jun Liu.

At least 163 records · Page 9Linked to original sources
PubMed2005

Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis.

The Wnt signaling pathway acts ubiquitously in metazoans to control various aspects of embryonic development. Wnt ligands bind their receptors Frizzled and low-density lipoprotein receptor-related protein 5/6 and function through Disheveled (Dvl), Axin, adenomatous polyposis coli, glycogen synthase kinase 3beta, and casein kinase (CK) 1 to stabilize beta-catenin and induce lymphocyte enhancer-binding factor (LEF)/T cell factor (TCF)-dependent transcriptional activities. To identify previously unrecognized Wnt signaling modulators, a genome-wide functional screen was performed using large-scale arrayed cDNA collections. From this screen, both known components and previously uncharacterized regulators of this pathway were identified, including beta-catenin, Dvl1, Dvl3, Fbxw-1, Cul1, CK1epsilon, CK1delta, and gamma-catenin. In particular, a previously unrecognized activator, LRRFIP2 (leucine-rich repeat in Flightless interaction protein 2), was found that interacts with Dvl to increase the cellular levels of beta-catenin and activate beta-catenin/LEF/TCF-dependent transcriptional activity. The function of LRRFIP2 is blocked when a dominant negative Dvl (Xdd1) is coexpressed. Expression of LRRFIP2 in Xenopus embryos induced double axis formation and Wnt target gene expression; a dominant negative form of LRRFIP2 suppresses ectopic Wnt signaling in Xenopus embryos and partially inhibits endogenous dorsal axis formation. These data suggest that LRRFIP2 plays an important role in transducing Wnt signals.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Actin gene in prawn, Macrobrachium rosenbergii: characteristics and differential tissue expression during embryonic development.

An actin gene (named Mar-actin) from the commercial prawn, Macrobrachium rosenbergii, was isolated, sequenced and gene expression was characterized. The cDNA sequence was 1281 bp in length and contained 1131 bp open reading frame encoding 376 amino acids. The amino acid sequence deduced from the nucleotide sequence showed high identity (70.3% to 98.1%) with other known actins of various organisms, highest with that of the European flounder (98.1%). The 3' untranslated region (3' UTR) of the Mar-actin mRNA has a high A+U content (approximately 78%) and contains one AUUUUUA and two repeats of the AUUUA motifs, that may function in regulating mRNA decay. Northern blot analysis revealed that the Mar-actin gene was expressed predominantly in muscle tissues. Transcripts in hepatopancreas were barely detectable. Expression of the Mar-actin gene varied during embryonic development and reached the maximal level at the zoea stage. This is the first report describing the complete sequence and expression pattern of the actin gene in prawns.

Actins↗
PubMed2005

Stable transfection of extrinsic Smac gene enhances apoptosis-inducing effects of chemotherapeutic drugs on gastric cancer cells.

AIM: To explore the feasibility of enhancing apoptosis-inducing effects of chemotherapeutic drugs on human gastric cancer cells by stable transfection of extrinsic Smac gene. METHODS: After Smac gene was transferred into gastric cancer cell line MKN-45, subclone cells were obtained by persistent G418 selection. Cellular Smac gene expression was determined by RT-PCR and Western blotting. After treatment with mitomycin (MMC) as an apoptotic inducer, in vitro cell growth activities were investigated by trypan blue-staining method and MTT colorimetry. Cell apoptosis and its rates were determined by electronic microscopy, annexin V-FITC and propidium iodide staining flow cytometry. Cellular caspase-3 protein expression and its activities were assayed by Western blotting and colorimetry. RESULTS: When compared with MKN-45 cells, the selected subclone cell line MKN-45/Smac had significantly higher Smac mRNA (3.12+/-0.21 vs 0.82+/-0.14, t = 7.52, P<0.01) and protein levels (4.02+/-0.24 vs 0.98+/-0.11, t = 8.32, P<0.01). After treatment with 10 microg/mL MMC for 6-24 h, growth inhibition rate of MKN-45/Smac (15.8+/-1.2-54.8+/-2.9%) was significantly higher than that of MKN-45 (5.8+/-0.4- 24.0+/-1.5%, t = 6.42, P<0.01). Partial MKN-45/Smac cancer cells presented characteristic morphological changes of apoptosis under the electronic microscope with an apoptosis rate of 36.4+/-2.1%, which was significantly higher than that of MKN-45 (15.2+/-0.8%, t = 9.25, P<0.01). Compared with MKN-45, caspase-3 expression levels in MKN-45/Smac were improved significantly (3.39+/-0.42 vs 0.96+/-0.14, t = 8.63, P<0.01), while its activities were 3.25 times as many as those of MKN-45 (0.364+/-0.010 vs 0.112+/-0.007, t = 6.34, P<0.01). CONCLUSION: Stable transfection of extrinsic Smac gene and its over-expression in gastric cancer cell line can significantly enhance cellular caspase-3 expression and activities, ameliorate apoptosis-inducing effects of mitomycin C on cancer cells, which is a novel strategy to improve chemotherapeutic effects on gastric cancer.

