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Biomedical subjects

F Bai

Publications and source records attributed to F Bai.

At least 19 recordsLinked to original sources

Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIMS: Osteopontin (OPN) is known to be associated with metastasis in many types of cancers. Since OPN is a highly phosphorylated and glycosylated protein, the modification after transcription is very important to its function. In hepatocellular carcinoma (HCC), the elevated expression of OPN at mRNA levels and its relationship with metastasis and poorer prognosis of the patients have been reported. However, the prognostic impact of OPN at protein levels on the patients with hepatitis B virus (HBV)-related HCC after hepatectomy is still limited. PATIENTS AND METHODS: The expression of OPN was examined at protein level by using immunohistochemistry in 72 patients who underwent hepatectomy for HBV-related HCC, and its prognostic significance in disease-free and overall survival of the patients was also analyzed by log-rank test and multivariate Cox regression analyses. RESULTS: Thirty-nine of 72 (54.17%) HBV-related HCC specimens were positive for OPN with cytoplasmic staining. OPN was highly expressed in the specimens with capsular infiltration compared to those without (P<0.05), and also was significantly related with portal vein invasion (P<0.01) and lymph node invasion (P<0.01). The mean disease-free survival (DFS) was only 13.55+/-14.77 months when the HBV-related HCC specimens highly expressed OPN compared to 36.00+/-18.68 months for those with low expression (P<0.001). The overall survival (OS) of the patients was 18.63+/-17.28 months when the HCC over-expressed OPN compared to 42.59+/-16.85 months for HCC with the low expressed OPN (P<0.001). Multivariate analysis showed that OPN over-expression was the strongest independent adverse prognostic factor for both DFS (P=0.01) and OS (P=0.014). CONCLUSIONS: OPN over-expression was closely related to capsular infiltration, venous invasion, lymph node metastasis, and also with worse prognosis, suggesting that OPN might be deemed as a useful molecular marker for predicting the prognosis of HCC.

Adult↗

Protein expression changes in the nucleus accumbens and amygdala of inbred alcohol-preferring rats given either continuous or scheduled access to ethanol.

Chronic ethanol (EtOH) drinking produces neuronal alterations within the limbic system. To investigate changes in protein expression levels associated with EtOH drinking, inbred alcohol-preferring (iP) rats were given one of three EtOH access conditions in their home-cages: continuous ethanol (CE: 24h/day, 7days/week access to EtOH), multiple scheduled access (MSA: four 1-h sessions during the dark cycle/day, 5 days/week) to EtOH, or remained EtOH-naïve. Both MSA and CE groups consumed between 6 and 6.5g of EtOH/kg/day after the 3rd week of access. On the first day of EtOH access for the seventh week, access was terminated at the end of the fourth MSA session for MSA rats and the corresponding time point (2300h) for CE rats. Ten h later, the rats were decapitated, brains extracted, the nucleus accumbens (NAcc) and amygdala (AMYG) microdissected, and protein isolated for 2-dimensional gel electrophoretic analyses. In the NAcc, MSA altered expression levels for 12 of the 14 identified proteins, compared with controls, with six of these proteins altered by CE access, as well. In the AMYG, CE access changed expression levels for 22 of the 27 identified proteins, compared with controls, with 8 of these proteins altered by MSA, as well. The proteins could be grouped into functional categories of chaperones, cytoskeleton, intracellular communication, membrane transport, metabolism, energy production, or neurotransmission. Overall, it appears that EtOH drinking and the conditions under which EtOH is consumed, differentially affect protein expression levels between the NAcc and AMYG. This may reflect differences in neuroanatomical and/or functional characteristics associated with EtOH self-administration and possibly withdrawal, between these two brain structures.

Alcohol Drinking↗

Rheology and hydrodynamic properties of Tolypocladium inflatum fermentation broth and its simulation.

