Biomedical subjects

Bo Hu

Publications and source records attributed to Bo Hu.

At least 37 records · Page 2Linked to original sources

PubMed2005

Power law distribution of wealth in population based on a modified Equíluz-Zimmermann model.

We propose a money-based model for the power law distribution (PLD) of wealth in an economically interacting population. It is introduced as a modification of the Equíluz and Zimmermann (EZ) model for crowding and information transmission in financial markets. Still, it must be stressed that in the EZ model a PLD without exponential correction is obtained only for a particular parameter, while our pattern will give the exact PLD within a wide range. The PLD exponent depends on the model parameters in a non-trivial way and is exactly calculated in this paper. The numerical results are in excellent agreement with the analytic prediction, and also comparable with empirical data of wealth distribution.

Journal Article↗

PubMed2005

Molecular determinants of glycine-independent desensitization of NR1/NR2A receptors.

Glycine-independent desensitization is thought to be an important regulatory mechanism for the function of N-methyl-D-aspartate (NMDA) receptors. Previous studies have suggested that the molecular determinants for glycine-independent desensitization are located at two distinct domains of NR2A, i.e., the amino-terminal domain (ATD) and the pre-M1 domain. Since the glycine-independent desensitization described in these earlier studies was a mixture of glycine-independent desensitization and zinc-dependent apparent desensitization, the exact role of these two domains in glycine-independent desensitization remains in question. In the present study, we show that deletion of the ATD of NR2A or mutating the pre-M1 region of NR2A causes no detectable changes in the degree or the time constant of glycine-independent desensitization. Therefore, the ATD and the pre-M1 domain of NR2A play no significant role in glycine-independent desensitization of NR1/NR2A receptors. On the other hand, several residues in the lurcher motif of either NR1 or NR2A are critical for the glycine-independent desensitization of NR1/NR2A receptors. In addition to NR1a(A653T) and NR2A(A651T), NR1a(T648C), NR1a(A649C), NR2A(T646C), and NR2A(A647C) show significantly reduced glycine-independent desensitization. Since all these mutations also alter the proton sensitivity or deactivation time constants of NR1/NR2A receptors, our data suggest that the channel gating and desensitization of NMDA receptors share common molecular determinants and that the lurcher motif of NR1 and NR2A is critical for both processes.

Binding Sites↗

PubMed2005

Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1 metalloprotease, and laminin 5 gamma 2 correlates with the invasiveness of human glioma.

Diffuse infiltration of malignant human glioma cells into surrounding brain structures occurs through the activation of multigenic programs. We recently showed that angiopoietin-2 (Ang2) induces glioma invasion through the activation of matrix metalloprotease-2 (MMP-2). Here, we report that up-regulation of Ang2, MMP-2, membrane type 1-MMP (MT1-MMP), and laminin 5 gamma 2 (LN 5 gamma 2) in tumor cells correlates with glioma invasion. Analyses of 57 clinical human glioma biopsies of World Health Organization grade I to IV tumors displaying a distinct invasive edge and 39 glioma specimens that only contain the central region of the tumor showed that Ang2, MMP-2, MT1-MMP, and LN 5 gamma 2 were co-overexpressed in invasive areas but not in the central regions of the glioma tissues. Statistical analyses revealed a significant link between the preferential expression of these molecules and invasiveness. Protein analyses of microdissected primary glioma tissue showed up-regulation and activation of MT1-MMP and LN 5 gamma 2 at the invasive edge of the tumors, supporting this observation. Concordantly, in human U87MG glioma xenografts engineered to express Ang2, increased expression of MT1-MMP and LN 5 gamma 2, along with MMP-2 up-regulation, in actively invading glioma cells was also evident. In cell culture, stimulation of glioma cells by overexpressing Ang2 or exposure to exogenous Ang2 promoted the expression and activation of MMP-2, MT1-MMP, and LN 5 gamma 2. These results suggest that up-regulation of Ang2, MMP-2, MT1-MMP, and LN 5 gamma 2 is associated with the invasiveness displayed by human gliomas and that induction of these molecules by Ang2 may be essential for glioma invasion.

