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Biomedical subjects

Min Zhou

Publications and source records attributed to Min Zhou.

At least 73 records · Page 4Linked to original sources
PubMed2004

Helical supramolecules and fibers utilizing leucine zipper-displaying dendrimers.

We describe a new family of discrete supramolecules comprising leucine-zipper peptides noncovalently assembled upon cognate leucine zippers fused to a dendrimer core. Circular dichroism and sedimentation equilibrium experiments clearly demonstrate that each leucine-zipper dendrimer (D-EZ4 or D-KZ4) can noncovalently display four leucine zippers on their surface that can be utilized for the multivalent display of protein cargo. Furthermore, we show that matched leucine-zipper dendrimers (D-EZ4/D-KZ4) can self-organize into fibers at neutral pH, providing a new scaffold for nanotechnology.

Amino Acid Sequence↗
PubMed2004

VSD: a database for schizophrenia candidate genes focusing on variations.

Schizophrenia is a common mental disease characterized by delusions, hallucinations, and formal thought disorder. It has been demonstrated with genetic evidence that the disease is a polygenic disorder. Pharmacological, neurochemical, and clinical studies have suggested a number of schizophrenia susceptibility loci. In order to systematically search for genes with small effect in the development of schizophrenia, a database called VSD was established to provide variation data for publicly available candidate genes. Most of the genes encode neurotransmitter receptors, neurotransmitter transporters, and the enzymes involved in their metabolism. Other candidate genes extracted from published literature are also included. The variation information has been collected from publicly available mutation and polymorphism databases such as dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the most abundant form of collected variations. Reference sequences from NCBI's RefSeq database are used as references when positioning variation at transcript and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid changes in the functional sites or domains of proteins are distinguished since they are more likely to affect protein function and would be target SNPs for association studies. In addition to variation data, gene descriptions, enzyme information, and other biological information for each gene locus are also included. The latest version of VSD contains 23,648 variations assigned to a total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be accessed via the World Wide Web (www.chgb.org.cn/vsd.htm) and will be developed as an up-to-date and comprehensive locus-specific resource for identifying susceptibility genes for schizophrenia.

Databases, Nucleic Acid↗
PubMed2004

Regulation of insulin secretion and expression of SUR1 gene by chronic exposure to free fatty acids in rat pancreatic beta cells.

To study the effects of free fatty acids on insulin secretion and expression of SUR1 gene in rat pancreatic B cells in vitro, and to explore the molecular mechanisms in lipotoxicity inducing insulin secretion dysfunction, pancreatic islet cells were isolated and digested from male SD rats. Purified islets were incubated with either 0.25 mmol/L palmitate or 0.125 mmol/L oleate for 48 h in vitro. Then islets were stimulated with either 5.6 mmol/L or 16.7 mmol/L glucose for 1 h. Insulin release was measured by using radioimmunoassay, and the expression of SUR1 gene mRNA was quantified by reserve transcription-polymerase chain reaction (RT-PCR). The islets exposed to both palmitate and oleate for 48 h showed an increased basal and a decreased glucose-indused insulin release as compared with control islets. Palmitate increased basal insulin secretion by 110% (P< 0.01), decreased glucose stimulated insulin secretion by 43% (P<0.01); while oleate increased basal insulin secretion by 80% (P<0.01) and decreased glucose stimulated insulin secretion by 32 % (P<0.05). RT-PCR showed that oleate significantly suppressed SUR1 gene expression by 64 % (P<0.01) as compared with the control group, while palmitate group manifested a light decrease of 15% (P>0.05) of SUR1 gene expression. Our results suggested that chronic exposure to free fatty acids of pancreatic beta cells inhibited glucose stimulated insulin secretion. Regulation of SUR1 gene expression may be involved in such effects, which may also be one of the molecular mechanisms in lipotoxocity inducing beta cells secretion dysfunction.

ATP-Binding Cassette Transporters↗
PubMed2004

Antiproliferative activity of Goldfussia psilostachys ethanolic extract on K562 leukemia cells.

A dose-dependent and significant (P<0.01) antiproliferative effect of Goldfussia psilostachys ethanolic extract was observed on K562 cells. The IC(50) is ca. 0.5 microg/ml. The extract markedly increases the proportion of cell in G2/M phases and decreases the population of cells in G0/G1 phases. Moreover, the antimitotic effect is correlated with polymerization of microtubule assembly. These results indicate that G. psilostachys ethanolic extract inhibits the proliferation of K562 cells and disrupts the normal dynamic of microtubules during mitosis.

Animals↗
PubMed2004

Automation of protein purification for structural genomics.

