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Biomedical subjects

Xin Zhou

Publications and source records attributed to Xin Zhou.

At least 127 records · Page 7Linked to original sources

[Genetic association of apoE and apoCI gene polymorphisms with coronary heart disease].

OBJECTIVE: To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease (CHD) in China. METHODS: apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD (age: 65.0 +/- 10.5 years) and 350 controls (age: 63.6 +/- 8.3 years). The haplotype frequencies were estimated. RESULTS: The frequencies of apoE E4/3 genotype (26.9%) and epsilon4 (14.5%) in CHD group were significantly higher than that in the control group (12.6%, 7.0%), P <0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-epsilon4/apoCI-H2 was estimated to be responsible for 9.86% of CHD. CONCLUSION: When the subjects carrying both epsilon4 and H2 alleles, they would have higher risk of suffering from CHD than controls.

Adult↗

[Monitoring of the residue of fosthiazate in water samples using solid-phase extraction coupled with gas chromatography/mass spectrometry].

Solid-phase extraction (SPE) coupled with gas chromatography/mass spectrometry (GC/MS) was used to determine the fosthiazate residue in water samples. The water samples were first filtered through cellulose filters (0.45 microm pore size). A 100 mL volume of filtered water, in which 1 mL of methanol has been added, was then passed through a pre-conditioned 3 cm C18 cartridge at a flow-rate of 1.5 mL/min. Elution was performed by 1 mL of methanol. The eluant was finally dried under reduced pressure for solvent evaporation. The volume was quantitatively adjusted to 0.5 mL with methanol. The analysis was carried out on GC/MS. The mass spectrometer was operated in selected ion monitoring (SIM) mode. According to mass spectrum of fosthiazate, three selected ions at m/z of 126, 195, 283, respectively, were monitored for identification and quantification. High sensitivity and selectivity were achieved by using this method. The limit of detection for fosthiazate in water samples was determined to be 56.4 ng/L. The linearity was demonstrated over a wide range of concentrations covering from 0.282 to 141 microg/L. The recoveries were more than 85.5% and the relative standard deviations for the overall procedure were less than 4.42%. The fosthiazate residue was detected in the water samples from a pool near cropland where fosthiazate was used. The results demonstrate the suitability of the SPE-GC/MS approach for the analysis of fosthiazate in water.

Gas Chromatography-Mass Spectrometry↗

[The association of sulfotransferase1A1 His allele and breast cancer in Han ethnic Chinese women].

OBJECTIVE: To assess the relationship between SULT1A1 Arg213His polymorphism and breast cancer in Hans of Chinese women, as well as the interaction of the polymorphism and related risk factor of breast cancer. METHODS: Distribution of Arg213His polymorphism of the SULT1A1 gene was detected by using PCR-RFLP in 209 cases of breast cancer and 426 matched healthy controls. The OR of susceptibility of SULT1A1 genotypes to breast cancer and the r value of interaction with exposure factors using multivariate logistic regression. RESULTS: (1) There was no significant difference in genotype of Arg/Arg, Arg/His and His/His of SULT1A1 between case and control (P = 0.12). The frequency of His allele was 13.6% and 9.5% in were determined case and control, respectively, P = 0.03; (2) Compared with Arg/Arg genotype, the risk of Arg/His and His/His was increased, P for trend = 0.04; The OR of His allele (Arg/His + His/His) was 2.60 (95% CI: 1.12 - 6.05, P = 0.04); (3) As for the interaction between gene and related exposure factors, His allele strengthen the effect of endogenous estrogen exposure (interaction index r > 1), and weaken the effect of factors related to exposure of some procarcinogen in dietary (r < 1), both being multiplicative interaction model. CONCLUSION: SULT1A1 His allele is positively associated with the risk of breast cancer, and an interaction exist between this allele and related exposure factors.

Adult↗

Decrease of intracellular ATP content downregulated UCP2 expression in mouse hepatocytes.