Angiopoietin-2↗

PubMed2005

[Analysis on chemical and physical properties of Beijing super dust storm in spring of 2004].

On March 27, 2004 a super dust storm occurred in Beijing. The concentration of the aerosol and the element concentration of the aerosol were analyzed. The velocity of wind and radiation of ground were also measured. TSP increased 300 - 400 percent. PM2.5 increased 200 - 300 percent, but the concentration of the fine particle decreased. The elements like Na, Mg, Al, Mn and Fe mainly distribute in coarse particles. The contaminated elements such as Zn and Pb mainly distribute in fine particles. The contaminated elements mainly come from local source. The total radiation reduced 37.8 percent. With the increased of the velocity of the wind, the concentration of the coarse particle increased notability, the concentration of the fine particle decreased.

Air Pollutants↗

PubMed2004

Differential effects on current kinetics by point mutations in the lurcher motif of NR1/NR2A receptors.

The extracellular proton site has emerged as the key site in regulating N-methyl-d-aspartate (NMDA) receptor function. However, the molecular determinants for the proton-sensitive gating of NMDA receptors are still not clearly delineated. The highly conserved lurcher motif plays an important role in determining the proton sensitivity of NMDA receptors. Mutations of several residues in the lurcher motif of either NR1 or NR2A significantly reduce proton sensitivity of recombinant NR1/NR2A receptors. It remains uncertain how these residues play a role in proton inhibition of NMDA receptors. Mutations of these residues could directly reduce the proton affinity. Alternatively, they could alter the proton IC(50) indirectly by increasing channel open probability. In the present study, we recorded the macroscopic NMDA currents in HEK 293 cells with a piezo-based rapid solution exchange system. We show that zinc slows the deactivation of NR1a(A653T)/NR2A receptors and NR1a/NR2A(A651T) receptors. However, NR1a(T648C)/NR2A, NR1a/NR2A(T646C), NR1a(A649C)/NR2A, NR1a/NR2A(A647C), and NR1a(A653T)/NR2A exhibit significantly slower rise time and deactivation time constants under nominally zinc-free conditions. Our data suggest that the channel open probability for these mutant receptors may be significantly increased. The reduction in proton sensitivity by these mutations could be accounted for, at least partially, by the increased channel open probability. In contrast, NR1a/NR2A(A651T) exhibits normal macroscopic currents, suggesting that the reduction of proton sensitivity by this mutation cannot be attributed to any significant change of open probability. Further experiments are needed to determine the exact role of this residue in proton-sensitive gating of NMDA receptors.

Amino Acid Motifs↗

PubMed2004

Resistive wall mode in collisionless quasistationary plasmas.

The stability analysis of the n=1 resistive wall mode is carried out for a simplified model of collisionless tokamak plasma. It is found that the trapped particle compressibility and the resonance between the mode and the precession drift frequency lead to a significant improvement of the beta stability limits. It is shown that, within the frame of the simplified model, the resistive wall mode can be fully suppressed and the plasma can be stable up to the wall beta limits for a slow plasma rotation.

Journal Article↗

PubMed2004

Genetic variation of Cordyceps sinensis, a fruit-body-producing entomopathogenic species from different geographical regions in China.

Cordyceps sinensis is one of the most valuable medicinal fungi in the Orient. It is naturally distributed in the eastern extension area of the Qinghai-Tibet plateau, at an altitude over 4000 m high. In order to investigate genetic variation and evolutionary relationships of C. sinensis from different geographical regions, 17 isolates of C. sinensis were collected from different provinces and the complete sequences of rDNA ITS were determined. On the basis of 5.8S rDNA and ITS region analysis, it was clearly shown that the ITS sequences within C. sinensis are highly homologous regardless of geographical origin. The distance values between the sequences in this study were lower than 0.03. This implied that C. sinensis from different geographic regions are the same species; they are not different species or a species complex. The results also showed that distance values between C. sinensis and Hirsutella sinensis are of the same order as those within C. sinensis from different geographic regions. This confirmed our previous results that C. sinensis should only have H. sinensis as its asexual stage whatever the geographic region from which the samples were collected. An rDNA ITS clone library was established to obtain further evidence for the interpretation of the fungal community structure from C. sinensis and to confirm the accuracy of the taxonomic identities produced by directly sequencing the rDNA ITS region. The discrimination between intraspecies of C. sinensis might provide additional data for the authentication of medicinal material at the species or intraspecies level.

