Biomedical subjects

Bin Liu

Publications and source records attributed to Bin Liu.

At least 181 records · Page 10Linked to original sources

PubMed2004

Mesoscale organization of CuO nanoribbons: formation of "dandelions".

A two-tiered organizing scheme with multiple-length scales for construction of dandelion-like hollow CuO microspheres has been elucidated: (1) mesoscale formation of rhombic building units from smaller nanoribbons via oriented aggregation and (2) macroscopic organization of these units into the CuO microspheres. This self-assembly concept may also be applicable to other metal oxides by creating geometric constraints for constructional units.

Journal Article↗

PubMed2004

K317, R319, and E320 within the proximal C-terminus of the bradykinin B2 receptor form a motif important for phospholipase C and phospholipase A2 but not connective tissue growth factor related signaling.

We showed previously that large domain exchanges between the bradykinin B2 (BKB2) and angiotensin II type 1a (AT1a) receptors can result in functional hybrids. However, when we proceeded to exchange the entire bradykinin B2 receptor (BKB2R) C-terminal tail with the AT1aR C-terminus, the hybrid, while continuing to bind BK and be endocytosed as wild type (WT) BKB2R, lost much of its ability to activate phosphatidylinositol (PI) turnover or the release of arachidonic acid (ARA). In this study, we constructed chimeric receptors within the proximal C-terminus between the BKB2R and AT1aR or bradykinin B1 receptor (BKB1R). The mutant and WT receptor cDNAs were stably transfected into Rat-1 cells. Also, point mutations were generated to evaluate the role of the individual residues within this region. These chimeric studies revealed that the proximal portion of the BKB2R C-tail is crucial for G protein-linked BKB2R functions. This region could not be swapped with the AT1aR to obtain a BK activated PI turnover or ARA release. Further studies demonstrated that the distal portion (325-330) of this region is exchangeable; however, the middle portion (317-324) is not. Small motif exchanges within this section identified the KSR and EVY motifs as crucial for G(alphaq), G(alphai) related signaling of the BKB2R. Point mutations then showed that the charged amino acids K317, R319, and E320 are the residues critical for linking to PI turnover and ARA release. However, these proximal chimeras showed normal receptor uptake. Interestingly, while apparently not activating G protein-linked signaling, the proximal tail AT1aR exchange mutant and the entire C-terminus exchange hybrid continued to cause a substantial bradykinin effected increase in connective tissue growth factor (CTGF) mRNA level, as WT BKB2R.

Amino Acid Motifs↗

PubMed2004

Room temperature solution synthesis of monodispersed single-crystalline ZnO nanorods and derived hierarchical nanostructures.

In this work, we report a room temperature wet-chemical approach to synthesize highly regulated, monodispersed ZnO nanorods and derived hierarchical nanostructures. In particular, ZnO has been prepared into single-crystalline conical or prismatic nanorods, and various hierarchical structures such as hexagonally branched, reversed umbrella-type, and cactus-like ZnO nanostructures comprising individual c-oriented nanorods. Depending on the synthetic conditions used, the diameter of nanorods can be controlled with a size down to 10-30 nm, while the aspect ratio can be controlled up to 50-100. Various preparative parameters, such as initial reactant concentrations, solvents, ligands, surfactants, precursor salts, and reaction time, have been systematically examined. Due to slow reactions at room temperature, excellent crystallinity and high morphological yield (100% in most cases) have been achieved via tuning the synthetic parameters. Our photoluminescence and UV measurements also confirm the attained crystal perfection and size uniformity.

Journal Article↗

PubMed2004

Regulation of the SM-20 prolyl hydroxylase gene in smooth muscle cells.

SM-20 encodes an intracellular prolyl hydroxylase that acts on hypoxia inducible factor (HIF)-1alpha, targeting it for proteasomal degradation. By decreasing HIF-alpha, SM-20 is thought to modulate the expression of hypoxia-regulated genes. SM-20 expression in the arterial wall is restricted to smooth muscle cells, which play a critical role in atherosclerosis and arterial injury. To further elucidate the regulation of SM-20 in smooth muscle, we cloned and analyzed the rat SM-20 promoter. In transient transfections, the SM-20 promoter displayed approximately 6-fold greater activity in smooth muscle cells vs. fibroblasts. Deletion analysis and electrophoretic mobility shift assays demonstrated that SM-20 transcription was regulated by two Sp1/Sp3 sites. A shift in binding to the Sp1/Sp3 sites, a decrease in Sp1 and Sp3 protein levels, and the emergence of a lower molecular weight form of Sp1 were seen in serum-deprived or post-confluent SMC, suggesting that SM-20 is regulated during smooth muscle cell differentiation.