Mitochondrial uncoupling protein 2 (UCP2) plays an important role in regulating energy metabolism. We previously reported that UCP2 expression in steatotic livers is increased which leads to diminished hepatic ATP stores and renders steatotic hepatocytes vulnerable to ischemic damage. In this study, reagents that inhibit the production of ATP were used to mimic an ischemic state in the liver in order to investigate the effects of decreased intracellular ATP levels on UCP2 expression in a murine hepatocyte cell line (HEP6-16). Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), an oxidative phosphorylation uncoupler, was found to decrease intracellular ATP levels in a dose- and time-dependent manner. Relatively high concentrations of FCCP from 8 to 80 microM were required to reduce the intracellular concentration of ATP. The inhibitory effect of FCCP on intracellular ATP was significantly potentiated by 2-deoxy-D-glucose, an inhibitor of glycolysis that when administered alone had no negative effect on cellular ATP levels in mouse hepatocytes. Decreased intracellular ATP levels were accompanied by lower UCP2 mRNA expression. Upon removal of FCCP and/or 2-deoxy-D-glucose and reculture with normal medium, ATP and UCP2 mRNA levels returned to normal within a few hours. Mitochondrial membrane potential in HEP6-16 cells was dissipated by 80 microM FCCP but not 8 microM FCCP, suggesting that the downregulation of UCP2 expression by FCCP was not related to mitochondrial potential changes. Consequently, the in vitro manipulation of ATP stores is consistent with the in vivo observations associated with ischemia/reperfusion injury.

Adenosine Triphosphate↗

The expression of epidermal growth factor and transforming growth factor-beta1 in the stenotic tissue of congenital pelvi-ureteric junction obstruction in children.

PURPOSE: The aim of this study was to test the hypothesis that expression of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta 1) may be altered in stenotic tissue of patients with congenital hydronephrosis caused by pelviureteric junction (PUJ) obstruction and to evaluate the role of these 2 growth factors. METHODS: The expression of EGF and TGF-beta 1 was evaluated in tissue specimens in 25 children with PUJ obstruction and 15 controls with normal PUJs by immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. All the signals of mRNA products were normalized to the mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) a housekeeping gene, as a ratio. RESULTS: On RT-PCR study, the amount of TGF-beta 1 mRNA in stenotic tissue was higher than in controls, in addition, EGF gene expression in the obstructed junction was significantly lower than in normal junctions. The TGF-beta 1 to GAPDH ratio was 0.57 +/- 0.26 and 0.36 +/- 0.19 in the stenotic tissue and the normal ureter, respectively (P =.012). The EGF to GAPDH ratio was 0.17 +/- 0.08 and 0.37 +/- 0.14 in the stenotic tissue and the normal ureter, respectively (P =.0001). Furthermore, the positive correlations were found between TGF-beta1 gene and protein expression (r = 0.601; P =.001), TGF-beta 1 gene and drainage clearance half-time (T1/2) (r = 0.474; P =.017), TGF-beta 1 protein expression, and T1/2 (r = 0.516; P =.008). A negative correlation was found between EGF gene and T1/2 (r = -0.448; P =.025). On immunolabeling and in situ hybridization labeling, the expression of TGF-beta 1 protein was strongly positive and confined to the muscle cells, spindle cells, and collagen fibers in the stenotic tissue; the expression of TGF-beta 1 mRNA was moderately positive and mainly distributed in the collagen of the stenotic segment, both the expression of EGF protein and mRNA were negative in the normal ureter. CONCLUSIONS: There were increased TGF-beta 1 mRNA expression and decreased EGF mRNA expression in the stenotic tissue after clinical ureteropelvic junction obstruction. The alteration of EGF and TGF-beta 1 expression may be involved in the pathogenesis of congenital hydronephrosis.

Child↗

Photoinduced electron transfer in alpha-helical polypeptides: dependence on conformation and electron donor-acceptor distance.