Animals↗

PubMed2004

Rapid inhibition of the glutamate-induced increase of intracellular free calcium by magnesium in rat hippocampal neurons.

By using Fura-2/AM, the effects of magnesium (Mg2+) on the glutamate-induced increase of intracellular free calcium ([Ca2+]i) in the cultured hippocampal neurons and the features were investigated by integrated photoelectric detecting system. The experiments were designed to three groups (The drug was spit to the cells for 20 s): Group A receiving 1 x 10(-5) mol/L glutamate; Group B receiving 1 x 10(-5) mol/L glutamate and 1 x 10(-5) mol/L Mg2+ simultaneously; Group C receiving 1 x 10(-5) mol/L glutamate again after [Ca2+]i in group B back to the baseline. The results showed that in group A, [Ca2+]i was obviously increased. In group B, the changes in [Ca+] i and the peak value were significantly decreased. Moreover, the elevation of Phase 1 was slowed down and Phase 2 was shortened to some extent, and the plateau phase between them was relatively prolonged. In group C, calcium oscillation similar to that in group A occurred, but both the Phase 1 and Phase 2 were shortened and the delta[Ca2+]i was slightly decreased. It was suggested that Mg2+ could quickly inhibit the rise of [Ca2+]i induced by glutamate in the cultured hippocampal neurons in rats.

Animals↗

PubMed2004

Identification of two novel alternatively spliced Neuropilin-1 isoforms.

Neuropilin-1 (NRP1) is a coreceptor to a tyrosine kinase receptor for both the vascular endothelial growth factor (VEGF) family and semaphorin (Sema) family members. NRP1 plays versatile roles in angiogenesis, axon guidance, cell survival, migration, and invasion. NRP1 contains three distinct extracellular domains, a1a2, b1b2, and c. We report here the identification of two novel soluble human NRP1 isoforms, which we named sIIINRP1 and sIVNRP1. These soluble NRP1 isoforms were generated by alternative splicing of the NRP1 gene, a common regulatory mechanism occurring in cell surface receptor families. Both sIIINRP1 and sIVNRP1 contain a1a2 and b1b2 domains, but no c domain, and the rest of the NRP1 sequence. Additionally, sIIINRP1 is missing 48 amino acids within the C-terminus of the b2 domain. Both sIIINRP1 and sIVNRP1 are expressed in human cancerous and normal tissues. These molecules are capable of binding to VEGF165 and Sema3A. Furthermore, recombinant sIIINRP1 and sIVNRP1 proteins inhibit NRP1-mediated MDA-MB-231 breast cancer cell migration. These results indicate the multiple levels of regulation in NRP1 function and suggest that these two novel NRP1 isoforms are useful antagonists for NRP1-mediated cellular activities.

Alternative Splicing↗

PubMed2004

A PSTAIRE CDK-like protein localizes in nuclei and cytoplasm of Physarum polycephalum and functions in the mitosis.