A physico-chemical, two phase simulated pseudoplastic fermentation (SPF) broth was investigated in which Solka Floc cellulose fibre was used to simulate the filamentous biomass, and a mixture of 0.1% (w/v) carboxymethyl cellulose (CMC) and 0.15 M aqueous sodium chloride was used to simulate the liquid fraction of the fermentation broth. An investigation of the rheological behaviour and hydrodynamic properties of the SPF broth was carried out, and compared to both a fungal Tolypocladium inflatum fermentation broth and a CMC solution in a 50 L stirred tank bioreactor equipped with conventional Rushton turbines. The experimental data confirmed the ability of the two phase SPF broth to mimic both the T. inflatum broth bulk rheology as well as the mixing and mass transfer behaviour. In contrast, using a homogeneous CMC solution with a similar bulk rheology to simulate the fermentation resulted in a significant underestimation of the mass transfer and mixing times. The presence of the solid phase and its microstructure in the SPF broth appear to play a significant role in gas holdup and bubble size, thus leading to the different behaviours. The SPF broth seems to be a more accurate simulation fluid that can be used to predict the bioreactor mixing and mass transfer performance in filamentous fermentations, in comparison with CMC solutions used in some previous studies.

Ascomycota↗

EBSD study of the orientation dependence of substructure characteristics in a model Fe-30wt%Ni alloy subjected to hot deformation.

The aim of the present investigation was to determine the orientation dependence of substructure characteristics in an austenitic Fe-30wt%Ni model alloy subjected to hot plane strain compression. Deformation was carried out at a temperature of 950 degrees C using a strain rate of 10 s(-1) to equivalent strain levels of approximately 0.2, 0.4, 0.6 and 0.8. The specimens obtained were analysed using a fully automatic electron backscatter diffraction technique. The crystallographic texture was characterized for all the strain levels studied and the subgrain structure was quantified in detail at a strain of 0.4. The substructure characteristics displayed pronounced orientation dependence. The major texture components, namely the copper, S, brass, Goss and rotated Goss, generally contained one or two prominent families of parallel larger-angle extended subboundaries, the traces of which on the longitudinal viewing plane appeared systematically aligned along the {111} slip plane traces, bounding long microbands subdivided into slightly elongated subgrains by short lower-angle transverse subboundaries. Relatively rare cube-orientated grains displayed pronounced subdivision into coarse deformation bands containing large, low-misorientated subgrains. The misorientation vectors across subboundaries largely showed a tendency to cluster around the sample transverse direction. Apart from the rotated Goss texture component, the stored energy levels for the remaining components were principally consistent with the corresponding Taylor factor values.

Alloys↗

Gene expression and characteristics of a novel fibrinolytic enzyme (subtilisin DFE) in Escherichia coli.

AIMS: The objective of this study is to actively express a novel fibrinolytic enzyme, subtilisin DFE (douchi fibrinolytic enzyme), in Escherichia coli. METHODS AND RESULTS: The DNA fragments encoding pro-subtilisin DFE was amplified and cloned into the vector pET32a to obtain N-terminal Trx fusion expression plasmid. The recombinant subtilisin DFE was successfully expressed and processed in the soluble fraction of E. coli BL21(DE3) in a similar fashion as the endogenous one of Bacillus amyloliquefaciens DC-4, resulting in an active enzyme. Moreover, active enzyme can also be refolded from inclusion body. CONCLUSIONS: Active subtilisin DFE can be expressed and processed in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidences that subtilisin DFE can be actively expressed in E. coli and the pro-peptide is essential for guiding the proper folding into the active conformation. As such, large quantities of recombinant subtilisin DFE can be produced for pharmacological and clinical research.

Bacillus↗

Multiferroic BaTiO3-CoFe2O4 Nanostructures.

We report on the coupling between ferroelectric and magnetic order parameters in a nanostructured BaTiO3-CoFe2O4 ferroelectromagnet. This facilitates the interconversion of energies stored in electric and magnetic fields and plays an important role in many devices, including transducers, field sensors, etc. Such nanostructures were deposited on single-crystal SrTiO3 (001) substrates by pulsed laser deposition from a single Ba-Ti-Co-Fe-oxide target. The films are epitaxial in-plane as well as out-of-plane with self-assembled hexagonal arrays of CoFe2O4 nanopillars embedded in a BaTiO3 matrix. The CoFe2O4 nanopillars have uniform size and average spacing of 20 to 30 nanometers. Temperature-dependent magnetic measurements illustrate the coupling between the two order parameters, which is manifested as a change in magnetization at the ferroelectric Curie temperature. Thermodynamic analyses show that the magnetoelectric coupling in such a nanostructure can be understood on the basis of the strong elastic interactions between the two phases.