Long distance electron transfer in proteins is a multiple-pathway process whose kinetics is modulated by the dynamics of flexible peptide chains. Such complexity can be observed even in relatively simple systems, eg. donor bridge acceptor, where the bridge is a polypeptide alpha-helix. We have investigated a series of 24-residue helical polypeptides that exist as monomers in water alcohol media. The principal chromophore and electron acceptor, a pyrene moiety, is connected to the N-terminus via a flexible linker. The electron donor, a tryptophan residue, was placed various distances away from the pyrene-labeled terminus. Time-resolved emission spectroscopy, associated with the fluorescent pendant, pyrene, was employed to study the photoinduced electron-transfer kinetics for the polypeptide analogs. Mechanisms involving only through-bond pathways could not account for the pattern of measured fast charge-separation rates. When the electron donor was placed far enough from the acceptor (i.e. at least six residues apart), a decrease in the electron-transfer rates with the donor acceptor distance was observed. The emission decays for polypeptides with the electron donor exhibited complex behavior and could not be fit using a single-exponential function. For the treatment of the time-resolved data, a multi-exponential model was developed that is based on the assumption of a Gaussian distribution of the classical electronic coupling beta values among the conformers responsible for the observed electron-transfer processes. This approach proved to be informative because, in addition to the mean values of the electron-transfer rate constants, the widths of the distributions of these rates illustrate the size of the conformational space explored by the flexible chains that provide pathways for electron transfer.

Amino Acid Sequence↗

Suppression of HIV-1 replication by HIV-1-irrelevant CD8+ cytotoxic T lymphocytes resulting in preservation of persistently HIV-1-infected cells in vitro.

CD8+ cells of asymptomatic HIV-1 carriers (AC) contain HIV-1-specific cytotoxic T lymphocytes (CTLs) but suppress HIV-1 replication in a class I major histocompatibility complex (MHC-I)-unrestricted manner. In order to selectively investigate the HIV-1-suppressive function of CTLs apart from HIV-1-specific cytotoxicity, HIV-1-irrelevant allo-specific CTLs were established from an HIV-1-uninfected individual and their HIV-1-suppressive activity against autologous CD4+ peripheral blood mononuclear cells (PBMC) was examined. We found that these CTLs significantly suppressed both R5 and X4-HIV-1 replication in either acutely or persistently infected autologous PBMC. Although these CTLs partially killed HIV-1-infected PBMC through Fas ligand, CTLs still suppressed late steps of HIV-1 replication in the presence of neutralizing antibodies to Fas ligand. HIV-1 replication in PBMC that had been suppressed by CTLs was reversible following depletion of CTLs from culture, analogous to the previous observation for CD8+ cell-depleted PBMC of AC. Induction of HIV-1 replication by CTL-depletion was amplified by addition of newly prepared CD4+ cells or activation with staphylococcal enterotoxin B. Our results indicate that CTLs can suppress HIV-1 replication in PBMC in an antigen-nonspecific manner and preserve infected cells in a state capable of restarting HIV-1 replication and transmission.

CD4-Positive T-Lymphocytes↗

Flagellin of enteropathogenic Escherichia coli stimulates interleukin-8 production in T84 cells.

The type III secretion system (TTSS) of enteropathogenic Escherichia coli (EPEC) has been associated with the ability of these bacteria to induce secretion of proinflammatory cytokines, including interleukin-8 (IL-8), in cultured epithelial cells. However, the identity of the effector molecule directly involved in this event is unknown. In this study, we determined that the native flagellar filament and its flagellin monomer are activators of IL-8 release in T84 epithelial cells. Supernatants of wild-type EPEC strain E2348/69 and its isogenic mutants deficient in TTSS (escN) and in production of intimin (eae), grown in Luria-Bertani broth, elicited similar amounts of IL-8 secretion by T84 cells. In contrast, supernatants of EPEC fliC mutants and of B171, a nonflagellated EPEC strain, were defective in inducing IL-8 release, a phenotype that was largely restored by complementation of the fliC gene in the mutant lacking flagella. Purified flagella from E. coli K-12, EPEC serotypes H6 and H34, and enterohemorrhagic E. coli serotype H7 all induced IL-8 release in T84 cells. Induction of IL-8 by purified flagella or His-tagged FliC from EPEC strain E2348/69 was dose dependent and was blocked by a polyclonal anti-H6 antibody. Finally, the mitogen-activated protein kinases (Erk1 and -2 and Jnk) were phosphorylated in flagellin-treated T84 cells, and inhibition of the p38 and Erk pathways significantly decreased the IL-8 response induced by EPEC flagellin. Our data clearly indicate that FliC of EPEC is sufficient to induce IL-8 release in T84 cells and that activation of the Erk and p38 pathways is required for IL-8 induction.

Adhesins, Bacterial↗

Death pathways activated in CaCo-2 cells by Clostridium perfringens enterotoxin.