CDKs play key roles in controlling cell cycle progression in all eukaryotes. In plants, multiple CDKs are present, among which the best characterized CDKs are PSTAIRE CDKs. In this study, we carried out Western blot, immunoelectron microscopy and antibody treatment with an anti-PSTAIRE monoclonal antibody to explore the subcellular localization and functions of PSTAIRE CDKs in Physarum polycephalum. The results of western blot and immunoelectron microscopy showed that in P. polycephalum, a PSTAIRE CDK-like protein was 34 kD in molecular weight and located in both nuclei and cytoplasm. In nuclei, the protein was mainly associated with chromosomes and nucleoli. The expression of the PSTAIRE CDK-like protein in both the plasmodia and nuclei showed little fluctuation through the whole cell cycle. When treated with an anti-PSTAIRE monoclonal antibody at early S phase, the cells were arrested in S phase, and the mitotic onset of P. polycephalum was blocked for about 1 h when treated at early G2 phase. Our data indicated that the PSTAIRE CDK- like protein has a direct bearing on the mitosis.

Animals↗

PubMed2004

NMDA and AMPA receptors mediate intracellular calcium increase in rat cortical astrocytes.

AIM: To study the effect of glutamate on the intracellular calcium signal of pure cultured rat astrocytes and the role of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in the procedure. METHODS: The fluorescence of calcium was measured by Fura-2/AM (F(345)/F(380)). RESULTS: L-Glutamate induced [Ca(2+)](i) increase in most of the cells in concentration- and time-dependent manner. NMDA 50 mmol/L induced the fluorescence increase by almost three to four times, while the effect of AMPA 50 mmol/L was just half of that of D-(-)-2-amino-5-phosphonopentanoic acid (D-AP-5; a selective antagonist of the NMDA receptor). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX, a selective antagonist of the AMPA receptor) abolished the effects of NMDA and AMPA, respectively. D-AP-5 and CNQX simultaneously or respectively attenuated the effect of L-glutamate at different degrees, but could not abolish it entirely. CONCLUSION: Glutamate modulated intracellular Ca(2+) of pure cultured rat astrocytes through different pathways. The activation of NMDA and AMPA receptors took part in the complex mechanisms.

2-Amino-5-phosphonovalerate↗

PubMed2004

[A SC35-like protein is localized in the nucleus of Physarum polycephalum].

After being labeled with an anti-SC35 antibody, the specimens of Physarum polycephalum at S, G2, prophase, metaphase and ana-telophase were observed with an Hitachi electron microscope and gold particles marking the location of the SC35-like protein were mainly found in the nucleus,indicating the existence of a SC35-like protein in it. Judging from the densities of the gold particles in the individual domains of the nucleus, the SC35-like protein was principally located in the nucleolar domain and interchromatin domain during G2 and prophase, and the protein was distributed in the interchromosome domain at metaphase and ana-telophase when the nucleus was disintegrated, suggesting that the nucleolus and interchromatin (interchromosome) domain are the two main locations of the SC35-like protein in the nucleus. Further observations upon the nucleolus revealed that the density of the gold particles in the dense fibrillar component (DFC) of the nucleolus was much higher than that of the fibrillar center (FC), demonstrating that the protein was largely situated in the DFC rather than FC.

Animals↗

PubMed2004

[NMR study on the determination of structure in the protected glucosamineoside].

The protected glucosamines 5, 8, 9, 12, 13 and the protected diglucosamines 10 and 11 were prepared from D-glucosamine hydrochloride, trichloroacetonitrile, trichlorocthoxycarbonyl chloride and trimethylsilyl trifluoromethanesulfonate (TMSOTf). They were new products and their structures were characterized by means of 1H NMR and 13C NMR. The data of 1H NMR indicated that the chemical shift of NH of them were moved remarkably to the low field 5.07-5.26 compared with that of D-glucosamine hydrochloride. The data J(1, 2) of the compounds 9, 10, 11, 12, 13 were between 7.2 and 8.8 Hz, which showed their structures were beta configuration, while the data J(1, 2) were between 3.00 and 4.96 Hz in the compounds 5 and 6, which showed their structures were alpha configuration. H-2 was situated in the higher field, which delta was between 3.10 and 4.30. The data of 13C NMR showed that the delta of C-1 laid in the lowest field and the delta of C-2 laid in the higher field, as were the delta of H-1 and H-2 in NMR. Commonly speaking, if the delta of C-1 was greater than 100, the structure of the compound was beta configuration such as compound 9 (delta = 101.9). On the contrary, if the delta of C-1 was less than 100, the structures were alpha configuration like compound 5 (delta = 95.20) and 6 (delta = 97.21). The chemical shift of other carbon and hydrogen in the ring were discussed. The progression of Carbon in the compound 6 were distinguished conveniently and clearly by using DEPT (Distortionless Enhancement by Polarization Transfer) and 13C NMR.