A critical issue in structural genomics, and in structural biology in general, is the availability of high-quality samples. The additional challenge in structural genomics is the need to produce high numbers of proteins with low sequence similarities and poorly characterized or unknown properties. 'Structural-biology-grade' proteins must be generated in a quantity and quality suitable for structure determination experiments using X-ray crystallography or nuclear magnetic resonance (NMR). The choice of protein purification and handling procedures plays a critical role in obtaining high-quality protein samples. The purification procedure must yield a homogeneous protein and must be highly reproducible in order to supply milligram quantities of protein and/or its derivative containing marker atom(s). At the Midwest Center for Structural Genomics we have developed protocols for high-throughput protein purification. These protocols have been implemented on AKTA EXPLORER 3D and AKTA FPLC 3D workstations capable of performing multidimensional chromatography. The automated chromatography has been successfully applied to many soluble proteins of microbial origin. Various MCSG purification strategies, their implementation, and their success rates are discussed in this paper.

Automation↗
PubMed2004

[Clinical effect of escin on patients with cutaneous pruritus caused by blood stasis and wind-dryness].

OBJECTIVE: To observe the clinical effect of escin on patients with cutaneous pruritus caused by blood stasis and wind-dryness and to prove the theory that "wind should be treated by regulating blood disorder, and wind disappears after activating blood" in traditional Chinese medicine (TCM). METHODS: Fifty-one patients were randomly divided into escin-treated group (n=30) and loratadine-treated group (n=21). The patients in the escin-treated group were treated with escin for 4 weeks (300 mg, b.i.d.), and the patients in the loratadine-treated group were treated with loratadine (10 mg, q.d.). Symptom score reducing index (SSRI) was used to assess the pruritus degree, lesion range and lesion shape before the treatment, 2 weeks and 4 weeks after the treatment, respectively. RESULTS: Two weeks after the treatment, the effective rate of the escin-treated group was 63.3%, and the effective rate of the loratadine-treated group was 67.0%. Four weeks after the treatment, the effective rates were 86.7% and 80.0% in escin- and loratadine-treated groups respectively. There was no statistical difference in total scores of SSRI in two groups (P>0.05), and the scores of pruritus degree and lesion shape also had no statistical difference (P>0.05), while the score of lesion range of the escin-treated group was lower than that of the loratadine-treated group (P<0.05). CONCLUSION: Escin has satisfactory effect in treating pruritus caused by blood stasis and wind-dryness. The study confirms the TCM theory that "wind should be treated by regulating blood disorder, and wind disappears after activating blood".

Adult↗
PubMed2004

[Effect of S-2-(3-aminopropylamino) ethyl phosphorothioic acid on apoptosis and proliferation inhibition of HL-60 cell line].

To study the effects of S-2-(3-aminopropylamino) ethyl phosphorothioic acid (WR-2721, amifostine) on proliferation inhibition and apoptosis of HL-60 human leukemia cell line, the cell apoptosis rate of HL-60 was determined by annexin V/PI double staining method. Cell proliferation and chemotherapy sensitivity were analyzed with XTT assay, and the changes of cell cycle were observed through flow cytometry. The results showed that WR-2721 could significantly inhibit HL-60 cell proliferation. After treatment (30 min, 37 degrees C) with WR-2721, the sensitivity of HL-60 cells to VP16 was enhanced, and the IC(50) descended from 52.5 micro g/ml to 40.5 microg/ml. After 72 hours treatment of HL-60 cells with WR-2721, the early apoptotic cells (annexin V-FITC positive/PI negative) were increased from (5.5 +/- 1.9)% to (48.5 +/- 8.4)% (P < 0.001), late apoptotic cells (annexin V-FITC positive/PI positive) were increased from (1.2 +/- 0.5)% to (39.0 +/- 4.0)% (P < 0.001), and HL-60 cells were arrested in G(2)-M phase. In conclusion, WR-2721 treatment can enhance HL-60 cell chemotherapy sensitivity to VP16, inhibit proliferation, induce apoptosis and accumulation of cells in G(2)-M phase.

Amifostine↗
PubMed2004

Genetic polymorphism in matrix metalloproteinase-9 and the susceptibility to chronic obstructive pulmonary disease in Han population of south China.