Antibiotics, Antineoplastic↗
PubMed2005

Dementia subtypes in China: prevalence in Beijing, Xian, Shanghai, and Chengdu.

BACKGROUND: Prevalences of Alzheimer disease (AD) and vascular dementia (VaD) in China reportedly differ from those in Western countries. OBJECTIVE: To estimate prevalence of AD and VaD in 4 regions of China. DESIGN: Cross-sectional, population-based prevalence survey with a stratified, multistage cluster sampling design. SETTING: Rural (n = 99) and urbanized (n = 71) communities of Beijing, Xian, Shanghai, and Chengdu. PARTICIPANTS: A sample of 34 807 community residents (94% of those eligible) 55 years or older. MAIN OUTCOME MEASURES: Participants were screened with the Chinese Mini-Mental State Examination. Those who screened positive (n = 3950) underwent a standardized diagnostic workup. Screening sensitivity was assessed in a 3.3% random sample (n = 1008 of the 30 857 who passed the screening). Diagnoses of AD and VaD were made according to National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer Disease and Related Disorders Association and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, respectively. Final diagnoses were made after a 6-month confirmation interval. RESULTS: We identified 732 AD cases and 295 VaD cases. Prevalence in persons 65 years or older was 3.5% (95% confidence interval, 3.0%-3.9%) for AD and 1.1% (95% confidence interval, 0.9%-1.1%) for VaD. After post hoc correction for negative screening errors, prevalence increased to 4.8% for AD and remained at 1.1% for VaD. CONCLUSION: Prevalence of dementia subtypes in China is comparable with that in Western countries.

Aged↗
PubMed2005

Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution.

This study was conducted to investigate the effect of reversible protein self-association on the viscosity of concentrated monoclonal antibody solutions. The viscosities of the monoclonal antibody solutions were measured by either a capillary viscometer or a cone-plate rheometer at different protein concentrations, pH, and ionic strength. Soluble aggregates were determined by size exclusion chromatography, light scattering, and analytical ultracentrifugation. Self-association of protein at high protein concentration was monitored by sedimentation equilibrium analysis using a preparative ultracentrifuge and a microfractionator. The viscosity of one of the monoclonal antibodies investigated is highly dependent on protein concentration, pH, and ionic strength of buffer and charged excipients. This antibody shows the highest viscosity near its pI at low ionic strength conditions. Sedimentation equilibrium analysis suggests that this antibody tends to reversibly self-associate at high protein concentration. The self-association appears to be quite weak and is not detectable by sedimentation velocity and size exclusion chromatography at low protein concentration. There are no significant differences in the amounts of non-dissociable soluble aggregates formed between low viscosity and high viscosity samples. These results suggest that the reversible multivalent self-association of this protein appears to be mediated mainly by electrostatic interactions of charged residues and results in unusually high viscosity of this monoclonal antibody in solution at low ionic strength conditions.

Animals↗
PubMed2005

Synthesis and characterization of HPMC derivatives as novel duodenum-specific coating agents.

HPMC (Hydroxypropyl methylcellulose) was chemically modified, using maleic anhydrides, to obtain pH-sensitive HPMCAM (Hydroxypropyl methylcellulose acetate maleate) polymers for use as novel duodenum-specific coating agents. The pharmaceutical properties of HPMCAM, such as film forming, acid values, pH-sensitive values, water vapor permeability, tensile strength and Tg, were investigated, and found to show good film forming properties. The pH-sensitive values were 3.0 to 3.7. In vitro results demonstrate that HPMCAM could completely suppress drug release within 2h in a simulated gastric fluid (pH 1.2) and rapidly release the drug in a simulated pathological duodenal fluid (pH 3.4). These results indicate that HPMCAM might be a useful material for a duodenum-specific drug delivery system.