Glucosamine↗

PubMed2003

Pioglitazone inhibits LOX-1 expression in human coronary artery endothelial cells by reducing intracellular superoxide radical generation.

OBJECTIVE: LOX-1, a novel lectin-like receptor for oxidized LDL (ox-LDL), is expressed in response to ox-LDL, angiotensin II (Ang II), tumor necrosis factor (TNF)-alpha, and other stress stimuli. It is highly expressed in atherosclerotic tissues. Peroxisome proliferator-activated receptor (PPAR)-gamma ligands, such as pioglitazone, exert antiatherosclerotic effects. This study examined the regulation of LOX-1 expression in human coronary artery endothelial cells (HCAECs) by pioglitazone. METHODS AND RESULTS: Fourth generation HCAECs were treated with ox-LDL, Ang II, or TNF-alpha with or without pioglitazone pretreatment. All 3 stimuli upregulated LOX-1 expression (mRNA and protein). Pioglitazone, in a concentration-dependent manner, reduced LOX-1 expression (P<0.01 versus ox-LDL, Ang II, or TNF-alpha alone). Ox-LDL, Ang II, and TNF-alpha each enhanced intracellular superoxide radical generation, and pioglitazone pretreatment reduced superoxide generation (P<0.01 versus ox-LDL, Ang II, or TNF-alpha). Furthermore, all 3 stimuli upregulated the expression of the transcription factors nuclear factor-kappaB and activator protein-1 (determined by electrophoretic mobility shift assay), and pioglitazone pretreatment reduced this expression (P<0.01 versus ox-LDL, Ang II, or TNF-alpha). To determine the biological significance of pioglitazone-mediated downregulation of LOX-1, we studied monocyte adhesion to ox-LDL-treated HCAECs. Pioglitazone reduced the adhesion of monocytes to activated HCAECs in a fashion similar to that produced by antisense to LOX-1 mRNA. CONCLUSIONS: These observations suggest that the PPAR-gamma ligand pioglitazone reduces intracellular superoxide radical generation and subsequently reduces the expression of transcription factors, expression of the LOX-1 gene, and monocyte adhesion to activated endothelium. The salutary effect of PPAR-gamma ligands in atherogenesis may involve the inhibition of LOX-1 and the adhesion of monocytes to endothelium.

Angiotensin II↗

PubMed2003

A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.

There is growing evidence for the intracellular role of cytokines and growth factors, but the pathways by which these activities occur remain largely obscure. Previous work from our laboratory identified the constitutive, aberrant expression of the 31-kDa IL-1 alpha precursor (pre-IL-1 alpha) in the nuclei of fibroblasts from the lesional skin of patients with systemic sclerosis (SSc). We established that pre-IL-1 alpha expression was associated with increased fibroblast proliferation and collagen production. Further investigation has led to the identification of a mechanism by which nuclear expression of pre-IL-1 alpha affects fibroblast growth and matrix production. By using a yeast two-hybrid method, we found that pre-IL-1 alpha binds necdin, a nuclear protein with growth suppressor activity. We mapped the region of pre-IL-1 alpha responsible for necdin binding and found it to be localized near the N terminus, a region that is present on pre-IL-1 alpha, but not the mature 17-kDa cytokine. Expression studies demonstrated that pre-IL-1 alpha associates with necdin in the nuclei of mammalian cell lines and regulates cell growth and collagen expression. Our results provide the first evidence, to our knowledge, of a nuclear target for pre-IL-1 alpha. Based on these findings, we propose that the constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of SSc fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin, and by counteracting its effects on cell growth and collagen production.