BACKGROUND: There are many candidate genes for chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase-9 (MMP-9) plays an essential role in tissue remodeling and repair associated with development of COPD. In this study we investigated the correlation between MMP-9 gene polymorphism and COPD susceptibility in the Han population of South China. METHODS: We examined the frequency of polymorphic genotypes of the MMP-9 promoter (-1562C/T) in 100 COPD patients and 98 healthy smokers by restriction fragment length polymorphism. RESULTS: The frequencies of polymorphic genotypes in promoters of MMP-9 were C/C 86%, C/T 14% in COPD group; and C/C 98%, C/T 2% in the control group. There were significant differences between the two groups (P < 0.01). The allele frequencies were also significantly different between the COPD group and the control group (C allele frequency: 93% vs 99%, T allele frequency: 7% vs 1%, P < 0.05 respectively). CONCLUSION: The genetic polymorphism in promoters of MMP-9 gene is associated with the susceptibility to COPD in the Han population of South China.

Adult↗
PubMed2004

[Protective effects of amifostine on hematopoietic stem/progenitor cells against chemotherapeutic damage].

The aim was to study the protective effects of amifostine (AMF) on normal hematopoietic stem/progenitor cells against the chemotherapeutic damage from etoposide (VP-16). The cord blood mononuclear cells (CBMNC), fresh and frozen peripheral blood stem cells (PBSC), and HL-60 cells were divided into AMF, AMF + VP-16, VP-16 and control groups, each group cell viability was determined by using trypan blue exclusion test, the CFU-GM culture was used to count cells, the apoptosis was detected by flow cytometry. The results showed that in CBMNC, fresh and frozen PBSC samples, cell viability and the number of CFU-GM in AMF + VP-16 group were all significantly higher than those in VP-16 group (P < 0.05); the CFU-GM incidence in AMF + VP-16 group was higher than that in VP-16 group, and the GFU-GM life in AMF + VP-16 group was also longer than that of latter, in CBMNC samples, the number of CFU-GM in AMF groups was higher than that in control group, but there was no statistical significance between the two groups (P > 0.05), in HL-60 cell apoptotic rate in AMF + VP-16 group was little higher than that in VP-16 group, but no statistical significance between these two groups (P > 0.05). It is concluded that AMF can significantly protect normal hematopoietic stem/progenitor cells against the damage from VP-16. Moreover, AMF does not affect cytotoxity of VP-16 on HL-60 cells, and can not stimulate the growth and differentiation of cord hematopoietic stem/progenitor cells directly.

Amifostine↗
PubMed2004

[The application of human mutation databases].

Researches on genome mutation are becoming more and more important with the finish of human genome DNA draft. This review is to classify the existing human mutation databases, including mutation database, SNP(single nucleotide polymorphisms) databases, mutation databases about disease, mutation databases about proteins, mutation databases about map and mutation information about specific gene. We also give advice on how to utilize these mutation databases, and discuss problems of existing databases.

Databases, Factual↗
PubMed2003

Electrophysiologically "complex" glial cells freshly isolated from the hippocampus are immunopositive for the chondroitin sulfate proteoglycan NG2.

We have recently described a subgroup of isolated glial fibrillary acidic protein-positive (GFAP+) hippocampal astrocytes that predominantly express outwardly rectifying currents (which we term "ORAs" for outwardly rectifying astrocytes), which are similar to the currents already described for hippocampal GFAP- "complex glia." We now report that post-recording staining of cells that were first selected as "complex" by morphology and then confirmed by their electrophysiological characteristics were NG2+ approximately 90% of the time. Also, the morphology of freshly isolated NG2+ cells differs from that of isolated GFAP+ ORAs in having a smaller and round cell body with thinner processes, which usually are collapsed back onto the soma. Upon detailed examination, NG2+ cells were found to differ quantitatively in some electrophysiological characteristics from GFAP+ ORAs. The outward, transient K+ currents (IKa) in the NG2+ cells showed a slower decay than the IKa in ORAs, and their density decreased in NG2+ cells from older animals. The other two major cation currents, the voltage-activated Na+ and outwardly delayed rectifier K+ currents, were similar in NG2+ cells and ORAs. To further distinguish isolated complex cells from outwardly rectifying GFAP+ astrocytes, we performed immunocytochemistry for glial markers in fixed, freshly isolated rat hippocampal glia. NG2+ cells were negative for GFAP and also for the astrocytic glutamate transporters GLT-1 and GLAST. Thus the isolated hippocampal NG2+ glial cells, though having an electrophysiological phenotype similar to that of ORAs, are an immunologically and morphologically distinct glial cell population and most likely represent NG2+ cells in situ.

Amino Acid Transport System X-AG↗
PubMed2003

Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8.