Clostridium perfringens enterotoxin (CPE), a 35-kDa polypeptide, induces cytotoxic effects in the enterocyte-like CaCo-2 cell culture model. To identify the mammalian cell death pathway(s) mediating CPE-induced cell death, CaCo-2 cultures were treated with either 1 or 10 micro g of CPE per ml. Both CPE doses were found to induce morphological damage and DNA cleavage in CaCo-2 cells. The oncosis inhibitor glycine, but not a broad-spectrum caspase inhibitor, was able to transiently block both of those pathological effects in CaCo-2 cells treated with the higher, but not the lower, CPE dose. Conversely, a caspase 3/7 inhibitor (but not glycine or a caspase 1 inhibitor) blocked morphological damage and DNA cleavage in CaCo-2 cells treated with the lower, but not the higher, CPE dose. Collectively, these results indicate that lower CPE doses cause caspase 3/7-dependent apoptosis, while higher CPE doses induce oncosis. Apoptosis caused by the lower CPE dose was shown to proceed via a classical pathway involving mitochondrial membrane depolarization and cytochrome c release. As the CPE concentrations used in this study for demonstrating apoptosis and oncosis have pathophysiologic relevance, these results suggest that both oncosis and apoptosis may occur in the intestines during CPE-associated gastrointestinal disease.

Apoptosis↗

A combination of Ang II and carbon tetrachloride accelerates process of hepatic fibrosis.

OBJECTIVE: To assess whether Angiotensin II (Ang II) and carbon tetrachloride (CCl(4)) used in combination could accelerate the process of fibrosis and whether Ang II play a role in exagerating hepatic fibrosis in rats. METHODS: Ang II was injected into the abdominal cavity of Sprague-Dawley (SD) rats together with subcutaneous injection of CCl(4). Rats were killed after 14 and 28 d. Blood serum and liver specimen were collected. The extent of fibrosis in the stained liver tissue sections was determined with the KS 400 Image Analysis System. RESULTS: Rats receiving Ang II and CCl(4) for 28 d showed extensive liver fibrosis. Along with the increase of hepatic fibrosis, the serum concentration of Ang II went up gradually. CONCLUSIONS: A combination of Ang II and CCl(4) would accelerate the process of hepatic fibrosis. Ang II probably took part in the occurrence of heparic fibrosis.

Alanine Transaminase↗

[An experimental study of the intracellular distribution and the activation of mitogen-activated protein kinases in myocardial cells in scalded rats].

OBJECTIVE: To investigate the intracellular distribution and the activation of mitogen-activated protein kinases (MAPKs) in myocardial cells in scalded rats. METHODS: Wistar rats were used in this study and forty of them were inflicted with 40% III degree scald on the back and eight normal ones as control. The samples of plasma and myocardial tissue were harvested at 1, 3, 6, 12 and 24 postburn hours (PBHs), and samples were also obtained from normal rats as control. The plasma CK-MB activity was determined by routine method. The activation states of all the members of MAPKs [p38 kinase, ERKs (extracellular signal-regulated protein kinases) and JNK (c-Jun N-terminal kinase)] in the myocardial tissue samples were detected by Western blotting. The tissue slides were stained by immunohistochemistry methods. RESULTS: Activation of p38 kinase and ERK with nuclear translocation was found postburn, especially during 1, 3 and 6 PBHs (P < 0.01). But there was no activation of JNK during 1 - 24 PBHs. The plasma CK-MB content increased at 3 PBH and reached summit at 12 PBHs (P < 0.05 - 0.01). CONCLUSION: p38 kinase and ERK signal pathways might play important roles in the early postburn injury of myocardial cells, inducing myocardial injury.

Animals↗

[Meta-analysis for relationship between apoE gene polymorphism and coronary heart disease].

OBJECTIVE: To evaluate relationship between ApoE gene polymorphism and coronary heart disease (CHD). METHODS: Meta-analysis was applied with a random-effect model for the collected data. RESULTS: Difference in pooled frequencies, d, of apoE genotypes E3/2, E4/2, E3/3, E4/3 and E4/4 between case and control groups were 2.3%, -0.8%, -8.5%, 10.5% and 0.9%, respectively. Difference in pooled frequencies, d, of apoE alleles epsilon2, epsilon3 and epsilon4 were -1.5%, -4.2% and 5.8%, respectively, with a statistical significance between four groups. CONCLUSIONS: apoE gene polymorphism was involved in coronary heart disease. Persons with apoE E3/3 genotype or epsilon3 allele were not susceptible to CHD, but those with apoE E4/4 genotype or epsilon4 allele had higher risk suffering from CHD than others.