Amino Acid Sequence↗

PubMed2003

Oxidized LDL through LOX-1 modulates LDL-receptor expression in human coronary artery endothelial cells.

Experimental studies have shown that oxidized low-density lipoprotein (ox-LDL) up-regulates its receptor LOX-1. Both ox-LDL and LOX-1 are expressed in atherosclerotic plaques. Native LDL concentrations are elevated in atherosclerosis, suggesting a reduction in LDL-receptors. We hypothesized that ox-LDL via LOX-1 could influence the expression of LDL-receptors. This study was designed to examine the interaction between ox-LDL, LOX-1, and LDL-receptors in human coronary artery endothelial cells (HCAECs). HCAECs were incubated with ox-LDL (10-80 microg/ml) for 3-24h. Ox-LDL decreased the expression of LDL-receptor in a concentration- and time-dependent fashion. The effects of ox-LDL were mediated by its endothelial receptor LOX-1, since pretreatment of HCAECs with a blocking antibody to LOX-1 (JTX92, 10 microg/ml) prevented the effect of ox-LDL on LDL-receptor expression. The role of LOX-1 was further confirmed by the use of an antisense to LOX-1 mRNA, which also blocked the effect of ox-LDL in LDL-receptor expression. In other experiments, ox-LDL as expected induced superoxide anion generation; and pretreatment of HCAECs with the anti-oxidants trolox and alpha-tocopherol (each 10 microM) inhibited the formation of superoxide anions as well as the down-regulation of LDL-receptor in response to ox-LDL. These studies provide the first evidence that ox-LDL via LOX-1 modulates LDL-receptor expression in HCAECs. The generation of free radicals elicited by ox-LDL may be a key step in this process.

Antioxidants↗

PubMed2003

Overexpression of vascular endothelial growth factor by MCF-7 breast cancer cells promotes estrogen-independent tumor growth in vivo.

Alteration of the phenotype of breast cancers from estrogen-dependent to estrogen-independent growth often leads to the failure of antiestrogenic tumor therapies. We report that overexpression of vascular endothelial growth factor (VEGF) by estrogen-dependent MCF-7 breast cancer cells could abolish estrogen-dependent tumor growth in ovariectomized mice. In the absence of estrogen, MCF-7 VEGF-expressing tumors with increased vessel density showed growth kinetics similar to, or even greater than, that of parental MCF-7 tumors with estrogen supplementation. Overexpression of VEGF by MCF-7 cells or treatment on parental MCF-7 cells with recombinant VEGF also stimulated cell proliferation in culture. Our data suggest that VEGF stimulation of MCF-7 tumor angiogenesis and growth is mediated by both autocrine and paracrine mechanisms.

Animals↗

PubMed2003

Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2.

A hallmark of highly malignant human gliomas is their infiltration of the brain. We analyzed a large number of primary human glioma biopsies and found high levels of expression of an angiogenic regulator, angiopoietin-2 (Ang2), in the invasive areas, but not in the central regions, of those tumors. In the invasive regions where Ang2 was overexpressed, increased levels of matrix metalloprotease-2 (MMP-2) were also apparent. Consonant with these features, intracranial xenografts of glioma cells engineered to express Ang2 were highly invasive into adjacent brain parenchyma compared with isogenic control tumors. In regions of the Ang2-expressing tumors that were actively invading the brain, high levels of expression of MMP-2 and increased angiogenesis were also evident. A link between these two features was apparent, because stable expression of Ang2 by U87MG cells or treatment of several glioma cell lines with recombinant Ang2 in vitro caused activation of MMP-2 and acquisition of increased invasiveness. Conversely, MMP inhibitors suppressed Ang2-stimulated activation of MMP-2 and Ang2-induced cell invasion. These results suggest that Ang2 plays a critical role in inducing tumor cell infiltration, and that this invasive phenotype is caused by activation of MMP-2.

Angiogenesis Inducing Agents↗