Tumor necrosis factor-alpha (TNFalpha) and granulocyte macrophage colony-stimulating factor (GM-CSF) individually enhance monocyte matrix metalloproteinase-9 (MMP-9) but induce MMP-1 only when added in combination. Because interferon-gamma (IFNgamma) is also found at inflammatory sites, we determined its effect on monocyte MMPs in the presence or absence of TNFalpha and GM-CSF. IFNgamma alone did not stimulate monocyte MMP-9 or MMP-1; however, in the presence of GM-CSF it induced MMP-1 and enhanced MMP-1 stimulated by GM-CSF and TNFalpha. IFNgamma induced MMP-1 in the presence of GM-CSF through the stimulation of TNFalpha production through a mechanism involving both p38 and ERK1/2 MAPKs, in which GM-CSF stimulated ERK1/2 whereas IFNgamma activated p38. In support of this conclusion TNFalpha neutralizing antibody and antibodies against TNF receptor I and -II blocked the induction of MMP-1 by GM-CSF and IFNgamma. In contrast to its effects on MMP-1, IFNgamma inhibited TNFalpha-induced MMP-9 through a caspase 8-dependent pathway as demonstrated by the restoration of MMP-9 with caspase 8 inhibitors. Moreover, the phosphorylation of STAT1 by IFNgamma was blocked by an inhibitor of caspase 8, indicating that STAT1 had a suppressive effect on MMP-9. Caspase 8-mediated phosphorylation of STAT1 through p38 MAPK as shown by the inhibition of IFNgamma-induced phosphorylation of p38 by caspase 8 inhibitors. Activation of caspase 8 by IFNgamma did not result in increased apoptosis. Thus IFNgamma in the presence of GM-CSF and/or TNFalpha differentially regulates monocyte MMPs through induction of TNFalpha and a novel mechanism involving caspase 8 that is independent of apoptosis.

Apoptosis↗
PubMed2003

How can enzymes be so efficient?

Dudley Williams and his colleagues discuss how ligands can gain binding energy to their receptors, and substrate transition states to their enzymes, by tightening the protein structures, with a decrease in their dynamic behaviour.

Binding Sites↗
PubMed2003

Differential regulation of lipopolysaccharide-induced monocyte matrix metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases.

Signal transduction events in monocyte matrix metalloproteinase (MMP) production have been shown to include a PGE(2)-cAMP-dependent step. To determine earlier pathway components, we examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of monocyte MMP-1 and MMP-9, two major MMPs induced by LPS. Stimulation with LPS resulted in the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen-activated kinase p38. The p38-specific inhibitor SB203580 suppressed p38 activity and MMP-1 mRNA and protein, but increased ERK activity and MMP-9 mRNA and protein. In contrast, the MAPK kinase 1/2-specific inhibitor PD98059 inhibited MMP-1 and MMP-9. However, both MAPK inhibitors decreased the production of cyclooxygenase-2 and PGE(2), but only the inhibition of MMP-1 by SB203580 was reversed by PGE(2) or dibutyryl cAMP. Examination of the effect of these MAPK inhibitors on the promoters of MMP-1 and MMP-9 revealed that PD98059 inhibited the binding of transcription factors to all of the MMP promoter-specific complementary oligonucleotides tested. However, SB203580 only inhibited the binding of MMP-1-specific CREB and SP 1 oligonucleotides, which was reversed by PGE(2). Additionally, SB203580 enhanced transcription factor binding to the oligonucleotides complementary to a NF-kappaB site in the promoter of MMP-9. Thus, LPS induction of MMP-1 production by monocytes is regulated by both ERK1/2 and p38, whereas MMP-9 stimulation occurred mainly through the ERK1/2 pathway. Moreover, p38 regulates MMP-1 mainly through a PGE(2)-dependent pathway, whereas ERK1/2-mediated MMP-1 and MMP-9 production involves the activation of additional MMP promoter sites through a PGE(2)-independent mechanism.

Cells, Cultured↗
PubMed2003

Ligand binding energy and catalytic efficiency from improved packing within receptors and enzymes.

Some small molecules bind to their receptors, and transition states to enzymes, so strongly as to defy current understanding. We show that in the binding of biotin to streptavidin, the streptavidin structure becomes better packed. We conclude that this contraction of the streptavidin structure promotes biotin binding. The improved packing is associated with positively cooperative binding, occurring with a benefit in enthalpy and a cost in entropy. Evidence indicating that catalytic efficiency can also originate via improved packing in some enzyme transition states, derived from the work of others, is presented. Negatively cooperative ligand binding is concluded to induce converse effects (less efficient packing, a cost in enthalpy, and a benefit in entropy). It applies to the binding of O(2) to haemoglobin, which indeed occurs with a hitherto unreported loosening of the amide backbones of the haemoglobin monomers.

Animals↗