Animals↗

PubMed2004

A novel replicating circular DNAzyme.

10-23 DNAzyme has the potential to suppress gene expressions through sequence-specific mRNA cleavage. However, the dependence on exogenous delivery limits its applications. The objective of this work is to establish a replicating DNAzyme in bacteria using a single-stranded DNA vector. By cloning the 10-23 DNAzyme into the M13mp18 vector, we constructed two circular DNAzymes, C-Dz7 and C-Dz482, targeting the beta-lactamase mRNA. These circular DNAzymes showed in vitro catalytic efficiencies (kcat/K(M)) of 7.82 x 10(6) and 1.36 x 10(7) M(-1) x min(-1), respectively. Their dependence on divalent metal ions is similar to that found with linear 10-23 DNAzyme. Importantly, the circular DNAzymes were not only capable of replicating in bacteria but also exhibited high activities in inhibiting beta-lactamase and bacterial growth. This study thus provides a novel strategy to produce replicating DNAzymes which may find widespread applications.

Base Sequence↗

PubMed2004

Activation of epidermal growth factor receptor causes astrocytes to form cribriform structures.

Epidermal growth factor receptor (EGFR) is expressed in reactive astrocytes following injury in the CNS. However, the effects of activation of the EGFR pathway in astrocytes are not well established. In the present study, we demonstrate that activation of EGFR causes optic nerve astrocytes, as well as brain astrocytes, to form cribriform structures with cavernous spaces. Formation of the cribriform structures is dependent on new protein synthesis and cell proliferation. Platelet-derived growth factor and basic fibroblast growth factor were not effective. Smooth muscle cells and epithelial cells do not form cribriform structures in response to EGFR activation. The formation of the cribriform structures appears to be related to a guided migration of astrocytes and the expression of integrin beta1 and extracellular fibronectin in response to activation of EGFR. The EGFR pathway may be a specific, signal transduction pathway that regulates reactive astrocytes to form cavernous spaces in the glial scars following CNS injury and in the compressed optic nerve in glaucomatous optic nerve neuropathy.

Adult↗

PubMed2004

Characterization of tectoRNA assembly with cationic conjugated polymers.

Association between RNAs with preprogrammed molecular recognition units can be quantified by using cationic, water-soluble conjugated polymers. The method uses a fluorophore-labeled probe RNA (RNA-F*), which is treated with a target structure (RNA-T). Heterodimer formation, (RNA-T/RNA-F*), increases the total negative charge on the F*-bearing macromolecule and reduces the number of negatively charged molecules (relative to unbound RNA-T+ RNA-F*). On the basis of electrostatic interactions, we anticipated more effective binding between CCP and (RNAT/RNA-F*), a reduction of the average CCP- - -F* distance, and more effective FRET upon excitation of the conjugated polymer. The resulting signals benefit from the optical amplification characteristic of emissive conjugated polymers. Solution dissociation constants can be determined by monitoring F* intensity changes as a function of [RNA-F*] and the ratio: [I(T) - I(NB)]/I(NB), where I(T) and I(NB) are the F* intensities in the presence of the target RNA (RNA-T) and a nonbinding RNA (RNA-NB), respectively, while keeping the concentration of the conjugated polymer constant. By focusing on [I(T) - I(NB)]/I(NB) as a function of RNA concentration, one can detect the concentration range wherein increased fluorescence is the result of dimerization.

Base Sequence↗

PubMed2004

Characterizing potentials using the structure of a one-dimensional chain demonstrated using a dusty plasma crystal.

A procedure was developed to characterize the interparticle potential in a lattice that is confined by an external potential. The first of the two steps is to characterize the confining potential, which can be done using various schemes involving observations of particle motion. The second step is to characterize the interparticle potential using measurements of the equilibrium particle positions. This can be done with either of two methods developed here, a force-balance method or a simpler equation-of-state method. To demonstrate and test these methods, an experiment and a molecular dynamics simulation were performed with a one-dimensional Coulomb chain of particles confined in a parabolic potential. The experiment used a dusty plasma consisting of charged microspheres levitated in the plasma sheath above a narrow groove in a lower electrode.

Journal Article↗

PubMed2004

Direct photolysis of estrogens in aqueous solutions.