Berberine↗
PubMed2005

Changes in integrin expression during adipocyte differentiation.

3T3-L1 preadipocytes require cAMP for maximal differentiation. Microarray analysis reveals that the integrins alpha5 and alpha6 are coordinately regulated by cAMP. alpha5 expression is gradually diminished during adipogenesis, whereas alpha6 is increased. Overexpression of alpha5 in preadipocytes results in enhanced proliferation and attenuated differentiation. Conversely, alpha6 overexpression is without effect. The GTPase Rac is normally inhibited during differentiation. However, overexpression of integrin alpha5 increases Rac activity. Constitutively active but not dominant-negative Rac inhibits differentiation when overexpressed in preadipocytes, implying its role downstream of alpha5 integrin in maintaining preadipocytes in an undifferentiated state. Moreover, alpha6 integrin is critically involved in clustering growth-arrested preadipocytes on basement membrane Matrigel. Perturbation of such clustering enhances Rho activity and promotes growth-arrested preadipocytes to reenter the cell cycle. These findings demonstrate a role for integrin alpha6 in connecting morphogenesis with signaling processes leading to terminal differentiation.

3T3-L1 Cells↗
PubMed2005

The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.

Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.

Adipocytes↗
PubMed2005

Osmotic tolerance and membrane permeability characteristics of rhesus monkey (Macaca mulatta) spermatozoa.

Biophysical characteristics of the plasma membrane, such as osmotic sensitivity and water and cryoprotectant permeability are important determinants of the function of spermatozoa after cryopreservation. A series of experiments was conducted with rhesus macaque spermatozoa at 23 degrees C to determine their: (1) cell volume and osmotically inactive fraction of the cell volume; (2) permeability coefficients for water and the cryoprotectants dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol; (3) tolerance to anisosmotic conditions; and (4) motility after a one step addition and removal of the four cryoprotectants. An electronic particle counter and computer aided semen analysis were used to determine the cell volume and permeability coefficients, and motility, respectively. Rhesus spermatozoa isosmotic cell volume was 27.7+/-3.0 microm3 (mean+/-SEM) with an osmotically inactive cell fraction of 51%. Hydraulic conductivity in the presence of dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol was 1.09+/-0.30, 0.912+/-0.27, 1.53+/-0.53, and 1.94+/-0.47 microm/min/atm, respectively. Cryoprotectant permeability was 1.39+/-0.31, 2.21+/-0.32, 3.38+/-0.63, and 6.07+/-1.1 (x10(-3)cm/min), respectively. Rhesus sperm tolerated all hyposmotic exposures. However, greater than 70% motility loss was observed after exposure to solutions of 600 mOsm and higher. A one step addition and removal of all four cryoprotectants did not cause significant motility loss. These data suggest that rhesus sperm are tolerant to hyposmotic conditions, and ethylene glycol may be the most appropriate cryoprotectant for rhesus sperm cryopreservation, as it has the highest permeability coefficient of the tested cryoprotectants.

Animals↗
PubMed2005

Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis.

PURPOSE: To understand and quantify intraocular pressure (IOP) measurement errors introduced by corneal variables during applanation tonometry using a cornea biomechanical model. SETTING: Department of Ophthalmology, Biomedical Engineering Center, The Ohio State University, Columbus, Ohio, USA. METHODS: The model assumed an overall resultant pressure that was based on the summation of the applanation pressure, the true IOP, and the surface tension caused by the tear film to determine the final deformation of the corneal apex during IOP measurement. Corneal resistance was varied according to the cornea's biomechanical properties, thickness, and curvature, and the effect of each variable on the accuracy of IOP tonometry readings was examined quantitatively. RESULTS: The model demonstrated that tonometry readings do not always reflect true IOP values. They deviate when corneal thickness, curvature, or biomechanical properties vary from normal values. Based on the model, predicted IOP readings have a 2.87 mm Hg range resulting from the variation in the corneal thickness in the normal population and a 1.76 mm Hg range from the variation in the corneal radius of curvature. Considering that Young's modulus of the corneal varies from 0.1 to 0.9 MPa in the normal population, the model predicts tonometry IOP readings will have a range of 17.26 mm Hg because of the variation in this corneal biomechanical parameter alone. CONCLUSIONS: The simulation based on the model demonstrated quantitatively that variations in each corneal variable cause errors in tonometry IOP readings. The simulation results indicate that differences in corneal biomechanics across individuals may have greater impact on IOP measurement errors than corneal thickness or curvature.