Apolipoproteins E↗

Nonunique steady states in the disordered harmonic chain.

The heat transport in disordered harmonic chains (DHCs) with arbitrary heat baths is studied, based on a general formulation developed by Dhar [Phys. Rev. Lett. 86, 5882 (2001)]. The obtained temperature profile of a steady state is very unusual for any heat bath: (i) it is not unique, but dependent on the initial condition; (ii) it may be highly nonlinear, even though the temperature difference of the two ends of the system is in zero limit, and the temperature gradient inverted Delta T is not inversely proportional to the system size; and (iii) when a DHC is coupled to two thermostats with the same temperature, the temperature of the system is still not uniform. The localized higher frequency normal modes induced by the mass disorders are responsible for these strange properties.

Journal Article↗

Classification of amino acids based on statistical results of known structures and cooperativity of protein folding.

It has been found that the 20 kinds of amino acids have different frequencies of occurrence in alpha,beta, and coil structures [P. Y. Chou and G. D. Fasman, Biochemistry 13, 211 (1974)]. Based on more known structures of proteins, frequencies for each amino acid in alpha and beta secondary structures are recalculated. Next step, under the approximation ignoring the chain connectivity of proteins, energy parameters to form alpha and beta secondary structures for each amino acid are obtained. According to the hydrophobicity and energies in alpha and beta secondary structures, 20 kinds of amino acids are classified. The results suggest that dividing amino acids to five or nine groups is desirable. At last, a protein model considering both two-body hydrophobic interaction and one-body energy to form secondary structures, hydrophobic-polar alphabeta model, is introduced. It is shown that the consistency among various energy terms makes the cooperativity of protein folding closer to the experiments.

Amino Acid Sequence↗

[Influence of TGF beta(1) on expression of Smad7 mRNA and protein in rat liver cells].

OBJECTIVE: To investigate the influence of exogenous transforming growth factor beta 1 (TGFbeta1) on growth and signal inhibitor Smad7 protein and its mRNA in BRL cells (rat liver cell line). METHODS: BRL cells were incubated with TGFbeta1 and divided into 0 minute group, 90 minute group and 24 hour group according to the time of incubation with TGFbeta1. Morphologic changes were observed. The expression of Smad7 mRNA and protein was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immnuohistrochemistry. RESULTS: Growth stagnancy and morphologic change of cells was not seen among the three groups. The expression levels of Smad7 mRNA was the highest in 90-minute group and the lowest in 0-minute group, and the 24-hour group took the second place. Most of the Smad7 immune positive granules were observed in cytoplasm. CONCLUSION: TGFbeta1 does not induce growth stagnancy in BRL cells during the period of 90 minutes to 24 hours. There is a relation of effectiveness for a given period of time between the level of Smad7 and TGFbeta1 stimulation.

Animals↗

The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells in the periosteum and in the condensed mesenchyme of membranous skeletal elements cannot differentiate into osteoblasts. These cells do, however, express Runx2/Cbfa1, another transcription factor required for bone formation. In contrast, Osx is not expressed in Runx2/Cbfa1 null mice. Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells.

Animals↗

Aminoguanidine renders inducible nitric oxide synthase knockout mice more susceptible to Salmonella typhimurium infection.

Aminoguanidine (AG), a nitric oxide synthase (NOS) inhibitor, has been widely used to study the role of inducible NOS (iNOS) in host defense against infections caused by various pathogens including Salmonella typhimurium. iNOS has been reported to play an important role in host defense against S. typhimurium infection both in vitro and in vivo. In this report we show those AG treatment lead to weight loss in both wild-type and iNOS knockout mice, and rendered them more susceptible to Salmonella infection. These results suggest that AG may have side effects other than the inhibition of iNOS, and that data obtained from studies using AG should be interpreted with caution.

Animals↗