Direct photolysis of two estrogens 17beta-estradiol (E2) and estrone (E1) in aqueous solutions radiated by UV-light and UV-Vis-light was studied preliminarily. The results suggest that the photolysis of E2 in aqueous solutions occurs under irradiation with UV disinfection lamp (lambda = 254 nm, 30 W), while E1 can also undergo photolysis under irradiation with a high-pressure mercury lamp (lambda > or = 365 nm, 125 W). The photolysis reactions of E2 and E1 at the concentration of 3.0-20 mgl(-1) in aqueous solutions were all in accordance with pseudo-first-order law. The photolysis rate of estrogens in aqueous solutions reached the lowest value at pH approximately 5.0, while the highest at pH 8.0 over the range of 2.0-8.0. The higher the initial concentration of the two estrogens, the lower the rate of photolysis.

Estradiol↗

PubMed2004

Group velocity dispersion effects with water and lipid in 1.3 microm optical coherence tomography system.

Optical coherence tomography (OCT) has been introduced for the diagnosis of vulnerable plaques in the coronary arteries. When an OCT system images through tissue and biological liquids, group velocity dispersion (GVD) will occur, which may be useful in tissue characterization. This study compares the water and lipid induced GVD effects, important constituents in plaque, on the axial resolution. The point-spread function (PSF) was measured when a target mirror was immersed in either water or lipid. A Fourier transform was performed on the PSF data. No significant GVD was observed in oil up to 15 mm thickness. Water depths greater than 6 mm significantly broadened the PSF. This indicates that the distortion of the spectrum can be attributed to the GVD in water. These results suggest that when imaging through tissue (such as when performing intravascular imaging in vivo) one may be able to distinguish different tissue types for diagnostic purposes.

Biomimetic Materials↗

PubMed2004

Interpolyelectrolyte complexes of conjugated copolymers and DNA: platforms for multicolor biosensors.

Interchain interactions modulate the frequency of emission from a cationic water-soluble conjugated polymer. The polymer, PFPB, is obtained by a Suzuki copolymerization of p-phenylenebisboronic acid with a 95:5 mixture of 2,7-dibromo-9,9-bis(6'-bromohexyl)fluorene and 4,7-dibromo-2,1,3-benzothiadiazole, followed by quarternization of the pendant groups by addition of NMe3. The structure of PFPB contains 5% of the 2,1,3-benzothiadiazole (BT) chromophore within a cationic poly(fluorene-co-phenylene) polymer chain. The emission of PFPB is blue under dilute conditions (<1 x 10-6 M in repeat units) and green at higher concentrations. Energy transfer to dye-labeled ss-DNA is more efficient, relative to the parent polymer poly(9,9-bis(6'-N,N,N,-trimethylammonium)hexyl)fluorene-co-alt-1,4-phenylene) dibromide (PFP), as a result of improved spectral overlap. By using a peptide nucleic acid (PNA-C*) labeled with a red-emitting chromophore one can obtain three different emission colors, depending on the nature of the substrate under interrogation. If no ss-DNA is present, the solution emits blue. With a ss-DNA that is noncomplementary to PNA-C*, green emission is observed. Red emission occurs upon addition of ss-DNA complementary to the PNA sequence.

Biosensing Techniques↗

PubMed2004

Hemangiopoietin, a novel human growth factor for the primitive cells of both hematopoietic and endothelial cell lineages.

The cells of hematopoietic and vascular endothelial cell lineages are believed to share a common precursor, termed hemangioblast. However, the existence of a growth factor acting relatively specifically on hemangioblasts remains unclear. Here we report the identification of hemangiopoietin (HAPO), a novel growth factor acting on both hematopoietic and endothelial cell lineages. In vitro in the human system, recombinant human HAPO (rhHAPO) significantly stimulated the proliferation and hematopoietic and/or endothelial differentiation of human bone marrow mononuclear cells and of purified CD34+, CD133+, kinase domain receptor-positive (KDR+), or CD34+/KDR+ cell populations. In the murine system, rhHAPO stimulated the proliferation of long-term culture-initiating cells (LTC-ICs) as well as CD34+ and stem cell antigen-1 (Sca-1+) cell subsets. In vivo, subcutaneous injection of rhHAPO into normal mice resulted in a significant increase in bone marrow hematopoietic cells. Furthermore, irradiated mice injected with rhHAPO had an enhanced survival rate and accelerated hematopoiesis. Our data suggest that HAPO is a novel growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages and that HAPO may have a clinical potential in the treatment of various cytopenias and radiation injury and in the expansion of hematopoietic and endothelial stem/progenitor cells.

Abortion, Spontaneous↗

PubMed2004

[Germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in China Han people].