Biomechanical Phenomena↗
PubMed2005

p16 tumor suppressor therapy in salivary adenoid cystic carcinoma cell line SACC83.

OBJECTIVE: This study aimed to determine the growth inhibitory effects of transfecting the wild-type p16 gene into human salivary adenoid cystic carcinoma (SACC) cells in vitro. METHODS: p16 cDNA was cloned into pDOR-neo plasmid by recombination technique, and the human eukaryotic expression vector, pDOR-p16 , was constructed. P16 gene was transfected into SACC83 cells using the liposome method, and the expression of the transfected genes was detected by RT-PCR. The efficacy of transfection was determined by MTT-based colorimetric formats. The DNA metabolic rate of transfected cells was measured by 3 H-TdR incorporation. To describe the cell division phase, the cell cycles of the p16 -transfected gene cells and untransfected cells were analyzed by flow cytometry. RESULTS: The growths in vitro of the p16-transfected cells were inhibited significantly. 3H-TdR incorporation showed a decreased DNA metabolic rate of p16-transfected cells, and flow cytometry suggested a significant increase of the cells in the G1 phase and decrease in the S phase. CONCLUSION: The study confirmed the reversal effect of wild-type p16 on malignant phenotype of the salivary adenoid cystic carcinoma and provides valuable data for further clinical trial of gene therapy with p16.

Carcinoma, Adenoid Cystic↗
PubMed2005

Directed spatial organization of zinc oxide nanorods.

The ability to precisely place nanomaterials at predetermined locations is necessary for realizing applications using these new materials. Using an organic template, we demonstrate directed growth of zinc oxide (ZnO) nanorods on silver films from aqueous solution. Spatial organization of ZnO nanorods in prescribed arbitrary patterns was achieved, with unprecedented control in selectivity, crystal orientation, and nucleation density. Surprisingly, we found that caboxylate endgroups of omega-alkanethiol molecules strongly inhibit ZnO nucleation. The mechanism for this observed selectivity is discussed.

Journal Article↗
PubMed2005

Chronic arsenic exposure and urinary 8-hydroxy-2'-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China.

OBJECTIVE: Recent studies have shown that generation of reactive oxidants during arsenic metabolism can play an important role in arsenic-induced injury. The purpose of this study was to examine the relationship between arsenic in drinking water and oxidative stress in humans by measuring 8-Hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: We performed a cross-sectional study in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 of the 143 inhabitants (93.7%) of the village participated in the study. The levels of 8-OHdG, arsenic and its metabolites were measured in urine collected from the participants. Regression analyses were performed to investigate the relationship between arsenic species and 8-OHdG levels in urine. RESULTS: In the polluted village, monomethylarsenic was significantly higher in subjects with arsenic dermatosis than those without dermatosis despite no difference in mean levels of arsenic in well water between both types of subject. For subjects with arsenic dermatosis, arsenic species and metabolites in urine are significantly associated with 8-OHdG, while there was no statistically significant relationship for subjects without arsenic dermatosis. For all residents of the polluted village, the levels of dimethylarsenic and 8-OHdG were significantly higher for those who had been exposed to well water for more than 12 years. CONCLUSIONS: These results provide evidence of a link between exposure to arsenic from drinking water and oxidative stress, which may play an important role in arsenic-involved injuries.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

An efficient method for rapid amplification of Arisaema heterophyllum agglutinin gene using a genomic walking technique.

The genomic sequence of Arisaema heterophyllum agglutinin (AHA), a mannose-binding lectin (MBL), was cloned through a novel genomic walking technique. Adaptor ligation reactions and subsequent amplifications with adaptor primer and multiple specific primers were used to generate specificity in this method. The method allowed for the amplification of over 1 kb of genomic DNA sequence immediately upstream and downstream from the 5' and 3' ends of full-length cDNAs. For aha gene, the upstream regions contained a putative transcription initiation start site and other sequences commonly found in eukaryotic promoters. The downstream regions of aha contained two polyadenylation signals. Our study demonstrated that aha had no intron like mannose-binding lectin genes cloned from other plant species so far. This efficient method, based on a genomic walking technique, was useful for the cloning of promoters, insertion sites, and other sequences of interest without constructing and screening genomic libraries.