Journal Article↗

Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium.

The agouti related protein (AgRP) exerts its anabolic effects on food intake by antagonising the alpha-melanocyte stimulating hormone (alpha-MSH) at its receptors, melanocortin receptors 3 and 4 (MC3R and MC4R). A single nucleotide polymorphism (SNP) in the promoter of the human AgRP (hAgRP), -38C>T, was associated with low body fatness. The -38T allele that was associated with low body fatness also resulted in lower promoter activity. Here we report a novel SNP, -3019G>A, again in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the -38C>T SNP (linked alleles: -3019A/-38T and -3019G/-38C). Functional analyses in a human adrenal and two mouse hypothalamus cell lines showed that the -3019A allele had significantly higher promoter activity. Hence, the two linked alleles (-3019A and -38T) had opposite effects on promoter function and yet they were both associated with low body fatness. The region encompassing the -38C>T SNP had approximately 1000-fold higher activity than the region encompassing the -3019G>A SNP, potentially determining the net functional effect between these two SNPs.

Agouti-Related Protein↗

Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus.

Stress-induced neuronal atrophy and death in the hippocampus may play an important role in the etiology of clinical depression. Conventional antidepressants can stimulate hippocampal neurogenesis after chronic administration. AMPA receptor potentiators (ARPs) such as LY392098 and LY451616 are active in both the forced swim test and the tail suspension test, two behavioral despair procedures widely used to predict antidepressant efficacy. Unlike traditional antidepressants, this group of compounds does not affect extracellular concentrations of biogenic amines. In this study, we investigated the effect of LY451646 on progenitor cell proliferation in adult rat hippocampus. Male Sprague-Dawley rats (n = 4-5 per group) received either single or chronic (21 days) doses of LY451646 (0.025-0.5 mg/kg). Bromodeoxyuridine (BrdU) injections and immunohistochemistry were performed 30 min and 24 h after the last drug injection, respectively. Results show that chronic LY451646 treatment increased progenitor cell proliferation (approximately 45%) in the dentate gyrus in a dose-dependent manner. This upregulation of BrdU labeling appeared as an increase in the number of cells arranged in clusters. Similarly, a significant increase in the number of cells in clusters was observed after a single injection of LY451646 (0.05 mg/kg), although the increase in total number of BrdU-positive cells (approximately 30%) did not reach statistical significance. This is the first in vivo study showing the modulation of progenitor cell proliferation by an ARP. These findings suggest that the antidepressant-like activity of ARPs in animals may be attributed, at least in part, to the regulation of progenitor cell proliferation in the hippocampus.

Animals↗

The agouti-related protein and body fatness in humans.

OBJECTIVE: The objective of this study was to examine the impact of a single nucleotide polymorphism (SNP) (-38C>T) in the promoter of the human agouti-related protein (hAgRP) gene on promoter affinity for transcription factors (TFs) and its possible association with body composition phenotypes. DESIGN: Electrophoretic mobility shift assays for the functional studies and association analyses for the population studies. SUBJECTS AND METHODS: Nuclear extracts were isolated from the mouse hypothalamus cell line GT1-7 and subjected to binding assays using oligonucleotide probes corresponding to the -38C>T region and an antibody for the E12/E47 TFs. Individuals (n = 259) from the HERITAGE Family Study were genotyped for the -38C>T SNP and used in the association studies. RESULTS: Electrophoretic mobility shift and supershift assays confirmed binding of the E12/E47 TF to the -38C>T site in a genotype-dependent manner. The T allele was found exclusively in the black subjects while the genotype with the higher binding affinity, CC, was significantly associated with high BMI, fat mass, and percent body fat in the black subjects of the HERITAGE Family Study. CONCLUSIONS: The E12/E47 TF could play a role in the regulation of hAgRP expression while the population studies suggest that the TT genotype of the -38C>T SNP could play a protective role against the development of obesity in the black population of the HERITAGE Family Study.