OBJECTIVE: To detect BRCA1 and BRCA2 gene germline mutation in the Chinese breast cancer families. METHODS: Samples of peripheral blood were collected to prepare genomic DNA by conventional techniques from 15 inherited breast cancer patients from 14 breast cancer families, 76 sporadic breast cancer patients, and 100 healthy controls based on informed consent. Exons 4, 8, 11 and 18 - 20 of BRCA1, and exons 1 - 14, 17 - 24 and 27 of BRCA2, were analyzed using DNA direct sequencing. RESULTS: Six single nucleotide polymorphisms (SNPs) were found on the exon 11 of BRCA1, 2 being silent changes without change of amino acid coding, and 4 with change of amino acid coding among which 2 were polymorphic amino acid alterations and 2 were pathogenic SNPs, i.e. mutational sites. One novel BRCA1 mutation, C1196T (Pro 359 Leu), was identified in a family breast cancer patients, who was diagnosed at the age of 37. Another BRCA1 mutation, Trp 372 stop was found in a breast cancer patient who was diagnosed at the age 29. Eight SNPs were found on the exon3, 10 and 11 of BRCA2, among which 5 were silent changes and 3 were polymorphic amino acid alterations. A1093C (Asn289His) in exon 10 and A 3199G (Asn991Asp) in exon 11 being found simultaneously in the patients of 2 families but not appearing in pool DNA sample, and Asn 371 His appearing as A/C heterozygote in pool DNA sample. CONCLUSION: Two pathogenic SNPs have been found in BRCA1 and may be related to early-onset breast cancer. One of them may be a novel mutation characterized of familial breast cancer in China.

Base Sequence↗

PubMed2004

Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase.

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra and depletion of the neurotransmitter dopamine in the striatum. Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. Mechanistic studies using animal systems such as the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent PD model have revealed the involvement of the brain's immune cells and free radical-generating processes. We recently reported that dextromethorphan (DM), a widely used anti-tussive agent, attenuated endotoxin-induced dopaminergic neurodegeneration in vitro. In the current study, we investigated the potential neuroprotective effect of DM and the underlying mechanism of action in the MPTP rodent PD model. Mice (C57BL/6J) that received daily MPTP injections (15 mg free base/kg body weight, s.c.) for 6 consecutive days exhibited significant degeneration of the nigrostriatal dopaminergic pathway. However, the MPTP-induced loss of nigral dopaminergic neurons was significantly attenuated in those mice receiving DM (10 mg/kg body weight, s.c.). In mesencephalic neuron-glia cultures, DM significantly reduced the MPTP-induced production of both extracellular superoxide free radicals and intracellular reactive oxygen species (ROS). Because NADPH oxidase is the primary source of extracellular superoxide and intracellular ROS, we investigated the involvement of NADPH oxidase in the neuroprotective effect of DM. Indeed, the neuroprotective effect of DM was only observed in the wild-type but not in the NADPH oxidase-deficient mice, indicating that NADPH oxidase is a critical mediator of the neuroprotective activity of DM. More importantly, due to its proven safety record of long-term clinical use in humans, DM may be a promising agent for the treatment of degenerative neurological disorders such as PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Mapping tumor epitope space by direct selection of single-chain Fv antibody libraries on prostate cancer cells.

The identification of tumor-specific cell surface antigens is a critical step toward the development of targeted therapeutics for cancer. The epitope space at the tumor cell surface is highly complex, composed of proteins, carbohydrates, and other membrane-associated determinants including post-translational modification products, which are difficult to probe by approaches based on gene expression. This epitope space can be efficiently mapped by complementary monoclonal antibodies. By selecting human antibody gene diversity libraries directly on the surface of prostate cancer cells, we have taken a functional approach to identifying fully human, tumor-specific monoclonal antibodies without prior knowledge of their target antigens. Selection conditions have been optimized to favor tumor-specific antibody binding and internalization. To date, we have discovered >90 monoclonal antibodies that specifically bind and enter prostate cancer cells, with little or no binding to control cells. These antibodies are able to efficiently deliver intracellular payloads when attached to nanoparticles such as liposomes. In addition, a subset of the antibodies displayed intrinsic antiproliferative activity. These tumor-specific internalizing antibodies are likely to be useful for targeted therapeutics either alone or in combination with effector molecules. The antigens they bind constitute a tumor-specific internalizing epitope space that is likely to play a significant role in cancer cell homeostasis. Targeting components of this epitope space may facilitate development of immunotherapeutic and small molecule-based strategies as well as the use of other therapeutic agents that rely upon delivery to the interior of the tumor cell.