Arisaema↗
PubMed2005

Online clustering algorithms for radar emitter classification.

Radar emitter classification is a special application of data clustering for classifying unknown radar emitters from received radar pulse samples. The main challenges of this task are the high dimensionality of radar pulse samples, small sample group size, and closely located radar pulse clusters. In this paper, two new online clustering algorithms are developed for radar emitter classification: One is model-based using the Minimum Description Length (MDL) criterion and the other is based on competitive learning. Computational complexity is analyzed for each algorithm and then compared. Simulation results show the superior performance of the model-based algorithm over competitive learning in terms of better classification accuracy, flexibility, and stability.

Algorithms↗
PubMed2005

Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients.

PURPOSE: Regulatory T cells (T-reg) that control harmful autoimmune T cells in the periphery may also suppress the immune response against cancer. In this study we investigated the possible involvement of CD4(+)CD25(high) T-reg in the immune impairment of patients with acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: The frequencies and phenotypes of CD4(+)CD25(high) T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4(+)CD25(high) T cells, CD4(+)CD25(high), and CD4(+)CD25(-) T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4(+)CD25(high) and CD4(+)CD25(-) T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4(+)CD25(high) T cells were respectively evaluated by 7AAD and ki67 binding cells using flow cytometry. RESULTS: Compared with healthy controls, AML patients had a higher proportion of CD4(+)CD25(high) T cells in peripheral blood. These cells were CD45-RA(-), CD69(-), CD45-RO(+), CD95(+), and intercellular CTLA-4(+), and secreted low levels of TNF-alpha and IL-10, but no IL-2, IL-4, IL-5, and IFN-gamma. They inhibited the proliferation and cytokine production (IL-2, IFN-gamma) of CD4(+)CD25(-) T cells, but improved IL-10 production under the co-culture of both subsets with stimulation, thus behaving as T-reg. Notably, CD4(+)CD25(high) T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. CONCLUSIONS: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.

Adolescent↗
PubMed2005

The activity profile of the NhaD-type Na+(Li+)/H+ antiporter from the soda Lake Haloalkaliphile Alkalimonas amylolytica is adaptive for the extreme environment.

In extreme alkaliphiles, Na(+)/H(+) antiporters play a central role in the Na(+) cycle that supports pH homeostasis, Na(+) resistance, solute uptake, and motility. Properties of individual antiporters have only been examined in extremely alkaliphilic soil Bacillus spp., whereas the most alkaline natural habitats usually couple high pH with high salinity. Here, studies were conducted on a Na(+)(Li(+))/H(+) antiporter, NhaD, from the soda lake haloalkaliphile Alkalimonas amylolytica. The activity profile of A. amylolytica NhaD at different pH values and Na(+) concentrations reflects its unique natural habitat. In membrane vesicles from antiporter-deficient Escherichia coli EP432 (DeltanhaA DeltanhaB), the pH optimum for NhaD-dependent Na(+)(Li(+))/H(+) antiport was at least 9.5, the highest pH that could be tested; no activity was observed at pH < or =8.5. NhaD supported low Na(+)/H(+) antiport activity at pH 9.5 that was detectable over a range of Na(+) concentrations from 10 mM to at least 800 mM, with a 600 mM optimum. Although A. amylolytica nhaD was isolated by complementing the Li(+) sensitivity of the triple mutant E. coli strain KNabc (DeltanhaA DeltanhaB DeltachaA), sustained propagation of nhaD-bearing plasmids in this strain resulted in a glycine (Gly(327))-->serine mutation in a putative cytoplasmic loop of the mutant transporter. The altered activity profile of NhaD-G327S appears to be adaptive to the E. coli setting: a much higher activity than wild-type NhaD at Na(+) concentrations up to 200 mM but lower activity at 400 to 600 mM Na(+), with a pH optimum and minimal pH for activity lower than those of wild-type NhaD.

Adaptation, Biological↗