Adipose Tissue↗

Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils.

Polymorphonuclear neutrophils (PMN) are phagocytic cells constitutively programmed for apoptotic cell death. Exposure to GM-CSF delays apoptosis as measured by annexin-V staining and cell morphological change. We found that STAT5B, STAT1, and STAT3 DNA-binding activity was induced by GM-CSF. We also detected activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway after GM-CSF treatment which was inhibited by treatment with the PI 3-kinase inhibitors, wortmannin and LY294002. We investigated whether STAT or PI 3-kinase activity was necessary for the pro-survival response of GM-CSF in PMN. Exposure of PMN to GM-CSF in the presence of either AG-490, antisense STAT3 oligonucleotides, or wortmannin resulted in a partial inhibition of GM-CSF-mediated pro-survival activity. GM-CSF induced a time-dependent increase in the mRNA and protein expression of the anti-apoptotic Bcl-2-family protein, Mcl-1. We examined the hypothesis that Janus kinase/STAT and PI 3-kinase regulation of Mcl-1 contributed to GM-CSF-delayed apoptosis. Using either AG-490 or wortmannin alone, we observed a dose-dependent inhibition of GM-CSF-induced Mcl-1 expression. Using suboptimal doses of AG-490 and wortmannin, we found that both drugs together had an additive effect on delayed apoptosis and Mcl-1 expression. These data suggest that cooperative regulation of Mcl-1 by the Janus kinase/STAT and PI 3-kinase pathways contribute to GM-CSF-delayed apoptosis.

Apoptosis↗

Photophysical process of hexadecyl 4-biphenylamino benzoate.

The photophysical properties of hexadecyl 4-biphenylamino benzoate (HBAB), the molecule of which possesses a polar end composed of donor (triphenylamino group) and acceptor (ester group) and a long non-polar alkyl tail, have been carefully studied in different conditions. The results show that the twisted intramolecular charge transfer (TICT) emission is given in polar solvents at room temperature and intramolecular charge transfer (ICT) emission is given at 77 K. These can be supported by the solvent effect, temperature effect and the quenching process.

Acetates↗

Photophysical processes of 1,3-dicarbazolypropane.

The photophysical processes of 1,3-dicarbazolypropane (DCZP), which possesses two fluorogen, carbazoly, and one carbonic chain composed of three carbon atoms, were studied. The formation of intermolecular excimer, intramolecular excimer and triple exciplexes have been investigated in the system of DCZP and 1,4-dinitrilebenzene (DNB) with steady state fluorescence spectroscopy. The experimental results show that with the addition of DNB into the lower concentration solution of DCZP in benzene, the fluorescence of intramolecular excimer of DCZP, (D-D)*, is quenched while the ((D-D)A)* type triple exciplex (one molecule of DCZP with one molecule of DNB) is formed and with the addition of DNB into higher concentration solution of DCZP, the formation of (DDA)* type triple exciplex (two molecules of DCZP with one molecule of DNB) is also confirmed.

Carbazoles↗

Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice.

Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on 1-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

Animals↗

Serotonergic neurotoxicity of 3,4-(+/-)-methylenedioxyamphetamine and 3,4-(+/-)-methylendioxymethamphetamine (ecstasy) is potentiated by inhibition of gamma-glutamyl transpeptidase.