Antibodies, Neoplasm↗

PubMed2004

Andrographolide reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation.

Inflammation plays an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease. Recent reports have indicated that andrographolide (ANDRO) has an anti-inflammatory effect by modulating macrophage and neutrophil activity. Whereas microglia, the counterpart of macrophages in the brain, are pivotal in the inflammatory process in the central nervous system, the effect of ANDRO on inflammation-mediated neurodegeneration has not been examined. In this study, we show that both pretreatment and post-treatment with ANDRO exhibited a significant protective effect against lipopolysaccharide (LPS)-induced neurotoxicity in mixed neuron-glia cultures, as determined by [(3)H]dopamine uptake and immunocytochemical analysis. In contrast, ANDRO showed no protective effect on 1-methyl-4-phenyl-pyridine (0.5 microM)-induced neurotoxicity in neuron-enriched cultures. ANDRO significantly attenuated LPS-induced microglial activation and production of reactive oxygen species, tumor necrosis factor-alpha, nitric oxide, and prostaglandin E(2). Furthermore, ANDRO dose-dependently attenuated LPS-induced inducible nitric-oxide synthase and cyclooxygenase-2 protein expression in BV-2 microglia, as determined by Western blot. These findings demonstrate that ANDRO reduces inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuron-glia cultures by inhibiting microglial activation. In addition, these results indicate that ANDRO may have clinical utility for the treatment of inflammation-related neurodegenerative disorders such as Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

PubMed2004

Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy.

BACKGROUND: Gene therapy offers a new strategy for cancer treatment. Adenoviruses represent the most widely used gene therapy vector and feature an excellent safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor penetration and tumor selective oncolysis and consequently offer potential efficacy for metastatic disease treatment. We evaluated five CRAds as candidate clinical agents for ovarian cancer therapy: RGDCRADcox-2R, Ad5VEGFE1, Ad5/3VEGFE1, Ad5-Delta24RGD, and Ad5/3-Delta24. METHODS: DNA replication by these five CRAds, wild-type adenovirus, and an E1-deleted control was measured in purified primary ovarian cancer cell spheroids by quantitative PCR. CRAd-mediated oncolysis was quantified in ovarian cancer cell monolayers and three-dimensional spheroids by cellular viability assays. The therapeutic efficacy of each CRAd was tested by intraperitoneal administration in mice with peritoneally disseminated human ovarian cancer. RESULTS: An increase in viral DNA was noted in primary tumor cell spheroids for all replicative viruses tested. Variation was noted in viral DNA replication between patient samples. All five CRAds induced remarkable oncolysis. They also prolonged survival in vivo compared with the wild-type control group. CONCLUSIONS: All five CRAds tested showed robust DNA replication, oncolysis, and in vivo therapeutic efficacy. Each virus has potential for clinical testing, and such further testing will ultimately determine its safety and relative usefulness. Variation of CRAd DNA replication between different patient samples suggests that target tissue features, such as surface receptors and endogenous transcription factors, may affect CRAd infectivity and replicativity. Evaluation of such factors may become important to optimize cancer therapy for individual patients.

Adenocarcinoma↗

PubMed2004

Effects of L-tetrahydropalmatine on the expressions of bcl-2 and bax in rat after acute global cerebral ischemia and reperfusion.

To investigate the effects of L-Tetrahydropalmatine (L-THP) on the expressions of bcl-2, bax and neuronal apoptosis after cerebral ischemia and reperfusion, 60 Wistars rats were randomly divided into 3 groups: sham-operation group (group S, n = 20), ischemic-reperfusion group treated with saline (group I, n = 20) and ischemia-reperfusion group treated with L-THP (group T, n = 20). The rat model of global cerebral ischemia and reperfusion was induced by Pulsinelli's four-vessel occlusion method. The expression of bcl-2 and bax mRNA was detected by in situ hybridization and reverse transcriptional polymerase chain reaction (RT-PCR). The number of apoptotic neurons was examined by terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) method. Compared with group S, the expression of bcl-2 and bax mRNA in group I was increased significantly (P<0.01), and the number of apoptotic neurons increased either (P< 0.01). After L-THP treatment, the expression of bcl-2 mRNA was up-regulated (P< 0.01) and that of bax mRNA was down-regulated (P<0.01); the number of apoptotic neurons was decreased (P<0.01). Our results indicated that bcl-2 may suppress apoptosis and bax promote apoptosis after cerebral ischemia and reperfusion. L-THP could ameliorate cerebral ischemia and reperfusion damage by reducing the apoptosis through regulating bcl-2 and bax.

Animals↗