Reactive metabolites play an important role in 3,4-(+/-)-methylenedioxyamphetamine (MDA) and 3,4-(+/-)-methylenedioxymethamphetamine (MDMA; ecstasy)-mediated serotonergic neurotoxicity, although the specific identity of such metabolites remains unclear. 5-(Glutathion-S-yl)-alpha-methyldopamine (5-GSyl-alpha-MeDA) is a serotonergic neurotoxicant found in the bile of MDA-treated rats. The brain uptake of 5-GSyl-alpha-MeDA is decreased by glutathione (GSH), but sharply increases in animals pretreated with acivicin, an inhibitor of gamma-glutamyl transpeptidase (gamma-GT) suggesting competition between intact 5-GSyl-alpha-MeDA and GSH for the putative GSH transporter. gamma-GT is enriched in blood-brain barrier endothelial cells and is the only enzyme known to cleave the gamma-glutamyl bond of GSH. We now show that pretreatment of rats with acivicin (18 mg/kg, ip) inhibits brain microvessel endothelial gamma-GT activity by 60%, and potentiates MDA- and MDMA-mediated depletions in serotonin (5-HT) and 5-hydroxylindole acidic acid (5-HIAA) concentrations in brain regions enriched in 5-HT nerve terminal axons (striatum, cortex, hippocampus, and hypothalamus). In addition, glial fibrillary acidic protein (GFAP) expression increases in the striatum of acivicin and MDA (10 mg/kg) treated rats, but remains unchanged in animals treated with just MDA (10 mg/kg). Inhibition of endothelial cell gamma-GT at the blood-brain barrier likely enhances the uptake into brain of thioether metabolites of MDA and MDMA, such as 5-(glutathion-S-yl)-alpha-MeDA and 2,5-bis-(glutathion-S-yl)-alpha-MeDA, by increasing the pool of thioether conjugates available for uptake via the intact GSH transporter. The data indicate that thioether metabolites of MDA and MDMA contribute to the serotonergic neurotoxicity observed following peripheral administration of these drugs.

3,4-Methylenedioxyamphetamine↗

Correlation between induction of the mac25 gene and anti-proliferative effects of 1alpha,25(OH)2-D3 on breast cancer and leukemic cells.

In the differentiation of a myelomonocytic cell line U937 treated with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2-D3], transient proliferation was observed prior to cell growth arrest. The expression of the p21 and p27 genes increased transiently and decreased quickly in the proliferation, suggesting that other genes may contribute to the growth arrest of the cell line after reduction of the p21 and p27 genes. The mac25 gene was isolated as a gene associated with cellular senescence and growth suppression. Despite a previous report that retinoic acid (RA) induced the mac25 gene, the mac25 gene did not increase in U937 cells treated with RA but did increase in the cells treated with 1alpha,25(OH)2-D3. The high level of the expression of the mac25 gene was detected for four days after the 1alpha,25(OH)2-D3 treatment. Therefore, mac25 may contribute to the growth arrest of U937 cells treated with 1,25-D3. The growth responses to 1alpha,25(OH)2-D3 and the expression of the mac25 gene of three other cancer cell lines (Saos-2, U2OS and MCF7) were studied. Although the growth suppression was observed in MCF7 cells treated with 1alpha,25(OH)2-D3 dose-dependently (1-100 nM of 1alpha,25(OH)2-D3), the treatment of 100 nM of 1alpha,25(OH)2-D3 had no effect on the growth of Saos-2 and U2OS cells. The expression of the mac25 gene was up-regulated in MCF7 cells treated with 100 nM of 1alpha,25(OH)2-D3, whereas no transcript of the mac25 gene was detected in Saos-2 and U2OS cells even when they were treated with 100 nM of 1alpha,25(OH)2-D3. These results suggest that the cellular response to 1alpha,25(OH)2-D3 may depend on the induction of the mac25 gene.

Blotting, Northern↗

SMRT as a T3SF-binding protein.

p53-binding consensus-like sequence (T3SF) is located in the murine promoter region of tissue inhibitor of metalloproteinase 3 gene. To identify the genes that encode proteins that bind to T3SF DNA sequence, we screened a cDNA library using the Southwestern technique. The SMRT gene was cloned as one of the candidates. Addition of antibody against SMRT reduced the intensity of a band that is supposed to contain SMRT in electrophoresis mobility shift assay, although antibody against p53 had no effect. Ultraviolet (UV)-irradiation reduced the intensity of the SMRT complex whereas p53 complex was stabilized by UV-irradiation. These results suggest that SMRT may bind to T3SF sequence in p53-independent manner and dissociate from the sequence by UV irradiation.

Binding Sites↗